Summary of your 'study carrel' ============================== This is a summary of your Distant Reader 'study carrel'. The Distant Reader harvested & cached your content into a collection/corpus. It then applied sets of natural language processing and text mining against the collection. The results of this process was reduced to a database file -- a 'study carrel'. The study carrel can then be queried, thus bringing light specific characteristics for your collection. These characteristics can help you summarize the collection as well as enumerate things you might want to investigate more closely. This report is a terse narrative report, and when processing is complete you will be linked to a more complete narrative report. Eric Lease Morgan Number of items in the collection; 'How big is my corpus?' ---------------------------------------------------------- 514 Average length of all items measured in words; "More or less, how big is each item?" ------------------------------------------------------------------------------------ 4882 Average readability score of all items (0 = difficult; 100 = easy) ------------------------------------------------------------------ 49 Top 50 statistically significant keywords; "What is my collection about?" ------------------------------------------------------------------------- 475 SARS 391 CoV-2 153 COVID-19 91 CoV 67 ACE2 66 MERS 56 patient 54 RNA 30 China 29 Fig 22 cell 20 figure 20 COV-2 19 protein 19 Coronavirus 17 covid-19 16 PCR 15 infection 13 virus 12 vaccine 12 East 10 human 10 RBD 10 Cov-2 9 clinical 9 Wuhan 8 severe 8 IFN 7 drug 7 coronavirus 7 Middle 7 3CL 6 respiratory 6 antibody 4 transmission 4 pro 4 olfactory 4 Disease 4 CNS 3 study 3 site 3 flavonoid 3 dna 3 disease 3 day 3 compound 3 cancer 3 animal 3 air 3 Vero Top 50 lemmatized nouns; "What is discussed?" --------------------------------------------- 13631 patient 12121 infection 11657 virus 10747 cell 10366 coronavirus 9438 protein 8398 study 7356 % 6482 disease 5532 antibody 4986 case 4773 vaccine 4503 syndrome 4159 response 4055 receptor 3952 treatment 3787 drug 3508 analysis 3377 transmission 3294 sample 3266 host 3186 day 2998 result 2937 spike 2789 sequence 2786 time 2783 datum 2761 symptom 2689 lung 2519 inhibitor 2484 animal 2413 model 2390 risk 2374 genome 2368 test 2330 mouse 2313 outbreak 2300 assay 2293 activity 2254 system 2216 pandemic 2208 effect 2186 level 2171 coronaviruse 2165 protease 2133 replication 2132 pneumonia 2109 gene 2041 trial 2035 site Top 50 proper nouns; "What are the names of persons or places?" -------------------------------------------------------------- 37257 SARS 24030 CoV-2 10202 CoV 9305 COVID-19 5304 MERS 4994 al 4037 ACE2 3991 et 3883 . 3826 RNA 2987 S 2574 China 2332 Coronavirus 1843 PCR 1793 Fig 1578 Wuhan 1254 RT 1235 East 1208 Middle 1195 RBD 961 M 901 T 874 Health 850 Table 848 CoVs 837 Disease 765 IgG 761 C 732 S1 717 IFN 694 TMPRSS2 636 Syndrome 626 Respiratory 612 3CL 610 Novel 603 S2 589 IgM 575 N 560 CT 540 IL-6 537 COV-2 533 Vero 529 II 520 J 506 CoV-1 501 ELISA 480 March 460 Human 456 USA 455 United Top 50 personal pronouns nouns; "To whom are things referred?" ------------------------------------------------------------- 5300 we 5144 it 1525 they 940 i 594 them 292 he 210 us 136 she 128 itself 98 you 67 one 53 themselves 16 him 10 nsp10 8 ourselves 6 mg 6 himself 4 ours 4 nsp15 4 me 3 ⍬ 3 nsp7 3 mrnas 3 her 2 theirs 2 il-6r 2 covid-19 2 's 1 − 1 βcovs 1 ys110 1 yis26g81 1 ybs20 1 y.org/protp 1 wuhan-12 1 turns 1 the~5-fold 1 theaflavin 1 sdpp4 1 s230 1 s 1 pubchem 1 protein−protein 1 percpcy5.5 1 pdcs 1 oneself 1 mine 1 mace2 1 ile188 1 il6 Top 50 lemmatized verbs; "What do things do?" --------------------------------------------- 72198 be 14674 have 7558 use 4521 show 3933 include 3413 base 3263 report 2943 bind 2941 associate 2891 infect 2332 identify 2323 cause 2300 suggest 2280 find 2069 do 1976 increase 1974 develop 1903 detect 1757 provide 1746 compare 1713 induce 1710 follow 1639 test 1598 confirm 1547 indicate 1546 inhibit 1512 reduce 1512 perform 1498 neutralize 1483 require 1478 observe 1388 target 1381 relate 1358 treat 1335 consider 1331 lead 1283 reveal 1259 contain 1252 know 1231 emerge 1231 demonstrate 1169 describe 1151 determine 1122 result 1109 express 1106 involve 1072 mediate 1055 make 1050 obtain 1029 prevent Top 50 lemmatized adjectives and adverbs; "How are things described?" --------------------------------------------------------------------- 7978 viral 7618 respiratory 5963 not 5960 human 5754 severe 5726 - 5643 clinical 5144 also 4610 high 4561 acute 4293 other 3198 more 3107 covid-19 2906 immune 2901 novel 2880 such 2624 however 2456 positive 2356 potential 2316 low 2272 different 2223 well 2085 specific 2064 first 1997 most 1982 antiviral 1960 anti 1892 only 1801 further 1750 new 1741 early 1632 inflammatory 1542 several 1523 as 1520 available 1450 non 1441 important 1439 therapeutic 1372 negative 1370 like 1354 possible 1352 molecular 1341 similar 1326 infected 1325 structural 1248 thus 1237 therefore 1226 many 1226 large 1212 recent Top 50 lemmatized superlative adjectives; "How are things described to the extreme?" ------------------------------------------------------------------------- 628 most 329 least 278 high 243 good 218 Most 112 large 89 low 86 late 69 close 41 early 34 great 29 strong 29 bad 17 near 16 long 15 big 13 small 9 steep 9 short 9 fast 7 new 5 safe 5 old 4 furth 4 common 3 weak 3 N95s 2 simple 2 harsh 2 grave 2 deep 2 S4A 2 S1B 2 Least 2 CoV-2-host 1 young 1 tricky 1 tremeGENE 1 tough 1 topmost 1 strict 1 slow 1 slight 1 s40726 1 quick 1 nsp42nsp5 1 nonsevere 1 n(t 1 lmert 1 leftmost Top 50 lemmatized superlative adverbs; "How do things do to the extreme?" ------------------------------------------------------------------------ 1369 most 231 least 40 well 6 worst 3 highest 2 lowest 2 long 2 fast 2 close 1 topmost 1 mir-1273d 1 leftmost 1 hard 1 furthest 1 early 1 -detect 1 -3.9 Top 50 Internet domains; "What Webbed places are alluded to in this corpus?" ---------------------------------------------------------------------------- 135 doi.org 38 www.who.int 20 www.gisaid.org 18 github.com 14 www 13 creativecommons.org 12 www.cdc.gov 11 www.ncbi.nlm.nih.gov 10 clinicaltrials.gov 9 nextstrain.org 8 orcid.org 7 www.worldometers.info 6 www.mdpi.com 6 www.fda.gov 5 www.rcsb.org 5 www.nature.com 5 creat 4 www.epicentro.iss.it 4 covid19.who.int 3 zinc.docking.org 3 www.proteinatlas.org 3 www.nih.gov 3 www.hivresearch.org 3 www.ebi.ac.uk 3 www.clinicaltrials.gov 3 virological.org 3 pubs.acs.org 3 biorender.com 2 www.virology.net 2 www.sigmaaldrich.com 2 www.natureindex.com 2 www.mohfw.gov.in 2 www.medrxiv.org 2 www.isrctn.com 2 www.genomedetective.com 2 www.frontiersin.org 2 www.dpz.eu 2 www.cogconsortium.uk 2 www.bioinformatics.babraham.ac.uk 2 www.ambion.com 2 swissmodel.expasy.org 2 sars-coronavirus-2.info 2 mafft.cbrc.jp 2 isaric4c.net 2 gnomad.broadinstitute.org 2 gisaid.org 2 dx.doi.org 2 creativecommons 2 coronavirus.jhu.edu 2 clinical Top 50 URLs; "What is hyperlinked from this corpus?" ---------------------------------------------------- 14 http://www 12 http://doi.org/10.1101/2020.09.24.20191411 12 http://doi.org/10.1101/2020.08.31.20183095 12 http://doi.org/10.1101/2020.03.08.20032821 11 http://doi.org/10.1101/2020.09.21.20198838 10 http://doi.org/10.1101/2020.06.15.20131672 9 http://www.gisaid.org/ 9 http://www.gisaid.org 8 http://doi.org/10.1101/2020.11.11.20229062 7 http://doi.org/10.1101/2020.10.08.20209544 6 http://doi.org/10.1101/2020.09.29.20203125 6 http://doi.org/10.1101/2020.08.06.20169433 6 http://doi.org/10.1101/2020.06.17.20133504 6 http://creativecommons.org/licenses/by/4.0/ 5 http://doi.org/10.1101/2020.09.18.20189647 5 http://creativecommons.org/ 5 http://creat 5 http://clinicaltrials.gov/ 4 http://www.who.int 4 http://www.epicentro.iss.it/coronavirus/sars-cov-2 3 http://www.worldometers.info/coronavirus/ 3 http://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports/ 3 http://www.nature.com/reprintsPublisher's 3 http://www.clinicaltrials.gov 3 http://nextstrain.org/ 3 http://nextstrain.org 3 http://doi.org/10.1101/2020.04.30.20086116 3 http://doi.org/10 2 http://zinc.docking.org/substances/subsets/fda/ 2 http://www.worldometers.info/ 2 http://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports 2 http://www.who.int/emergencies/ 2 http://www.who.int/csr/disease/coronavirus 2 http://www.who.int/ 2 http://www.rcsb.org/pdb 2 http://www.rcsb.org/ 2 http://www.proteinatlas.org/ 2 http://www.ncbi.nlm.nih.gov/genbank/sars-cov-2-seqs/ 2 http://www.ncbi.nlm.nih.gov/genbank 2 http://www.isrctn.com/ISRCTN66726260 2 http://www.genomedetective.com/app/typingtool/cov/ 2 http://www.fda.gov/ 2 http://www.cdc.gov/ncidod/sars/labdiagnosis.htm 2 http://www.cdc.gov/coronavirus/ 2 http://sars-coronavirus-2.info 2 http://mafft.cbrc.jp/alignment/server/ 2 http://gnomad.broadinstitute.org/ 2 http://github.com/rrwick/Porechop 2 http://gisaid.org 2 http://doi.org/10.1101/2020.07.16.20155143 Top 50 email addresses; "Who are you gonna call?" ------------------------------------------------- 3 consortiumcontact@cogconsortium.uk 2 research@f1000.com 1 vivek.gupta@mq.edu.au 1 tmadani@kau.edu.sa 1 teresa.lambe@ndm.ox.ac.uk 1 support@bmj.com.visi 1 support@bmj.com 1 simon.graham@pirbright.ac.uk 1 sghosh@iitj.ac.in 1 reprints@rsna.org 1 rbaric@email.unc.edu 1 qinlab313@163.com 1 qincf@bmi.ac.cn 1 nitin.chitranshi@mq.edu.au 1 kubyshkin_av@mail.ru 1 journals.permissions@oup.com 1 joaquim.segales@irta.cat 1 howchang@stanford.edu 1 gming@pennmedicine.upenn.edu 1 erich.gulbins@uni-due.de 1 dbarouch@bidmc.harvard.edu 1 cmfraser@tigr.org Top 50 positive assertions; "What sentences are in the shape of noun-verb-noun?" ------------------------------------------------------------------------------- 141 receptor binding domain 57 coronavirus indicating person 45 cov infected patients 41 cov-2 infected patients 31 cov-2 neutralizing antibodies 25 study did not 21 cov-2 is not 21 cov-2 is still 20 cells were then 19 virus was not 17 cov-2 has not 17 cov-2 is more 16 cov-2 is also 16 studies have also 16 vaccine induces sars 15 cov has not 15 cov-2 is highly 15 cov-2 test results 14 cov-2 was not 14 infection causes neuronal 14 receptor binding domains 13 cells were also 13 coronavirus causing severe 13 cov-2 is essential 13 covid-19 is still 13 infection is not 13 patients did not 13 samples were positive 12 ace2 is also 12 cells were further 12 cov-2 does not 12 cov-2 is able 12 covid-19 is not 12 protein reduces s1 12 rna was not 11 coronavirus neutralizing antibodies 11 cov-2 is likely 11 cov-2 is similar 11 covid-19 confirmed cases 11 covid-19 is higher 11 patients tested positive 10 cov infected dcs 10 cov is not 10 cov neutralizing antibodies 10 cov was first 10 cov-2 uses ace2 10 patients do not 10 receptor binding site 10 rna was also 10 treatment is not Top 50 negative assertions; "What sentences are in the shape of noun-verb-no|not-noun?" --------------------------------------------------------------------------------------- 4 cov-2 is not yet 4 study had no role 2 antibodies are not functional 2 cases has no co 2 cov has no importance 2 cov is not well 2 cov-2 are not entirely 2 cov-2 is not completely 2 cov-2 is not detectable 2 cov-2 is not fully 2 covid-19 is not only 2 covid-19 is not well 2 infection does not significantly 2 infection have not yet 2 infection is not yet 2 patients is not clear 2 patients was not available 2 study has not yet 2 virus was no longer 1 % had no runny 1 . found no correlation 1 ace2 are not equivalent 1 ace2 is no longer 1 ace2 is not appreciably 1 ace2 is not capable 1 ace2 is not essential 1 analyses are not subordinate 1 analyses does not necessarily 1 analyses showed no abnormalities 1 analysis were not degs 1 antibodies are not present 1 antibodies have not yet 1 antibodies is not protective 1 antibody are no longer 1 antibody did not significantly 1 antibody is not always 1 cases had no symptoms 1 cases have no symptoms 1 cases showed no co 1 cases showed no significant 1 cases were not asymptomatic 1 cells did not significantly 1 cells is not clear 1 cells were not as 1 cells were not persistent 1 coronavirus is not yet 1 coronavirus requiring no significant 1 cov are no longer 1 cov are not fully 1 cov does not closely A rudimentary bibliography -------------------------- id = cord-298989-qk0k2lmz author = , Umesh title = Identification of new anti-nCoV drug chemical compounds from Indian spices exploiting SARS-CoV-2 main protease as target date = 2020-05-13 keywords = CoV-2; SARS; ligand summary = title: Identification of new anti-nCoV drug chemical compounds from Indian spices exploiting SARS-CoV-2 main protease as target Carnosol exhibited highest binding affinity -8.2 Kcal/mol and strong and stable interactions with the amino acid residues present on the active site of SARS-CoV-2 Mpro. Our virtual screening results suggest that these small chemical molecules can be used as potential inhibitors against SARS-CoV-2 Mpro and may have an anti-viral effect on nCoV. SARS-CoV-2 main protease, a potential drug target, crystal structure (PDB-ID: 6Y84) was available and used for docking simulation and identification of potential drug molecule form Indian spices. Details of various kinds of interaction shown between the amino acids near the active site of SARS-CoV-2 main protease along with their respective inhibitor constant (Ki) and biological source and binding energy. Potential inhibitor of COVID-19 main protease (Mpro) from several medicinal plant compounds by molecular docking study doi = 10.1080/07391102.2020.1763202 id = cord-319184-voc0eqb9 author = Abduljalil, Jameel M. title = Laboratory diagnosis of SARS-CoV-2: available approaches and limitations date = 2020-06-14 keywords = CoV-2; SARS summary = Clinical 397 evaluation of the cobas SARS-CoV-2 test and a diagnostic platform switch during 48 398 hours in the midst of the COVID-19 pandemic Molecular Diagnosis of COVID-19 by the Novel, Highly Sensitive and Specific COVID-406 19-RdRp/Hel Real-Time Reverse Transcription-PCR Assay Validated In Vitro Rapid and visual detection of 2019 458 novel coronavirus (SARS-CoV-2) by a reverse transcription loop-mediated isothermal 459 amplification assay Transcription Loop-Mediated Isothermal Amplification Assays Targeting SARS-CoV-2 Transcription Loop-Mediated Isothermal Amplification Method for Rapid Detection of 467 SARS-CoV-2 Development of a reverse 469 transcription-loop-mediated isothermal amplification as a rapid early-detection method for 470 novel SARS-CoV-2 Mediated Isothermal Amplification Method for Rapid Detection of SARS-CoV-2 Development and clinical application of a 500 rapid IgM-IgG combined antibody test for SARS-CoV-2 infection diagnosis Novel Antigen-Based Rapid Detection Test for the Diagnosis of SARS-CoV-2 in Serological immunochromatographic 525 approach in diagnosis with SARS-CoV-2 infected COVID-19 patients doi = 10.1016/j.nmni.2020.100713 id = cord-324856-hf969tav author = Abir, Tanvir title = Factors Associated with the Perception of Risk and Knowledge of Contracting the SARS-Cov-2 among Adults in Bangladesh: Analysis of Online Surveys date = 2020-07-21 keywords = Bangladesh; COVID-19; Cov-2; SARS summary = title: Factors Associated with the Perception of Risk and Knowledge of Contracting the SARS-Cov-2 among Adults in Bangladesh: Analysis of Online Surveys Since the sheer illness of the whole country is sufficient to destroy the health care system, this current study is to examine changes of individual perception of risk for contracting SARS-Cov-2, and the awareness level in Bangladesh during the early and late lockdowns implemented by the government of Bangladesh. In this study, males who were worried about contracting SARS-Cov-2 were more likely to perceive themselves as being at high risk of contracting the infection, as well as those who did not quarantine themselves or only did so at the request of the public health officers. Moreover, in India, it was found that a higher level of knowledge on COVID-19 was associated with the high-risk perception of contracting the infection during the consistent lockdown period [28] . doi = 10.3390/ijerph17145252 id = cord-297132-lhfa9fl5 author = Aghagoli, Ghazal title = Neurological Involvement in COVID-19 and Potential Mechanisms: A Review date = 2020-07-13 keywords = ACE2; COVID-19; CoV-2; SARS; patient summary = In this review, we synthesize a range of clinical observations and initial case series describing potential neurologic manifestations of COVID-19 and place these observations in the context of coronavirus neuro-pathophysiology as it may relate to SARS-CoV-2 infection. The novel 2019 coronavirus disease (COVID-19) caused by Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) results in a variety of symptoms including fever, cough, and fatigue [1] . The Kawasaki-like syndrome that is now described in young patients following COVID-19 infection and associated with a hyper-inflammatory state is further suggestive of a vascular inflammatory potential of SARS-CoV-2 [48, 49] . Once established in the CNS, SARS-CoV, the virus responsible for Severe Acute Respiratory Syndrome (SARS), has been shown to be capable of inducing rapid transneuronal spread and death of infected neurons in transgenic mice models expressing human ACE2 receptors [63] . doi = 10.1007/s12028-020-01049-4 id = cord-343302-g9vcchrh author = Agrawal, Anurodh Shankar title = Passive Transfer of A Germline-like Neutralizing Human Monoclonal Antibody Protects Transgenic Mice Against Lethal Middle East Respiratory Syndrome Coronavirus Infection date = 2016-08-19 keywords = CoV; East; MERS; Middle summary = title: Passive Transfer of A Germline-like Neutralizing Human Monoclonal Antibody Protects Transgenic Mice Against Lethal Middle East Respiratory Syndrome Coronavirus Infection Here, we further characterized this novel human mAb in our Tg mouse model of MERS-CoV infection and showed prophylactic and therapeutic protection of mice treated with m336 before and after a lethal challenge with the virus, respectively. In our studies, we noted that passively transferred with 1 mg and 0.1 mg of m336 monoclonal antibodies to individual mice 12 h prior to challenge with 1,000 LD 50 of MERS-CoV resulted in 100% and 75% protection against lethality, respectively (Fig. 1) , suggesting that using 0.1 mg m336/mouse as a prophylaxis is suboptimal to completely neutralize viral infection, thereby allowing residual viruses to replicate within lungs during the course of infection. doi = 10.1038/srep31629 id = cord-272113-j82z4q8x author = Akaji, Kenichi title = Design and Evaluation of Anti-SARS-Coronavirus Agents Based on Molecular Interactions with the Viral Protease date = 2020-08-27 keywords = 3CL; CoV; SARS; inhibitor summary = Instead of an exhaustive survey of the inhibitors [21] , we provide an overview of several typical inhibitors, and our recent efforts for the rational design of new scaffolds are discussed based on the inhibitory mechanism and structural interactions with SARS-CoV 3CL pro . Following the interaction with the active center of the SARS-CoV 3CL pro , the nucleophilic Cys145 thiolate generated by a proton-withdrawing effect caused by His41 at the catalytic dyad promotes a typical 1,4-addition to the α,β-unsaturated structure of the Michael acceptor ( Figure 3 ). These data also indicate that the corresponding S1 pocket of the SARS-CoV 3CL pro might accept a simple ring structure containing heteroatoms at this specific interaction site, which provides a clue to our design of a potent substrate-based inhibitor described later in this review. doi = 10.3390/molecules25173920 id = cord-304617-5ozf18lg author = Al-Khafaji, Khattab title = Using integrated computational approaches to identify safe and rapid treatment for SARS-CoV-2 date = 2020-05-15 keywords = CoV-2; Mpro; SARS; drug summary = The aim was to assess the effectiveness of available FDA approved drugs which can construct a covalent bond with Cys145 inside binding site SARS-CoV-2 main protease by using covalent docking screening. The 50 ns molecular dynamics simulation was conducted for saquinavir, ritonavir and remdesivir to evaluate the stability of these drugs inside the binding pocket of SARS-CoV-2 main protease. The got protein-drug complex structures from covalent docking were submitted to MD simulations (saquinavir, ritonavir, and remdesivir with SARS-CoV-2 Mpro). The effect of drug-protein interactions upon dynamics of biological system is a fundamental in drug discovery thereby we used RMSD to investigate the influence of saquinavir, ritonavir, and remdesivir upon the stability of SARS-CoV-2 Mpro. One of the more noteworthy findings in this study is that MD simulation analysis that saquinavir, ritonavir, and remdesivir can form stable interaction inside the binding site of SARS-CoV-2 Mpro. doi = 10.1080/07391102.2020.1764392 id = cord-354398-f3cg8gi1 author = Al-Saud, Haya title = Automated SARS-COV-2 RNA extraction from patient nasopharyngeal samples using a modified DNA extraction kit for high throughput testing date = 2020-09-20 keywords = COV-2; RNA; SARS summary = The high demand has created a global bottleneck in testing capacity, which prompted us to modify available resources to extract viral RNA and perform reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) to detect SARS-COV-2. The high demand has created a global bottleneck in testing capacity, which prompted us to modify available resources to extract viral RNA and perform reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) to detect SARS-COV-2. We validated the modified Invitrogen Forensic DNA Purification kit in extracting in-laboratory propagated SARS-COV-2 RNA by conducting manual and automated extractions on titrations from 15 000 copies to 60 copies of SARS-COV-2 followed by RT-qPCR methods: the commercially available TaqPath One-Step qRT-QP-CR kit (using the N, S, and ORF1b genes) and primers and probes from Metabion, Germany to establish an inhouse RT-qPCR assay based on E, RdRp2 and RdRp4 gene detection as per recommended SARS-COV-2 testing from CDC and WHO. doi = 10.5144/0256-4947.2020.373 id = cord-324978-9qfhsj3n author = Alagaili, Abdulaziz N. title = Middle East Respiratory Syndrome Coronavirus Infection in Dromedary Camels in Saudi Arabia date = 2014-02-25 keywords = CoV; MERS summary = The presence of viral nucleic acids in rectal and nasal swabs and a subset of serum and whole blood samples was assayed by reverse transcriptionquantitative PCR (RT-qPCR) with primers targeting the upE and ORF1a genome regions of MERS-CoV (16, 17) . Rectal and nasal swabs collected in parallel with serum samples from the same animals were assayed for MERS-CoV nucleic acids by RT-qPCR. PCR analysis of a random selection of serum and whole blood samples collected from nasal or rectal swab PCR-positive, seropositive, and seronegative DC revealed no evidence of viremia (see Table S1 in the supplemental material). Definitive evidence that DC can be infected with MERS-CoV was obtained when viral sequences were detected in nasal swabs from DC sampled in close proximity to outbreaks of the disease among humans in Qatar (11) and Jeddah, KSA (10) . doi = 10.1128/mbio.00884-14 id = cord-337835-78i6j11i author = Alfaraj, Sarah H. title = The impact of co-infection of influenza A virus on the severity of Middle East Respiratory Syndrome Coronavirus date = 2017-02-09 keywords = CoV; MERS summary = title: The impact of co-infection of influenza A virus on the severity of Middle East Respiratory Syndrome Coronavirus 1 We present four cases of combined infection with influenza and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection. A nasopharyngeal swab was positive for MERS-CoV with Ct value upE gene 37; ORF1A 36 and negative for Influenza. A nasopharyngeal swab was positive for MERS-CoV with Ct value upE gene 37; ORF1A 36 and negative for Influenza. A repeat swab after 3 days was negative for MERS-CoV but positive for influenza A. The NLST worked with the FES teams in the North West (NW) and West Midlands (WMids) regions of England to audit the reporting of Legionella cases with onset dates during each calendar year between 2012 and 2014, inclusive. WHO guidelines for investigation of cases of human infection with Middle East Respiratory Syndrome Coronavirus (MERS-CoV) doi = 10.1016/j.jinf.2017.02.001 id = cord-305704-grzrkff9 author = Almutairi, Abdulelah title = Dermatological Manifestations in Patients With SARS-CoV-2: A Systematic Review date = 2020-07-28 keywords = CoV-2; SARS summary = Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been initially defined as a disease of the respiratory tract; however, with the increasing number of patients and announcing that the virus became a pandemic, new systemic clinical manifestations are observed, including dermatological manifestations. The following step was filtering the results to include only original research studies investigating the different types of skin and dermatological clinical manifestations in patients with SARS-CoV-2. The results were then filtered to include only original research studies examining the different types of skin and dermatological clinical manifestations in patients with SARS-CoV-2. After searching the abstracts and reviewing the eligibility criteria in identified potential abstracts, a total of seven studies [14] [15] [16] [17] [18] [19] [20] were considered as eligible to be included in the present systematic review, covering a total of 555 patients with SARS-CoV-2 who had dermatological symptoms in the form of skin lesions. doi = 10.7759/cureus.9446 id = cord-321851-ku4z34lu author = Alosaimi, Bandar title = MERS-CoV infection is associated with downregulation of genes encoding Th1 and Th2 cytokines/chemokines and elevated inflammatory innate immune response in the lower respiratory tract date = 2020-02-29 keywords = CoV; MERS; respiratory; th1 summary = Our results showed a downregulation of Th2, inadequate (partial) Th1 immune response and high expression levels of inflammatory cytokines IL-1α and IL-1β and the neutrophil chemoattractant chemokine IL-8 (CXCL8) in the lower respiratory tract of MERS-CoV infected patients. The lower respiratory tract samples from MERS-CoV infected patients and healthy non-infected controls were used to quantify expression levels of the main 12 human pro-inflammatory cytokines and chemokines (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17A, IFN-γ, TNF-α, and GM-CSF). A side-by-side analysis of the data derived from the RT 2 -PCR profiling of pulmonary Th1/Th2 responses showed that genes encoding Th1 and Th2-related cytokines and chemokines were largely downregulated in the lower respiratory tract of MERS-CoV infected patients. Therefore, the high expression of inflammatory cytokines and downregulation of the Th1 and Th2 immune responses in the lower respiratory tracts of MERS-CoV infected patients may contribute to a more severe infection, higher case fatality, lung inflammation, and immunopathology. doi = 10.1016/j.cyto.2019.154895 id = cord-321855-7b1c2xdh author = Alshami, Alanoud title = Silent disease and loss of taste and smell are common manifestations of SARS-COV-2 infection in a quarantine facility: Saudi Arabia date = 2020-10-30 keywords = COV-2; PCR; SARS summary = title: Silent disease and loss of taste and smell are common manifestations of SARS-COV-2 infection in a quarantine facility: Saudi Arabia PRIMARY AND SECONDARY MEASURES: The clinical presentation, prevalence of asymptomatic carriers among SARS-COV-2 positive quarantined subjects, and the difference between virus clearance among symptomatic and asymptomatic individuals. The persistent positive PCR beyond 14 days observed in the mild symptomatic residents despite being symptoms free, warrant further studies to determine its implications on disease spread and control. have examined 24 asymptomatic infected individuals with a history of close contact with SARS-COV-2 confirmed cases and found that only 20% of them developed symptoms. Our findings are in light with a recent study that reported a 59% prevalence of loss of taste and smell in a cohort of COVID-19 patients [15] . Sudden onset of loss of smell and taste were prevalent in our study and were key symptoms of mild disease. doi = 10.1371/journal.pone.0241258 id = cord-294912-xl0wzi16 author = Alteri, Claudia title = Detection and quantification of SARS-CoV-2 by droplet digital PCR in real-time PCR negative nasopharyngeal swabs from suspected COVID-19 patients date = 2020-09-08 keywords = CoV-2; SARS; covid-19 summary = Since SARS-CoV-2-based disease (COVID-19) spreads as a pandemic, the necessity of a highly sensitive molecular diagnosis that can drastically reduce false negatives reverse transcription PCR (rtPCR) results, raises as a major clinical need. ddPCR-based assay detected SARS-CoV-2 genome in nasopharyngeal samples of 19 (34.5%) patients (median viral-load: 128 copies/mL, IQR: 72–345). Thanks to a ddPCR-based assay, we achieved a rapid and accurate SARS-CoV-2 diagnosis in rtPCR-negative respiratory samples of individuals with COVID-19 suspect, allowing the rapid taking care and correct management of these patients. In this study, the presence of SARS-CoV-2 genome was evaluated in 55 SARS-CoV-2 rtPCR negative nasopharyngeal swabs from COVID-19 suspected patients thanks to a quantitative ad hoc designed assay based on ddPCR. This proof-of-concept study shows that an in-house ddPCR-based assay can allow an efficient detection of SARS-CoV-2 at low copy number in symptomatic cases resulted negative by standard rtPCR. doi = 10.1371/journal.pone.0236311 id = cord-283956-zgrtux7i author = Amin, Sk. Abdul title = Fight against novel coronavirus: A perspective of medicinal chemists date = 2020-06-12 keywords = COVID-19; CoV-2; Mpro; SARS; drug summary = Like other RNA viruses, the functional significance of this Mpro or chymotrypsin-like protease (3CLpro) of SARS-CoV-2 emerges as an attractive drug target for the development of anti-viral agents. A group of scientists from the Cairo University, Egypt predicted COVID-19 spike binding site to a cell-surface receptor namely Glucose Regulated Protein 78 (GRP78) by employing structural bioinformatics in combination with protein-protein docking [55] . An early virtual screening (VS) study of FDA approved drugs (retrieved from Selleckchem Inc.) against the first resolved SARS-CoV-2 Mpro crystal structure (PDB: 6LU7) was performed. In another study, Elfiky [67] reported SARS-CoV-2 RdRp targeted molecular docking study of some anti-polymerase drugs which have been approved for use against various viruses. This study deals with the information currently available on potential targets for therapeutic invention and screening of new compounds or drug repurposing against SARS-CoV-2 (Figure 8 ). Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2 doi = 10.1016/j.ejmech.2020.112559 id = cord-272010-kc0gi3cj author = Anand, Sai Priya title = Interaction of Human ACE2 to Membrane-Bound SARS-CoV-1 and SARS-CoV-2 S Glycoproteins date = 2020-09-29 keywords = ACE2; CoV-2; SARS summary = The viral entry of SARS-CoV-2 depends on an interaction between the receptor-binding domain of its trimeric spike glycoprotein and the human angiotensin-converting enzyme 2 (ACE2) receptor. One potential therapeutic target receiving significant attention is the interaction between the SARS-CoV-2 spike (S) glycoprotein and its receptor, human angiotensin-converting enzyme 2 (ACE2). To better understand the interactions between membrane-bound SARS-CoV-1 and SARS-CoV-2 S glycoproteins with their receptor, human ACE2, we sought to determine the cooperativity of ACE2 within the respective trimers. Cryo-EM structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains Cryo-electron microscopy structures of the SARS-CoV spike glycoprotein reveal a prerequisite conformational state for receptor binding Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor Cryo-EM structure of the SARS coronavirus spike glycoprotein in complex with its host cell receptor ACE2 doi = 10.3390/v12101104 id = cord-310239-mmvuij3k author = Arentz, Susan title = Clinical significance summary: Preliminary results of a rapid review of zinc for the prevention and treatment of SARS-CoV-2 and other acute viral respiratory infections date = 2020-08-01 keywords = CoV-2; SARS; infection; zinc summary = Indirect evidence from systematic reviews have found zinc supplementation is effective for the prevention of acute respiratory infections in young children and zinc lozenges may reduce the duration of the common cold in adults. As of the 9 June 2020, the preliminary findings of a rapid review of zinc for the prevention or treatment Pending any definitive evidence, clinicians might consider assessing the zinc status of people with chronic disease co-morbidities and older adults as part of a SARS-CoV-2 clinical work-up, as both groups have a higher risk of zinc deficiency/insufficiency and poorer outcomes from SARS-CoV-2. The primary objective of this rapid review was to assess the effects of zinc on the incidence, duration and severity of acute upper or lower respiratory tract infections caused by SARS-CoV-2 infection in people of any age and of any zinc status when used as a preventive supplement or as a therapy. doi = 10.1016/j.aimed.2020.07.009 id = cord-347734-0z2kin6r author = Armann, J. P. title = Anti-SARS-CoV-2 IgG antibodies in adolescent students and their teachers in Saxony, Germany (SchoolCoviDD19): very low seropraevalence and transmission rates date = 2020-07-17 keywords = CoV-2; SARS summary = title: Anti-SARS-CoV-2 IgG antibodies in adolescent students and their teachers in Saxony, Germany (SchoolCoviDD19): very low seropraevalence and transmission rates However, there is reason to believe that children play a less significant role in SARS-CoV-2 transmission compared to influenza, making control measures focused on this age group less effective: Most countries-including Germany-report a much lower proportion of cases in children compared to their population size 4-6 . The findings from this unique study in older students and their teachers indicate that the prevalence of IgG antibodies against SARS-CoV-2 remains extremely low after the first wave of the corona pandemic in Germany. In fact, 5 of the 12 participants with antibodies against SARS-CoV-2 had a personal or household history of COVID-19, yielding a ratio of unidentified to identified cases of 2.4, which is much smaller than that previously assumed by some authors 9 . doi = 10.1101/2020.07.16.20155143 id = cord-271648-m2c5bvuj author = Ashour, Hossam M. title = Insights into the Recent 2019 Novel Coronavirus (SARS-CoV-2) in Light of Past Human Coronavirus Outbreaks date = 2020-03-04 keywords = China; CoV; MERS; RNA; SARS summary = Coronaviruses (CoVs) are RNA viruses that have become a major public health concern since the Severe Acute Respiratory Syndrome-CoV (SARS-CoV) outbreak in 2002. However, unlike SARS-CoV, human-to-human transmission of MERS-CoV is not easy and has not been confirmed except in cases of very close contact with infected patients in health care settings [67] . Similar to the adaptation of SARS-CoV to human host, MERSr-CoVs that are circulating in bats had to undergo several amino acid changes in RBD of S protein to become capable of infecting camels and humans ( Figure 2 ) [74] . S protein of severe acute respiratory syndrome-associated coronavirus mediates entry into hepatoma cell lines and is targeted by neutralizing antibodies in infected patients Characterization of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spike glycoprotein-mediated viral entry Fully human monoclonal antibody directed to proteolytic cleavage site in severe acute respiratory syndrome (SARS) coronavirus S protein neutralizes the virus in a rhesus macaque SARS model doi = 10.3390/pathogens9030186 id = cord-255883-mz6nyisw author = Asif, Muhammad title = COVID-19 and therapy with essential oils having antiviral, anti-inflammatory, and immunomodulatory properties date = 2020-08-14 keywords = COVID-19; CoV-2; RNA; SARC; SARS summary = Essential oils (EOs) have long been known to have anti-inflammatory, immunomodulatory, bronchodilatory, and antiviral properties and are being proposed to have activity against SARC-CoV-2 virus. An in vitro study conducted by Hoffmann and colleagues revealed that SARC-CoV-2 depends on cellular serine protease (TMPRSS2) for S proteins priming which are known to interact with human ACE2 receptors in the lungs and facilitate entry into the cells. The authors opted the following keywords to find relevant studies: "essential oils", "antiviral", "COVID-19", "SARC-CoV-2", "bronchodilation", "immunomodulatory'''', "anti-inflammatory'''', "corona virus''''. Thus, on the basis of these docking and in vitro studies, it is proposed that garlic essential oils and their isolated constituents, especially DAS, have potential to prevent the entry of virus into host cells as well as to activate molecular antioxidant pathways that decrease the secretions of culprit pro-inflammatory cytokines. Essential oils have long been known to have anti-inflammatory, antioxidant, immunomodulatory, and antiviral properties and are being proposed to have activity against SARC-CoV-2. doi = 10.1007/s10787-020-00744-0 id = cord-268468-036i1082 author = Asif, Muhammad title = The role of biosensors in COVID-19 outbreak date = 2020-09-18 keywords = COVID-19; CoV-2; PCR; SARS summary = In this review, the importance of biosensors including electrochemical, surface enhanced Raman scattering, field-effect transistor and surface plasmon resonance biosensors in the detection of SARS-CoV-2 has been underscored. In this outbreak, three different types of diagnosis tests are being used including (i) chest CT scan along with clinical indications, (ii) RNA detection using RT-PCR assay and (iii) lateral flow assays, full automatic chemiluminescence method, enzyme-linked immunosorbent assay (ELISA) for the determination of antibodies [5] . In this review, we have summarized the biosensor based technologies which are able to detect SARS-CoV-2 effectively. The peptide monolayer was successfully coated on SPR biosensor and further functionalized with virus nucleocapsid protein which was finally able to detect SARS-CoV-2 antibodies at nanomolar level. The sensing aptitude of the biosensor was evaluated employing antigen protein, self-cultured virus, and nasopharyngeal swab samples taken from people infected with COVID-19 pneumonia. doi = 10.1016/j.coelec.2020.08.011 id = cord-256508-ce59ovan author = Asselah, Tarik title = COVID-19: discovery, diagnostics and drug development date = 2020-10-08 keywords = COVID-19; China; CoV-2; RNA; SARS; infection; patient summary = To date, with the exception of intravenous Remdesivir and dexamethasone, which have modest effects in moderate to severe COVID-19, no strong clinical evidence supports the efficacy and safety of any other drugs against SARS-CoV-2. The current diagnostic strategy to identify patients with COVID-19 is to test samples taken from the respiratory tract to assess for the presence of SARS-CoV-2 specific nucleic acid targets [47] . The neutralization assay is a laboratory-based test that uses live virus and cell culture methods to determine if patient antibodies can prevent viral infection in vitro [72] . A randomized, controlled, openlabel trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection and severe respiratory illness COVID-19 was performed [126] . Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals doi = 10.1016/j.jhep.2020.09.031 id = cord-268034-7id7sfsu author = Auerswald, Heidi title = Assessment of Inactivation Procedures for SARS-CoV-2 date = 2020-05-28 keywords = CoV-2; SARS summary = This data demonstrates that all chemical (AVL, inactivating sample buffer and formaldehyde) and heat treatment (56°C and 98°C) methods tested completely inactivated viral loads of up to 5 log10. The buffers used in this lysis step yield varying results [11, 13, 15, 16] ; however, unlike 224 previous studies [11] , this study found that AVL buffer alone was successfully able to fully 225 inactivate up to 5 log10 of virus from three different primary isolates of SARS-CoV-2. Previous 234 studies have shown that GITC-lysis buffers are able to inactivate SARS-CoV-2 samples [11, 12] ; 235 however, the addition of Triton-X may be necessary for complete inactivation [11] . Therefore, formaldehyde treatment does not appear to be a 247 solution for increased molecular SARS-CoV-2 testing; however, it does remain a viable alternative 248 for sample inactivation or disinfection. doi = 10.1101/2020.05.28.120444 id = cord-342569-ja96xfns author = Azer, Samy A. title = COVID-19: Pathophysiology, diagnosis, complications and Investigational therapeutics date = 2020-08-05 keywords = COVID-19; CoV-2; SARS; patient summary = On 31 December 2019, the Chinese authorities reported to the World Health Organisation (WHO) an emerging of a novice coronavirus, currently the virus is known as SARS-CoV-2 and the disease name is coronavirus-19 disease (COVID19) , that has emerged in patients from Wuhan city, Hubel Province [1] . Recently it was debated that targeting the Notch signalling to prevent SARS-CoV-2 infection and interfering with the progression of COVID-19associated heart and lungs disease pathogenesis [13] . It is not clear whether the observed SARS-CoV-2-associated liver injury is cause by direct viral injury or related to hepatoxic drugs, coexisting systemic inflammatory changes, sepsis, respiratory distress syndrome-induced hypoxia, and multiple organ failure [18] . In patients with type 2 diabetes mellitus who are infected with COVID-19, it is important to remember that two receptor proteins ACE-2 and dipeptidyl peptidase-4 (DPP-4) are test can detect IgM, and IgG antibodies against SARS-CoV-2 in the serum, plasma, and whole blood [23] . doi = 10.1016/j.nmni.2020.100738 id = cord-355567-60sfv60p author = Azuma, Kenichi title = Environmental factors involved in SARS-CoV-2 transmission: effect and role of indoor environmental quality in the strategy for COVID-19 infection control date = 2020-11-03 keywords = COVID-19; CoV-2; Japan; SARS; air; ventilation summary = Recently, 36 researchers insisted on the potential risk of indoor airborne transmission of SARS-CoV-2 and the importance of sufficient and effective ventilation, particle filtration, and air sterilization as infection control measures inside buildings [43] . Therefore, the MHLW published a document titled "Prevention of the COVID-19 Clusters" Abbreviation: SARS-CoV severe acute respiratory syndrome coronavirus Fig. 1 Traditional Japanese office building HVAC systems: a a centralized HVAC system; and b a centralized ventilation system with an individual air-conditioning system on March 1, 2020 [94] , showing the need for adequate ventilation in buildings because a ventilation standard for infection control has not been established in general buildings in Japan and the characteristics of indoor spaces where the clusters occurred might include poor ventilation and crowding. doi = 10.1186/s12199-020-00904-2 id = cord-030934-t7akdu6x author = Bahrami, Afsane title = Genetic and pathogenic characterization of SARS-CoV-2: a review date = 2020-08-26 keywords = ACE2; COVID-19; CoV-2; SARS; Wuhan; coronavirus summary = The first case of Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported in December 2019. Bioinformatics analysis of the viral genome from one COVID-19 patient shared 89 and 82% sequence similarity with bat SARS-like-CoVZXC21 and human SARS-CoV, respectively [41] . In a recent report it was shown that SARS-CoV-2''s S-protein entry into 293/human ACE2 receptor cells is primarily mediated via endocytosis, and that PIKfyve, a TPC2 and cathepsin L are crucial for virus entry. Findings of an open-label nonrandomized clinical trial among 22 infected patients indicated that hydroxychloroquine treatment significantly reduced viral load in COVID-19 cases and its effectiveness is promoted by azithromycin [99] . The M, E, and N structural proteins of the severe acute respiratory syndrome coronavirus are required for efficient assembly, trafficking, and release of virus-like particles Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response doi = 10.2217/fvl-2020-0129 id = cord-322811-6lebh7ca author = Baig, Mirza S. title = Identification of a Potential Peptide Inhibitor of SARS-CoV-2 Targeting its Entry into the Host Cells date = 2020-06-26 keywords = ACE2; CoV-2; SARS summary = METHODS: Docking and Molecular Dynamics (MD) simulation studies revealed that designed peptide maintains their secondary structure and provide a highly specific and stable binding (blocking) to SARS-CoV-2. RESULTS: We have designed a novel peptide that could inhibit SARS-CoV-2 spike protein interaction with ACE2, thereby blocking the cellular entry of the virus. Currently, the computational analysis of structural differences in human ACE2 impact its binding to the SARS-CoV-2 spike protein, which thereby lays a foundation for the design and development of ACE2-based peptide inhibitors of SARS-CoV-2 [47] [48] [49] . After a detailed analysis of interface residues, a small stretch of the ACE2 PD N-terminal region (23-amino acids: Glu23 to Leu45) was found to be interacting majorly with the SARS-CoV-2 spike protein ( Fig. 2 and Table 1 ). Computational alanine (A) scanning was performed to identify the critically important amino acids of the 23aa peptide inhibitor involved in binding to the SARS-CoV-2 spike protein. doi = 10.1007/s40268-020-00312-5 id = cord-270550-if748w2n author = Bailey, Adam L. title = SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis date = 2020-11-05 keywords = ACE2; CoV-2; Fig; RNA; SARS summary = To ascertain whether human pluripotent stem cell-derived cardiomyocytes (hPSC-derived 150 CMs) can serve as an appropriate model to study cardiac SARS-CoV-2 infection, we measured 151 ACE2 mRNA expression in hPSC-derived CMs. Quantitative RT-PCR revealed that hPSC-152 derived CMs abundantly expressed ACE2 mRNA. We identified numerous host genes that were differentially 226 regulated upon SARS-CoV-2 infection in each of the examined cell types and two-dimensional 227 tissues (Fig. 3c) . 236 GO pathway analysis revealed that infected hPSC-derived CMs and two-dimensional co-237 culture tissues showed upregulation of genes associated with immune cell activation, stress-238 induced transcription, and responses to pathogens including viruses. Consistent with the 343 possibility that disrupted sarcomere gene expression might contribute to reduced EHT 344 contractility, immunostaining of hPSC-derived CMs infected with SARS-CoV-2 revealed evidence 345 of sarcomere loss 3 days following infection (Fig. 6c) , a time point that preceded cell death. doi = 10.1101/2020.11.04.364315 id = cord-257958-yehnlabq author = Barh, Debmalya title = Multi-omics-based identification of SARS-CoV-2 infection biology and candidate drugs against COVID-19 date = 2020-10-10 keywords = COVID-19; CoV-2; SARS; Table; analysis summary = In this paper, using multi-omics (interactome, proteome, transcriptome, and bibliome) data and subsequent integrated analysis, we present the biological events associated with SARS-CoV-2 infection and identify several candidate drugs against this viral disease. In this paper, we have used an integrative omics approach considering the SARS-CoV-2 infected host interactome, proteome, transcriptome, and bibliome datasets and analysed the COVID-19 associated host genetic information to identify common host pathways that are deregulated during SARS-CoV-2 infection and potential drugs targeting those pathways. In our analysis, we observed SARS-CoV-2 infection shares other viral pathways such as To identify pathway specific drugs, we used the genes involved in the five most important common pathways (viral processes including all the individual virus pathways, mRNA splicing, ubiquitin mediated proteolysis, cytokine signaling in immune system, and protein processing in endoplasmic reticulum). doi = 10.1016/j.compbiomed.2020.104051 id = cord-328996-3sf2i45r author = Barthélémy, Romain title = Efficacy of Almitrine in The Treatment of Hypoxemia in Sars-Cov-2 Acute Respiratory Distress Syndrome date = 2020-06-06 keywords = ARDS; Cov-2 summary = title: Efficacy of Almitrine in The Treatment of Hypoxemia in Sars-Cov-2 Acute Respiratory Distress Syndrome This monocenter retrospective study aimed to evaluate the association between almitrine 19 introduction and improvement of oxygenation in Sars-Cov-2 ARDS. Inclusion criteria in the study were: admission for respiratory failure, a diagnosis of ARDS 24 according to Berlin criteria 8 , laboratory confirmed Sars-Cov-2 infection, almitrine infusion in 25 ICU. In our 73 observational study, almitrine was associated with an increase in PaO 2 /FiO 2 ratio after 74 treatment. Furthermore, despite an associated improvement in PaO 2 /FiO 2 ratio, the majority 76 of patients receiving almitrine went on to needing additional rescue interventions or died. 77 This may be explained by the fact that, in our study, almitrine has been used as a rescue 78 therapy in severe patients with worsening hypoxemia and very low PaO 2 /FiO 2 ratio. doi = 10.1016/j.chest.2020.05.573 id = cord-274399-cd7cmpoj author = Barzin, Amir title = SARS-CoV-2 Seroprevalence among a Southern U.S. Population Indicates Limited Asymptomatic Spread under Physical Distancing Measures date = 2020-09-29 keywords = CoV-2; SARS; UNC summary = This is one of the first published seroprevalence studies from North Carolina and included multicenter, primary care, and emergency care facilities serving a low-density, suburban and rural population since description of the North Carolina state index case introducing the SARS-CoV-2 respiratory pathogen to this population. Asymptomatic infection by SARS-CoV-2 (with no clinical symptoms) was examined using an Emergency Use Authorization (EUA)-approved antibody test (Abbott) for the presence of SARS-CoV-2 IgG. This study identifies a very limited seroprevalence of SARS-CoV-2 among asymptomatic individuals accessing the UNC Health system. This study employed an EUA assay performed in a CLIA-certified laboratory on a venous blood sample, with demonstrated specificity to detect antibodies only to SARS-CoV-2, not to seasonal coronaviruses. Upon arrival for SARS-CoV-2 Seroprevalence in North Carolina ® routine care or scheduled visits for enrollment into the study, patients performed a consent procedure that included reviewing recent COVID-19 clinical history using UNC IRB-approved questionnaires. doi = 10.1128/mbio.02426-20 id = cord-331856-j0gedx43 author = Basile, K. title = Accuracy amidst ambiguity: false positive SARS-CoV-2 nucleic acid tests when COVID-19 prevalence is low date = 2020-09-30 keywords = CoV-2; SARS summary = In countries with a low prevalence of COVID-19 and a low pre-test probability, confirmation of positive nucleic acid test (NAT) results for SARS-CoV-2 is recommended given the potential for false positive results. [2] [3] [4] Initially, the Public Health Laboratory Network (PHLN) Australia recommended that confirmatory testing be performed on samples where SARS-CoV-2 RNA had been detected to ensure that the result was a true positive. In the context of Australia''s low prevalence of COVID-19 and thus low pre-test probability for infection, we recommend that all positive SARS-CoV-2 NAT results be confirmed by supplementary testing on the original nucleic acid extract and/or re-extraction of nucleic acid from the original sample (if available) and tested using another assay(s) with different gene targets and/or lower limits of detection 10 (Fig. 1) . doi = 10.1016/j.pathol.2020.09.009 id = cord-296219-zzg9hds0 author = Battaglini, Denise title = Neurological Manifestations of Severe SARS-CoV-2 Infection: Potential Mechanisms and Implications of Individualized Mechanical Ventilation Settings date = 2020-08-12 keywords = COVID-19; CoV-2; SARS; brain; patient summary = Within this Abbreviations: ACE2, angiotensin-converting enzyme-2; ANE, acute necrotizing encephalopathy; ARDS, acute respiratory distress syndrome; BALF, bronchoalveolar lavage fluid; BBB, blood brain-barrier; CA, Ammon''s horn; CD, cluster of differentiation; CI, confidence interval; CNS, central nervous system; CoV, coronavirus; COVID-19, coronavirus disease 2019; CT, computed tomography; CXCR, chemokine receptor; DIC, disseminated intravascular coagulation; DO 2 , oxygen delivery; DPP4, dipeptidyl dipeptidase-4; ECMO, extracorporeal membrane oxygenation; FiO 2 fraction of inspired oxygen; FOX, forkhead box; HLH, hemophagocytic lymphohistiocytosis; ICAM, intracellular adhesion molecule; ICH, intracerebral hemorrhage; ICP, intracranial pressure; IFN, interferon; MERS, Middle East respiratory syndrome; MHV, mouse hepatitis virus; MRI, magnetic resonance images; nCoV, novel coronavirus; OR, odds ratio; PaCO 2 , partial pressure of carbon dioxide; PaO 2 partial pressure of oxygen; PbtO 2 brain tissue oxygenation tension; PCR, polymerase chain reaction; PEEP, positive end-expiratory pressure; PRES posterior reversible encephalopathy syndrome; RM, recruitment maneuvers; RNA, ribonucleic acid; SARS, severe acute respiratory syndrome; TLRs, toll-like receptor; TMPRSS2 transmembrane serine protease 2; TNF, tumor necrosis factor; WHO, World Health Organization. doi = 10.3389/fneur.2020.00845 id = cord-352230-8mazd3eu author = Beeraka, Narasimha M. title = Strategies for Targeting SARS CoV-2: Small Molecule Inhibitors—The Current Status date = 2020-09-18 keywords = ACE-2; CoV-2; Nrf-2; SARS; TMPRSS2; coronavirus; infection summary = Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2) induced Coronavirus Disease 19 (COVID-19) cases have been increasing at an alarming rate (7.4 million positive cases as on June 11 2020), causing high mortality (4,17,956 deaths as on June 11 2020) and economic loss (a 3.2% shrink in global economy in 2020) across 212 countries globally. SARS-CoV-2 infection is mediated by the binding of viral Spike proteins (S-protein) to human cells through a 2-step process, which involves Angiotensin Converting Enzyme-2 (ACE2) and Transmembrane Serine Protease (TMPRSS)-2. Therefore, in this review, we have reviewed structural features of SARS-CoV-2 with special emphasis on key molecular targets and their known modulators that can be considered for the development of NSMIs. COVID-19 is a devastating disease caused by a coronavirus related to the one that caused outbreaks of Severe Acute Respiratory Syndrome (SARS) in the year 2002 (1, 2) . doi = 10.3389/fimmu.2020.552925 id = cord-350451-lf27iuwk author = Benedetti, Francesca title = SARS‐CoV‐2: March toward adaptation date = 2020-07-11 keywords = CoV-2; SARS summary = A third factor still subject of debate is how and how much the mutations observed in SARS-CoV-2 provide an indication of viral fitness and adaptation, and their role first into the initial phases of transmission and now during the reduction of viral spreading. The worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel human pathogen, first detected in China quickly became a global health emergency, culminating with the World Health Organization publicly proclaiming the SARS-CoV-2 outbreak as a pandemic (11 March 2020) . Several reports result show that SARS-CoV-2 is rapidly moving across countries, and new mutation hotspots are emerging in different parts of the genome. Although SARS-CoV-2 is less lethal than MERS-CoV, up to 20% of the infected people develop rapidly a severe disease characterized by interstitial pneumonia and acute respiratory distress syndrome that can ultimately lead to death. Davide Zella http://orcid.org/0000-0001-5576-5770 Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant doi = 10.1002/jmv.26233 id = cord-277076-yvsyo4l9 author = Berger, A. title = SARS date = 2019-09-12 keywords = CoV; SARS; antibody; human summary = Measures including source isolation of patientswho only became infectious after onset of clinical symptomsstrict infection control in health care facilities, timely identification and quarantining of exposed contacts, and perhaps also measures to increase social distance, such as travel warnings and screening of travelers, had led to this remarkable and remarkably rapid success. A further, small SARS outbreak occurred again in Guangdong in late 2003/early 2004; molecular analysis of virus isolates from human cases and animals sampled at the same place and time confirmed that this was zoonotically acquired from Paguma larvata. The laboratory diagnosis of SARS remains a challenge; in fact, despite the rapid identification of SARS-CoV as the etiological agent, testing contributed little to the successful control of the 2003 outbreak. A negative antibody test result later than 21 days after the onset of illness is likely to indicate that no infection with SARS-CoV has taken place. doi = 10.1016/b978-0-444-63951-6.00624-0 id = cord-288484-qy619tfg author = Bernard‐Valnet, R. title = Two patients with acute meningoencephalitis concomitant with SARS‐CoV‐2 infection date = 2020-05-30 keywords = CoV-2; SARS summary = doi = 10.1111/ene.14298 id = cord-301974-4wn40ivq author = Berry, Jody D title = Development and characterisation of neutralising monoclonal antibody to the SARS-coronavirus date = 2004-09-01 keywords = CoV; ELISA; SARS; Spike; western summary = A total of 15 l of SARS-CoV antigen (infected Vero cell lysate) or 5 g of highly purified virus is coated (per spot) for 1 h at 37 • C. c Protein specificity tests shown here were determined by Western immunoblot with purified virus and infected cell lysate under denaturing conditions (Fig. 1) . The four Western immunoblot negative, virus-neutralising mAbs were tested for their ability to bind native SARS-CoV in infected cells by immunofluorescence assay. While purified virus is clearly the optimal antigen tested in this series of experiments, the lower quality SARS-CoV-infected Vero cell lysates are, however, much easier to prepare for diagnostic assays. This paper describes the development of murine mAbs which recognise SARS-CoV antigens in ELISA, immuno-dotblot, Western immunoblot, on the surface of infected cells, and in neutralisation assays. doi = 10.1016/j.jviromet.2004.04.009 id = cord-335289-m4u96x2v author = Bhattacharya, Manojit title = Development of epitope‐based peptide vaccine against novel coronavirus 2019 (SARS‐COV‐2): Immunoinformatics approach date = 2020-03-05 keywords = COV-2 summary = authors: Bhattacharya, Manojit; Sharma, Ashish R.; Patra, Prasanta; Ghosh, Pratik; Sharma, Garima; Patra, Bidhan C.; Lee, Sang‐Soo; Chakraborty, Chiranjib title: Development of epitope‐based peptide vaccine against novel coronavirus 2019 (SARS‐COV‐2): Immunoinformatics approach Therefore, as the situation was getting worse and worse, the need for designing a suitable peptide vaccine component against the SARS-COV-2 was growing. The amino acid sequence of the targeted protein on SARS-COV-2 was collected from the National Centre for Biotechnological Information (NCBI) database. We obtained a total of 34 sequential linear B-cell epitopes of varying lengths from the IEDB server within spike glycoprotein of SARS-COV-2. In this study, we linked the 13 MHC-I and 3 MHC-II antigenic epitopes with (EAAAK) 3 linker peptide to construct a vaccine component. Moreover, the molecular docking of vaccine components with the TLR-5 proves the significance and effectiveness of these epitopes as an ideal vaccine candidate against SARS-COV-2. Development of epitope-based peptide vaccine against novel coronavirus 2019 (SARS-COV-2): Immunoinformatics approach doi = 10.1002/jmv.25736 id = cord-280662-gakayv6e author = Bian, Jingwei title = Angiotensin-converting enzyme 2 (ACE2): SARS-CoV-2 receptor and RAS modulator date = 2020-10-13 keywords = ACE2; CoV-2; RAS; SARS summary = Angiotensin-converting enzyme 2 (ACE2) was rapidly identified as the critical functional receptor for SARS-CoV-2. Given that ACE2 functions as both a SARS-CoV-2 receptor and a RAS modulator, the treatment for COVID-19 presents a dilemma of how to limit virus entry but protect ACE2 physiological functions. We propose five novel working modes for functional receptor for SARS-CoV-2 infection and the routes of ACE2-mediated virus entering host cells, as well as its regulatory mechanism. SARS-CoV-2 has been shown to share the same functional receptor, angiotensin-converting enzyme 2 (ACE2), with severe acute respiratory syndrome coronavirus (SARS-CoV) 4, 5 . SARS-CoV S-protein binding facilitates ADAM17-dependent ACE2 shedding and has been shown to induce viral entry into the cell 52 . Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2) doi = 10.1016/j.apsb.2020.10.006 id = cord-314793-kb319t4c author = Borroni, Barbara title = Diaphragmatic myoclonus due to SARS-CoV-2 infection date = 2020-10-22 keywords = CoV-2; SARS summary = Neurological signs in patients with SARS-CoV-2 have been widely reported, suggesting a neuroinvasive nature of virus [2, 3] . With the present observation, we report two cases of diaphragmatic myoclonus as neurological subacute manifestation of SARS-CoV-2 infection. The Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10072-020-04766-y) contains supplementary material, which is available to authorized users. Electromyographic recording confirmed rhythmic and synchronous contractions of the diaphragm at 3-Hz frequency as the cause of her abdominal movements (see Fig. 1 ), thus making the diagnosis of diaphragmatic myoclonus or van Leeuwenhoek''s disease [5] . Here, we draw attention to two patients who developed focal diaphragmatic myoclonus after SARS-CoV-2 infection. Indeed, three cases of generalized myoclonus due to SARS-CoV-2 infection have been recently reported [10] . With the present report of two cases, we confirm and extend the neurotropic properties of SARS-CoV-2 virus and point out to a further neurological clinical manifestation of the infection. doi = 10.1007/s10072-020-04766-y id = cord-317952-4oa9hfb4 author = Bourgonje, Arno R. title = Angiotensin‐converting enzyme‐2 (ACE2), SARS‐CoV‐2 and pathophysiology of coronavirus disease 2019 (COVID‐19) date = 2020-05-17 keywords = ACE2; COVID-19; CoV-2; SARS; clinical; disease; patient summary = ACE2 was highly expressed on lung alveolar epithelial cells and small intestinal epithelial cells, consistent with potential routes of viral transmission of SARS-CoV-2, as both respiratory and gastrointestinal systems share interfaces with the external environment. ACE2 expression in the lungs and SARS-CoV-2 viral load have been suggested to increase with age, which might provide an explanation to the higher disease severity observed in older patients with COVID-19 [35] . Both SARS-CoV-2 infection, directly mediated by ACE2 expression and activity, and superimposed disease triggers may be responsible for the observed pathological findings. Additionally, another study reported purpura and livedo racemosa in several severely affected COVID-19 patients with small vessel thrombosis with co-localization of complement and SARS-CoV-2 spike proteins on histopathology [148] .This indicates direct viral infection of the small skin vessels. Circulating plasma concentrations of ACE2 in men and women with heart failure and effects of renin-angiotensin-aldosterone-inhibitors: Potential implications for coronavirus SARS-CoV-2 infected patients doi = 10.1002/path.5471 id = cord-272654-hh29olk7 author = Bošnjak, Berislav title = Low serum neutralizing anti-SARS-CoV-2 S antibody levels in mildly affected COVID-19 convalescent patients revealed by two different detection methods date = 2020-11-02 keywords = CoV-2; Fig; SARS; covid-19 summary = We used a surrogate virus neutralization test (sVNT) and SARS-CoV-2 S protein-pseudotyped vesicular stomatitis virus (VSV) vector-based neutralization assay (pVNT) to assess the degree to which serum antibodies from coronavirus disease 2019 (COVID-19) convalescent patients interfere with the binding of SARS-CoV-2 S to ACE2. Similarly, anti-SARS-CoV-2 S IgA antibodies were present in 33/37 (89.2%) of the tested sera; two samples were diagnosed as borderline positive and two as negative Fig. 1 Qualitative analysis of serum total IgG (A) and IgA (B) antibodies against SARS-CoV-2 S1 in convalescent patients with mild or severe COVID-19 and healthy controls (HC) determined by ELISA. The median sVNT titer of the mildly affected convalescent cohort was 1:180, indicating that patients with mild COVID-19 produce relatively low amounts of SASRS-CoV-2 neutralizing antibodies (Fig. 2H ). This hypothesis is further supported by a positive correlation between the duration of symptoms and total anti-SARS-CoV-2 IgG, but not IgA, antibodies in convalescent patients with mild disease (Fig. 5A, B) . doi = 10.1038/s41423-020-00573-9 id = cord-256888-tdx12ccj author = Bradley, Benjamin T title = Histopathology and ultrastructural findings of fatal COVID-19 infections in Washington State: a case series date = 2020-07-16 keywords = COVID-19; CoV-2; SARS; USA; patient summary = To date, documentation of the histopathological features in fatal cases of the disease caused by SARS-CoV-2 (COVID-19) has been scarce due to sparse autopsy performance and incomplete organ sampling. 8 Post-mortem studies have shown pulmonary, renal, and small vessel injury, with particles resembling virus observed in the kidney by electron microscopy. By electron microscopy, aggregates of uniform, round enveloped particles ranging in size from around 70 nm to 100 nm with peripheral spike-like projections consistent with the morphology described for SARS-CoV-2 were observed in the lung, trachea, kidney, and large intestine of patient 8 and patient 13. [9] [10] [11] [12] We present a case series of autopsy findings in 14 patients who died after SARS-CoV-2 infection. The major histopathological observation in our series of patients who died with COVID-19 was diffuse alveolar damage-type lung injury in the acute or organising phases (12 [86%] of 14 patients). doi = 10.1016/s0140-6736(20)31305-2 id = cord-300716-urmogf97 author = Briguglio, Matteo title = Disentangling the Hypothesis of Host Dysosmia and SARS-CoV-2: The Bait Symptom That Hides Neglected Neurophysiological Routes date = 2020-06-05 keywords = COVID-19; CoV-2; SARS; nervous; olfactory summary = The respiratory condition COVID-19 arises in a human host upon the infection with SARS-CoV-2, a coronavirus that was first acknowledged in Wuhan, China, at the end of December 2019 after its outbreak of viral pneumonia. The respiratory condition COVID-19 arises in a human host upon the infection with SARS-CoV-2, a coronavirus that was first acknowledged in Wuhan, China, at the end of December 2019 after its outbreak of viral pneumonia. Keywords: smell, olfactory bulb, coronavirus, SARS-CoV-2, COVID-19, infections, virulence, host pathogen interactions THE SNIFFING OUT OF CORONAVIRUSES Named after their crown-like spikes, coronaviruses are large non-segmented single-stranded positive-sense enveloped RNA viruses that may spill out from animals to infect humans and cause respiratory diseases. It is urgent to discuss whether SARS-CoV-2 can gain access to the central nervous system through a nasal-nervous pathway or other routes and if the fatal respiratory failure may be associated with a neuronal injury in critical brain areas of the host. doi = 10.3389/fphys.2020.00671 id = cord-325959-uqg2xkie author = Bundschuh, Christian title = Evaluation of the EDI enzyme linked immunosorbent assays for the detection of SARS-CoV-2 IgM and IgG antibodies in human plasma date = 2020-06-08 keywords = CoV-2; SARS summary = METHODS: Using EDI(TM) Novel Coronavirus COVID-19 Enzyme Linked Immunosorbent Assays (ELISAs), we measured SARS-CoV-2 IgM and IgG antibodies in 64 SARS-CoV-2 RT-PCR confirmed COVID-19 patients with serial blood samples (n=104) collected at different time points from symptom onset. low "false" positivity rates for the EDI(TM) SARS-CoV-2 IgM and IgG ELISAs. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus that causes Coronavirus Disease 2019 (COVID-19), has recently emerged to cause a human pandemic. For the clinical evaluation we measured SARS-CoV-2 IgM and IgG antibodies in three different cohorts: First in a "positive cohort" of patients with SARS-CoV-2 RT-PCR confirmed 5 COVID-19 with serial blood samples at different time points from symptom onset. Furthermore, the clinical evaluation study demonstrated high "true" positivity rates in the SARS-CoV-2 RT-PCR confirmed COVID-19 patients with symptom onset after 15 days with 94.4% for IgM and 100% for IgG SARS-CoV-2 doi = 10.1016/j.cca.2020.05.047 id = cord-348384-8cvt1fo6 author = Butsashvili, M. title = Knowledge of novel coronavirus (SARS-COV-2) among a Georgian population date = 2020-05-19 keywords = COV-2; SARS summary = This study reports results of a survey designed to understand attitudes and knowledge regarding SARS-COV-2 virus among Georgian population, including health care workers (HCWs). 20% of HCWs as well as other study subjects believe that SARS-COV-2 vaccine and medications do exist but are simply not available in Georgia. This study reports results of a survey designed to understand attitudes and knowledge regarding SARS-COV-2 virus and perceptions of preventive measures among the Georgian population, including health care workers (HCWs). We collected information on demographic data (age, gender, marital status, education, employment status), knowledge of symptoms and transmission modes of coronavirus, perceived differences between coronavirus and influenza, availability of antiviral medication and vaccination. In response to the question "Are you afraid of getting infected with SARS-COV-2?" almost half of study participants (46.3%) said "no." The majority of survey respondents correctly identified the transmission route and symptoms of the new coronavirus (96.9% and 98.0%, respectively). doi = 10.1101/2020.05.14.20101642 id = cord-304263-5kddk5fa author = C., Selvaa Kumar title = Comparative docking studies to understand the binding affinity of nicotine with soluble ACE2 (sACE2)-SARS-CoV-2 complex over sACE2 date = 2020-10-08 keywords = ACE2; CoV-2; SARS summary = In summary, nicotine showed a profound binding affinity for the sACE2-INS1 complex than the sACE2 alone paving for the clinical trials to validate its therapeutic efficacy as a bitter compound against the SARS-CoV-2 virulence. Research studies unveiled the interaction between the structural spike 1 (S1) protein of SARS-CoV-2 with the nicotinic acetylcholine receptors (nAChRs) that are likely to intervene with its biological function (20, 21) . Thus, the insilico study performed to unveil the nicotine''s urge for binding with the soluble ACE2 with or without SARS-CoV-2 in compliance with its interaction with the known human neuronal alpha4-beta2 nicotine-acetylcholine receptor (nN-AChR). We found the reported structural protein template of ACE2-SARS-CoV-2 complex with the enlisted PDB ID: 6VW1 (24) incomplete with numerous missing amino acid residues. Structural binding characteristics of nicotine with the soluble angiotensinconverting enzyme 2 (sACE2)-SARS-CoV-2 complex in the context of its interaction with the neuronal nicotinic acetylcholine receptor (nN-AChR). doi = 10.1016/j.toxrep.2020.10.002 id = cord-303517-8971aq02 author = Cajamarca-Baron, Jairo title = SARS-CoV-2 (COVID-19) in Patients with some Degree of Immunosuppression date = 2020-10-16 keywords = COVID-19; China; CoV-2; Coronavirus; SARS; infection; patient summary = 27, 28 Among other comorbidities, chronic kidney disease is associated with in-hospital mortality, as are cancer and cerebrovascular disease, demonstrated through two meta-analyses that included over fifteen thousand patients ( Table 2) ; studies suggest that superficial fungal infections and psoriasis confer vulnerability to COVID-19; a body mass index (BMI) > 40 kg/m2 is an independent risk factor for complications from the infection; and there are discouraging results regarding underlying neurological disease and SARS-CoV-2. It is even possible that such disease-modifying therapies and their immunosuppressive effect may play a protective role during 19-COVID infection by preventing or dampening hyperimmune activity that, in some cases, could lead to clinical deterioration; there is even a report of a patient with primary progressive multiple sclerosis receiving treatment with ocrelizumab and becoming infected with SARS-CoV-2, in the context of lymphopenia and hypogammaglobulinema expected for this type of treatment, without generating major clinical complications, this hypothesis is obviously limited for now only to academic deductions and limited information. doi = 10.1016/j.reumae.2020.08.001 id = cord-293890-thfros7x author = Carbo, Ellen C. title = Coronavirus discovery by metagenomic sequencing: a tool for pandemic preparedness date = 2020-08-21 keywords = CoV-2; SARS summary = METHODS: The performance of a viral metagenomic protocol in a clinical setting for the identification of novel coronaviruses was tested using clinical samples containing SARS-CoV-2, SARS-CoV, and MERS-CoV, in combination with databases generated to contain only viruses of before the discovery dates of these coronaviruses, to mimic virus discovery. Additionally, the efficacy of detection of novel coronaviruses using capture probes targeting vertebrate viruses [10] [11] known before the current pandemic was analyzed using a SARS-CoV-2 clinical sample. After extraction of human reads, FASTQ files generated for SARS-CoV-2 samples (with and without viral enrichment) were uploaded for classification and de novo assembly by the commercial webbased tool Genome Detective v1.120 (www.genomedetective.com, accessed 2020-05-11) [9] , using a reference database (generated 2019-09-21). In this study, we evaluated the performance of a metagenomic sequencing protocol for the identification of emerging viruses using clinical samples in combination with a simulated reference database. doi = 10.1016/j.jcv.2020.104594 id = cord-308252-qwoo7b1l author = Cardinale, Vincenzo title = Intestinal permeability changes with bacterial translocation as key events modulating systemic host immune response to SARS-CoV-2: A working hypothesis date = 2020-09-16 keywords = CoV-2; SARS; covid-19; patient summary = During the course of severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and 2 (SARS-CoV-2) infection, this pathway is unbalanced due to intestinal involvement and systemic inflammatory response. This review provides evidence on gut-liver axis involvement in Covid-19 as well as insights into the hypothesis that intestinal endotheliitis and permeability changes with bacterial translocation are key pathophysiologic events modulating systemic inflammatory response. Since inflammation seems to upregulate ACE2 expression [17] , it is important to understand whether patients with inflammatory bowel disease (IBD) are more susceptible to Covid-19 and the cytokine release syndrome (CRS) associated with lung injury and fatal outcome [21] . While the risk of SARS-CoV-2 infection in IBD patients depends on several universal risk factors, including social distancing [22] , older age and comorbidities have been associated with a negative outcome in IBD, whereas IBD treatments have not, highlighting that acute IBD flare prevention and inflammation reduction may avoid severe Covid-19 [23] . doi = 10.1016/j.dld.2020.09.009 id = cord-326013-5i35zdmv author = Carpinteiro, Alexander title = Pharmacological inhibition of acid sphingomyelinase prevents uptake of SARS-CoV-2 by epithelial cells date = 2020-10-29 keywords = CoV-2; SARS; VSV summary = The data justify clinical studies investigating whether amitriptyline, a safe drug used clinically for almost 60 years, or other antidepressants that functionally block acid sphingomyelinase prevent SARS-CoV-2 infection. Pretreatment of the cells with 5, 10, 20, or 25 µM amitriptyline prevented the activation of acid sphingomyelinase and the release of ceramide upon infection with pp-VSV-SARS-CoV-2 spike for 30 min (Fig. 3B, Fig. 4A ). Treating Vero cells with neutralizing antibodies to spike or with recombinant ACE2 protein prevented the activation of acid sphingomyelinase and the release of ceramide upon infection with pp-VSV-SARS-CoV-2 spike (Fig. 3B, Fig. 4A Amitriptyline and other drugs with similar structure and properties have been clinically used for many years (since 1962) to treat patients with depressive disorder. Best results were obtained with venlafaxin, fluoxetine, escitalopram and mirtazipine, drugs that were also shown in the present study to inhibit acid sphingomyelinase and ceramide release upon pp-VSV-SARS-CoV-2 spike infection. doi = 10.1016/j.xcrm.2020.100142 id = cord-354597-xubsodnk author = Carvalho, Alexandre title = SARS-CoV-2 Gastrointestinal Infection Causing Hemorrhagic Colitis: Implications for Detection and Transmission of COVID-19 Disease date = 2020-04-17 keywords = CoV-2; SARS; patient summary = Recent reports from China have described concomitant digestive symptoms, such as nausea, vomiting, diarrhea, and abdominal pain, in patients with confirmed SARS-CoV-2 pulmonary infection (5) (6) (7) (8) and the presence of SARS-CoV-2 RNA in fecal samples (8, 9) . We present a case of SARS-CoV-2 gastrointestinal infection causing acute hemorrhagic colitis and signaling COVID-19 disease which endoscopy confirmed colonic injury and helped exclude other etiologies of disease. On hospital day 4, 9 days after the onset of her digestive symptoms, the patient developed a cough; nasopharyngeal swabs were sent for comprehensive viral detection, including SARS-CoV-2 RNA (Quest Diagnostics). Given the patient''s elevated C-reactive protein and persistent abdominal pain and bloody diarrhea, a flexible sigmoidoscopy was performed on hospital day 4 to evaluate for evidence of inflammatory bowel disease or ischemic colitis. doi = 10.14309/ajg.0000000000000667 id = cord-323666-t7cshj05 author = Cegolon, L. title = Nasal Disinfection for the Prevention and Control of COVID-19: A Scoping Review on Potential Chemo-preventive Agents. date = 2020-08-18 keywords = COVID-19; CoV-2; SARS summary = Figure 1 reports the corresponding changes as percentage or odds; the latter detects the improvement of the index score better than the former because it is able to overcome the ceiling effects J o u r n a l P r e -p r o o f Therefore, in addition to an effective treatment for symptomatic patients, there is an urgent need to abate the carriage of SARS-CoV-2 in the human nasal cavity of asymptomatic/pre-symptomatic individuals, in order to contain the transmission of the novel coronavirus within the community. The abstracts of the original articles were explored for the following terms: mechanism(s) of action, tolerability and any evidence of toxic effects or selection of resistant strains, whether the treatment was tested in vitro (in particular against SARS-CoV-2), or reached the clinical trials stage, or is currently marketed/promoted/sold. doi = 10.1016/j.ijheh.2020.113605 id = cord-283709-y59h5bw8 author = Chan, Renee W Y title = Tropism and replication of Middle East respiratory syndrome coronavirus from dromedary camels in the human respiratory tract: an in-vitro and ex-vivo study date = 2014-08-28 keywords = CoV; MERS; NRCE; human summary = We aimed to compare MERS-CoV isolates from dromedaries in Saudi Arabia and Egypt with a prototype human MERS-CoV to assess virus replication competence and cell tropism in ex-vivo cultures of human bronchus and lung. INTERPRETATION: The similarity of virus tropism and replication competence of human and dromedary MERS-CoV from the Arabian peninsula, and genetically diverse dromedary viruses from Egypt, in ex-vivo cultures of the human respiratory tract suggests that dromedary viruses from Saudi Arabia and Egypt are probably infectious to human beings. We aimed to compare MERS-CoV isolates from dromedaries in Saudi Arabia and Egypt with the prototype human MERS-CoV EMC strain to assess virus replication competence and cell tropism in ex-vivo cultures of human bronchus and lung. To assess the infection potential of dromedary camel Middle East respiratory syndrome coronavirus (MERS-CoV) strains for humans, genetic analysis should be complemented with phenotypic characterisation in physiologically relevant invitro cell cultures. doi = 10.1016/s2213-2600(14)70158-4 id = cord-320619-r466dc5t author = Chand Dakal, Tikam title = SARS-CoV-2 Attachment to Host Cells is Possibly Mediated via RGD-Integrin Interaction in a Calcium-dependent Manner and Suggests Pulmonary EDTA Chelation Therapy as a Novel Treatment for COVID 19 date = 2020-11-05 keywords = ACE2; CoV-2; RGD; SARS summary = title: SARS-CoV-2 Attachment to Host Cells is Possibly Mediated via RGD-Integrin Interaction in a Calcium-dependent Manner and Suggests Pulmonary EDTA Chelation Therapy as a Novel Treatment for COVID 19 The higher expression of integrins in lungs along with their previously known high binding affinity (∼K(D) = 4.0nM) for virus RGD motif could serve as a possible explanation for high infectivity of SARS-CoV-2. This study is the first study to present striking evidence (substantiated by existing facts in literature) favoring the role of calcium and other divalent ions (magnesium, manganese etc.) in RGD-integrins mediated virus attachment with the host cells for and that lowering the concentration of calcium and other divalent ions in lungs could be a possible mechanism to avert SARs-CoV-2 infection and invasion. A number of motifs were predicted in the spike protein sequence such as RGD (from 403-405 aa in receptor binding domain of SARS-CoV-2) ( Table 2 ). doi = 10.1016/j.imbio.2020.152021 id = cord-310221-car394ou author = Chandrashekar, Abishek title = SARS-CoV-2 infection protects against rechallenge in rhesus macaques date = 2020-05-20 keywords = CoV-2; Fig; SARS summary = We developed a rhesus macaque model of SARS-CoV-2 infection and observed that macaques had high viral loads in the upper and lower respiratory tract, humoral and cellular immune responses, and pathologic evidence of viral pneumonia. We developed a rhesus macaque model of SARS-CoV-2 infection and observed that macaques had high viral loads in the upper and lower respiratory tract, humoral and cellular immune responses, and pathologic evidence of viral pneumonia. On day 2 following challenge, both necropsied animals demonstrated multifocal regions of inflammation and evidence of viral pneumonia, including expansion of alveolar septae with mononuclear cell infiltrates, consolidation, and edema (Fig. 3, A and B) . SARS-CoV-2 infection in rhesus macaques led to humoral and cellular immune responses (Fig. 2) and provided protection against rechallenge (Fig. 5) . In summary, SARS-CoV-2 infection in rhesus macaques induced humoral and cellular immune responses and provided protective efficacy against SARS-CoV-2 rechallenge. doi = 10.1126/science.abc4776 id = cord-347460-9vechh4x author = Chang, Feng-Yee title = Immunologic aspects of characteristics, diagnosis, and treatment of coronavirus disease 2019 (COVID-19) date = 2020-06-04 keywords = COVID-19; CoV; IFN; MERS; SARS; infection summary = Three components are crucial for SARS-CoV induced diseases: 1) the role of CD8+ T cells in defense against the virus, which causes apoptosis in the infected cells, 2) interactions of the virus with macrophages and dendritic cells, which initiate the early innate and subsequent adaptive immune responses, and 3) type I interferon (IFN) system, an innate response against viral infections, which can inhibit virus replication in the early phase. Existing information suggests that the SARS-CoV-infected airways and alveolar epithelial cells secrete abundant chemokines to attract immune cell infiltrations to the lungs, including macrophages and neutrophils, thereby causing damage due to high levels of proinflammatory cytokines and other mediators secreted by these cell types. After a decade of research on coronavirus, unfortunately, still there are no licensed vaccines, effective specific antivirals, nor drug combinations supported by high-level evidence to treat the infection, especially for newly emerging strains such as SARS-COV-2 [59] . doi = 10.1186/s12929-020-00663-w id = cord-335137-5qt286kc author = Chatterjee, Swapan K. title = Molecular Pathogenesis, Immunopathogenesis and Novel Therapeutic Strategy Against COVID-19 date = 2020-08-11 keywords = ACE2; COVID-19; CoV-2; SARS; cell summary = It is believed that interaction between angiotensin converting enzyme 2 (ACE2) cell receptor and viral Spike protein mediates the coronavirus entry into human respiratory epithelial cells and establishes the host tropism. The most significant surface protein is spike glycoprotein which interferes in establishing the association between the human respiratory epithelial cells to the virus via cell surface membrane receptor angiotensin-converting enzyme 2 (ACE2) and finally establishes the host tropism (Li et al., 2003) . A recent study suggests that prediction of SARS-CoV-2 spike glycoprotein structure, glycan shield pattern and pattern of glycosylation has great inference on understanding the viral camouflage as well as the outline of cell entry, and also facilitate the development of new small-molecule drugs, vaccines, antibodies, and screening of the human host targets (Song et al., 2018) . Various studies have proved that SARS-CoV-2 infection initiation and spread of disease into the host cells mainly depends upon S protein priming by TMPRSS2 (Transmembrane protease serine type 2), the serine protease. doi = 10.3389/fmolb.2020.00196 id = cord-340042-intxyu46 author = Chaudhry, Sundas Nasir title = New insight on possible vaccine development against SARS-CoV-2 date = 2020-09-11 keywords = COVID-19; CoV-2; SARS; vaccine; virus summary = In December 2019, a novel virus, namely COVID-19, caused by SARS-CoV-2, developed from Wuhan, Hubei territory of China, which used its viral spike glycoprotein receptor-binding domain (RBD) for the entrance into a host cell by binding with ACE-2 receptor and cause acute respiratory distress syndrome (ARDS). Different subunits of spike proteins like the S1 and S2 subunits, and the receptor-binding domain (RBD) are the critical elements for the formation of a vaccine against the newly emerged virus that helped in producing T cell responses and protective immunity against SARS-CoV-2 [29] . The recombinant protein is known as one of the emerging fields for the development of a vaccine against viruses due to several properties including tight binding to specific ACE-2 receptor, provoke immune protection against viral infections, increase antibody-dependent viral entry, and promote antigenicity against virus like SARS-CoV [52] . doi = 10.1016/j.lfs.2020.118421 id = cord-337825-ujq9mxk7 author = Chen, Bin title = Overview of lethal human coronaviruses date = 2020-06-10 keywords = ACE2; CoV; CoV-2; East; MERS; Middle; SARS; coronavirus; protein summary = Coronaviruses are the largest +ssRNA viruses and contain at least 14 ORFs, 16 protein combines with viral RNA to form a nucleocapsid, which is involved in the replication of SARS-CoV and is the most abundant protein in virus-infected cells. MERS-CoV can infect T-cells from human lymphoid organs and causes the peripheral blood inducing apoptosis by intrinsic and extrinsic pathways, thus avoiding host immune response detection method, Nanopore Targeted Sequencing, also has the potential for efficiently detecting viruses in a reasonable time. The structural and accessory proteins M, ORF 4a, ORF 4b, and ORF 5 of Middle East respiratory syndrome coronavirus (MERS-CoV) are potent interferon antagonists Middle East respiratory syndrome coronavirus (MERS-CoV) entry inhibitors targeting spike protein Identification of a receptor-binding domain in the S protein of the novel human coronavirus Middle East respiratory syndrome coronavirus as an essential target for vaccine development Receptor-binding domain of SARS-CoV spike protein induces highly potent neutralizing antibodies: implication for developing subunit vaccine doi = 10.1038/s41392-020-0190-2 id = cord-031079-9lxhvyyb author = Chen, Li title = The effects of chloroquine and hydroxychloroquine on ACE2 related coronavirus pathology and the cardiovascular system: An evidence based review date = 2020-07-27 keywords = ACE2; CoV-2; HCQ; SARS summary = CQ and HCQ may be potential inhibitors of SARS-CoV-2 entry into host cells, which is mediated via the angiotensin-converting enzyme 2 (ACE2), and may also inhibit subsequent intracellular processes which lead to COVID-19, including damage to the cardiovascular system. CQ and HCQ could potentially be useful drugs in the treatment of COVID-19 and other ACE2 involved virus infections, but the antiviral effects of CQ and HCQ need to be tested in more well-designed clinical randomized studies and their actions on the cardiovascular system need to be further elucidated. CQ and its more soluble and less toxic metabolite HCQ are primarily used for prophylaxis and treatment of malaria, but they have also been reported to effectively inhibit the effects of certain viruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza A H5N. 40, 41 Several studies have reported that 3% to 29% of COVID-19 patients develop acute respiratory distress syndrome (ARDS) which is a common complication and cause of death as a result of SARS-CoV-2 infection. doi = 10.1093/function/zqaa012 id = cord-300041-1d9xu4ts author = Chen, Sharon C-A title = Focus on SARS-CoV-2 and COVID-19 date = 2020-10-08 keywords = CoV-2; SARS summary = In contrast, more recent pandemics have been dominated by viruses such as influenza H1N1 and H3N2, localised epidemics by Ebola virus, severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1), MERS-CoV, and now, SARS-CoV-2, the causative agent of COVID-19. However, by having a single edition, with broad focus on human pathology of SARS-CoV-2 infection, we aim to provide the readers of Pathology with insights from different areas of COVID-19 diagnosis. 2 Substantive progress continues to be made in the arena of diagnostic tests for SARS-CoV-2 infection with improvements in molecular diagnostics, rapid antigen detection tests and serological assays. We continue to be faced by the risk of pandemics and we must learn from our observations at present with SARS-CoV-2 infection, and resulting COVID-19 disease. Virus isolation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for diagnostic and research purposes Rapid deployment of pathology services to a remote Australian quarantine setting during the COVID-19 pandemic doi = 10.1016/j.pathol.2020.09.010 id = cord-350737-nrtrhq1f author = Chen, Xinchun title = Serology of Severe Acute Respiratory Syndrome: Implications for Surveillance and Outcome date = 2004-04-01 keywords = CoV; SARS; patient summary = A virus from the family Coronaviridae, termed "SARS coronavirus" (SARS CoV), has been identified as the cause [2] [3] [4] [5] [6] [7] , and criteria for laboratory confirmation of SARS CoV infection have been provided by WHO, on the basis of the following methods: (1) detection of SARS CoV RNA by reversetranscription polymerase chain reaction (RT-PCR); (2) serological detection of SARS CoV-related antibody; and (3) isolation of SARS CoV by cell culture [4] . Using an indirect immunofluorescence assay and parallel acute and convalescent serum samples obtained from patients with SARS, tested for IgG antibody to SARS CoV, Peiris et al. In addition, our results indicated that 9 (25.0%) of 36 patients with probable SARS CoV infection had not produced detectable anti-SARS CoV antibody by day 21 after the onset of fever; this implies that 25.0% of patients with SARS might be misdiagnosed by the laboratory confirmation guidelines that WHO currently recommends [5] . doi = 10.1086/380397 id = cord-350015-mg5wiihj author = Chen, Yiyin title = Aging in COVID-19: Vulnerability, immunity and intervention date = 2020-10-31 keywords = China; CoV-2; SARS; covid-19 summary = The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic was first reported in Wuhan, China in December 2019, moved across the globe at an unprecedented speed, and has caused a profound and yet still unfolding health and socioeconomic impacts. We hypothesize that age-related decline and dysregulation of immune function, i.e., immunosenescence and inflammaging play a major role in contributing to heightened vulnerability to severe COVID-19 outcomes in older adults. Therefore, age-associated reduction in type 1 IFN response coupled with direct viral suppression could serve as a critical innate immune mechanism that leads to poor cell mediated immunity and increased vulnerability of older adults against SARS-CoV-2 infection with therapeutic implication (Sallard et al., 2020) . On the other hand, children with COVID-19 manifested lower levels of T cell activation than adult COVID-19 patients (Moratto et al., 2020) , suggesting better immune system control and regulation in response to SARS-CoV-2 infection in children. doi = 10.1016/j.arr.2020.101205 id = cord-311762-f6muhf3d author = Chen, Yu Wai title = Prediction of the SARS-CoV-2 (2019-nCoV) 3C-like protease (3CL (pro)) structure: virtual screening reveals velpatasvir, ledipasvir, and other drug repurposing candidates date = 2020-02-21 keywords = 3CL; CoV-2; SARS summary = title: Prediction of the SARS-CoV-2 (2019-nCoV) 3C-like protease (3CL (pro)) structure: virtual screening reveals velpatasvir, ledipasvir, and other drug repurposing candidates Therefore, we are confident to prepare a structural model of the SARS-CoV-2 3CL pro by molecular modelling (Extended data 7 , Figure S1 ), which will be immediately useful for in silico development of targeted treatment. After we submitted the first draft of this study, the crystal structure of SARS-CoV-2 3CL pro was solved and released (PDB ID 6LU7), which confirms that the predicted model is good within experimental errors (Extended data 7 , Figure S2 ). By analogy, these compounds were speculated to act on SARS-CoV 3CL pro specifically, but there is as yet no crystal structure to support that, although docking studies were carried out to propose various binding modes 20-23 . • Tab S2.docx (The results of virtual screening of drugs on the active site of SARS-CoV-2 3CL pro crystal structure). doi = 10.12688/f1000research.22457.1 id = cord-275946-ofd2ipvs author = Cheng, Matthew P. title = Serodiagnostics for Severe Acute Respiratory Syndrome–Related Coronavirus-2: A Narrative Review date = 2020-06-04 keywords = COVID-19; CoV-2; SARS; antibody summary = Accurate serologic tests to detect host antibodies to severe acute respiratory syndrome–related coronavirus-2 (SARS-CoV-2) will be critical for the public health response to the coronavirus disease 2019 pandemic. This article discusses key use cases for SARS-CoV-2 antibody detection tests and their application to serologic studies, reviews currently available assays, highlights key areas of ongoing research, and proposes potential strategies for test implementation. Appropriately designed seroepidemiologic studies will play an essential part in the public health response to the COVID-19 pandemic by characterizing transmission dynamics, refining disease burden estimates, and providing insight into the kinetics of humoral immunity to SARS-CoV-2. Serologic surveillance studies can also assess the accumulation of persons with antibody responses over time to estimate incidence of SARS-CoV-2 infection (57, 58) and can track age-and jurisdiction-specific disease susceptibility and identify at-risk populations (59) . doi = 10.7326/m20-2854 id = cord-282338-u01qv3uc author = Cherry, James. D. title = The chronology of the 2002–2003 SARS mini pandemic date = 2004-11-05 keywords = CoV; SARS; case summary = SARS-CoV disease should be considered at a minimum in the differential diagnoses for persons requiring hospitalisation for pneumonia confirmed radiographically or acute respiratory distress syndrome without identifiable aetiology and who have one of the following risk factors in the 10 days before the onset of illness: (1) Travel to mainland China, Hong Kong, or Taiwan, or close contact with an ill person with a history of recent travel to one of these areas, or; (2) Employment in an occupation associated with a risk for SARS-CoV exposure (e.g. healthcare worker with direct patient contact or worker in a laboratory that contains live SARS-CoV) or; (3) Part of a cluster of cases of atypical pneumonia without an alternative diagnosis. doi = 10.1016/j.prrv.2004.07.009 id = cord-327654-9g8zcxaa author = Chi, Xiaojing title = Humanized single domain antibodies neutralize SARS-CoV-2 by targeting the spike receptor binding domain date = 2020-09-10 keywords = CoV-2; Fig; RBD; SARS summary = Here, using SARS-CoV-2 spike receptor-binding domain (RBD) as a bait, we generate a panel of humanized single domain antibodies (sdAbs) from a synthetic library. Competitive ligand-binding experiments suggest that the sdAbs either completely block or significantly inhibit the association between SARS-CoV-2 RBD and viral entry receptor ACE2. To determine whether sdAbs targeted different antigenic regions on the SARS-CoV-2 RBD surface, we performed a competition-binding assay using a real-time biosensor (Fig. 3) . Fc fusion sdAbs in culture supernatants were affinity purified with HiTrap Protein A HP antibody purification columns ( Supplementary Fig. 2 ) and analyzed in both reducing and non-reducing conditions in Western blot using an anti-human IgG to detect Fc. As shown in Fig. 4c , the size of the constructed intact sdAb-Fc is around 80 KDa in the non-reducing condition, but a 40 KDa monomer was observed by prior treatment in reducing condition to break disulfide bonds. doi = 10.1038/s41467-020-18387-8 id = cord-274141-vujx538o author = Chinsembu, Kazhila C. title = Coronaviruses and Nature’s Pharmacy for the Relief of Coronavirus Disease 2019 date = 2020-10-06 keywords = COVID-19; CoV; SARS; TCM summary = De Clercq (2005 suggested that it was feasible to develop SARS-CoV fusion inhibitors analogous to enfuvirtide, a linear 36-amino acid synthetic peptide marketed under the trade name Fuzeon, an approved anti-HIV drug that inhibits the entry of the virus into cells. It was hypothesized that specific flavonoids, such as quercetin, hesperetin, and myricetin (7) and their glycosylated derivatives, may play an effective role in inhibiting SARS-CoV entry into host cells, specifically by binding with high affinity to the spike protein, helicase, and protease sites on the ACE receptor (Ngwa et al. Although the ongoing SARS-CoV-2 global pandemic should remind scientists that current options for treating life-threatening zoonotic coronavirus infections are very limited , medicinal plants offer a strong pipeline for the discovery of novel lead compounds that can be converted into new drugs to treat COVID-19. doi = 10.1007/s43450-020-00104-7 id = cord-333498-d25qfq0f author = Chitranshi, Nitin title = Evolving geographic diversity in SARS-CoV2 and in silico analysis of replicating enzyme 3CL(pro) targeting repurposed drug candidates date = 2020-07-09 keywords = 3CL; CoV-2; Fig; Pangolin; SARS; pro summary = Recent release of the high-resolution crystal structure for the main proteinase 3CL pro (Protein Data Bank, PDB ID: 6Y2G), describing an additional amide bond with the α-ketoamide inhibitor pyridone ring to enhance the half-life of the compound in plasma [16] is suggested to accelerate the targeted drug discovery efforts. Since the initial stages of the SARS-CoV-2 outbreak, laboratories and hospitals around the world have sequenced viral genome data with unprecedented speed, enabling real-time understanding of this novel disease process, which will hopefully contribute to the development of novel candidate drugs. In contrast, our docking studies revealed that bilobetin, predicted almost comparable binding energy with that of amentaflavone (− 8.29 kcal/mol) suggesting that mutation in SARS-CoV-2 3CL pro could potentially disrupt hydrogen bonding or induce some conformational change that could result in alterations in the binding site thus affecting inhibitor interactions with the enzyme active site residues. doi = 10.1186/s12967-020-02448-z id = cord-337812-arivkkj0 author = Chu, Ling-Hon Matthew title = Rapid peptide-based screening on the substrate specificity of severe acute respiratory syndrome (SARS) coronavirus 3C-like protease by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry date = 2006-03-07 keywords = 3CL; CoV; SARS; peptide summary = To screen the substrate specificity of SARS-CoV 3CL pro in a rapid and highthroughput manner in contrast to the traditional tedious procedures, we applied the matrix-assisted laser desorption/ionization time-of-flight mass spectrometric (MALDI-TOF MS) analysis in combination with the novel "cartridge replacement" solid-phase peptide synthesis approach to investigate the biological significance of amino acid residues in the P2, P3, P4, P1¢, P2¢, and P3¢ positions that are flanking the conserved Gln residue in the P1 position at the SARS-CoV 3CL pro cleavage site (Schechter and Berger 1967; Fan et al. In this study, we used MALDI-TOF MS analysis in combination with the solid-phase peptide synthesis approach to examine the biological significance of amino acid residues in a total of six target positions at the SARS-CoV 3CL pro cleavage sites, including the P2, P3, and P4 positions at the amino side of the P1 position; and the P1¢, P2¢, and P3¢ positions at the carboxyl side of the P1 position (Table 1) . doi = 10.1110/ps.052007306 id = cord-322913-sq9mq6f1 author = Ciabattini, Annalisa title = Shelter from the cytokine storm: pitfalls and prospects in the development of SARS-CoV-2 vaccines for an elderly population date = 2020-11-06 keywords = COVID-19; CoV-2; SARS; age; response; vaccine summary = The complex and still unclear immunopathological mechanisms of SARS-CoV-2 infection, together with the progressive age-related decline of immune responses, and the lack of clear correlates of protection, make the design of vaccination strategies for older people extremely challenging. The complex and still unclear immunopathological mechanisms of SARS-CoV-2 infection, together with the progressive age-related decline of innate and adaptive immune responses, and the lack of a clear correlate of protection, make the design of vaccination strategies for older people extremely challenging (Fig. 3 ). doi = 10.1007/s00281-020-00821-0 id = cord-340305-jtvn9tlm author = Cimolai, Nevio title = A Minimalist Strategy Towards Temporarily Defining Protection for COVID-19 date = 2020-09-19 keywords = COVID-19; CoV-2; SARS; antibody summary = At this time, the best correlates with protection from natural coronavirus infections are systemic neutralizing antibody and mucosal IgA. Others have found strong correlations between neutralizing antibodies and EIA-detected antibodies to various SARS-CoV-2 antigens [41, 42] .Some have found diversity in immune responses contingent on the nature of presenting disease [38, 43] . With the availability of viral antigen, most scientists in the know-how would be able to fashion a test for antibody determination in short order and most would likely choose an enzyme immunoassay (EIA) (or nearly equivalent non-enzymebased assay) for its potential of automation and widespread use. Sensitive and specific detection of low-level antibody responses in mild Middle East Respiratory Syndrome coronavirus infections A highly specific and sensitive serological assay detects SARS-CoV-2 antibody levels in COVID-19 patients that correlate with neutralization SARS-CoV-2 assays to detect functional antibody responses that block ACE2 recognition in vaccinated animals and infected patients doi = 10.1007/s42399-020-00533-4 id = cord-275454-an8xvow3 author = Clark, Andrew E title = Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Screening With Specimen Pools: Time to Swim, or Too Deep for Comfort? date = 2020-09-28 keywords = CoV-2; SARS summary = We read with interest the study appearing in this issue by Li et al, who utilized a pooled sample strategy and a point-of-care (POC) reverse transcriptase-polymerase chain reaction (RT-PCR) assay for screening asymptomatic airline passengers arriving from areas of high SARS-CoV-2 prevalence. At the time of this writing, 2 reference laboratories in the United States (Quest Diagnostics and LabCorp) have received emergency use authorizations from the US Food and Drug Administration to use pooled specimens for SARS-CoV-2 detection [2] . In this work, pooling was performed in a 10:1 ratio, meaning 10 patient specimens were combined and tested using a single SARS-CoV-2 assay. At our institution, we are aware of patients who underwent preprocedure SARS-CoV2 screening utilizing the same assay deployed in this work, only to be diagnosed with active, symptomatic COVID-19 within 5 days of testing. doi = 10.1093/cid/ciaa1145 id = cord-341453-9yrvjlpx author = Clay, Candice C title = Severe acute respiratory syndrome-coronavirus infection in aged nonhuman primates is associated with modulated pulmonary and systemic immune responses date = 2014-03-19 keywords = CD8; CoV; SARS; aged; figure summary = The aim of this study was to determine how the peripheral and mucosal immune responses to SARS-CoV infection compare in the aged and juvenile nonhuman primate host and to determine how this may impact viral replication levels. No virus was detected in any sample collected from either age group at 10 d.p.i. To determine if advanced age correlated with increased severity of lung pathology, a comprehensive histological analysis of the respiratory tract following SARS-CoV infection was conducted in aged and juvenile animals. To determine how mucosal cytokines in SARS-CoV infection compared to systemic responses and how age may impact mucosal cytokine expression; the inflammatory protein profile was evaluated by bead-based arrays in standardized-collected lung tissue from the proximal portion of the right caudal lobe. Although no age-dependent differences were observed in the frequency of naïve (CD45RA + CCR7+) CD8 T cells in peripheral blood, there were significantly lower levels of these cells in the lung and lymph node of aged animals during SARS-CoV infection ( Figure 6A -C; unpaired student T-tests). doi = 10.1186/1742-4933-11-4 id = cord-031289-uxoz0xhk author = Coccolini, Federico title = SARS-CoV-2 Is Present in Peritoneal Fluid in COVID-19 Patients date = 2020-05-18 keywords = CoV-2; SARS summary = title: SARS-CoV-2 Is Present in Peritoneal Fluid in COVID-19 Patients The present article represents the very first positive result describing the presence of the virus in peritoneal fluid during an emergency surgical procedure in a COVID-19 sick patient. Interestingly, the nasal swab contained less SARS-CoV-2 RNA virus compared to the viral fluid that scored positive in 2 targets out of 3. This indicates that the viral load in the peritoneal fluid was higher compared to the upper respiratory material and suggests that the surgical operation was indeed a procedure at risk of infection. As no information exist about the virus passage to peritoneal cavity and fluids, present data may suggest that potentially all people even those with mild to moderate respiratory symptoms by SARS-CoV-2 could present viral load in peritoneal fluid, thus increasing the exposure and contagion risks for the entire surgical staff.Peritoneal fluid contamination with blood of feces may interfere with the virus detection. doi = 10.1097/sla.0000000000004030 id = cord-328000-i9tzr13z author = Cockrell, Adam S. title = Modeling pathogenesis of emergent and pre-emergent human coronaviruses in mice date = 2018-07-24 keywords = CoV; DPP4; MERS; SARS summary = Three different strategies were employed for development of SARS-CoV mouse models: (i) different mouse species (or subspecies) were challenged with wildtype human SARS-CoV isolates in order to find a model that allows for replication and reflects severe respiratory disease symptoms observed in infected human patients; (ii) mice were genetically engineered to modify the host receptor, which facilitated productive SARS-CoV replication and pathogenesis; and (iii) adaptive evolution of wild-type SARS-CoV to a chosen mouse species was done to enhance pathogenesis, and associated clinical phenotypes in vivo. To adapt SARS-CoV to cause severe acute respiratory disease in mouse lungs, 6-week-old female BALB/c mice were intra-nasally infected with the clinical Urbani isolate (Roberts et al. Virus infection studies in CC mouse lines, including SARS-CoV, have led to mapping of high and low host response alleles as they relate to development of clinical signs of disease following viral pathogenesis (Bottomly et al. doi = 10.1007/s00335-018-9760-9 id = cord-279940-i2rgjpxf author = Comentale, Giuseppe title = Sars-Cov-2 interference in HEME production: is it the time for an early predictive biomarker? date = 2020-06-29 keywords = Cov-2; Sars summary = In particular, thrombosis seems to drive the entire disease course: Sars-Cov-2 infection triggers a large thrombophilic response that results in diffuse occlusion of the smaller vessels, especially in the lungs where the result is a wide thrombotic microangiopathy [5] explaining the radiologic "ground glass" pattern. Furthermore, as IL-1 was shown to be a major culprit in the development of many cardiovascular diseases [11] , its involvement in the Sars-Cov-2 infection could explain the high mortality and morbidity rate among cardiopathic patients. Identifying the mechanisms by which Sars-Cov-2 damages the human body, focusing on the structural proteins, could be a possible strategy to finding an effective solution. From this point of view, Sars-Cov-2 seems to be very similar to malaria: many clinical and scientific reports have shown that Covid-19, not only can be successfully treated with chloroquine but also, like malaria, appears to be diagnosed much more frequently in blood group A patients [14] . doi = 10.1007/s00109-020-01945-4 id = cord-311125-v9ddes3c author = Cooper, Keiland W. title = COVID-19 and the chemical senses: supporting players take center stage date = 2020-07-01 keywords = ACE2; COVID-19; CoV-2; SARS; cell; olfactory summary = Given data suggesting that ACE2 is necessary for SARS-CoV2 to infect host cells, researchers have used a variety of approaches to discern the pattern of expression of ACE2 and other viral entry proteins across the tissue landscape, with the goal of inferring possible target cells and disease mechanisms. It remains unclear whether SARS-CoV-2 (given that it likely does not directly infect OSNs, and thus cannot pass directly through the olfactory nerve, see However, scSeq and immunostaining of the mouse OB has revealed -as in the nose -that bulb neurons do not express detectable levels of ACE2 ( Figure 2 ) . This model suggests that neural function is altered indirectly due to sequelae of SARS-CoV-2 infection of peripheral support cells, including (but not limited to) local inflammation and changes in OSN gene expression and ciliary structure. Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia doi = 10.1016/j.neuron.2020.06.032 id = cord-312670-hi3fjne4 author = Corman, V. M. title = Coronaviren als Ursache respiratorischer Infektionen date = 2019-08-27 keywords = CoV; Infektionen; MERS; SARS summary = Zusätzlich zu diesen ständig im Menschen zirkulierenden Varianten wurden in den vergangenen Jahren zwei CoV im Menschen gefunden, nämlich SARS-CoV und MERS-CoV, die aus dem Tierreservoir auf den Menschen übergegangen sind und bei einem deutlich größeren Anteil der Infizierten schwere virale Pneumonien mit tödlichem Verlauf auslösen [25, 28] . Obwohl die Mehrzahl der Infektionen mit den vier endemischen CoV nur leichte Atemwegserkrankungen verursacht, können alle HCoV auch schwere Hier steht eine Anzeige. Inwiefern diese sekundären Infektionen auf die intensivmedizinische Behandlung und Beatmung zurückzuführen sind oder ein spezifisches grundsätzliches Risiko einer CoV-Infektion darstellen, ist noch nicht verstanden. Jedoch ist eine spezifische Labordiagnostik bei Verdacht auf eine Infektion mit endemi-schen CoV bei harmlosem Verlauf und Patienten ohne besonderes Risiko für die Entstehung von Komplikationen auch nicht indiziert. Bei der typischerweise unspezifischen Klinik von MERS-CoV-Infektionen sollte auch die Möglichkeit einer Infektion mit anderen Pathogenen in Betracht gezogen werden [26] . RKI (2015) Schwere respiratorische Erkrankungen in Verbindung mit Middle East Respiratory Syndrome Coronavirus (MERS-CoV). doi = 10.1007/s00108-019-00671-5 id = cord-332723-rz1iilsv author = Creager, Hannah M. title = Clinical evaluation of the BioFire® Respiratory Panel 2.1 and detection of SARS-CoV-2 date = 2020-07-06 keywords = CoV-2; SARS summary = Since 30% of nasopharyngeal swab specimens have a SARS CoV-2 Ct >30 and thus detection of virus in low titers is clinically relevant, a sample with a high titer was diluted and each 10 fold dilution was tested in triplicate and compared against 6 other EUA approved SARS CoV-2 assays. These data suggested that the BioFire® RP2.1 panel, along with four other SARS CoV-2 assays (Roche cobas, Cepheid Xpert Xpress, BioFire® Defense COVID19, and NECoV19), consistently detected viral RNA at the 10-7 dilution. Ten-fold serial dilutions of a natural nasopharyngeal swab specimen with known high positivity for SARS-CoV-2 RNA (E gene detected at a cycle threshold (Ct) of 16.6 by the cobas SARS-CoV-2 assay) were prepared with a diluent of pooled NPS. Comparison of SARS-CoV-2 Detection from Nasopharyngeal Swab Samples by the Roche cobas(R) 6800 SARS-CoV-2 Test and a Laboratory-Developed Real-Time RT-PCR test doi = 10.1016/j.jcv.2020.104538 id = cord-344266-ug2uew71 author = Crema, E. title = The SARS-COV-2 outbreak around the Amazon rainforest: the relevance of the airborne transmission date = 2020-08-07 keywords = COV-2; SARS; air summary = Currently, this phenomenon has gained tragic relevance due to the uncontrolled dispersion of the Covid-19 throughout the planet, since airborne transmission is one of the forms of viral contamination, as well as the direct reception of drops exhaled by a contaminated person and the contact with infected surfaces. A relevant study issued in the journal Nature revealed the existence of the RNA of the SARS-COV-2 in aerosols collected from the air of several closed environments and open places of two hospitals in Wuhan dedicated only to patients infected with Covid-19 (12) . This indication is based only on old studies about the direct transmission by larger drops, dangerously ignoring the contamination by the virus airborne in droplets that remain suspended in the air for several hours, and even days after the environment has been visited by an infected person. doi = 10.1101/2020.08.06.20169433 id = cord-322957-clf8f90t author = Crespo, Javier title = Resumption of activity in gastroenterology departments. Recommendations by SEPD, AEEH, GETECCU and AEG date = 2020-04-28 keywords = COVID-19; CoV-2; IBD; SARS; patient summary = The general objectives of these recommendations include: • To protect our patients against the risks of infection with SARS-CoV-2 and to provide them with high-quality care. These recommendations are based on the sparse, changing evidence available, and will be updated in the future according to daily needs and the availability of expendable materials to suit them; in each department they will be implemented depending upon the cumulative incidence of SARS-CoV-2 infection in each region, and the burden the pandemic has represented for each hospital. These recommendations are based on the sparse, changing evidence available, and will be updated in the future according to daily needs and the availability of expendable materials to suit them; in each department they will be implemented depending upon the cumulative incidence of SARS-CoV-2 infection in each region, and the burden the pandemic has represented for each hospital. doi = 10.1016/j.gastre.2020.04.001 id = cord-352123-0bflqj1c author = Csiszar, Anna title = Companion animals likely do not spread COVID-19 but may get infected themselves date = 2020-08-07 keywords = COVID-19; CoV-2; SARS; animal summary = Recent evidence suggests that SARS-CoV-2, similar to other coronaviruses, can infect several species of animals, including companion animals such as dogs, cats, and ferrets although their viral loads remain low. In late March 2020, the Federal Agency for the Safety of the Food Chain (FASFC) in Belgium reported that a pet cat was diagnosed to be infected with SARS-CoV-2 [21, 22] , showing that felines living in the household of people with COVID-19 are at risk of contracting the disease and may potentially spread the virus. On April 23, it was reported that two pet cats in New York state have tested positive for the SARS-CoV-2, which are the first confirmed COVID-19 cases in companion animals in the USA [22] . In the current SARS-CoV-2 pandemic, the situation is rapidly evolving and in the light of the recent evidence, we should be aware of the possibility that humans can be potentially infected with COVID-19 by animals, including by pet cats, dogs, or other domesticated species. doi = 10.1007/s11357-020-00248-3 id = cord-314171-431buxxr author = Dariya, Begum title = Understanding novel COVID-19: its impact on organ failure and risk assessment for diabetic and cancer patients date = 2020-05-06 keywords = ACE2; CoV-2; SARS; covid-19; patient summary = In this review article, we have presented the effect of SARS-CoV-2 infection in comorbid patients and discussed organ failure caused by this virus. The mRNA and protein ACE2 expression levels are higher in these patients with cardiac disease, creating an increased risk for severe COVID-19 complications, including heart failure. After SARS-CoV-2 binds with ACE2, the virus degrades it, and thus the free angiotensin II induces acute lung injury [58] . Thus, targeting the binding site of the ACE2 receptor and SARS-CoV-2 with antibodies or therapeutic drugs might provide a successful treatment strategy. Moreover, this also increases the level of soluble ACE2 that competitively binds with SARS-CoV-2, causing delayed entry of the virus into cells and protecting against lung injury. The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2 doi = 10.1016/j.cytogfr.2020.05.001 id = cord-303216-1pbuywz6 author = Das, Gaurav title = Neurological Insights of COVID-19 Pandemic date = 2020-04-22 keywords = COVID-19; CoV-2; SARS summary = If scientific reports relevant to the SARS-CoV-2 virus are noted, it can be seen that the virus owes much of its killer properties to its unique structure that has a stronger binding affinity with the human angiotensin-converting enzyme 2 (hACE2) protein, which the viruses utilize as an entry point to gain accesses to its hosts. The intriguing part though is that recently reported studies have noted altered mental health in some COVID-19 patients showing symptoms like anosmia and ageusia thereby indicating a neuroinvasive nature of the virus. The neurological manifestations of SARS-CoV-2 have been recently recognized from CT scan images and MRI scan of the brain of a patient who contracted COVID-19 and showed symptoms of necrotizing hemorrhagic encephalopathy. The brain reportedly, like most other organs, expresses the hACE2 considered to be the entry point of the SARS-CoV-2 viruses in humans and is therefore not immune to viral infection. doi = 10.1021/acschemneuro.0c00201 id = cord-257105-vrwuaknf author = Davies, Julie title = Neuropilin-1 as a new potential SARS-CoV-2 infection mediator implicated in the neurologic features and central nervous system involvement of COVID-19 date = 2020-09-15 keywords = SarS; coV-2; olfactory summary = Preclinical studies have suggested that neuropilin-1 (NRP1), which is a transmembrane receptor that lacks a cytosolic protein kinase domain and exhibits high expression in the respiratory and olfactory epithelium, may also be implicated in COVID-19 by enhancing the entry of SARS-CoV-2 into the brain through the olfactory epithelium. This study presents a detailed in silico analysis of the expression of nrP1 in the human brain, highlighting the potential role of nrP1 as an additional SarS-coV-2 infection mediator in the CNS via NRP1-expressing cells. Given this newly identified role of nrP1 in enhancing SarS-coV-2 entry into the cnS, characterizing the precise expression of nrP1 in the human brain becomes important in the context of the neurologic involvement of coVid-19. Finally, the parolfactory gyri which receive inputs from the olfactory bulb and provide input to the limbic system, also exhibit nrP1 expression, and so their potential involvement in the SarS-coV-2 infection of the cnS merits further research. doi = 10.3892/mmr.2020.11510 id = cord-342220-lrqt2gcw author = Dearlove, Bethany title = A SARS-CoV-2 vaccine candidate would likely match all currently circulating variants date = 2020-09-22 keywords = CoV-2; Fig; SARS; d614 summary = Although the closest currently available bat sequences are fairly divergent from SARS-CoV-2, their characteristics (insertion at S1/S2 cleavage site, high diversity, and similarity between specific gene fragments and particular strains) together with their known adaptive properties (high recombination and host-switching rates and evidence of positive selection) support that these bat viruses constitute While the evolutionary rate is likely to decrease over time (18) , it is important to monitor the introduction of any mutation that may compromise the potential efficacy of vaccine candidates derived from the first available SARS-CoV-2 sequences. In S, only site 614 was estimated to be under diversifying selection in a majority of subsampled alignments (58%); evidence of diversifying selection indicates that genetic diversity increases in the viral population (i.e., there was a higher proportion of mutations causing an amino acid change than not at site 614, or, the nonsynonymous/synonymous substitution rates ratio, dN/dS, was over 1, P < 0.1) (SI Appendix, Fig. S4 ). doi = 10.1073/pnas.2008281117 id = cord-285168-qkadqohe author = Delatorre, Edson title = Tracking the onset date of the community spread of SARS-CoV-2 in Western Countries date = 2020-04-23 keywords = CoV-2; SARS summary = Here, we estimate the probable onset date of the community spread of SARS-CoV-2 from the cumulative number of deaths reported during the early stage of the epidemic in Western Europe and the Americas. Our results support that SARS-CoV-2 probably started to spread locally in all western countries analyzed between the middle of January and early February 2020, thus long before community transmission was officially recognized and control measures were implemented. In some countries (Italy and Netherlands) community transmission was traced long before (2-4 weeks) the first confirmed SARS-CoV-2 infection case; while in others (Spain, France, United Kingdom, Germany, and Belgium) the onset date roughly coincides with the time of detection of the first imported cases (Figure 1 ). That quite long period of cryptic community transmission (> 4 weeks) in all analyzed countries draws attention to the great challenge of tracking the early global spread of SARS-CoV-2 and supports that control measures should be adopted at least as soon as first imported cases are detected in a new geographic region. doi = 10.1101/2020.04.20.20073007 id = cord-290056-x74cq2k5 author = Delgado-Roche, Livan title = Oxidative Stress as Key Player in Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) infection date = 2020-04-30 keywords = CoV; SARS summary = doi = 10.1016/j.arcmed.2020.04.019 id = cord-266511-g5h4tazp author = Deslandes, A title = SARS-COV-2 was already spreading in France in late December 2019 date = 2020-05-03 keywords = COV-2; SARS summary = We report here a case of a patient hospitalized in December 2019 in our intensive care, of our hospital in the north of Paris, for hemoptysis with no etiological diagnosis and for which RT-PCR was performed retrospectively on the stored respiratory sample which confirmed the diagnosis of COVID-19 infection. After its onset in December 2019 in China, the new coronavirus (SARS-COV-2) spreads widely in several countries, causing COVID-19 illness. 8 Clinical symptomatology between COVID-19 and ILIis similar,we therefore decided retrospectively to look for SARS-COV2 in respiratory samples collected in the intensive care units (ICUs) of our hospital near Paris. We reviewed medical record of ICUs patients admitted for ILI between December 2, 2019 and January 16, 2020, with a negative RT-PCR performed at admission. Samples taken from patients with both ILI symptoms (fever higher than 38.5°C, cough, rhinitis, sore throat or myalgia) and ground glass opacity according to their medical record underwent SARS-COV-2 RT-PCR. doi = 10.1016/j.ijantimicag.2020.106006 id = cord-279255-v861kk0i author = Dhama, Kuldeep title = Coronavirus Disease 2019–COVID-19 date = 2020-06-24 keywords = COVID-19; China; CoV-2; MERS; SARS; Wuhan; clinical; coronavirus; human; infection; novel; outbreak summary = Recently, a new type of viral infection emerged in Wuhan City, China, and initial genomic sequencing data of this virus do not match with previously sequenced CoVs, suggesting a novel CoV strain (2019-nCoV), which has now been termed severe acute respiratory syndrome CoV-2 (SARS-CoV-2). Compared to diseases caused by previously known human CoVs, COVID-19 shows less severe pathogenesis but higher transmission competence, as is evident from the continuously increasing number of confirmed cases globally. Recently, a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID19) , emerged in late 2019, and it has posed a global health threat, causing an ongoing pandemic in many countries and territories (1) . Health workers worldwide are currently making efforts to control further disease outbreaks caused by the novel CoV (originally named 2019-nCoV), which was first identified in Wuhan City, Hubei Province, China, on 12 December 2019. doi = 10.1128/cmr.00028-20 id = cord-327063-ea7a1xfl author = Dhama, Kuldeep title = SARS-CoV-2 jumping the species barrier: zoonotic lessons from SARS, MERS and recent advances to combat this pandemic virus date = 2020-08-02 keywords = COVID-19; China; CoV-2; Coronavirus; Health; MERS; SARS; human summary = The present review presents a comprehensive overview of COVID-19 and SARS-CoV-2, with emphasis on the role of animals and their jumping the cross-species barriers, experiences learned from SARSand MERS-CoVs, zoonotic links, and spillover events, transmission to humans and rapid spread, and highlights the new advances in diagnosis, vaccine and therapies, preventive and control measures, one health concept along with recent research developments to counter this pandemic disease. Further research exploring the SARS-CoV-2 associated zoonosis and mechanisms accounting for its initial transmission from animals to humans, will lead to sort out the spread of this virus as well as design and develop appropriate prevention and control strategies to counter COVID-19. The present comprehensive manuscript presents an overview on COVID-19, an emerging SARS-CoV-2 infectious disease while focusing mainly on the events and circumstantial evidences with regards to this virus jumping the species barriers, sharing a few lessons learned from SARS-and MERS-CoVs, zoonotic spillover events (zoonosis), acquiring transmission ability to infect humans, and adopting appropriate preventive and control measures [42] . doi = 10.1016/j.tmaid.2020.101830 id = cord-266885-a5fdeuvv author = Dlotko, P. title = Covid-19 clinical data analysis using Ball Mapper date = 2020-04-15 keywords = Cov-2; SARS summary = doi = 10.1101/2020.04.10.20061374 id = cord-266444-rw94yls8 author = Dominguez Andres, Ana title = SARS-CoV-2 ORF9c Is a Membrane-Associated Protein that Suppresses Antiviral Responses in Cells date = 2020-08-19 keywords = CoV-2; Fig; ORF9c; SARS; protein summary = doi = 10.1101/2020.08.18.256776 id = cord-333682-ktbnrkwh author = Dong, Yunzhu title = Antibodies in the breast milk of a maternal woman with COVID-19 date = 2020-07-03 keywords = CoV-2; SARS summary = A maternal woman was positive for SARS-CoV-2 tested in throat swabs but negative tested in other body fluids, and she had IgG and IgA detected in breast milk. Although clinical and laboratory characteristics, and outcomes of pregnant women with COVID-19 have been reported [4], there are no continuously monitored data about the viral loads in several body fluids of the maternal women that would bring potential risks of SARS-CoV-2 infection to neonates [8] . The titers of IgG antibody in breast milk were 2.34, 3.02, 2.84, 2.79, and 3.35, respectively, when three SARS-CoV-2 negative maternal woman''s breast milk were tested as control (mean titer 0.98) (Figure 1, panel D) . (D) Titers of IgG antibody to SARS-CoV-2 in maternal woman''s breast milk determined using ELISA. doi = 10.1080/22221751.2020.1780952 id = cord-350959-bsbz3a1l author = Dovey, Zachary title = Impact of COVID-19 on Prostate Cancer Management: Guidelines for Urologists date = 2020-06-16 keywords = China; CoV-2; SARS; patient; risk summary = There is also epidemiological evidence that PCa patients have increased incidence and mortality from SARS-CoV-2 infection due to gender differences, age, and higher propensity for risk factors (eg, respiratory disease, obesity, hypertension, and smoking status). Patient summary Prostate cancer patients can be followed up remotely until the severe acute respiratory syndrome coronavirus 2 pandemic resolves, but higher-risk cases may have treatment expedited to limit any negative impact on prostate cancer outcomes. As shown in Table 2 , PCa patients with either diabetes or hypertension should seek advice from their physicians to optimize their treatment, especially if this includes ACE inhibitors or ARBs [32] , to reduce their risk of SARS-CoV-2 infection and morbidity. Tewari Prostate cancer (PCa) patients may have an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and mortality. doi = 10.1016/j.euros.2020.05.005 id = cord-308583-vtmwv8zl author = Du, Qishi title = Molecular modeling and chemical modification for finding peptide inhibitor against severe acute respiratory syndrome coronavirus main proteinase date = 2005-02-15 keywords = CoV; SARS summary = In this research we study the cleavage mechanism, the properties of the relevant chemical bonds, and the catalytic interactions between the octapeptides and the SARS CoV M pro using molecular mechanical and quantum chemical simulations to provide useful insights for the chemical modification. The docking calculation between SARS CoV M pro and the octapeptide AVLQSGFR was performed using the molecular although still bound to the active site, the peptide has lost its cleavability after its scissile bond was modified from a hybrid peptide bond to a strong bond. Fig. 5B is the contour map of differential electronic density of the peptide bond Gln-Ser in the octapeptide AVLQSGFR, obtained by subtracting the electron density in the gaseous phase from the electron density in the background [23] of SARS CoV M pro and solvent water molecules. For the peptide inhibitor of proteinase, the chemical modification to cleavable octapeptide should focus on the scissile peptide bond between R 1 and R 1 0 to be cleaved by SARS CoV M pro . doi = 10.1016/j.ab.2004.10.003 id = cord-328003-yovp8squ author = Duan, Liangwei title = The SARS-CoV-2 Spike Glycoprotein Biosynthesis, Structure, Function, and Antigenicity: Implications for the Design of Spike-Based Vaccine Immunogens date = 2020-10-07 keywords = ACE2; CoV-2; RBD; SARS; protein summary = Here, we provide a comprehensive overview of the wealth of research related to the SARS-CoV-2 S glycoprotein biosynthesis, structure, function, and antigenicity, aiming to provide useful insights into the design and development of the S protein-based vaccines as well as therapeutics to prevent or treat the ongoing global spread of SARS-CoV-2/COVID-19. Prefusion structures of human coronavirus HKU1 (HCoV-HKU1) and mouse hepatitis virus S protein ectodomains without two consecutive proline mutations reveal only fully closed conformation (37, 42) , similar to that observed for a full-length, wild-type prefusion form of the SARS-CoV-2 S glycoprotein (41) . Therefore, SARS-CoV-2 evades immune surveillance also through conformational masking, which is well-documented for HIV-1 (43, 44) ; while at the same time, the S protein could transiently sample the functional state to engage ACE2, consistent with the notion that the fusion glycoprotein of highly pathogenic viruses have evolved to perform its functions while evading host neutralizing antibody responses. doi = 10.3389/fimmu.2020.576622 id = cord-343317-97n1j0jj author = Duan, Xiaohua title = Identification of Drugs Blocking SARS-CoV-2 Infection using Human Pluripotent Stem Cell-derived Colonic Organoids date = 2020-05-02 keywords = CoV-2; Fig; SARS; cell summary = Multiple cell types in the COs can be infected by a SARS-CoV-2 pseudo-entry virus, which was further validated in vivo using a humanized mouse model. Multiple cell types in the COs can be infected by a SARS-CoV-2 pseudo-entry virus, which was further validated in vivo using a humanized mouse model. The organoids infected with SARS-CoV-2 pseudo-entry virus at MOI=0.01 showed a strong signal at 24 hpi (Fig. 2a) . The mRNAs of SARS-CoV-2 pseudo-entry virus, including VSV-NS, VSV-N, and VSV-M, were detected in all five cell populations (Fig. 2f) , but not in the uninfected COs (Extended Data Fig. 2f) . Immunohistochemistry detected luciferase in ACE2 + and Villin + cells, suggesting these are permissive to SARS-CoV-2 pseudo-entry virus infection in vivo (Fig. 2k) . Next, we adapted hPSC-COs to a high throughput screening platform and probed the Prestwick FDA-approved drug library to identify drug candidates capable of blocking SARS-CoV-2 pseudo-virus infection. doi = 10.1101/2020.05.02.073320 id = cord-294108-uvnh0s9r author = Dube, Taru title = Repurposed Drugs, Molecular Vaccines, Immune‐Modulators, and Nanotherapeutics to Treat and Prevent COVID‐19 Associated with SARS‐CoV‐2, a Deadly Nanovector date = 2020-10-25 keywords = COVID-19; CoV-2; FDA; Phase; RNA; SARS; patient; vaccine; virus summary = [2, [8] [9] [10] This article discusses SARS-CoV-2 nanostructure, the virus biology in connection to its epidemiology, clinical manifestations, and potential and future therapeutic options including repurposed drugs, vaccine/protein therapies, immune therapies, and nanotherapeutics. Mechanisms such as inhibition of viral enzymes (DNA and RNA polymerases, 3CL pro, TMPRSS2, reverse transcriptase, neuraminidase, endonucleases, and other proteases) or processes such as ACE2 cellular receptor inhibitors and endosomal acidification mediators prohibiting viral fusion; molecules interfering with glycosylation of the viral protein, viral assembly, new viral particle transport, and release, and immunomodulation of cytokine release can be potential targets in developing various antiviral drugs for the SARS-CoV-2. [85] A randomized, placebo-controlled, Phase IV clinical trial assessing the safety and efficacy of umifenovir as an adjuvant therapy to the combined therapeutic regimen of IFN 1a, lopinavir/ritonavir and hydroxychloroquine in moderate to severe COVID-19 patients (NCT04350684) is underway. doi = 10.1002/adtp.202000172 id = cord-317355-z5tk3v3b author = Dunker, Susanne title = No SARS-CoV-2 detected in air samples (pollen and particulate matter) in Leipzig during the first spread date = 2020-10-13 keywords = CoV-2; SARS summary = title: No SARS-CoV-2 detected in air samples (pollen and particulate matter) in Leipzig during the first spread Air samples collected at our measuring station in Leipzig and purified pollen were analyzed for SARS-CoV-2 typical signals or for virus-induced cytopathic effects, to test if the virus could bind to bioaerosols and if so, whether these complexes are infectious. We therefore aimed at investigating whether SARS-CoV-2 can bind to pollen or other kind of particulate matter within bioaerosols sampled at our station in Leipzig and if so, whether these complexes are infectious. In none of these samples SARS-CoV-2 typical For a detailed analysis of a possible correlation between concentrations of the most abundant pollen, particulate matter and registered Covid-19 cases, a correlation matrix was created with R (package "PerformanceAnalytics") (Fig. 2) . doi = 10.1016/j.scitotenv.2020.142881 id = cord-273182-djb0ozrt author = Díez, José María title = Cross-neutralization activity against SARS-CoV-2 is present in currently available intravenous immunoglobulins date = 2020-09-09 keywords = CoV; IVIG; MERS; SARS summary = Recently, we reported cross-reactivity in ELISA binding assays against antigens of SARS-CoV, SARS-CoV-2 and MERS-CoV with Flebogamma R DIF 5 and 10% and Gamunex R -C, two currently available intravenous IGs (IVIG) [23] . Six different lots of Flebogamma DIF and Gamunex-C were tested at several dilutions for cross-reactivity against SARS-CoV, SARS-CoV-2 and MERS-CoV by: ELISA techniques; and well-established neutralization assays in cell cultures. For SARS-CoV-2 MAD6 isolate, all IVIG lots, except F1 (inconclusive results) showed a significant neutralizing activity and reached PRNT 50 titers ranging from 4.5 to >5 (Figure 2 ). This neutralizing activity correlates with the cross-reactivity to different coronavirus antigens observed in ELISA-binding assays with IVIG, as shown in a previous study [23] . • Intravenous immunoglobulin products were tested against severe acute respiratory syndrome coronavirus 2 in cell culture neutralization assays. doi = 10.2217/imt-2020-0220 id = cord-296237-i9cti2ok author = Díez, José-María title = Cross-neutralization activity against SARS-CoV-2 is present in currently available intravenous immunoglobulins date = 2020-06-19 keywords = CoV-2; IVIG; MERS; SARS summary = Recently, ELISA binding cross-reactivity against components of human epidemic coronaviruses with currently available intravenous immunoglobulins (IVIG) Gamunex-C and Flebogamma DIF (5% and 10%) have been reported. Conclusion In cell culture neutralization assays, the tested IVIG products contain antibodies with significant cross-neutralization capacity against SARS-CoV-2 and SARS-CoV. Recently, cross-reactivity in ELISA binding assays against antigens of SARS-CoV, SARS-CoV-2, and MERS-CoV has been reported with currently available intravenous immunoglobulins (IVIG) such as Gamunex-C and Flebogamma DIF 19 . In this study, the neutralization capacity of the IVIG products Gamunex-C and Flebogamma DIF against these epidemic human coronaviruses -SARS-CoV, SARS-CoV-2, and MERS-CoV-was evaluated. Six different lots of Flebogamma DIF and Gamunex-C were tested at several dilutions for cross-reactivity against SARS-CoV, SARS-CoV-2, and MERS-CoV by: i) ELISA techniques; and ii) well-stablished neutralization assays in cell cultures. For SARS-CoV-2 MAD6 isolate, all IVIG lots, except F1 (inconclusive results) showed a significant neutralizing activity and reached PRNT50 titers ranging from 4.5 to >5 (Figure 2 ). doi = 10.1101/2020.06.19.160879 id = cord-353524-3w970ycx author = Dömling, Alexander title = Chemistry and Biology of SARS-CoV-2 date = 2020-05-22 keywords = CoV-2; RNA; SARS; drug summary = Given that SARS-CoV-2 and SARS-CoV share very high identical sequence in their 3CLpro, these HIV protease inhibitors are currently again repurposed for the treatment of COVID-19 (Chinese Clinical Trial Registry: ChiCTR2000029539). 30, 31 The interplay of the ACE receptor in cardiovascular diseases (with the well-known drug class of ACE inhibitors) and as the docking point for SARS-CoV-2 cellular infection is a current point of intense debate and research. For example, the crystal structure of SARS-CoV-2 N protein RNA-binding domain was just published and will give structural insight as a potential drug target. Potential broad spectrum inhibitors of the coronavirus 3CLpro: A virtual screening and structure-based drug design study Severe acute respiratory syndrome coronavirus papain-like novel protease inhibitors: design, synthesis, protein-ligand X-ray structure and biological evaluation Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites doi = 10.1016/j.chempr.2020.04.023 id = cord-315685-ute3dxwu author = Ehaideb, Salleh N. title = Evidence of a wide gap between COVID-19 in humans and animal models: a systematic review date = 2020-10-06 keywords = COVID-19; CoV-2; SARS; model summary = The systematic search identified 101 studies and 326 preprints, of which 400 articles were excluded because they were reviews, non-original articles, unrelated to the COVID-19 infection, or experimental animals that do not support SARS-CoV-2 replication such as pigs, ducks, and chickens ( Fig. 1 and Additional file 2). The aims were to investigate the pathogenesis of COVID-19 (n = 15), testing drugs and vaccines (n = 14), the host Table 1 Search strategy and selection criteria We searched the MEDLINE, as well as BioRxiv and MedRxiv preprint servers for original research describing or using an animal model of SARS-CoV-2 induced COVID published in English from January 1, 2020, to May 20, 2020. We used the search terms (COVID-19) OR (SARS-CoV-2) AND, (animal models), (hamsters), (nonhuman primates), (macaques), (rodent), (mice), (rats), (ferrets), (rabbits), (cats), and (dogs). We used the search terms (COVID-19) OR (SARS-CoV-2) AND, (animal models), (hamsters), (nonhuman primates), (macaques), (rodent), (mice), (rats), (ferrets), (rabbits), (cats), and (dogs). doi = 10.1186/s13054-020-03304-8 id = cord-307489-2liu4anc author = Elavia, Nasha title = An Atypical Presentation of Acute Pulmonary Embolism With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Pneumonia date = 2020-05-23 keywords = CoV-2; SARS summary = title: An Atypical Presentation of Acute Pulmonary Embolism With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Pneumonia Clinical presentation and severity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) varies greatly amongst patients, as supported by recent literature. Here, we would like to describe a case of acute bilateral pulmonary embolism (PE) presenting with atypical gastrointestinal symptoms in a patient with SARS-CoV-2 infection. This atypical presentation of PE is unique to our case and highlights the significance of a high index of clinical suspicion for SARS-CoV-2 and its associated thrombogenic effect, even in patients with atypical symptoms. Here, we would like to describe a case of acute bilateral pulmonary embolism (PE) in a patient with SARS-CoV-2 pneumonia who mainly presented with gastrointestinal symptoms. Our patient however presented mainly with gastrointestinal symptoms, which have been reported with SARS-CoV-2; however, with significant hypoxia in the absence of a respiratory viral syndrome although with a low pretest probability for PE, we decided to further evaluate the patient for hypoxia. doi = 10.7759/cureus.8249 id = cord-315064-2mgv9j6n author = Escher, Felicitas title = Detection of viral SARS‐CoV‐2 genomes and histopathological changes in endomyocardial biopsies date = 2020-06-12 keywords = COVID-19; CoV-2; Germany; SARS summary = Accordingly, we prospectively analysed endomyocardial biopsies (EMBs) from a cohort of 104 samples of patients with suspected myocarditis or unexplained heart disease for the presence of SARS-CoV-2 RNA by RT-qPCR and hints for histopathological injury. Up to 8 EMBs each of 104 patients [mean age: 57.90 ± 16.37 years; left ventricular ejection fraction (LVEF): 33.7 ± 14.6%, sex: n = 79 male/25 female] with suspected myocarditis or unexplained heart failure were analysed between 3 February and 26 March 2020 in German clinical centres in accordance with SARS-CoV2 spread in Germany. In this study, we established for the first time the evidence of SARS-CoV-2 genome detection in 5 of 104 EMBs of patients with suspected myocarditis or unexplained heart failure. Our finding of SARS-CoV-2 genome detection in EMBs of patients suffering from myocarditis/inflammatory cardiomyopathy cannot rule out or confirm the infection of cardiac cells but revealed incremental insights into organ-specific infection of SARS-CoV-2 using possibly macrophage migration as a shuttle from the lung to the heart. doi = 10.1002/ehf2.12805 id = cord-277399-0w8is9xm author = Esteves, Sandro C. title = SARS‐CoV‐2 pandemic and repercussions for male infertility patients: A proposal for the individualized provision of andrological services date = 2020-05-22 keywords = CoV-2; SARS; patient; sperm summary = The prolonged lockdown of health facilities providing non‐urgent gamete cryopreservation—as currently recommended by many reproductive medicine entities and regulatory authorities due to the SARS‐CoV‐2 pandemic will be detrimental for subgroups of male infertility patients. These groups include infertility patients (eg, azoospermic and cryptozoospermic) undergoing medical or surgical treatment to improve sperm quantity and quality, as well as males of reproductive age affected by inflammatory and systemic auto‐immune diseases who are about to start treatment with gonadotoxic drugs or who are under remission. Sperm banking should be considered in men with HH who respond to therapy, that is, have viable spermatozoa in the ejaculate, in particular, when the continuation of gonadotropin therapy during the SARS-CoV-2 pandemic is neither possible (eg, due to economic or logistic reasons), nor desired. We propose remedies to mitigate the consequences of a prolonged cessation of andrological services due to the SARS-CoV-2 pandemic to vulnerable subgroups of male infertility patients. doi = 10.1111/andr.12809 id = cord-256020-wrui3i2l author = Fadaka, Adewale Oluwaseun title = Understanding the epidemiology, pathophysiology, diagnosis and management of SARS-CoV-2 date = 2020-08-26 keywords = ACE-2; COVID-19; CoV-2; MERS; SARS; figure summary = The disease is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The disease is caused by SARS-CoV-2, a zoonotic pathogen that acquired mutations as it crossed the species barrier from bat to pangolin enabling it to infect humans. 5 The clinical symptoms of COVID-19 include fever, cough, and pneumonia, which makes the disease enormously dangerous with a high case fatality rate. 11 Symptoms of human SARS-CoV-1 infections include headache, fever and respiratory complications such as cough, dyspnea, and pneumonia. 81 The main goal of SARS-CoV-2 diagnosis is to accurately detect the virus and to minimize further transmissions by timely isolation and treatment of infected patients. 112 This implies that variation in ACE-2 expression in COVID-19 patients is likely to affect susceptibility, symptoms and intervention outcomes following SARS-CoV-2 infection. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): the epidemic and the challenges Comparative genetic analysis of the novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different populations doi = 10.1177/0300060520949077 id = cord-281684-m3m4mhye author = Fagre, Anna C. title = A potent SARS-CoV-2 neutralizing human monoclonal antibody that reduces viral burden and disease severity in Syrian hamsters date = 2020-09-28 keywords = ACE2; CoV-2; SARS summary = title: A potent SARS-CoV-2 neutralizing human monoclonal antibody that reduces viral burden and disease severity in Syrian hamsters We identified a panel of human monoclonal antibody clones from a yeast display library with specificity to the SARS-CoV-2 spike protein receptor binding domain that neutralized the virus in vitro. However, to date, there has been only a gross histological analysis of the lung pathological changes following infection and the impact of SARS-CoV-2 neutralizing antibody clones on lung immune infiltrates has yet to be fully assessed. Those antibody clones that blocked the interaction of the RBD with ACE2 and bound to native spike protein were then tested for neutralization of SARS-CoV-2 in a cytopathic effect (CPE) assay with Vero E6 cells. Potent neutralization of severe acute respiratory syndrome (SARS) coronavirus by a human mAb to S1 protein that blocks receptor association Emergence of SARS-CoV-2 spike RBD mutants that enhance viral infectivity through increased human ACE2 receptor binding affinity doi = 10.1101/2020.09.25.313601 id = cord-318204-t024w7h6 author = Fang, Ferric C title = The Laboratory Diagnosis of COVID-19-- Frequently-Asked Questions date = 2020-06-08 keywords = COVID-19; CoV-2; SARS summary = As communities attempt to re-open following periods of shutdown, the detection of both SARS-CoV-2 and specific antibodies recognizing the virus will become increasingly important as a means to assess infection and immunity in individuals and communities. In view of the less than ideal sensitivity of an NP swab to detect SARS-CoV-2 infection, it may be useful to repeat testing in a patient in whom the clinical suspicion is high (32) . Although the primary use of serologic tests is to determine prior exposure to SARS-CoV-2, the detection of specific antibodies may support the diagnosis of COVID-19 in a patient with a high clinical suspicion but negative PCR tests (57-59). Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China Early detection of SARS-CoV-2 antibodies in COVID-19 patients as a serologic marker of infection doi = 10.1093/cid/ciaa742 id = cord-313344-rqvi2ksc author = Farcas, Gabriella A. title = Fatal Severe Acute Respiratory Syndrome Is Associated with Multiorgan Involvement by Coronavirus date = 2005-01-15 keywords = CoV; SARS summary = Severe acute respiratory syndrome (SARS) is characterized by pulmonary compromise; however, patients often have evidence of other organ dysfunction that may reflect extrapulmonary dissemination of SARS coronavirus (SARS-CoV). The purpose of the present study was to investigate the presence of SARS-CoV, the degree of viral dissemination, and the viral loads in multiple organ samples from all patients who died of SARS during the Toronto outbreak (March to September 2003) and underwent a postmortem examination and compare the results with those found in patients who died of other causes during the outbreak. A total of 212 discrete postmortem organ samples, including lung, liver, spleen, kidney, small bowel, large bowel, lymph nodes, heart, and skeletal muscle, were prospectively collected from the 21 patients who died of SARS and underwent autopsies. doi = 10.1086/426870 id = cord-298850-tgxfki7n author = Figuero-Pérez, Luis title = Anakinra as a potential alternative in the treatment of severe acute respiratory infection associated with SARS-CoV-2 refractory to tocilizumab date = 2020-10-15 keywords = CoV-2; SARS summary = title: Anakinra as a potential alternative in the treatment of severe acute respiratory infection associated with SARS-CoV-2 refractory to tocilizumab Several studies have proposed that anti-IL-6 receptor antibodies, such as tocilizumab, play an important role in the treatment of severe acute respiratory infection associated with SARS-CoV-2. We present a case report of a 51-year-old man diagnosed with severe respiratory infection associated with SARS-CoV-2 that was refractory to antiviral and anti-IL-6 treatment, with a favourable clinical outcome and analytical improvement after treatment with anti-IL-1 (anakinra). We present the case of a 51-year-old patient with bilateral pneumonia secondary to SARS-CoV-2 infection refractory to treatment with tocilizumab who showed improvement after treatment with anakinra. The "cytokine storm" secondary to SARS-CoV-2 infection determines severe COVID-19 disease. 3 The use of anti-IL-6 antibodies in the treatment of SARS-CoV-2 infection is currently under study, being one of the current pillars of COVID-19 disease treatment. doi = 10.1016/j.reumae.2020.06.008 id = cord-339009-wcoch07b author = File, Thomas M. title = Severe Acute Respiratory Syndrome: Pertinent Clinical Characteristics and Therapy date = 2012-08-23 keywords = CoV; SARS; case; patient; respiratory summary = Because the causative agent of SARS is • one or more clinical findings of respiratory illness (e.g. cough, contagious, preventative measures focus on avoidance of exposhortness of breath, difficulty in breathing, or hypoxia) sure, and infection control strategies for suspected patients and • travel within 10 days of onset of symptoms to an area with contacts. [12] Of the reported cases was updated to include laboratory criteria for evidence of infection 64% were from China, 19% from Hong Kong, 8% from Taiwan, with the SARS-associated coronavirus (SARS-CoV). Algorithm for evaluating and managing patients requiring hospitalization for radiographically confirmed pneumonia, in the absence of person-toperson transmission of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) anywhere in the world. doi = 10.2165/00151829-200504020-00003 id = cord-252767-as841xo0 author = Fischer, Bastian title = SARS-CoV-2 IgG seroprevalence in blood donors located in three different federal states, Germany, March to June 2020 date = 2020-07-16 keywords = CoV-2; SARS summary = We determined seroprevalence of IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 3,186 regular blood donors in three German federal states between 9 March and 3 June 2020. We determined seroprevalence of IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 3,186 regular blood donors in three German federal states between 9 March and 3 June 2020. To determine an approximation of the actual rate of people who have recovered from COVID-19, representative of the German population, we determined the anti-SARS-CoV-2 IgG seroprevalence of regular blood donors resident in three different German federal states between March and June 2020. The Figure shows the anti-SARS-CoV-2 IgG distribution in blood donors with equivocal (ratio: ≥ 0.8 to < 1.1) and clearly seropositive (ratio: ≥ 1.1) test results. Distribution of anti-SARS-CoV-2 IgG ratios of blood donors with seropositive and equivocal test results, Germany, March-June 2020, (n = 3,186) doi = 10.2807/1560-7917.es.2020.25.28.2001285 id = cord-264814-v4wnmg03 author = Flanagan, Katie L. title = Progress and Pitfalls in the Quest for Effective SARS-CoV-2 (COVID-19) Vaccines date = 2020-10-02 keywords = CD8; COVID-19; CoV-2; SARS; cell; dna; table; vaccine summary = Herein, we review the current knowledge about the immune response to this novel virus as it pertains to the design of effective and safe SARS-CoV-2 vaccines and the range of novel and established approaches to vaccine development being taken. Herein, we review the current knowledge about the immune response to this novel virus as it pertains to the design of effective and safe SARS-CoV-2 vaccines and the range of novel and established approaches to vaccine development being taken. Comprehensive safety studies are particularly critical because some candidate vaccines use platform technologies that have not been examined extensively in human subjects to date, including some of the viral vectors, mRNA and nanoparticle constructs, and because of the potential for enhanced disease and adverse events related to aberrant immune responses to be seen upon infection pre-and post-licensure. doi = 10.3389/fimmu.2020.579250 id = cord-310624-3kojrkz7 author = Flores-Alanis, Alejandro title = The receptor binding domain of SARS-CoV-2 spike protein is the result of an ancestral recombination between the bat-CoV RaTG13 and the pangolin-CoV MP789 date = 2020-08-27 keywords = CoV-2; MP789; SARS summary = In the present work we performed a genetic analysis of the Spike glycoprotein (S) of SARS-CoV-2 and other related coronaviruses (CoVs) isolated from different hosts in order to trace the evolutionary history of this protein and the adaptation of SARS-CoV-2 to humans. RESULTS: Based on the sequence analysis of the S gene, we suggest that the origin of SARS-CoV-2 is the result of recombination events between bat and pangolin CoVs. The hybrid SARS-CoV-2 ancestor jumped to humans and has been maintained by natural selection. Although the S protein of RaTG13 bat CoV has a high nucleotide identity with the S protein of SARS-CoV-2, the phylogenetic tree and the haplotype network suggest a non-direct parental relationship between these CoVs. Moreover, it is likely that the basic function of the receptor-binding domain (RBD) of S protein was acquired by the SARS-CoV-2 from the MP789 pangolin CoV by recombination and it has been highly conserved. doi = 10.1186/s13104-020-05242-8 id = cord-275926-rj23z7po author = Fontanella, Marco M. title = Neurosurgical practice during the SARS-CoV-2 pandemic: a worldwide survey date = 2020-05-05 keywords = CoV-2; Italy; SARS summary = 3. Institutional plans for the SARS-CoV-2 outbreak: any special measures adopted for SARS-CoV-2 positive neurosurgical patients were investigated, i.e. their screening rate and method, any changes in surgical indications, planning and activity for oncologic procedures, non-emergency surgeries, and subarachnoid hemorrhages (SAHs). The same correlation was found with regards to the medical perception of disease activity (Q2) in different countries, and only few respondents (3%) claimed their country was not facing the outbreak during the time period studied: among them, neurosurgeons from Germany were probably the most "wrong", since their country had between 10 4 to 10 5 SARS-CoV2 patients during the study period (Fig. 4A) . 5 India and Pakistan have been reported to be the world''s best respondents to the SARS-COV-2 pandemic, 22-24 thus reflecting high rates of neurosurgical activity reorganizations. doi = 10.1016/j.wneu.2020.04.204 id = cord-019048-29wzpwvr author = Franks, Teri J. title = Coronavirus date = 2013-08-26 keywords = CoV; DAD; SARS summary = From discovery to mid-September 2013, HCoV-EMC, renamed MERS-CoV, (de Groot 2013 ) caused 132 laboratory-confi rmed cases of severe acute pneumonia including 58 deaths. Certain structural proteins are common to all coronaviruses: the spike glycoprotein S, an envelope glycoprotein that mediates receptor-binding and membrane fusion; the envelope spanning glycoprotein M, which contributes to the thickness of the envelop; the envelope protein E, which has been identifi ed as a virulence factor SARS-CoV ; and the nucleocapsid protein N, with its function in genome encapsidation, RNA synthesis and translation, and as a type I interferon antagonist ( Fig. 13 .2 ). Initial signs and symptoms of SARS are nonspecifi c and common, which generates a wide differential diagnosis of respiratory pathogens including infl uenza virus, parainfl uenza Fig. 13.4 Acute-phase DAD in SARS patient. Severe acute respiratory syndrome coronavirus as an agent of emerging and reemerging infection doi = 10.1007/978-3-642-40605-8_13 id = cord-254395-tu4aqczj author = Froggatt, Heather M. title = Development of a Fluorescence-Based, High-Throughput SARS-CoV-2 3CL(pro) Reporter Assay date = 2020-10-27 keywords = 3CL; CoV-2; Fig; SARS summary = This experimentally optimized reporter assay allows for antiviral drug screening in human cell culture at biosafety level 2 (BSL2) with high-throughput compatible protocols. This reporter-based assay allows for antiviral drug screening in human cell culture at biosafety level 2 (BSL2) with high-throughput compatible sample processing and analysis. With the aim of generating a protease reporter compatible with SARS-CoV-2 and other present and future coronaviruses to support viral inhibitor screening, we selected CoV 3CL pro as our protease target. (C) Quantification of fluorescence from 293T cells 48 h after transfection with each FlipGFP reporter and either the SARS-CoV-2 3CL pro or an influenza virus protein (A/PR8/1834 NP). To observe whether these FlipGFP constructs background fluoresced without CoV 3CL pro activity, we transfected cells with each reporter or a superfolder GFP (sfGFP) expression plasmid. Development of a FlipGFP CoV 3CL pro reporter-based assay for protease inhibitor screening in human cells. doi = 10.1128/jvi.01265-20 id = cord-313517-5ipj2z86 author = Fung, Joshua title = Antigen Capture Enzyme-Linked Immunosorbent Assay for Detecting Middle East Respiratory Syndrome Coronavirus in Humans date = 2019-09-14 keywords = CoV; ELISA; MERS summary = Though the gold standard for diagnosing MERS-CoV infection in humans is still nucleic acid amplification test (NAAT) of the up-E region, an antigen capture enzyme-linked immunosorbent assay (ELISA) could also be of use for early diagnosis in less developed locations. In the present method, a step-by-step guide to perform a MERS-CoV nucleocapsid protein (NP) capture ELISA using two NP-specific monoclonal antibodies is provided for readers to develop their in-house workflow or diagnostic kit for clinical use and for mass-screening project of animals (e.g., dromedaries and bats) to better understand the spread and evolution of the virus. Nucleic acid amplification test (NAAT, e.g., real-time reverse transcription quantitative polymerase chain reaction [real-time RT-qPCR]), virus isolation, transmission electron microscopy, immunohistochemistry, and serological methods (e.g., antigen capture enzyme-linked immunosorbent assay [ELISA] and immunofluorescence assay [IFA] ) have been developed and used for MERS-CoV diagnosis [2] [3] [4] [5] [6] [7] . doi = 10.1007/978-1-0716-0211-9_7 id = cord-322837-tqgwgvo0 author = Gable, Lance title = Legal and Ethical Implications of Wastewater SARS-CoV-2 Monitoring for COVID-19 Surveillance date = 2020-06-24 keywords = CoV-2; SARS summary = Even if reliability and efficacy are established, limits on sample and data collection, use, and sharing, must also be considered to prevent undermining privacy and autonomy in order to implement these public health strategies consistent with legal and ethical considerations. The proposed use of wastewater screening to detect SARS-CoV-2 viral RNA has the potential to greatly enhance our technical capabilities to identify, track, pinpoint, and quantify 32 Second, public health authorities could use this information to justify increased testing among people living in homes or working at sites close to where the virus has been found in wastewater, or to implement neighborhood-wide screening programs in these areas. Wastewater screening for SARS-CoV-2 could provide an important tool to detect new outbreaks of COVID-19 and to target resources to intervene to stop the spread of the disease; however, scientific research must establish the efficacy of such testing in identifying communitybased COVID-19 infections before its use can be considered as the basis for public policy. doi = 10.1093/jlb/lsaa039 id = cord-252600-bvh1o64r author = Galasiti Kankanamalage, Anushka C. title = Structure-guided design of potent and permeable inhibitors of MERS coronavirus 3CL protease that utilize a piperidine moiety as a novel design element date = 2018-04-25 keywords = CoV; MERS; SARS summary = We describe herein the structure-guided design and evaluation of a novel class of inhibitors of MERS-CoV 3CL protease that embody a piperidine moiety as a design element that is well-suited to exploiting favorable subsite binding interactions to attain optimal pharmacological activity and PK properties. The structure-guided design of inhibitor (I) encompassed the following steps: (a) we first determined a high resolution X-ray crystal structure of MERS-CoV 3CLpro in complex with GC376 ( Fig. 2/Panel A) . Validation of this idea was obtained by synthesizing extended inhibitor GC813 and determining a high resolution X-ray crystal structure of the MERS-CoV 3CLpro:GC813 complex ( Fig. 2/Panel B) . More importantly, representative aldehyde bisulfite adduct compounds 10a and 10c display potent inhibition toward MERS-CoV in both enzyme and cell-based systems, with low cytotoxicity (CC 50 > 100 mM) ( Table 2 and Fig. 4 ). doi = 10.1016/j.ejmech.2018.03.004 id = cord-280774-r2xm164s author = Gallizzi, Romina title = Management of pernio‐like cutaneous manifestations in children during the outbreak of covid‐19. date = 2020-09-19 keywords = CoV-2; SARS summary = The increased number of cases of pernio-like lesions compared to the cases per year we usually observe, the mild temperatures of those months in Southern Italy and the concomitant lockdown, led us to hypothesize a possible correlation with SARS-CoV-2 infection. This is useful to highlight, as in our case, the D-dimer of our patients was weakly increased, a condition perfectly correlated with the mild symptoms of SARS-CoV-2 putative infection presented. In a report of 19 adolescent patients with a clinical diagnosis of pernio-like lesions nasopharyngeal swab and IgG serology for SARS-CoV-2 nucleocapsid protein were negative. Why some children who come into contact with the SARS-CoV-2 do not develop striking respiratory symptoms but present pernio-like lesions with negativity on diagnostic tests? This pathogenic mechanism could explain the appearance of pernio-like lesions due to SARS-CoV-2 infection. In conclusion, we think there is a correlation between pernio-like lesions and SARS-CoV-2 infection, but further studies are needed to prove it. doi = 10.1111/dth.14312 id = cord-324102-75v4ebag author = Garcia Rodriguez, Alejandro title = SARS-COV-2 infection during pregnancy, a risk factor for eclampsia or neurological manifestations of COVID-19? Case report date = 2020-10-06 keywords = COV-2; SARS summary = title: SARS-COV-2 infection during pregnancy, a risk factor for eclampsia or neurological manifestations of COVID-19? BACKGROUND: There are no published cases of tonic-clonic seizures and posterior bilateral blindness during pregnancy and Severe Acute Respiratory Syndrome (SARS) Coronavirus (COV) 2 (SARS-COV-2) infection. CONCLUSION: The authors conclude that SARS COV-2 infection could promote brain endothelial damage and facilitate neurological complications during pregnancy. That is the reason why we present a case report of a pregnant woman infected with SARS-COV-2 who showed seizures and sudden blindness. Therefore, we consider that SARS-COV-2 infection during pregnancy could increase the risk of suffering posterior reversible leukoencephalopathy or preeclampsia/eclampsia syndrome. To our knowledge, this is the first report of a patient with COVID-19 presenting preeclampsia associated with eclampsia versus posterior reversible leukoencephalopathy without alarm signs or symptoms. We consider further studies are needed to confirm that SARS-COV-2 infection is a risk factor to develop neurological complications of pregnant woman during pregnancy. doi = 10.1186/s12884-020-03275-2 id = cord-255552-k1retwa4 author = Gassen, Nils C. title = Analysis of SARS-CoV-2-controlled autophagy reveals spermidine, MK-2206, and niclosamide as putative antiviral therapeutics date = 2020-04-15 keywords = CoV-2; SARS summary = Pharmacological modulation of metabolism-dependent cellular pathways such as autophagy reduced propagation of highly pathogenic Middle East respiratory syndrome (MERS)-CoV. In-depth analyses of autophagy signaling and metabolomics indicate that SARS-CoV-2 reduces glycolysis and protein translation by limiting activation of AMP-protein activated kinase (AMPK) and mammalian target of rapamycin complex 1 (mTORC1). Targeting of these pathways by exogenous administration of spermidine, AKT inhibitor MK-2206, and the Beclin-1 stabilizing, antihelminthic drug niclosamide inhibited SARS-CoV-2 propagation by 85, 88, and >99%, respectively. In the case of highly pathogenic Middle East respiratory syndrome 57 (MERS)-CoV, we recently showed that autophagy is limited by a virus-induced AKT1-dependent 58 activation of the E3-ligase S-phase kinase-associated protein 2 (SKP2), which targets the key autophagy 59 initiating protein Beclin-1 (BECN1) for proteasomal degradation (10). Direct blocking of the negative BECN1 regulator SPK2 by previously 175 described inhibitors SMIP004, SMIP004-7, valinomycin, and niclosamide (10) showed SARS-CoV-2 176 growth inhibition from 50 (SMIP004, SMIP004-7) to over 99% in case of valinomycin and niclosamide 177 (Figure 4a, lower panel, Figure S3d,e) . doi = 10.1101/2020.04.15.997254 id = cord-307701-fujejfwb author = Gaurav, Shubham title = Identification of unique mutations in SARS-CoV-2 strains isolated from India suggests its attenuated pathotype date = 2020-06-07 keywords = CoV-2; SARS summary = Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which was first reported in Wuhan, China in November 2019 has developed into a pandemic since March 2020, causing substantial human casualties and economic losses. In this study, we sequenced and analyzed the genomic information of the SARS-CoV-2 isolates from two infected Indian patients and explored the possible implications of point mutations in its biology. Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the cause of the novel human Corona Virus Disease COVID-19, first reported on November 17 th , 2019 in Wuhan, China [12] . In addition to structural and NSPs, SARS-CoV-2 genome also codes for at least two other viroporin candidates (other than the E protein), namely ORF3a and ORF8 [3] . Moreover, the 29-nucleotide deleted SARS CoV-1 strain had a 23-fold less viral replication as compared to its wild type, suggesting that this mutation effectively attenuated the virus. doi = 10.1101/2020.06.06.137604 id = cord-314135-udce22id author = Geisslinger, Franz title = Cancer Patients Have a Higher Risk Regarding COVID-19–and Vice Versa? date = 2020-07-06 keywords = ACE2; CoV-2; SARS; cancer; covid-19 summary = The responsible virus is called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and causes the coronavirus disease 2019 (COVID-19), which is mainly characterized by fever, cough and shortness of breath. We summarize the available literature on COVID-19 suggesting an increased risk for severe disease progression in cancer patients, and we discuss the possibility that SARS-CoV-2 could contribute to cancer development. The main symptoms of COVID-19, the lung disease following SARS-CoV-2 infection are fever, cough, shortness of breath and respiratory distress syndrome with risk for septic shock. Preliminary evidence suggests that such a cytokine storm in response to infection with SARS-CoV-2 is a major factor, promoting severe COVID-19 progress and subsequently disease fatality [8, 12] . Chemotherapy-and radiation therapy-induced immunosuppression is a major risk factor for cancer patients to acquire a severe and probably fatal SARS-CoV-2 infection. Expression of elevated levels of pro-inflammatory cytokines in SARS-CoV-infected ACE2+ cells in SARS patients: Relation to the acute lung injury and pathogenesis of SARS † doi = 10.3390/ph13070143 id = cord-257399-p6of5fno author = Gentry, Chris A title = Long-term hydroxychloroquine use in patients with rheumatic conditions and development of SARS-CoV-2 infection: a retrospective cohort study date = 2020-09-21 keywords = CoV-2; March; SARS; infection summary = METHODS: This retrospective cohort study included de-identified information of all veterans in the US Veterans Health Administration clinical administrative database aged 18 years or older with rheumatoid arthritis, systemic lupus erythematosus, or associated rheumatological conditions (based on International Classification of Diseases, 10th edition, diagnostic codes) who were alive on March 1, 2020. We aimed to examine whether patients with rheuma tological conditions receiving chronic hydroxy chloroquine therapy are at less risk of developing SARS-CoV-2 infection compared with a propensity-matched group of patients not receiving hydroxychloroquine. Our study takes advantage of a setting in which a specific group of patients has been receiving chronic hydroxy chloroquine over several months to years as a novel virus emerges among the population, setting up an ideal premise to test the hypothesis that hydroxychloroquine might be effective in preventing SARS-CoV-2 infection. doi = 10.1016/s2665-9913(20)30305-2 id = cord-311848-8n9ee57a author = Giesen, Nicola title = Evidence-based Management of COVID-19 in Cancer Patients – Guideline by the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO) date = 2020-09-21 keywords = AII; COVID-19; CoV-2; SARS; cancer; patient summary = It was prepared by the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO) by critically reviewing the currently available data on SARS-CoV-2 and COVID-19 in cancer patients applying evidence-based medicine criteria. We do not 285 recommend to delay/discontinue radiotherapy, targeted therapy, endocrine therapy or surgery in 286 cancer patients without suspected/confirmed SARS-CoV-2 infection (DII u ) as no impact on mortality 287 of such prior treatments was seen in several large cohort studies of 20, 31, 40, 94 288 In patients with COVID-19, it is strongly recommended to delay/discontinue chemotherapy, if 289 possible, as chemotherapy within two weeks of admission was a major risk factor for severe COVID-290 19 in a large Chinese cohort study (AII u ). Clinical characteristics and risk factors 38 associated with COVID-19 disease severity in patients with cancer in Wuhan, China: a multicentre, 39 retrospective, cohort study doi = 10.1016/j.ejca.2020.09.009 id = cord-267115-6jqdi417 author = Giobbe, Giovanni Giuseppe title = SARS-CoV-2 infection and replication in human fetal and pediatric gastric organoids date = 2020-06-24 keywords = CoV-2; Fig; PCW; RNA; SARS; infection summary = doi = 10.1101/2020.06.24.167049 id = cord-345356-gn1iwis0 author = Glebov, Oleg O. title = Understanding SARS‐CoV‐2 endocytosis for COVID‐19 drug repurposing date = 2020-06-02 keywords = COVID-19; CoV-2; SARS; cell summary = Given that most viruses use endocytosis to enter the host cell, mechanistic investigation of SARS‐CoV‐2 infection needs to consider the diversity of endocytic pathways available for SARS‐CoV‐2 entry in the human lung epithelium. Taken together, the above evidence suggests that SARS-CoV-2 may employ distinct endocytic pathways for cell entry in the upper and lower respiratory tract (Fig. 1) . This approach would allow tracking of the virus in relation to other endocytic pathways and also to investigate the effect of viral infection on the general membrane trafficking network of the host cell. Taken together, the combination of adequate cell models with the newly developed SARS-CoV-2 toolkit and established tools of membrane trafficking research is well-poised to deliver a key insight into the mechanisms underlying COVID-19 infection. Furthermore, considering that various viruses may use the same endocytic pathways of the host cell [15] , targeting viral entry at the point of endocytosis holds a more general promise for the development of broad-spectrum antiviral drugs [51] . doi = 10.1111/febs.15369 id = cord-308857-otsrexqu author = Goel, Saurav title = Resilient and Agile Engineering Solutions to Address Societal Challenges such as Coronavirus Pandemic date = 2020-05-28 keywords = COVID-19; CoV-2; SARS; coronavirus; figure; human; mask; surface; virus summary = This newly identified disease is caused by a new strain of the virus being referred to as Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS CoV-2; formerly called 2019-nCoV). We review the current medical and manufacturing response to COVID-19, including advances in instrumentation, sensing, use of lasers, fumigation chambers and development of novel tools such as lab-on-the-chip using combinatorial additive and subtractive manufacturing techniques and use of molecular modelling and molecular docking in drug and vaccine discovery. However, the coronavirus isolated from pangolins is 99% similar in a specific region of the Spike protein, which corresponds to the 74 amino acids involved in the Angiotensin-Converting Enzyme 2 (ACE 2) receptor binding domain, which allows the virus to enter human cells to infect them as shown in Figure 2 (b). (figures reprinted with permission) Our nasal lining tissue contains a rich number of cell receptors called angiotensinconverting enzyme 2 (ACE2), which are favourable sites for the SARS CoV-2 to attach its spiked protein to, thus paving way for the entrance of the virus inside the body. doi = 10.1016/j.mtchem.2020.100300 id = cord-351011-v4zmksio author = Golden, Joseph W. title = Human angiotensin-converting enzyme 2 transgenic mice infected with SARS-CoV-2 develop severe and fatal respiratory disease date = 2020-07-09 keywords = CoV-2; Fig; SARS; mouse summary = In contrast to non-transgenic mice, intranasal exposure of K18-hACE2 animals to two different doses of SARS-CoV-2 resulted in acute disease including weight loss, lung injury, brain infection and lethality. In comparison with the normal lung architecture in uninfected control animals, infected mice necropsied on day 3, and those succumbing to disease on days 5-11, had varying levels of lung injury including area of lung consolidation characterized by inflammation/expansion of 145 alveolar septa with fibrin, edema and mononuclear leukocytes and infiltration of vessel walls by numerous mononuclear leukocytes (Fig 3A, Fig S4, and Table S1 ). Importantly, in our study some animals at the lower dose survived infection despite significant Infection of K18-hACE2 mice by SARS-CoV-2 produces a disease similar to that observed in acute human cases, with development of an acute lung injury associated with edema, production 285 of inflammatory cytokines and the accumulation of mononuclear cells in the lung. doi = 10.1101/2020.07.09.195230 id = cord-304479-uxp1kg86 author = Goodarzi, Pedram title = Coronavirus disease 2019 (COVID-19): Immunological approaches and emerging pharmacologic treatments date = 2020-08-08 keywords = COVID-19; CoV-2; SARS; clinical; patient; treatment summary = Finally, recently, a case report study from Japan shows that orally inhaled ciclesonide alleviates the local inflammation in the lung of patients with COVID-19 pneumonia and inhibits the propagation of the virus by antiviral activity [60] . In the same way, a recent case-report study showed that the adoptive transfer therapy of human umbilical cord blood derived-mesenchymal stem cells (hUCMSCs) to a Chinese female patient afflicted with acute COVID19 syndromes improved her laboratory tests and CT images [69] . In vitro evidence of activity against SARS-CoV-2 in infected Vero E6 cells reported with high concentrations of the drug [104, 105, 142] FPV significantly improved the latency to relief for pyrexia and cough [99] FPV in patients with COVID-19 led to decrease of viral load and significant improvement in chest imaging compared with the control arm [98] doi = 10.1016/j.intimp.2020.106885 id = cord-263532-q044i7ym author = Goyal, Bhupesh title = Targeting the Dimerization of the Main Protease of Coronaviruses: A Potential Broad-Spectrum Therapeutic Strategy date = 2020-05-13 keywords = CoV; SARS; pro summary = doi = 10.1021/acscombsci.0c00058 id = cord-277487-jgbjxgh1 author = Graham, Simon P. title = Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19 date = 2020-06-20 keywords = CoV-2; IFN; SARS; pig summary = Clinical development of the COVID-19 vaccine candidate ChAdOx1 nCoV-19, a replication-deficient simian adenoviral vector expressing the full-length SARS-CoV-2 spike (S) protein was initiated in April 2020 following non-human primate studies using a single immunisation. Whilst a single dose induced antigen-specific antibody and T cells responses, a booster immunisation enhanced antibody responses, particularly in pigs, with a significant increase in SARS-CoV-2 neutralising titres. Analysis of SARS-CoV-2 S protein-specific murine splenocyte responses by IFNγ ELISpot assay showed no statistically significant difference between the prime-only and primeboost vaccination regimens, in either strain of mouse ( Figure 1A ). IFN-γ ELISpot analysis of porcine peripheral blood mononuclear cells (PBMC) showed responses on 42 dpv (2 weeks after boost) that were significantly greater in the prime-boost pigs compared to prime-only animals (p < 0.05; Figure 1C ). : SARS-CoV-2 S protein-specific antibody responses following ChAdOx1 nCoV-19 primeonly and prime-boost vaccination regimens in mice and pigs. doi = 10.1101/2020.06.20.159715 id = cord-353826-owoec2ud author = Graham, Simon P. title = Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19 date = 2020-07-27 keywords = CoV-2; IFN; SARS summary = Clinical development of the COVID-19 vaccine candidate ChAdOx1 nCoV-19, a replication-deficient simian adenoviral vector expressing the full-length SARS-CoV-2 spike (S) protein was initiated in April 2020 following non-human primate studies using a single immunisation. Analysis of SARS-CoV-2 S proteinspecific murine splenocyte responses by IFN-γ ELISpot assay showed no statistically significant difference between the primeonly and prime-boost vaccination regimens, in either strain of mouse (Fig. 1a) . SARS-CoV-2 S protein-specific antibody responses following ChAdOx1 nCoV-19 prime-only and prime-boost vaccination regimens in mice and pigs SARS-CoV-2 S protein-specific antibody titres in serum were determined by ELISA using recombinant soluble trimeric S (FL-S) and receptor binding domain (RBD) proteins. Small animal models have variable success in predicting vaccine efficacy in larger animals but are an important To analyse SARS-CoV-2 S-specific T cell responses, all mice were sacrificed on day 49 for isolation of splenocytes and pigs were blood sampled longitudinally to isolate PBMC. doi = 10.1038/s41541-020-00221-3 id = cord-349659-6drnriun author = Grant, Benjamin D. title = SARS-CoV-2 Coronavirus Nucleocapsid Antigen-Detecting Half-Strip Lateral Flow Assay Toward the Development of Point of Care Tests Using Commercially Available Reagents date = 2020-07-01 keywords = CoV-2; LFA; SARS summary = title: SARS-CoV-2 Coronavirus Nucleocapsid Antigen-Detecting Half-Strip Lateral Flow Assay Toward the Development of Point of Care Tests Using Commercially Available Reagents In this work, we present a half-strip LFA using commercially available antibodies for the detection of SARS-CoV-2. 10 Antigen detecting ELISAs were previously developed in 2004 for SARS-CoV-1, with limits of detection of approximately 50 pg/mL and clinical sensitivity as a function of days since onset that was significantly better than the useful time window for the current generation of SARS-CoV-2 serology assays. A dose response curve was generated for the half-strip LFA using two commercially available SARS-CoV-2 nucleocapsid (N) proteins, from Genemedi and Genscript. Analytical Chemistry pubs.acs.org/ac Article and determination of realistic limits of detection for a full strip LFA in multiple sample matrices will help point the way toward the best approach for an antigen detecting LFA for SARS-CoV-2. In this paper, we present a half-strip LFA for the detection of nucleocapsid protein of SARS-CoV-2. doi = 10.1021/acs.analchem.0c01975 id = cord-293852-r72c6584 author = Greco, S. title = Noncoding RNAs implication in cardiovascular diseases in the COVID-19 era date = 2020-10-31 keywords = ACE2; COVID-19; CoV-2; Disease; RNA; SARS; patient summary = Different studies found that the values of cardiac Troponins were increased in COVID-19 patients with more severe disease [4, 5, [68] [69] [70] , indicating an association of SARS-CoV-2 with myocardial damage. Moreover, the single-cell RNA-sequencing (scRNAseq) approach has been used to profile the SARS-CoV-2 host-response in the PBMCs of COVID-19 patients, and to comprehensively characterize the immunological changes [124] [125] [126] [127] [128] [129] [130] . However, SARS-CoV-2 infection of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) induced cytotoxic effects and RNA-seq findings highlighted significant transcriptional changes in gene pathways related to cellular metabolism and immune response [131] [132] [133] . This analysis also revealed several host-derived lncRNAs differentially expressed in COVID-19 patient-derived lung tissue, and in SARS-CoV-2 infected epithelial cells, including MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) and NEAT1 (nuclear-enriched autosomal transcript 1) [151] (Fig. 5) . doi = 10.1186/s12967-020-02582-8 id = cord-294527-fct2y5vn author = Guadarrama-Ortiz, Parménides title = Neurological Aspects of SARS-CoV-2 Infection: Mechanisms and Manifestations date = 2020-09-04 keywords = Barré; COVID-19; CoV-2; Guillain; SARS; patient summary = The human infection of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a public health emergency of international concern that has caused more than 16.8 million new cases and 662,000 deaths as of July 30, 2020. Although coronavirus disease 2019 (COVID-19), which is associated with this virus, mainly affects the lungs, recent evidence from clinical and pathological studies indicates that this pathogen has a broad infective ability to spread to extrapulmonary tissues, causing multiorgan failure in severely ill patients. In this context, SARS-CoV-2 can also cause viral meningitis and encephalitis, as demonstrated by a recent report of a 64-yearold patient with laboratory-confirmed COVID-19 who presented neurologic manifestations during the infection, including lethargy, clonus, and pyramidal signs in the lower limbs as well as stiff neck and Brudzinski sign (76) . Future studies are required to evaluate the serologic features of anti-glycolipid antibodies in patients with COVID-19 to elucidate possible mechanisms underlying the association between SARS-CoV-2 infection and Guillain-Barré syndrome. doi = 10.3389/fneur.2020.01039 id = cord-325014-n7mnhk2v author = Gujski, Mariusz title = Prevalence of Current and Past SARS-CoV-2 Infections among Police Employees in Poland, June–July 2020 date = 2020-10-11 keywords = COVID-19; CoV-2; PCR; SARS summary = As the time window for a positive RT-PCR result is short, serological testing, which provides information about whether a person has been exposed to SARS-CoV-2, may be useful for epidemiological purposes to detect the overall burden of previous infection in a given community. The aim of this study was to determine the prevalence of current and past SARS-CoV-2 infections among police employees, a high-risk population due to their professional duties, during the COVID-19 epidemic. Neither sex (p =0.155) nor other variables listed in Figure 2 were significantly associated with the IgG results ( Figure 2 A logistic regression model predicting a positive anti-SARS-CoV-2 IgM+IgA index was developed (Cox and Snell R Square at 0.015 andNagelkerke R Square at 0.033). After including all variables listed in Figures 1 and 2 along with the number of registered cases and deaths due to COVID-19 (per 10,000 inhabitants), only 4 variables showed a correlation with a positive anti-SARS-CoV-2 IgM+IgA index. doi = 10.3390/jcm9103245 id = cord-338775-gh3a0wuf author = Gulersen, Moti title = Histopathological evaluation of placentas after diagnosis of maternal SARS-CoV-2 infection date = 2020-08-15 keywords = CoV-2; SARS summary = Study Design Retrospective cohort study of women diagnosed with SARS-CoV-2 infection who delivered at a single center from April 9th to April 27th, 2020, and had placental specimens reviewed by pathology. Histopathological characteristics were evaluated in each placenta and the incidence of these findings were compared between placentas after diagnosis of maternal SARS-CoV-2 infection and historical controls, as well as between placentas from patients with or without typical symptoms related to infection. Conclusions Based on our data, there are no significant placental histopathological changes that occur after diagnosis of SARS-CoV-2 infection in the third trimester of pregnancy compared to a gestational age-matched historical control group. The results of our study did not demonstrate significant placental histopathological changes 229 occurring after diagnosis of SARS-CoV-2 infection in the third trimester of pregnancy compared 230 to a gestational-age-matched historical control group with a similar incidence of antepartum or Pathology for examination or due to history of melanoma. doi = 10.1016/j.ajogmf.2020.100211 id = cord-346987-fbqqf00i author = Guo, Yongwen title = Controls of SARS-CoV-2 transmission in orthodontic practice date = 2020-06-05 keywords = COVID-19; CoV-2; SARS; patient summary = ABSTRACT The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has attracted worldwide concerns because of its high person-to-person infectivity and lethality, and it was labeled as a pandemic as the rapid increase of confirmed cases in most areas around the world became evident. Although the spread of COVID-19 has been effectively controlled in China and many areas have gradually resumed work and classes, orthodontic participants are still under high risks of SARS-CoV-2 infection. What''s more, the close contact between dental staffs and patients as well as the droplets and aerosols generated during treatment containing saliva and blood further increase the risk of SARS-CoV-2 transmission in dental practice 5 . We must constantly bear in mind that the threat of infection is not visible which poses a challenge on the orthodontic practice thus effective control measures should be taken to prevent the transmission of SARS-CoV-2 and protect both practitioners and patients from the COVID-19. doi = 10.1016/j.ajodo.2020.05.006 id = cord-265128-i0d4lxko author = Gurung, Arun Bahadur title = Unravelling lead antiviral phytochemicals for the inhibition of SARS-CoV-2 M(pro) enzyme through in silico approach date = 2020-05-22 keywords = CoV; MERS; SARS summary = Among coronaviruses, the main protease (M(pro)) is an essential drug target which, along with papain-like proteases catalyzes the processing of polyproteins translated from viral RNA and recognizes specific cleavage sites. The present study is aimed at the identification of promising lead molecules for SARS-CoV-2 M(pro) enzyme through virtual screening of antiviral compounds from plants. The binding affinity of selected small drug-like molecules to SARS-CoV-2 M(pro), SARS-CoV M(pro) and MERS-CoV M(pro) were studied using molecular docking. Structure-based drug design primarily relies on molecular docking to identify lead molecules against the target proteins from chemical libraries [12, 13] . The natural products such as traditional medicines and plant-derived compounds (phytochemicals) are the rich sources of promising antiviral drugs [14] . The binding energies and inhibition constants of the phytochemicals with the SARS-CoV-2 M pro enzyme were compared with that of a set of twelve FDA approved antiviral drugs-a) Viral doi = 10.1016/j.lfs.2020.117831 id = cord-348696-86nbwon2 author = Güemes-Villahoz, Noemi title = Novel Insights into the Transmission of SARS-CoV-2 Through the Ocular Surface and its Detection in Tears and Conjunctival Secretions: A Review date = 2020-08-18 keywords = COVID-19; CoV-2; SARS; ocular summary = title: Novel Insights into the Transmission of SARS-CoV-2 Through the Ocular Surface and its Detection in Tears and Conjunctival Secretions: A Review A multicenter study which documented potential risk factors for SARS-CoV-2 transmission in patients requiring intubation [7] reported that unprotected eye contact with secretions from infected patients was the most predictive variable for transmission to healthcare workers. A recent study evaluated the ocular tropism of SARS-CoV-2 in patients with confirmed COVID-19. Of the 56 subjects investigated there was only one patient who gave a history of prior pterygium surgery, with conjunctivitis and a positive PCR result from the conjunctival swab highlighting the importance of an intact ocular surface in resisting virus invasion [25] . Despite ocular complications not being a common clinically detectable manifestation of SARS-CoV-2 infection, recent evidence suggests that ocular exposure may represent a major transmission route for the virus. Evaluation of coronavirus in tears and conjunctival secretions of patients with SARS-CoV-2 infection SARS-CoV-2 RNA detection in tears and conjunctival secretions of COVID-19 patients with conjunctivitis doi = 10.1007/s12325-020-01442-7 id = cord-281529-2rec51xg author = Haagmans, Bart L title = Middle East respiratory syndrome coronavirus in dromedary camels: an outbreak investigation date = 2013-12-17 keywords = CoV; East; MERS; PCR summary = We tested for the presence of MERS-CoV in dromedary camels from a farm in Qatar linked to two human cases of the infection in October, 2013. 13 Both MERS-CoV spike protein binding antibodies and virus neutralising antibodies were reported in dromedary camels from diff erent regions, including Oman and Egypt, but no virus shedding could be detected and, therefore, the signifi cance of these observations remained an issue of debate. The camel MERS-CoV clustered with viral sequences obtained from the two human cases related to the farm and with a sequence from Hafr-Al-Batin as the next closest relative (fi gure 1). However, virological testing was unable to detect MERS-CoV viral sequences in camels, probably because only faecal and serum samples were analysed. Our report describes the fi rst detection of MERS-CoV in dromedary camels on a farm in Qatar that had been linked to human cases of the disease. doi = 10.1016/s1473-3099(13)70690-x id = cord-351649-87g7g5au author = Haagmans, Bart L. title = SARS date = 2009-01-30 keywords = CoV; SARS; vaccine summary = Because the disease in macaques caused by SARS-CoV infection was pathologically similar to that seen in human patients with SARS, and since the virus should induce highly cross-reactive neutralizing antibodies to protect against newly emerging viruses related to SARS-CoV and protect both the gastrointestinal and respiratory tract in the absence of significant side effects. African green monkeys immunized via the respiratory tract with two doses of a recombinant Newcastle disease virus encoding the S protein developed a relatively high titer of SARS-CoV neutralizing antibodies and upon challenge demonstrated a 1000-fold zoonotic coronaviruses. Recombinant modified vaccinia virus Ankara expressing the spike glycoprotein of severe acute respiratory syndrome coronavirus induces protective neutralizing antibodies primarily targeting the receptor binding region A single immunization with a rhabdovirus-based vector expressing severe acute respiratory syndrome coronavirus (SARS-CoV) S protein results in the production of high levels of SARS-CoV-neutralizing antibodies doi = 10.1016/b978-0-12-369408-9.00036-6 id = cord-341234-2zgfcrwc author = Hallak, Jorge title = Concise practice recommendations for the provision of andrological services and assisted reproductive technology for male infertility patients during the SARS-CoV-2 in Brazil date = 2020-09-02 keywords = ACE2; CoV-2; SARS; patient summary = title: Concise practice recommendations for the provision of andrological services and assisted reproductive technology for male infertility patients during the SARS-CoV-2 in Brazil Recently, a group of 27 experts from 15 countries and five continents has argued that postponing andrological services and male infertility care during the COVID-19 pandemic could permanently compromise the prospects of biological parenthood for ''time-sensitive'' patients, thus resulting in a devastating psychological impact on men undergoing fertility-related treatment (1) . A recent probabilistic pilot study conducted in seven districts of the city of São Paulo to estimate the prevalence of herd immunity showed that about 5.2% individuals had SARS-CoV-2 IgG antibodies, corresponding to an overall infection rate We reiterate that andrological services and male infertility care cannot be considered low priority during the current SARS-CoV-2 pandemic, particularly for the most vulnerable patients, like those with cancer, patients using immunosuppressive therapy, and the azoospermic/cryptozoospermic men under medical or post-surgical treatment to improve spermatogenesis. doi = 10.1590/s1677-5538.ibju.2020.06.03 id = cord-268206-ino9srb6 author = Hamed, Manal A. title = An overview on COVID-19: reality and expectation date = 2020-06-01 keywords = COV-2; COVID-19; RNA; SARS summary = Recently, severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), commonly known as coronavirus disease-2019 (COVID-19) has rapidly spread across China and around the world. In the current SARS-COV-2 pandemic, Wu and McGoogan (2020) showed that patients with chronic diseases, including diabetes, were at higher risk for severe COVID-19 infection and mortality. The former (S) is the wild type which is milder while the latter (L) is the novel one which resulted in high binding affinity between SARS-COV-2 virus with angiotensin-converting enzyme 2 receptor in human cells. The use of convalescent plasma was recommended before as an important treatment during outbreaks of Ebola virus, Middle East respiratory syndrome coronavirus, SARS-COV-1, H5N1 avian influenza, and H1N1 influenza (Zhou et al. In a study involving patients with pandemic influenza (H1N1) and SARS virus, treatment of severe infection with convalescent plasma was associated with reduced respiratory viral load, serum cytokine response, and mortality (Cheng et al. doi = 10.1186/s42269-020-00341-9 id = cord-294136-e69ao8j0 author = Han, Dongsheng title = COVID-19: Insight into the asymptomatic SARS-COV-2 infection and transmission date = 2020-08-27 keywords = COV-2; COVID-19; China; SARS summary = successfully isolated SARS-CoV-2 from throat swabs of two asymptomatic patients in a cell culture of Caco-2 cells, suggesting the potential for presymptomatic transmission [16] ; (5) Increasing studies show clear epidemiological evidence of human-to-human asymptomatic spread of COVID-19 (described in the following section); (6) Asymptomatic infection tends to be, but is not only, identified among young people (<20 years old) [14, 15, [17] [18] [19] ; And (7) the majority (>90%) of asymptomatic patients appears to have a milder clinical course during hospitalization [15] , but the severity of the symptoms of the secondary patients infected by SARS-COV-2 from asymptomatic patients varies based on their physical constitution [2, 20] . As the transmission of SARS-COV-2 may occur in the early course of infection and a high viral load in respiratory samples could be detected [13] , RT-PCR testing for this virus is more suitable for screening at earlier stages of infection in key populations, such as patients with obvious symptoms and close contacts of asymptomatic patients [35] . doi = 10.7150/ijbs.48991 id = cord-297941-7yut9vt4 author = Haq, M. title = Seroprevalence and Risk Factors of SARS CoV-2 in Health Care Workers of Tertiary-Care Hospitals in the Province of Khyber Pakhtunkhwa, Pakistan date = 2020-09-30 keywords = CoV-2; SARS summary = In the recent past many studies from the developed countries have been published on the prevalence of SARS CoV2 antibodies and the risk factors of COVID 19 in healthcare-workers but little is known from developing countries. Methods: This cross-sectional study was conducted on prevalence of SARS CoV2 antibody and risk factors for seropositivity in HCWs in tertiary care hospitals of Peshawar city, Khyber Pakhtunkhwa province Pakistan. To our knowledge this is the first study of assessing SARS-CoV-2 antibodies of HCWs form both public and private tertiary care hospitals in Peshawar, Pakistan. To our knowledge this is the first study on prevalence of SARS CoV-2 antibodies in HCW of tertiary care hospitals in Pakistan. The risk of becoming positive for SARS-CoV-2 antibodies did not increase with history of direct contact with COVID patients within or outside the hospital. doi = 10.1101/2020.09.29.20203125 id = cord-299093-zp07aqpm author = Harrison, Andrew G. title = Mechanisms of SARS-CoV-2 transmission and pathogenesis date = 2020-10-14 keywords = ACE2; COVID-19; CoV-2; Coronavirus; SARS; severe summary = Thus, evasion of IFN signaling by SARS-CoV-2 and impaired IFN production in J o u r n a l P r e -p r o o f human peripheral blood immune cells might contribute to the productive viral replication, transmission, and severe pathogenesis during COVID-19, although further testing is warranted to fully dissect these putative evasion pathways [95] . For instance, Krt18-hACE2 and betaactin-hACE2-transgenic mice rapidly succumb to SARS-CoV-2 infection with lung infiltration of inflammatory immune cells inducing severe pulmonary disease, accompanied by evident thrombosis and anosmia, which partially recapitulate human COVID-19 [114] [115] . Furthermore, upon viral challenge, lymphocytes have expanded in rhesus macaque models around 5 dpi with complementary B-cell responses against SARS-CoV-2 Spike appearing 10-15 dpi in blood samples [125] ; expansion of these adaptive immune compartments was analogous to those observed in COVID-19 patients [37, 125, [132] [133] [134] . doi = 10.1016/j.it.2020.10.004 id = cord-297786-jz1d1m2e author = Hasan, Md. Mahbub title = Global and Local Mutations in Bangladeshi SARS-CoV-2 Genomes date = 2020-08-26 keywords = Bangladesh; CoV-2; SARS summary = Corona Virus Disease-2019 (COVID-19) warrants comprehensive investigations of publicly available Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2) genomes to gain new insight about their epidemiology, mutations and pathogenesis. In this study, we compared 207 of SARS-CoV-2 genomes reported from different parts of Bangladesh and their comparison with 467 globally reported sequences to understand the origin of viruses, possible patterns of mutations, availability of unique mutations, and their apparent impact on pathogenicity of the virus in victims of Bangladeshi population. Then, we studied the variants present in different isolates of Bangladesh to investigate the pattern of mutations, identify UMs, and discuss the pseudo-effect of these mutations on the structure and function of encoded proteins, with their role in pathogenicity. To understand the SARS-CoV-2 viral transmission in Bangladesh, we performed phylogenetic analysis on the selected 207 viral genomes reported from different districts of Bangladesh along with selected 467 globally submitted sequences as reported from 42 countries and 6 continents ( Figure 1 ). doi = 10.1101/2020.08.25.267658 id = cord-333547-88dkh6xd author = Hasan, Shadi W. title = Detection and Quantification of SARS-CoV-2 RNA in Wastewater and Treated Effluents: Surveillance of COVID-19 Epidemic in the United Arab Emirates date = 2020-10-19 keywords = CoV-2; RNA; SARS summary = Testing SARS-CoV-2 viral loads in wastewater has recently emerged as a method of tracking the prevalence of the virus and an early-warning tool for predicting outbreaks in the future. A limited number of studies have shown that the shedding period of SARS-CoV-2 in stool samples varies considerably, and can still be detected up to 27.9 ± 10.7 days after infection in some cases [9, 11] . Consequently, the main objectives of this study were: (i) to detect the presence of SARS-CoV-2 virus in municipal (untreated) wastewater and treated effluents of wastewater treatment plants (WWTPs) in the UAE; (ii) to quantify the viral concentration in viral gene copies per liter; and (iii) to explore whether these measurements mirror infections in the population in order to comment on the utility of this method to track the epidemiology of the disease. doi = 10.1016/j.scitotenv.2020.142929 id = cord-275138-033r259v author = Hayden, Frederick G title = Towards improving clinical management of Middle East respiratory syndrome coronavirus infection date = 2014-07-31 keywords = CoV; MERS summary = Many agents have inhibitory activity in vitro for coronaviruses, including some licensed drugs, 7-9 but it is unclear whether their human pharmacology and tolerability would enable suffi cient doses to be given to exert antiviral eff ects in patients with MERS-CoV. 4 Ribavirin and interferon combinations are associated with modest Centre For Infections/Public Health England/Science Photo Library antiviral eff ects in MERS-CoV inoculated rhesus macaques given high doses. 7 For MERS-CoV, low neutralising antibody responses and inability to acquire suffi cient convalescent plasma from survivors with comorbidities might restrict the eff ectiveness of this treatment, although these limitations might not apply to infected health-care workers. With support as needed from international partners like WHO and ISARIC, 11 regional governments, and funders, Middle Eastern colleagues have both the opportunity and the responsibility to undertake studies to advance the understanding of eff ective prevention and treatment strategies for MERS-CoV and any future novel CoV outbreaks. doi = 10.1016/s1473-3099(14)70793-5 id = cord-301693-3hsu2u1k author = He, Yuwen title = Value of Viral Nucleic Acid in Sputum and Feces and Specific IgM/IgG in Serum for the Diagnosis of Coronavirus Disease 2019 date = 2020-08-06 keywords = CoV-2; Guangzhou; SARS summary = To improve the detection rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we analyzed the results of viral nucleic acid and serum-specific antibody tests on clinical samples from 20 patients with SARS-CoV-2 infection diagnosed at the First Affiliated Hospital of Guangzhou Medical University in China. By comparing various sample types collected from COVID-19 patients, we revealed multiple pathways for SARS-CoV-2 shedding, and a prolonged detectable period for viral nucleic acid test in sputum specimens, demonstrating that the timeline of the viral shedding is of great value in determining the time of release from quarantine or discharge from hospital. We undertook a study on the viral nucleic acids of SARS-CoV-2 in swabs (nasal, pharyngeal), sputum and feces, as well as antibodies in the serum of COVID-19 patients admitted to the First Affiliated Hospital of Guangzhou Medical University, China. doi = 10.3389/fcimb.2020.00445 id = cord-032751-pmclolvh author = Head, Katharine J. title = A National Survey Assessing SARS-CoV-2 Vaccination Intentions: Implications for Future Public Health Communication Efforts date = 2020-09-23 keywords = COVID-19; CoV-2; SARS; vaccine summary = Research Question 2: What are the SARS-CoV-2 vaccine behavioral intentions of adults in the U.S. when a health care provider recommends the vaccine? Importantly, because vaccine intent and/or need may be different for people who were previously infected with SARS-CoV-2 and perceived threat variables (discussed below) are usually only measured for future threats, only participants who answered "no" to the question "do you believe that you''ve had COVID-19" are included in the current study (n = 3,159). Step 3 of the hierarchical regression model, with all variables included, less education was associated with lower intent to receive a SARS-CoV-2 vaccine. The health belief variables that were significant in the full regression model were all positively associated with intent to receive a SARS-CoV-2 vaccine. doi = 10.1177/1075547020960463 id = cord-337712-ylqgraos author = Heinz, Franz X. title = Profile of SARS-CoV-2 date = 2020-10-30 keywords = ACE2; CoV-2; Fig; SARS; virus summary = Despite these similarities, distinguishing features were identified that are likely to contribute to the biological differences observed between the two viruses, including the significantly higher rate of subclinical and mild infections caused by SARS-CoV-2, which makes control of virus spread currently so difficult. If expectations were too optimistic and results obtained with some of the front runners are disappointing, windows of opportunity will open for an arsenal of alternative developments in progress [54, 59] (https:// www.who.int/publications/m/item/draft-landscapeof-covid-19-candidate-vaccines, accessed 2 October 2020) These include subunit vaccines with S proteins stabilized in their prefusion conformation in combination with potent adjuvants, use of the RBD only as an immunogen instead of the whole S protein [67, 68] , other rationally designed immunogens [69] , other (non-Adeno) vector vaccines including replication-competent vectors [55, 70] , self-amplifying RNA vaccines [71] , live-attenuated vaccines [55] , DNA vaccines [72] , and intranasally applied vaccines with the potential to induce local immunity at the site of virus entry [73] . doi = 10.1007/s00508-020-01763-1 id = cord-286298-pn9nwl64 author = Helmy, Yosra A. title = The COVID-19 Pandemic: A Comprehensive Review of Taxonomy, Genetics, Epidemiology, Diagnosis, Treatment, and Control date = 2020-04-24 keywords = COVID-19; China; CoV-2; MERS; RNA; SARS; virus summary = doi = 10.3390/jcm9041225 id = cord-252456-971d0sir author = Hemida, Maged Gomaa title = The SARS-CoV-2 outbreak from a one health perspective date = 2020-03-16 keywords = CoV; MERS; SARS; virus summary = The SARS-CoV-2 is a new human coronavirus candidate recently detected in China that is now reported in people on inhabited continents. Currently, the case fatality rate is relatively low (⁓3.6%) compared to infections with severe acute respiratory syndrome coronavirus (SARS-CoV, (10%) and MERS-CoV (32%) [11] . Based on the previous emergence history of SARS-CoV, the presence of a large number of mammals and birds overcrowded in one place may give a chance for pathogens, particularly those with RNA genomes such as coronaviruses and influenza viruses, to emerge. Based on the previous experience from the other emerging diseases, particularly SARS-CoV and influenza viruses, avoiding the mixing of various species of animals, birds, and mammals, is highly suggested [51, 65, 66] . The process of decontamination of the virus-contaminated surfaces by the appropriate disinfectants or virucidal agents was successful in case of other respiratory viruses such as SARS-CoV and avian influenza [59] . doi = 10.1016/j.onehlt.2020.100127 id = cord-325902-33pxylb3 author = Hemida, Maged Gomaa title = Middle East Respiratory Syndrome Coronavirus and the One Health concept date = 2019-08-22 keywords = CoV; MERS summary = This is due to the animals, especially dromedary camels, play important roles in the transmission and sustainability of the virus, and the virus can be transmitted through aerosols of infected patients into the environment. Experimental MERS-CoV infection in both alpacas and llamas showed a similar pattern to that of dromedary camels (Crameri et al., 2016; Vergara-Alert et al., 2017) , which suggested that both animals might act as a model animal for the study of MERS-CoV in vivo. Very few studies reported the cross-reactivity between MERS-CoV and other coronaviruses such as the bovine coronavirus (BCoV) that might infect dromedary camels. Dromedary camels remain the amplifier of the virus; the close contact of these animals to the human population in certain regions of Africa and Asia may pose a great risk for human infection and indirectly contribute to the spread of the virus. Lack of middle East respiratory syndrome coronavirus transmission from infected camels doi = 10.7717/peerj.7556 id = cord-349262-gnqbyc6t author = Hemida, Maged Gomaa title = The Middle East respiratory syndrome coronavirus in the breath of some infected dromedary camels (Camelus dromedarius) date = 2020-10-14 keywords = CoV; East; MERS summary = title: The Middle East respiratory syndrome coronavirus in the breath of some infected dromedary camels (Camelus dromedarius) Dromedary camels remain the currently identified reservoir for the Middle East respiratory syndrome coronavirus (MERS-CoV). We tested nasal swabs, breath samples from animals within this herd by the real-time PCR. However, the nasal swabs are still the sample of choice in the diagnosis of MERS-CoV among the infected dromedary camel population. Detection of the virus in the air of positive camel''s herd [5, 6] may suggest the virus is excreted in the breath of the infected animals in high concentration. The aim of our study was to test the possibility of MERS-CoV shedding in the breath of the infected dromedary camels. Longitudinal study of Middle East respiratory syndrome coronavirus infection in dromedary camel herds in Saudi Arabia Dromedary camels and the transmission of Middle East respiratory syndrome coronavirus (MERS-CoV) doi = 10.1017/s0950268820002459 id = cord-330597-nftwj0d5 author = Hopfer, Helmut title = Hunting coronavirus by transmission electron microscopy – a guide to SARS‐CoV‐2‐associated ultrastructural pathology in COVID‐19 tissues date = 2020-09-27 keywords = COVID-19; CoV-2; SARS; patient summary = Using micrographs from infected cell cultures and autopsy tissues, we show how coronavirus replication affects ultrastructure and put the morphological findings in the context of viral replication, which induces extensive remodelling of the intracellular membrane systems. To better understand the ultrastructural morphology of SARS-CoV-2 infection and COVID-19, we will first briefly discuss the pathogenesis of COVID-19 and coronavirus replication in general and then examine the TEM findings in more detail. All rights reserved Coronaviruses including SARS-CoV-2 and the morphological changes associated with replication can be visualised by TEM in infected cell lines (figure 3A-G) [81] [82] [83] [84] [85] 87, 88] or organoids [96, 97] . Based on the cell culture findings outlined above, we expect to find the same SARS-CoV-2 morphology and distribution in vesicles of autopsy and biopsy tissues of COVID-19 patients. doi = 10.1111/his.14264 id = cord-350855-gofzhff7 author = Hou, Yixuan J. title = SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract date = 2020-05-27 keywords = ACE2; CoV-2; SARS; figure summary = High-sensitivity RNA in situ mapping revealed the highest ACE2 expression in the nose with decreasing expression throughout the lower respiratory tract, paralleled by a striking gradient of SARS-CoV-2 infection in proximal (high) vs distal (low) pulmonary epithelial cultures. COVID-19 autopsied lung studies identified focal disease and, congruent with culture data, SARS-CoV-2-infected ciliated and type 2 pneumocyte cells in airway and alveolar regions, respectively. We measured the relative infectivity of the SARS-CoV-2 GFP virus in primary 283 cells based on the average peak titers and observed that infectivity exhibited the same 284 pattern as the ACE2 expression levels from the upper to lower respiratory tract ( Figure 285 6Bi-6Biv). Gene 1230 expression and in situ protein profiling of candidate SARS-CoV-2 receptors in human 1231 airway epithelial cells and lung tissue doi = 10.1016/j.cell.2020.05.042 id = cord-252232-vgq6gjpx author = Hou, Yuxuan title = Angiotensin-converting enzyme 2 (ACE2) proteins of different bat species confer variable susceptibility to SARS-CoV entry date = 2010-06-22 keywords = ACE2; CoV; SARS summary = Here, we extended our previous study to ACE2 molecules from seven additional bat species and tested their interactions with human SARS-CoV spike protein using both HIV-based pseudotype and live SARS-CoV infection assays. However, although the genetically related SARS-like coronavirus (SL-CoV) has been identified in horseshoe bats of the genus Rhinolophus [5, 8, 12, 18] , its spike protein was not able to use the human ACE2 (hACE2) protein as a receptor [13] . To this end, we have extended our studies to include ACE2 molecules from different bat species and examined their interaction with the human SARS-CoV spike protein. Our results show that there is great genetic diversity among bat ACE2 molecules, especially at the key residues known to be important for interacting with the viral spike protein, and that ACE2s of Myotis daubentoni and Rhinolophus sinicus from Hubei province can support viral entry. doi = 10.1007/s00705-010-0729-6 id = cord-291916-5yqc3zcx author = Hozhabri, Hossein title = The Global Emergency of Novel Coronavirus (SARS-CoV-2): An Update of the Current Status and Forecasting date = 2020-08-05 keywords = ACE2; COVID-19; China; CoV-2; Coronavirus; MERS; PCR; RNA; SARS summary = doi = 10.3390/ijerph17165648 id = cord-294069-7zr77r71 author = Hu, Xiaowen title = The distribution of SARS-CoV-2 contamination on the environmental surfaces during incubation period of COVID-19 patients date = 2020-09-30 keywords = CoV-2; SARS summary = In this study, we sampled the high-touch environmental surfaces in the quarantine room, aiming to detect the distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the environmental surfaces during the incubation period of coronavirus disease 2019 (COVID-19) patients. In addition, we synchronously sampled the high-touch environmental surfaces in the quarantine room, aiming to detect the SARS-CoV-2 distribution on the environmental surfaces during the incubation period of COVID-19 patients. Then, medical staffs stayed in hotel immediately sampled their nasopharyngeal swabs and environmental surfaces, and transferred them to the hospital for further diagnosis Additionally, the frequency of washing behaviors of patients at the quarantine room, including face washing, hands washing, tooth brushing, bathing and excrement, were shown in Table 2 . Air, Surface Environmental, and Personal Protective Equipment Contamination by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) From a Symptomatic Patient doi = 10.1016/j.ecoenv.2020.111438 id = cord-312652-zhccmfgw author = Hu, Xiumei title = Impact of Heat-Inactivation on the detection of SARS-CoV-2 IgM and IgG Antibody by ELISA date = 2020-06-20 keywords = CoV-2; IgM; SARS summary = According to Chinese Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7), SARS-CoV-2 specific IgM becomes detectable around 3-5 days after onset and IgG reaches a titration of at least 4-fold increase during convalescence compared with the acute [9] . In order to establish a safe and accurate method for detecting SARS-CoV-2 specific antibodies, we retrospectively assessed the impact of sera heat-inactivation at 56℃ for 30 minutes on the levels of SARS-CoV-2 IgM or IgG antibodies. Therefore, our analysis provide evidence that sera inactivated by heating at 56℃ for 30 minutes could reduce the risk of virus contamination, and would not impair the detection efficacy of SARS-CoV-2 IgM or IgG testing using this ELISA assay. In summary, sera inactivated by heating at 56℃ for 30 minutes could minimize the risk of virus contamination and did not impair the positive detection rate using SARS-CoV-2 antibody detection kit (ELISA-immunoassay) and eventually represents a valuable contribution to a safer COVID-19 serological diagnosis. doi = 10.1016/j.cca.2020.06.032 id = cord-322908-e3gok0ot author = Huang, Fangfang title = A review of therapeutic agents and Chinese herbal medicines against SARS-COV-2 (COVID-19) date = 2020-05-20 keywords = COVID-19; CoV-2; Coronavirus; SARS; chinese summary = In the absence of confirmed effective treatments, due to public health emergencies, it is essential to study the possible effects of existing approved antivirals drugs or Chinese herbal medicines for SARS-CoV-2. Meanwhile, this review also focus on the re-purposing of clinically approved drugs and Chinese herbal medicines that may be used to treat COVID-19 and provide new ideas for the discovery of small molecular compounds with potential therapeutic effects on novel COVID-19. In this review, we summarized potential Chinese herbal medicines ( Table 2 ) that may treat COVID-19 by targeting proteins such as Spike protein, ACE2, 3CLpro, PLpro and RdRp. We also predicted the binding affinities between these compounds and COVID-19 related targets by molecular docking, with a focus on six compounds: quercetin, andrographolide, glycyrrhizic acid, baicalin, patchouli alcohol, and luteolin. Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial doi = 10.1016/j.phrs.2020.104929 id = cord-302608-fw4pmaoc author = Huang, Jiao-Mei title = Evidence of the Recombinant Origin and Ongoing Mutations in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) date = 2020-03-19 keywords = CoV-2; SARS summary = However, RBD and key amino acid residues supposed to be crucial for human-to-human and cross-species transmission are homologues between SARS-CoV-2 and pangolin CoVs. These results from our analysis suggest that SARS-CoV-2 is a recombinant virus of bat and pangolin CoVs. Moreover, this study also reports mutations in coding regions of 125 SARS-CoV-2 genomes signifying its aptitude for evolution. The host specificity of virus particle is determined by amino acid sequence of RBD and is usually dissimilar among different CoVs. Therefore, RBD is a core determinant for tissue tropism and host range of CoVs. This article presents SARS-CoV-2 phylogenetic trees, comparison and analysis of genome, spike protein, and RBD amino acid sequences of different CoVs, deducing source and etiology of COVID-19 and evolutionary relationship among SARS-CoV-2 in human. The S-protein amino acid sequence identity between SARS-CoV-2 and related beta-CoVs showed that bat/Yunnan/RaTG13 shares highest similarity of 97.43%. doi = 10.1101/2020.03.16.993816 id = cord-309074-pys4aa60 author = Huang, Victoria W. title = Telehealth in the times of SARS-CoV-2 infection for the Otolaryngologist date = 2020-05-30 keywords = CoV-2; SARS; telemedicine summary = OBJECTIVE: In response to the American Academy of Otolaryngology – Head and Neck Surgery''s recommendations to limit patient care activities in the times of SARS-CoV-2, many elective surgeries have been canceled without patient clinics transitioning to virtual visits. In response to these evolving needs, the American Academy of Otolaryngology -Head and Neck Surgery (AAO-HNS) telemedicine committee has put forth new recommendations to prioritize novel applications of telehealth to help limit coronavirus disease pandemic spread while maintaining quality care 8 . As testing in the U.S. becomes more available in this era of SARS-CoV-2, telemedicine continues to take the main role of "forward triage", evaluating patients with respiratory symptoms before they arrive in hospitals 23 With the AAO-HNS recommending all otolaryngologists to limit patient care activities to time-sensitive, urgent, and emergent medical conditions, elective surgeries have been canceled with many outpatient clinics rescheduling appointments and transitioning to virtual visits 7, 8 . doi = 10.1016/j.wjorl.2020.04.008 id = cord-329011-spiuqngp author = Huang, Yuan title = Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19 date = 2020-08-03 keywords = ACE2; CoV-2; RBD; SARS summary = The spike (S) protein of SARS-CoV-2, which plays a key role in the receptor recognition and cell membrane fusion process, is composed of two subunits, S1 and S2. A large number of glycosylated S proteins cover the surface of SARS-CoV-2 and bind to the host cell receptor angiotensinconverting enzyme 2 (ACE2), mediating viral cell entry [8] . The SARS-CoV-2 S protein is highly conserved among all human coronaviruses (HCoVs) and is involved in receptor recognition, viral attachment, and entry into host cells. Structure of the S1 subunit The binding of virus particles to cell receptors on the surface of the host cell is the initiation of virus infection; therefore, receptor recognition is an important determinant of viral entry and a drug design target. Therefore, the development of antibodies targeting this functional motif may cross-bind and neutralize these two viruses and related CoVs. Antiviral peptides prevent SARS-CoV-2 membrane fusion and can potentially be used for the prevention and treatment of infection. doi = 10.1038/s41401-020-0485-4 id = cord-315288-fcx4q6mp author = Hussain, Mohammed Hassan title = Tracheal swab from front of neck airway for SARS-CoV-2; a bronchial foreign body date = 2020-08-27 keywords = CoV-2; SARS summary = We report the case of a bronchial foreign body, following a tracheostomy site swab for SARS-CoV-2, aiming to raise awareness and vigilance. We report the case of a bronchial foreign body, following a tracheostomy site swab for SARS-CoV-2, aiming to raise awareness and vigilance. This case highlights the need for clear guidance on how samples for SARS-CoV-2 are taken from patients with front of neck airways (laryngectomy/tracheοstomy) and the potential pitfalls involved. This case highlights the need for clear guidance on how samples for SARS-CoV-2 are taken from patients with front of neck airways (laryngectomy/tracheοstomy) and the potential pitfalls involved. Patients with front of neck airways, either in the form of a laryngectomy or tracheostomy stoma site, present a challenge in terms of testing for SARS-CoV-2. There is a need for clear guidance on how to test patients with front of neck airways for SARS-CoV-2. doi = 10.1136/bcr-2020-237787 id = cord-349117-xfir3m5p author = Hyseni, Inesa title = Characterisation of SARS-CoV-2 Lentiviral Pseudotypes and Correlation between Pseudotype-Based Neutralisation Assays and Live Virus-Based Micro Neutralisation Assays date = 2020-09-10 keywords = CoV-2; MNT; PNT; SARS; pseudotype summary = After fully characterising lentiviral pseudotypes bearing the SARS-CoV-2 spike protein, we employed them in pseudotype-based neutralisation assays in order to profile the neutralising activity of human serum samples from an Italian sero-epidemiological study. SARS CoV-2 strain 2019-nCov/Italy wild-type virus (LV), which was handled in a level 3 bio-containment facility (BSL 3), was used as positive control in order to evaluate the spike glycoprotein expression, while a ∆-envelope pseudotype, prepared with the same procedure, was used as a negative control. To verify the expression of the spike protein in the SARS-CoV-2 pseudotypes, the spike was detected by Western blot; sera from convalescent SARS-CoV-2 patients, which have been shown to have a high neutralising titre in microneutralisation with a live virus, were used as the primary antibody, and goat anti-Human IgG as the secondary antibody. doi = 10.3390/v12091011 id = cord-328289-3h3kmjlz author = Iadecola, Costantino title = Effects of COVID-19 on the nervous system date = 2020-08-19 keywords = COVID-19; CoV-2; SARS; patient summary = Another Parkinson''s disease patient with obesity, hypertension and diabetes, exhibited at autopsy, in addition to hypoxic-ischemic neuronal damage, microhemorrhages, white matter lesions and enlarged perivascular spaces, but no evidence of SARS-CoV-2 in the brain (Kantonen et al., 2020) . The encephalopathy is most likely a consequence of systemic factors, such as cytokine sickness, hypoxia and metabolic dysfunction due to peripheral organ failure, while the strokes seem to be related more to hypercoagulability and endothelial injury than to SARS-CoV-2 vasculitis affecting brain vessels. In some cases, the possibility of a SARS-CoV-2 encephalitis could not be ruled out based on the potential for the virus to infect neurons (Song et al., 2020) , but definitive clinical and pathological evidence of neurotropism is lacking. doi = 10.1016/j.cell.2020.08.028 id = cord-263945-yli5suxb author = Iancu, Gabriela Mariana title = Viral exanthema as manifestation of SARS-CoV-2 infection: A case report date = 2020-08-28 keywords = COVID-19; CoV-2; SARS summary = doi = 10.1097/md.0000000000021810 id = cord-331094-22366b81 author = Ianevski, Aleksandr title = Potential Antiviral Options against SARS-CoV-2 Infection date = 2020-06-13 keywords = COVID-19; CoV-2; SARS; Vero; figure summary = We also screened 136 safe-in-man broad-spectrum antivirals against the SARS-CoV-2 infection in Vero-E6 cells and identified nelfinavir, salinomycin, amodiaquine, obatoclax, emetine and homoharringtonine. After the initial screening, we identified apilimod, emetine, amodiaquine, obatoclax, homoharringtonine, salinomycin, arbidol, posaconazole and nelfinavir as compounds that rescued virus-infected cells from death (AUC from 285 to 585; Table S1 ). We next profiled transcriptional responses to nelfinavir, amodiaquine or both drugs in virus-or mock-infected Vero-E6 cells at 24 h. Anti-SARS-CoV-2 activity of safe-in man broad-spectrum antivirals in Vero-E6 cells. Here, we found that combinations of nelfinavir with salinomycin, amodiaquine, obatoclax, emetine or homoharringtonine were synergistic against SARS-CoV-2 in Vero-E6 cells. Thus, the amodiaquine and nelfinavir combination could result in better efficacy and decreased toxicity for the treatment of SARS-CoV-2 and perhaps other viral infections. Transcriptomic analysis of mock-and SARS-CoV-2-infected Vero-E6 cells treated with nelfinavir, amodiaquine or both drugs. doi = 10.3390/v12060642 id = cord-312160-2820aftb author = Ibrahim, Mahmoud A.A. title = In silico Drug Discovery of Major Metabolites from Spices as SARS-CoV-2 Main Protease Inhibitors date = 2020-10-08 keywords = CoV-2; SARS summary = Stabilities and binding affinities of the two identified natural spices were calculated over 40 ns molecular dynamics simulations and compared to an antiviral protease inhibitor (lopinavir). The binding energies of the investigated spices compounds with SARS-CoV-2 M pro were estimated using molecular mechanical-generalized Born surface area (MM-GBSA) approach with modified GB model (igb=2) implemented in AMBER16 software [27] . The physicochemical parameters of the most promising natural spices as SARS-CoV-2 M pro inhibitors were predicted using the online Molinspiration cheminformatics software %ABS was estimated as follows [28] : The online web-based tools of SwissTargetPredicition (http://www.swisstargetprediction.ch) were applied to predict the biological targets for the most promising natural spices as SARS-CoV-2 M pro inhibitors. Since the main protease of SARS-CoV-2 (M pro ) plays a critical role in the viral replication process, structure-based computational modeling of ligand-receptor interactions and molecular dynamics has been used to screen metabolites from common spices as potential M pro inhibitors. doi = 10.1016/j.compbiomed.2020.104046 id = cord-306177-5wefp31y author = Iheagwam, Franklyn Nonso title = Computer-Aided Analysis of Multiple SARS-CoV-2 Therapeutic Targets: Identification of Potent Molecules from African Medicinal Plants date = 2020-09-12 keywords = COVID-19; CoV-2; SARS; TMPRSS2 summary = e Unites States Food and Drug Administration-(USFDA-) approved drugs [26] , drugbank [27, 28] , traditional Ayurvedic, Chinese and natural medicine [20, [28] [29] [30] [31] , dark chemical matter, and fooDB [25] are some of the ZINC database subsets that have been rigourously screened for molecules to combat SARS-CoV-2 with main protease, RNA-dependent RNA polymerase, and angiotensin-converting enzyme-2 as the major therapeutic targets. Hence, this study analysed a plethora of natural products (NPs) from African medicinal plants with known bioactivities in human as therapeutic candidates targeting and inhibiting SARS-CoV-2 RNA synthesis, replication, structural protein function, and host-specific receptors/enzymes. In the course of drug discovery, structure-based virtual screening is a computational approach utilised to identify promising novel small chemical ligands from curated chemical compound databases with potential activity against drug targets [48] . doi = 10.1155/2020/1878410 id = cord-284498-54j6ys8s author = Ihsanullah, Ihsanullah title = Coronavirus 2 (SARS-CoV-2) in water environments: Current status, challenges and research opportunities date = 2020-10-16 keywords = CoV-2; SARS; covid-19; wastewater; water summary = Some of the significant challenges and research opportunities are the development of standard techniques for the detection and quantification of SARS-CoV-2 in the water phase, assessment of favorable environments for its survival and decay in water; and development of effective strategies for elimination of the novel virus from water. Development of effective standard techniques for the detection and quantification of SARS-CoV-2 in water, assessment of the existing water purification technologies and development of novel advanced water treatment systems are major challenges and open research opportunities. Furthermore, careful surveillance of water and wastewater to be used as an early warning tool for such outbreaks in future, understanding the survival and decay mechanism of the novel virus in water and wastewater, analysis of potential pathways of SARS-CoV-2 into water bodies are other potential research opportunities for environmental researchers [40] [41] [42] [43] [44] . doi = 10.1016/j.jwpe.2020.101735 id = cord-293056-kz3w0nfh author = Indes, Jeffrey E. title = Early Experience with Arterial Thromboembolic Complications in Patents with COVID-19 date = 2020-08-28 keywords = CoV-2; SARS summary = A retrospective case-control study design was used to identify, characterize and evaluate potential risk factors for arterial thromboembolic disease in SARS-CoV-2 positive patients. Although not statistically significant, in patients with arterial thromboembolism, patients who were SARS-CoV-2 positive compared to those testing negative or not tested tended to be male (66.7 % v. Treatment of arterial thromboembolic disease in the COVID-19 positive patients included open thromboembolectomy in 6 patients (40%), anticoagulation alone in 4 (26.7%) and 5 (33.3%) did not require or their overall illness severity precluded additional treatment. The SARS-CoV-2 positive group included patients with a range of COVID-19 16 symptomatology (mild to severe) as well as those tested as part of routine preoperative 17 preparation. Patients with arterial thrombosis who were SARS-CoV-10 2 positive had significantly higher D-dimer levels, BMI, were younger, and less often on 11 antiplatelet medications as compared to patients who were SARS-CoV-2 negative or not tested. doi = 10.1016/j.jvs.2020.07.089 id = cord-307860-iqk1yiw4 author = Ionescu, Mihaela Ileana title = An Overview of the Crystallized Structures of the SARS-CoV-2 date = 2020-10-24 keywords = 3cl; ACE2; CoV-2; PDB; RNA; SARS summary = Structures retrieved from PDB (August 12, 2020) were analyzed for relevant information on COVID-19 infection, synthesis of new inhibitors, SARS-CoV-2 interaction with host receptors, and the neutralizing antibodies interactions with spike glycoprotein. The first X-ray structure found (PDB ID 6LU7) belongs to the nonstructural protein 5 (3C-like protease) of the SARS-CoV-2 in complex with the Michael acceptor-based inhibitor N3 (PRD_002214). There is a cryo-EM crystal structure of the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) complex (nsp12/nsp8/nsp7) with the antiviral drug remdesivir (PDB ID 7BV2) [37] . Previous studies on the crystal structures of SARS-CoV S glycoprotein mutants neutralized by 80R-specific antibodies have been considered a hope for the immunotherapeutic Fig. 8 The phylogenetic tree (cladogram) of the CoVs Spike (S) sequences of CoVs with different origin. Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites doi = 10.1007/s10930-020-09933-w id = cord-328361-hyrke6j2 author = Ithete, Ndapewa Laudika title = Close Relative of Human Middle East Respiratory Syndrome Coronavirus in Bat, South Africa date = 2013-10-17 keywords = CoV; MERS summary = A novel clade 2c betacoronavirus, termed Middle East respiratory syndrome (MERS)-CoV, was recently identified as the causative agent of a severe respiratory disease that is mainly affecting humans on the Arabian Peninsula (1) . Extending on previous work (2), we described European Pipistrellus bat-derived CoVs that are closely related to MERS-CoV (3) . Screening for CoVs was done by nested reverse transcription PCR using broadly reactive oligonucleotide primers targeting a conserved region in the RNA-dependent RNA polymerase (RdRp) gene (online Technical Appendix). PCR amplicons for 4 positive specimens yielded alphacoronavirus sequences related to recently described bat alphacoronaviruses from South Africa (4) . A Bayesian phylogenetic analysis of the 816-nt RdRp sequence confirmed the close relationship between PML/2011 and MERS-CoV (Figure) . Genomic characterization of severe acute respiratory syndrome-related coronavirus in European bats and classification of coronaviruses based on partial RNA-dependent RNA polymerase gene sequences doi = 10.3201/eid1910.130946 id = cord-342538-5bwsm290 author = Izquierdo Lara, R. W. title = Monitoring SARS-CoV-2 circulation and diversity through community wastewater sequencing date = 2020-09-22 keywords = CoV-2; Netherlands; SARS; sample summary = Here we have explored the possibility of using next-generation sequencing (NGS) of sewage samples to evaluate the diversity of SARS-CoV-2 at the community level from routine wastewater testing, and compared these results with the virus diversity in patients from the Netherlands and Belgium. Low frequency variant (LFV) analysis showed that some known LFVs can be associated with particular clusters within a clade, different to those of their consensus sequences, suggesting the presence of at least 2 clades within a single sewage sample. Moreover, we detected a total of 51 novel mutations present in sewage consensus sequences that were not previously reported (supplementary Table S2 ), of which 48 were supported by coverage above the set thresholds to be considered as high quality (coverage >30x for Nanopore; and coverage >5X and Phred score >30 for Illumina). doi = 10.1101/2020.09.21.20198838 id = cord-312486-rumqopg0 author = Jacob, Chaim Oscar title = On the genetics and immunopathogenesis of COVID-19 date = 2020-09-10 keywords = ACE2; CoV-2; Kawasaki; SARS; cell; covid-19; patient; severe summary = The question is whether ACE2 expression levels are pertinent to SARS-CoV-2 infection only in the tissues relevant to viral entry and the lungs as its major target, [44, 45] or, given that COVID-19 in its severe form is a systemic disease with multi-organ disfunction [46, 47] , ACE2 expression levels may be important in multiple organs and tissues other than those of the respiratory system. However, the activation of multiple complement pathways, dysregulated neutrophil responses, endothelial injury, and hypercoagulability appear to be interlinked with SARS-CoV-2 infection and instead serve to drive the severity of the disease [91] . Regarding SLE, the prototypic systemic autoimmune disease, a group of investigators suggested that inherent epigenetic dysregulation causing hypomethylation and overexpression of ACE2, the functional receptor for SARS-CoV-2, might facilitate viral J o u r n a l P r e -p r o o f entry, viremia, and increased likelihood of cytokine storm in such patients [153] . doi = 10.1016/j.clim.2020.108591 id = cord-337105-jlmh79qv author = Jacob, Fadi title = Human Pluripotent Stem Cell-Derived Neural Cells and Brain Organoids Reveal SARS-CoV-2 Neurotropism Predominates in Choroid Plexus Epithelium date = 2020-09-21 keywords = CoV-2; SARS; cell; figure; infection summary = We optimized a protocol to generate choroid plexus organoids from hiPSCs and showed that productive SARS-CoV-2 infection of these organoids is associated with increased cell death and transcriptional dysregulation indicative of an inflammatory response and cellular function deficits. QPCR analysis also showed higher levels of ACE2 and TMPRSS2 expression in CPOs at 50 DIV and 100 DIV than in hippocampal organoids ( Figure S2D ) Together, these results show that our CPOs exhibit a similar transcriptome as adult human choroid plexus tissue and express markers for choroid plexus epithelial cells and SARS-CoV-2 receptors, representing a suitable experimental model to study SARS-CoV-2 infection. Our finding that dysregulated gene expression varies widely among hepatocyte, intestinal, and choroid plexus organoids infected with SARS-CoV-2 suggests unique responses in different cell types and highlights the need for diverse human cellular model systems when studying the disease. doi = 10.1016/j.stem.2020.09.016 id = cord-305931-0pgu2gvh author = Janus, Scott E title = COVID19: a case report of thrombus in transit date = 2020-06-17 keywords = CoV-2; SARS summary = In view of the fact that the utility of tissue plasminogen activator in this population is not well studied, we present this case of rapid improvement in oxygenation after successful lytic therapy for thrombus in transit in this patient with SARS-CoV-2. 4 Although the utility of tissue plasminogen activator (TPA) for thrombus in transit in other clinical settings has previously been reported, 5 the literature regarding cardiovascular events in SARS-CoV-2 remains scarce; we therefore describe the case of a 64-year-old male who presented with Learning points SARS-CoV-2 pneumonia, who was found to have extensive clot in transit on echocardiography and underwent successful lytic therapy. In view of the fact that the utility of TPA in this population is not well studied, 10 we present this case of rapid improvement in oxygenation after successful lytic therapy for thrombus in transit in this patient with SARS-CoV-2. doi = 10.1093/ehjcr/ytaa189 id = cord-300399-21xozruq author = Jayamohan, Harikrishnan title = SARS-CoV-2 pandemic: a review of molecular diagnostic tools including sample collection and commercial response with associated advantages and limitations date = 2020-10-18 keywords = CRISPR; CoV-2; PCR; RNA; SARS; covid-19; sample summary = This review paper examines current molecular diagnostic tools (Fig. 1) , such as amplification-based (including CRISPR-Cas based), antibody and antigen tests, and sequencing, utilized for the detection of SARS-CoV-2. In addition, we also discuss sample preparation aspects that are relevant to wider utilization and point-of-care (POC) deployment of COVID-19 diagnostic tests (PCR, isothermal amplification, and sequencing-including library preparation). RT-PCR broadly involves four steps-lysis of SARS-CoV-2 in the sample, purification of the viral RNA, reverse transcription to complementary DNA (cDNA), and amplification of specific regions of the cDNA, and finally, optical detection of the amplified cDNA. The assay can detect the virus from respiratory swab samples with sensitivity comparable to that of the US Centers for Disease Control and Prevention (CDC) SARS-CoV-2 real-time RT-PCR assay in 30-40 min. Evaluation of novel antigen-based rapid detection test for the diagnosis of SARS-CoV-2 in respiratory samples doi = 10.1007/s00216-020-02958-1 id = cord-353777-t8q99tlq author = Jia, Yong title = Analysis of the mutation dynamics of SARS-CoV-2 reveals the spread history and emergence of RBD mutant with lower ACE2 binding affinity date = 2020-04-11 keywords = CoV-2; SARS summary = The discrepant phylogenies for the spike protein and its receptor binding domain proved a previously reported structural rearrangement prior to the emergence of SARS-CoV-2. Despite that we found the spike glycoprotein of SARS-CoV-2 is particularly more conserved, we identified a mutation that leads to weaker receptor binding capability, which concerns a SARS-CoV-2 sample collected on 27th January 2020 from India. We provided first evidence that a mutated SARS-COV-2 with reduced human ACE2 receptor binding affinity have emerged in India based on a sample collected on 27th January 2020. The discrepant phylogenies for the spike protein and its 23 receptor binding domain proved a previously reported structural rearrangement prior to the emergence of SARSDespite that we found the spike glycoprotein of SARS-CoV-2 is particularly more conserved, we identified a mutation that 25 leads to weaker receptor binding capability, which concerns a SARS-CoV-2 sample collected on 27 th January 2020 from 26 doi = 10.1101/2020.04.09.034942 id = cord-267458-uofy7jyx author = Jiang, Xiao-Lin title = Transmission potential of asymptomatic and paucisymptomatic SARS-CoV-2 infections: a three-family cluster study in China date = 2020-04-22 keywords = CoV-2; SARS summary = doi = 10.1093/infdis/jiaa206 id = cord-325234-skshcrh1 author = Jin, Tingxu title = SARS-CoV-2 presented in the air of an intensive care unit (ICU) date = 2020-08-15 keywords = CoV-2; SARS; patient summary = Therefore, with an objective to test the hypothesis of airborne transmission of SARS-CoV-2, it is necessary to 1) determine whether SARS-CoV-2 particles are present in the indoor air and 2) determine whether recovered patients are still shedding virus, thus providing much-needed environmental evidence for the management of COVID-19 patients during the recovery period. To date, some studies have reported the presence of SARS-CoV-2 particles in the air in isolation rooms from hospitals treating COVID-19 patients (Yuanfang J,2020; Guo, Wang, Zhang, Li, & Chen,2020; Joshua L. Therefore, our study aims to 1) determine whether SARS-CoV-2 particles are present in the indoor air, with an objective to test the hypothesis of airborne transmission of SARS-CoV-2, and 2) determine whether recovered patients are still shedding SARS-CoV-2 particles, thus providing much-needed environmental evidence for the management of COVID-19 patients during the recovery period. Our findings revealed the presence of SARS-CoV-2 in the indoor air of the ICU and indicate that the virus may be shed via aerosol for days, even after a patient has tested negative. doi = 10.1016/j.scs.2020.102446 id = cord-274506-fzcuu4ma author = Jo, Seri title = Characteristics of flavonoids as potent MERS‐CoV 3C‐like protease inhibitors date = 2019-09-12 keywords = CoV; MERS; activity; flavonoid summary = While PLpro cuts the first three cleavage sites of its polyprotein, 3CLpro is responsible for cleavage of the remaining eleven locations resulting in release of a total of 16 non-structural proteins (nsp) in both SARS-and MERS-CoVs. The homodimeric form of 3CLpro is active in the presence of substrates. In this study, we used a proteolytic method to probe MERS-CoV 3CLpro inhibitory compounds with a synthetic peptide labelled with the EDANS-DABCYL FRET (Fluorescence resonance energy transfer) pair (Liu et al., 2005) . The proteolytic assay using MERS-CoV 3CLpro in the presence of Triton X-100 has been performed to differentiate artificial inhibitory activity of chemicals through non-specific binding with proteases by forming aggregate or complexation. The four compounds showed the severely reduced fluorescent intensity and thus represented their MERS-CoV 3CLpro inhibitory activity. In this study, we assayed the inhibitory activity of various flavonoids against MERS-CoV 3CLpro. The analysis of the four compounds with their homologs using an induced-fit docking study provided an insight of flavonoid scaffolds required to bind with MERS-CoV 3CLpro. doi = 10.1111/cbdd.13604 id = cord-334976-53cd16w5 author = Jo, Seri title = Flavonoids with inhibitory activity against SARS-CoV-2 3CLpro date = 2020-08-04 keywords = CoV-2; SARS; flavonoid summary = An in silico docking study showed that the binding modes of herbacetin and pectolinarin are similar to those obtained from the catalytic domain of SARS-CoV 3CLpro. Baicalin showed an effective inhibitory activity against SARS-CoV-2 3CLpro and its docking mode is different from those of herbacetin and pectolinarin. The proteolytic assay using SARS-CoV-2 3CLpro in the presence of Triton X-100 has been performed to differentiate the artificial inhibitory activity of chemicals through non-specific binding with proteases by forming aggregate or complexation. The compound showed the severely reduced fluorescent intensity and thus represented their SARS-CoV-2 3CLpro inhibitory activity. Among them, baicalin, herbacetin and pectolinarin revealed the prominent inhibitory activity against SARS-CoV-2 3CLpro. The binding modes of herbacetin and pectolinarin were similar to those obtained from the docking study of the catalytic domain of SARS-CoV 3CLpro 21 . In the previous results of SARS-CoV 3CLpro 21 , only the three effect flavonoids (herbacetin, pectolinarin, and rhoifolin) were mentioned. doi = 10.1080/14756366.2020.1801672 id = cord-348899-vynk8q8c author = Jo, Seri title = Inhibition of SARS-CoV 3CL protease by flavonoids date = 2019-11-14 keywords = CoV; SARS; Triton; flavonoid summary = A synthetic peptide labelled with an Edans-Dabcyl FRET (Fluorescence resonance energy transfer) pair 12 was used to search SARS-CoV 3CLpro inhibitory compounds against a flavonoid library. The proteolytic assay using the SARS-CoV 3CLpro in the presence of Triton X-100 has been performed to differentiate the artificial inhibitory activity of chemicals through non-specific binding with proteases by forming aggregate or complexation. The three compounds showed the severely reduced fluorescent intensity and thus represented their SARS-CoV 3CLpro inhibitory activity. The interactions between SARS-CoV 3CLpro and three inhibitory flavonoids were analysed to predict their binding affinities. We have created a library of flavonoids to systematically investigate SARS-CoV 3CLpro inhibitory compound by a FRET method. Herbacetin, rhoifolin and pectolinarin were the best inhibitory compounds against SARS-CoV 3CLpro in the flavonoid library. In order to predict the flavonoid scaffolds needed to interact with the catalytic site of SARS-CoV 3CLpro, an induced-fit docking study was performed and analysed. doi = 10.1080/14756366.2019.1690480 id = cord-338923-hc7gagnq author = Jääskeläinen, AJ title = Performance of six SARS-CoV-2 immunoassays in comparison with microneutralisation date = 2020-06-15 keywords = CoV-2; SARS summary = We compared the performance of six commercial immunoassays for the detection of SARS-CoV-2 IgG, IgA and IgM antibodies, including four automated assays [Abbott SARS-COV-2 IgG (CE marked), Diasorin Liaison® SARS-CoV-2 S1/S2 IgG (research use only, RUO), and Euroimmun SARS-CoV-2 IgG and IgA (CE marked)], and two rapid lateral flow (immunocromatographic) tests [Acro Biotech 2019-nCoV IgG/IgM (CE marked) and Xiamen Biotime Biotechnology SARS-CoV-2 IgG/IgM (CE marked)] with a microneutralisation test (MNT). Forty-one out of 62 COVID-19 patients showed neutralising antibodies.The specificity and sensitivity values of the commercial tests against MNT, respectively, were as follows: 95.1%/80.5% (Abbott Architect SARS-CoV-2 IgG), 94.9%/43.8% (Diasorin Liaison SARS-CoV-2 IgG; RUO), 68.3%/87.8% (Euroimmun SARS-CoV-2 IgA), 86.6%/70.7% (Euroimmun SARS-CoV-2 IgG), 74.4%/56.1% (Acro 2019-nCoV IgG), 69.5%/46.3% (Acro 2019-nCoV IgM), 97.5%/71.9% (Xiamen Biotime SARS-CoV-2 IgG), and 88.8%/81.3% (Xiamen Biotime SARS-CoV-2 IgM). In this study, we assessed the specificity and sensitivity of six commercial immunoassays for the detection of SARS-CoV-2 antibodies, including two rapid lateral flow tests, in comparison with a neutralisation test. doi = 10.1016/j.jcv.2020.104512 id = cord-350505-uh8r2vyz author = Kalantar-Zadeh, Kourosh title = Considering the Effects of Microbiome and Diet on SARS-CoV-2 Infection: Nanotechnology Roles date = 2020-05-01 keywords = CoV-2; Prevotella; SARS summary = [Image: see text] The impact of dietary patterns and the commensal microbiome on susceptibility to and severity of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has been largely ignored to date. 2 Therefore, the elucidation of host cytokine molecular pathways and microbiota components 17 as well as bacterial reactions in association with cytokine responses may provide novel microbiome-based therapeutic approaches to SARS-CoV-2 infection. Considering the presented discussion, nutritional and dietary strategies directed at restoring the well-known beneficial microbiota, which can possibly suppress viral infection in the elderly and those with underlying health problems, may be an effective strategy to mitigate the harmful effects of this virus. One approach, as a whole and to be undertaken prior to any viral infection, could include strengthening the intestinal barrier against pathogens, increasing intestinal motility, and reducing an underlying pro-inflammatory state by adopting a Many different direct or indirect microbiome pathways could contribute to SARS-CoV-2-gut interactions. doi = 10.1021/acsnano.0c03402 id = cord-292025-dr611nse author = Kam, Kai-qian title = Clinical Utility of Buccal Swabs for Severe Acute Respiratory Syndrome Coronavirus 2 Detection in Coronavirus Disease 2019–Infected Children date = 2020-06-13 keywords = CoV-2; SARS summary = From 23 March 2020 to 3 April 2020, all inpatient pediatric confirmed COVID-19 cases diagnosed via positive SARS-CoV-2 polymerase chain reaction (PCR) from nasopharyngeal swabs using the real-time reverse transcription (rRT)-PCR assay for the E gene were included in this study. In the 9 infected children with detectable SARS-CoV-2 in buccal specimens, the mean difference of Ct values between buccal and nasopharyngeal specimens for all infected patients was 10.7 (range, 6.1-16.1), and this was statistically significant (P < .001). Our findings confirm that SARS-CoV-2 can be detected in buccal specimens of infected children and that the viral load is the highest in the first week of illness or diagnosis. In our study, the average viral loads of buccal SARS-CoV-2 were consistently lower than the respective nasopharyngeal specimens, with substantial differences between the average Ct values. Two COVID-19-infected children had negative buccal specimens despite detectable nasopharyngeal viral load. doi = 10.1093/jpids/piaa068 id = cord-347351-emdj66vj author = Kampf, Günter title = Potential sources, modes of transmission and effectiveness of prevention measures against SARS-CoV-2 date = 2020-09-18 keywords = CoV-2; RNA; SARS; covid-19; patient; transmission summary = Originating from a single travel-associated primary case from China, the first documented chain of multiple human-to-human transmissions of SARS-CoV-2 outside of Asia allowed a detailed study of transmission events and identified several factors (e.g. cumulative face-toface contact, direct contact with secretions or body fluids of a patient, personal protective equipment) to classify contacts as low or high risk [32] . In the close surrounding of COVID-19 patients in hospitals SARS-CoV-2 RNA is detected more frequently compared to surfaces outside the patient rooms but samples were so far consistently negative for infectious virus. General disinfection of frequently touched surfaces in the public such as shopping carts or door handles is, however, unlikely to add any protective value because even in COVID-19 wards inanimate surfaces were mainly contaminated in the permanent and immediate surrounding of symptomatic patients (detection of viral RNA, not of infectious virus) and only rarely one room away [138] suggesting that the risk to find SARS-CoV-2 on frequently touched surfaces in the public is low. doi = 10.1016/j.jhin.2020.09.022 id = cord-338468-c0jv3i1t author = Kanduc, Darja title = From Anti-SARS-CoV-2 Immune Responses to COVID-19 via Molecular Mimicry date = 2020-07-16 keywords = CoV-2; SARS; hexapeptide; human; protein summary = Results: Immunoreactive epitopes present in SARS-CoV-2 were mostly composed of peptide sequences present in human proteins that—when altered, mutated, deficient or, however, improperly functioning—may associate with a wide range of disorders, from respiratory distress to multiple organ failure. In the wake of such results, in order to validate (or, as well, invalidate) the cross-reactivity hypothesis, investigation was expanded here by analyzing the peptide sharing between the human host and immunoreactive epitopes that are also present in SARS-CoV-2. Table 2 documents that numerous immunoreactive SARS-CoV-2 epitopes are composed mostly or, in many instances, uniquely of peptide sequences shared with human proteins. This study shows that hexapeptides from immunoreactive epitopes present in SARS-CoV-2 are widespread among a high number of human proteins. Table S2 : Hexapeptide sharing between 233 epitopes present in SARS-CoV-2 and human proteins. Table S3 : List and short description of 460 human proteins that share hexapeptides with the 233 SARS-CoV-2 epitopes. doi = 10.3390/antib9030033 id = cord-310807-p5cb6idp author = Kanwar, Anubhav title = Human Coronavirus-HKU1 Infection Among Adults in Cleveland, Ohio date = 2017-03-25 keywords = CoV; HKU1; adult summary = Coronavirus-HKU1 has been described predominantly among children less than 5 years of age in the United States with few studies characterizing the disease spectrum among adults. In this study, we report one of the largest case series of CoV-HKU1 infections among adults presenting with respiratory tract illness and describe their clinical characteristics. Clinical data analysis for adults (patients >18 years of age) included the following: age, gender, hospitalization status, length of hospitalization, clinical features, discharge diagnosis, outcome (death or survived), comorbidities (smoking, lung disease), laboratory and radiology results, intensive care unit (ICU) stay, oxygen use and duration, treatment provided, and exposure history. Similar studies describing HKU1 in pediatric and adult patients have also found an association with upper and lower respiratory tract illness [7, 9, 12, 15, 21] . Our study provides needed insight into clinical characteristics and severity associated with CoV-HKU1 infection in adults in the Northeast region of the United States. doi = 10.1093/ofid/ofx052 id = cord-270396-3bcnnyfq author = Karacin, Cengiz title = How does COVID-19 fear and anxiety affect chemotherapy adherence in patients with cancer date = 2020-07-17 keywords = COV summary = Aim: To investigate how COVID-19 fear and anxiety (COV-FA) affects chemotherapy adherence in patients with cancer. Data on patients'' age, sex, comorbidities, history of smoking, marital status, number of children, educational background, place of residence and household, cancer type, disease stage, CT regimen and date of CT postponement were obtained from the hospital records. In the present study, it was seen that the CT postponement rate increased significantly following the first COVID-19 case in Turkey and COV-FA was identified as the third most frequent reason for CT postponement. In the present study, the median TCBT of the patients who postponed CT due to COV-FA was 47 days (range . • We aimed to investigate how COVID-19 fear and anxiety (COV-FA) affects chemotherapy (CT) adherence in patients receiving active CT for cancer, and to identify the characteristics of patients who postponed their CT due to COV-FA, as well as the time to come back to treatment (TCBT) and the factors affecting TCBT in these patients. doi = 10.2217/fon-2020-0592 id = cord-331039-qgom2e3n author = Kavitha, Kuppuswamy title = 1,2,4 triazolo[1,5-a] pyrimidin-7-ones as novel SARS-CoV-2 Main protease inhibitors: In silico screening and molecular dynamics simulation of potential COVID-19 drug candidates date = 2020-09-22 keywords = CoV-2; Lopinavir; SARS; pro summary = A total of 1000 protease-inhibitor-like compounds available in the ZINC database were screened by molecular docking with SARS-CoV-2 M(pro) and the top 2 lead compounds based on binding affinity were found to be 1,2,4 triazolo[1,5-a] pyrimidin-7-one compounds. The objectives of this study were i) to identify evolutionarily important active site amino acids by structure-based sequence alignment of SARS-CoV-2 and SARS-CoV M pro enzymes ii) to identify potential non-covalent M pro inhibitors by screening protease-inhibitor-like compounds available in the ZINC database by molecular docking studies iii) prediction of absorption, distribution metabolism, excretion and toxicity properties of the top-scoring inhibitors using in silico methods iv) to validate the stable binding of the lead compounds with SARS-CoV-2 M pro by molecular dynamics (MD) simulations and v) to calculate thermodynamic binding energies for each lead compound -SARS-CoV-2 M pro complex using Molecular Mechanics Poisson-Boltzmann Surface Area (MM/PBSA) calculations. doi = 10.1016/j.bpc.2020.106478 id = cord-330343-p7a8chn4 author = Kelly-Cirino, Cassandra title = An updated roadmap for MERS-CoV research and product development: focus on diagnostics date = 2019-02-01 keywords = CoV; East; MERS; Middle; respiratory summary = ► Diagnostic research and development (R&D) needs to include point-of-care testing options, syndromic panels for differential diagnosis, a greater understanding of viral and antibody kinetics, improved access to clinical specimens, and establishment of international reference standards. Diagnostics play a central role in the early detection and control of outbreaks and can enable a more nuanced understanding of the disease kinetics and risk factors for the Middle East respiratory syndrome-coronavirus (MERS-CoV), one of the high-priority pathogens identified by the WHO. Diagnostics play a central role in the early detection and control of outbreaks and can enable a more nuanced understanding of the disease kinetics and risk factors for the Middle East respiratory syndrome-coronavirus (MERS-CoV), one of the high-priority pathogens identified by the WHO. In this review we identified sources for molecular and serological diagnostic tests used in MERS-CoV detection, case management and outbreak investigations, as well as surveillance for humans and animals (camels), and summarised the performance of currently available tests, diagnostic needs, and associated challenges for diagnostic test development and implementation. doi = 10.1136/bmjgh-2018-001105 id = cord-253862-jl1zhg13 author = Khalaf, Khalil title = SARS-CoV-2: Pathogenesis, and Advancements in Diagnostics and Treatment date = 2020-10-06 keywords = ACE-2; COVID-19; CoV-2; IFN; RNA; SARS; cell; patient summary = doi = 10.3389/fimmu.2020.570927 id = cord-278362-pwi48i20 author = Khan, Abbas title = Combined drug repurposing and virtual screening strategies with molecular dynamics simulation identified potent inhibitors for SARS-CoV-2 main protease (3CLpro) date = 2020-06-18 keywords = COV-2; SARS; Saquinavir; drug summary = title: Combined drug repurposing and virtual screening strategies with molecular dynamics simulation identified potent inhibitors for SARS-CoV-2 main protease (3CLpro) Furthermore, results from molecular dynamics simulation and total binding free energy revealed that Saquinavir and TCM5280805 target the catalytic dyad (His41 and Cys145) and possess stable dynamics behavior. In this study, the protein of SARS-COV-2 (3CLpro, also named 3-chymotrypsin-like protease) was subjected to drug repurposing and virtual screening for potent drug identification followed by molecular dynamics simulation and binding free energy calculation. In the current study, the repurposing of anti-HIV drugs against the SARS-COV-2 main protease was carried out using structure-based screening methods. In this study, based on the results of bioinformatics analysis, we targeted 3CLpro from SARS-COV-2 using drugs repurposing (anti-HIV drugs) virtual drugs screening (TCM) approaches to shortlist the most potent compounds for the possible treatment. doi = 10.1080/07391102.2020.1779128 id = cord-304792-8sdxqmkb author = Khan, Md. Abdullah-Al-Kamran title = SARS-CoV-2 proteins exploit host’s genetic and epigenetic mediators for the annexation of key host signaling pathways that confers its immune evasion and disease pathophysiology date = 2020-05-08 keywords = CoV-2; SARS; figure summary = title: SARS-CoV-2 proteins exploit host''s genetic and epigenetic mediators for the annexation of key host signaling pathways that confers its immune evasion and disease pathophysiology In this study we aimed to correlate how SARS-CoV-2 utilizes its proteins for tackling the host immune response; parallelly, how host epigenetic factors might play a role in this pathogenesis was also investigated. Also, enrichment analyses suggest that deregulated genes in SARS-CoV-2 infection are involved in heart development, kidney development, AGE-RAGE signaling pathway in diabetic complications etc. Our results suggest that SARS-CoV-2 integrates its proteins in different immune signaling pathway and other cellular signaling pathways for developing efficient immune evasion mechanisms, while leading the host to more complicated disease condition. We have utilized KEGG mapper tool (Kanehisa and Sato, 2020) for the mapping of 197 deregulated genes SARS-CoV-2 interacting host proteins in different cellular pathways. doi = 10.1101/2020.05.06.050260 id = cord-346819-11fkgzaa author = Khan, Mohd Imran title = Comparative genome analysis of novel coronavirus (SARS-CoV-2) from different geographical locations and the effect of mutations on major target proteins: An in silico insight date = 2020-09-03 keywords = CoV-2; Mpro; SARS; protein summary = title: Comparative genome analysis of novel coronavirus (SARS-CoV-2) from different geographical locations and the effect of mutations on major target proteins: An in silico insight A novel severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) causing COVID-19 pandemic in humans, recently emerged and has exported in more than 200 countries as a result of rapid spread. Main protease (Mpro), the therapeutic target protein of SARS with maximum reported inhibitors, was thoroughly investigated and the effect of mutation on the binding affinity and structural dynamics of Mpro was studied. The genome analysis of the SARS-CoV-2 strains from 13 different countries showed a large number of mutations within the major structural proteins. This study provides a deeper insight into the emergence of these mutations within the major structural as well as nsp encoded by the SARS-CoV-2 genome from different countries. Comparative genome analysis of novel coronavirus (SARS-CoV-2) from different geographical locations backbone RMSD was also noticed (Fig 4A) . doi = 10.1371/journal.pone.0238344 id = cord-304295-3mpymd8a author = Khan, Muhammad Muzamil title = Emergence of novel coronavirus and progress toward treatment and vaccine date = 2020-06-04 keywords = CoV-2; SARS; coronavirus summary = 10 Favipiravir was effectively used against influenza and has the potential to inhibit viral RNA synthesis and a new study also supports its activity against SARS-CoV-2. 15 In another recent study, Gao et al found that chloroquine phosphate reduced the symptoms of pneumonia in SARS-CoV-2 patients and shortening the duration of disease. 67 Different technologies are being utilized to F I G U R E 1 Mechanism of action of HCQ and CQ by blocking binding of virus with ACE-2 receptors and increasing endosomal pH and preventing fusion with the cell develop potential vaccine for SARS-CoV-2 including DNA and mRNAbased nanoparticles. Clinical study for safety and efficacy of favipiravir in the treatment of novel coronavirus pneumonia (COVID-19) In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) doi = 10.1002/rmv.2116 id = cord-279443-2e4gz2bo author = Khan, Suliman title = Transmission of SARS-CoV-2, Required Developments in Research and Associated Public Health Concerns date = 2020-06-09 keywords = CoV-2; SARS; covid-19; transmission summary = To identify and select the papers in this review we searched the published research and review articles relevant to origin and outbreaks of three human coronaviruses, and features, transmission, spread, entry mechanisms, infectiousness, control strategies, and animals hosts for SARS-CoV-2. Although it is important to know about the symptoms'' appearance and severity, however, understanding the transmission of the infection to healthy individuals from COVID-19 patients and zoonotic sources can be of great importance in the aspects of developing strategies to prevent and control the spread of COVID-19. This outbreak was reported to be caused by SARS-CoV, originated from market civets before its transmission and infection in humans (17) . Early claims came FIGURE 2 | The SARS-CoV-2 transmission from bats via unknown intermediate to humans causes infectiousness known as COVID-19 disease. According to the CDC report on coronavirus disease, individuals with underlying chronic medical conditions are at higher risk for contracting COVID-19 infection. doi = 10.3389/fmed.2020.00310 id = cord-309138-44qpk2vf author = Khanna, Kanika title = Herbal Immune-boosters: Substantial Warriors of Pandemic Covid-19 Battle date = 2020-10-03 keywords = ACE2; COVID-19; CoV-2; PAK1; SARS; infection summary = Moreover, AYUSH has recommended certain preventive and medicinal plants for prevention and prophylactic of COVID-19 including warm extracts of Tinospora cordifolia (advised for chronic fever), Andrograhis paniculata (advised for fever and cold), Cydonia oblonga, Zizyphus jujube and Cordia myxa (enhancing antioxidant, immune-modulatory, anti-allergic, smooth muscle relaxant, anti-influenza activity) and Ever since, has been elucidated that, PAK1 tends to cause cancers, viral diseases like HIV, Hepatitis, pappiloma, influenza, ebola, SARS and corona virus along with immune system suppression of hosts, henceforth, propolis would be quintessential in blocking COVID/coronavirus curbed fibrosis in respiratory tract and boosting the immunity of an individual (Maruta, 2014) . Potential Inhibitor of COVID-19 Main Protease (Mpro) From Several Medicinal Plant Compounds by Molecular Docking Study Molecular mechanism of action of repurposed drugs and traditional Chinese medicine used for the treatment of patients infected with COVID-19: A systematic review Traditional Chinese medicine in the treatment of patients infected with 2019-new coronavirus (SARS-CoV-2): a review and perspective doi = 10.1016/j.phymed.2020.153361 id = cord-323061-0i5w7vm9 author = Kharel Sitaula, Ranju title = Unfolding COVID-19: Lessons-in-Learning in Ophthalmology date = 2020-09-28 keywords = ACE2; CoV-2; SARS; ocular summary = 10 Epiphora and Conjunctival redness had been the first manifestation of SARS-CoV-2 infection in 3 reported cases till date which includes a member of National expert on pneumonia during his visit to endemic areas of Wuhan and an anesthesiologist contracting the virus from a known patient of novel coronavirus pneumonia during intubation in Italy; similarly, it was reported in a nurse working in the emergency department of ophthalmology who presented with viral conjunctivitis and watering as a first sign. Hence, our knowledge and understanding about the SARS-CoV-2 virus, modes of entry to the eye, hypothesis on the interaction with the Renin-Angiotensin System (RAS) system and ACE2 receptor and ocular pathogenesis and RT PCR analysis from the ocular secretions have been summarized below using text, tables, diagrams, and flowcharts. doi = 10.2147/opth.s259857 id = cord-306581-g3d0lqxp author = Khattab, Mohamed H. title = Early detection of SARS-CoV-2 from staging PET-CT date = 2020-09-29 keywords = CoV-2; SARS summary = METHODS: Here, we present a case study of a mildly symptomatic patient with anal cancer diagnosed with SARS-CoV-2 from a staging PET-CT scan. Given the ongoing COVID-19 pandemic, a nasopharyngeal swab with polymerase chain reaction (PCR) was obtained and was confirmed positive for the potentially lethal SARS-CoV-2 viral infection. In geographic regions with a Fig. 1 Screening positron emission tomography fused with computed tomography demonstrating fluorodeoxyglucose-avid multifocal, rounded, peripheral ground-glass nodules, some demonstrating the reversed halo sign, within the right lower, right middle, and left lower lung lobes concerning for an infectious process significant and increasing COVID-19 case burden, routine PCR testing in the absence of clinical or radiologic findings may be indicated in patients undergoing chemoradiation or radiation, and it is our institutional practice to test all patients receiving any chemotherapy or greater than 10 days of radiation. In the setting of asymptomatic or mildly symptomatic patients with confirmed SARS-CoV-2 infection, multidisciplinary discussion with oncology and infectious disease teams is important to ascertain the risks and benefits of delaying cancer therapy. doi = 10.1007/s13566-020-00436-w id = cord-343196-vlwzzrgc author = Kiambi, Stella title = Detection of distinct MERS-Coronavirus strains in dromedary camels from Kenya, 2017 date = 2018-11-28 keywords = MERS; cov summary = The MERS-CoV RNA-positive animals belonged to two different dromedary camel herds in Dabel and Lombolio, which are both located within Isiolo country. To experimentally confirm the presence of two independently circulating MERS-CoV strains and to rule out sample cross-contamination, we generated complete MERS-CoV genome sequences using a previously established protocol 10 . Other confirmed MERS-CoVpositive samples were assigned to two different MERS-CoV isolates ("Dabel" or "Lombolio") by amplifying and sequencing single-nucleotide polymorphisms in the spike gene and the open reading frame 3 (Supplementary Table) . The previously described clade C African MERS-CoV strains 4,5 had several mutations in the spike protein, which is responsible for cellular receptor interaction, virus entry, and antibody-directed virus neutralization 12 . An explanation for this observation may again be a lack of testing of imported animals and/or the fact that previous clade A/B MERS-CoV infections may have established herd immunity in the Arabian dromedary populations. doi = 10.1038/s41426-018-0193-z id = cord-336775-d4hi9myk author = Kirtipal, Nikhil title = From SARS to SARS-CoV-2, insights on structure, pathogenicity and immunity aspects of pandemic human coronaviruses date = 2020-08-13 keywords = ACE2; CoV; Coronavirus; MERS; RNA; SARS summary = Abstract Human Coronaviruses (HCoV), periodically emerging across the world, are potential threat to humans such as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) – diseases termed as COVID-19. Hence, acute respiratory distress syndrome (ARDS) is caused by cytokine storm that triggers a destruction in host cells via immune system and subsequently results into multiple organs failure or death as stated in case of SARS-CoV-2 outbreak; similar observations were noted in case of SARS-CoV infection (Kumar et al., 2020) . When developing novel therapeutic strategies to check the immunoregulatory cytokines such as TNFβ and IL6, investigation should be considered on the viral strain and targeted organ specificity; for example, SARS-CoV-2 has more affinity to ACE2 which are scattering on different organs like lung and kidney while MERS-like CoV can even infect T-cells. Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2) doi = 10.1016/j.meegid.2020.104502 id = cord-264267-weat0qs6 author = Kleine-Weber, Hannah title = Polymorphisms in dipeptidyl peptidase 4 reduce host cell entry of Middle East respiratory syndrome coronavirus date = 2020-01-21 keywords = CoV; DPP4; MERS; PBS summary = Four polymorphisms (K267E, K267N, A291P and Δ346-348) strongly reduced binding of MERS-CoV S to DPP4 and S protein-driven host cell entry, as determined using soluble S protein and S protein bearing rhabdoviral vectors, respectively. For host cell entry, the surface unit, S1, of MERS-CoV S binds to the cellular type-II transmembrane protein dipeptidyl peptidase 4 (DPP4, CD26) [15] . For the binding studies with solMERS-S1-Fc, a similar protocol was followed as described for the analysis of DPP4 surface expression with the exceptions that sol-MERS-S1-Fc was used instead of the primary antibody (1:10 dilution in PBS/BSA) and that an AlexaFluor488conjugated anti-human antibody (goat, 1:500 dilution in PBS/BSA, ThermoFisher Scientific) was employed as the secondary antibody. Reduced MERS-CoV S-driven host cell entry is caused by inefficient S protein binding to DPP4 harboring polymorphic amino acid residues. doi = 10.1080/22221751.2020.1713705 id = cord-300968-dtaasxk1 author = Kliger, Yossef title = From genome to antivirals: SARS as a test tube date = 2005-03-01 keywords = CoV; HIV; SARS summary = Abstract The severe acute respiratory syndrome (SARS) epidemic brought into the spotlight the need for rapid development of effective anti-viral drugs against newly emerging viruses. This strategy seems promising in developing anti-viral therapeutic peptides to other viruses that possess type 1 viral fusion proteins [e.g. measles virus and respiratory syncytial virus (RSV)], which share some structural motifs with HIV. Similar to HIV, binding of the viral spike glycoprotein to some receptor(s) on host cells is the first step in SARS-CoV infection. HIV entry involves the binding of the viral envelope glycoproteins (comprising gp120 and gp41, which are the homologous of SARS-CoV S1 and S2, respectively) to CD4 on the host cell plasma membrane. Following the rule: formation of the 6-helix bundle of the fusion core from severe acute respiratory syndrome coronavirus spike protein and identification of potent peptide inhibitors Characterization of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spike glycoproteinmediated viral entry Severe acute respiratory syndrome coronavirus (SARS-CoV) infection inhibition using spike protein heptad repeatderived peptides doi = 10.1016/s1359-6446(04)03320-3 id = cord-345381-9cckppk2 author = Klimek, Ludger title = Use of biologicals in allergic and type-2 inflammatory diseases during the current COVID-19 pandemic: Position paper of Ärzteverband Deutscher Allergologen (AeDA)(A), Deutsche Gesellschaft für Allergologie und Klinische Immunologie (DGAKI)(B), Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA)(C), Österreichische Gesellschaft für Allergologie und Immunologie (ÖGAI)(D), Luxemburgische Gesellschaft für Allergologie und Immunologie (LGAI)(E), Österreichische Gesellschaft für Pneumologie (ÖGP)(F) in co-operation with the German, Austrian, and Swiss ARIA groups(G), and the European Academy of Allergy and Clinical Immunology (EAACI)(H) date = 2020-09-07 keywords = CoV-2; SARS; covid-19; disease; infection; patient summary = title: Use of biologicals in allergic and type-2 inflammatory diseases during the current COVID-19 pandemic: Position paper of Ärzteverband Deutscher Allergologen (AeDA)(A), Deutsche Gesellschaft für Allergologie und Klinische Immunologie (DGAKI)(B), Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA)(C), Österreichische Gesellschaft für Allergologie und Immunologie (ÖGAI)(D), Luxemburgische Gesellschaft für Allergologie und Immunologie (LGAI)(E), Österreichische Gesellschaft für Pneumologie (ÖGP)(F) in co-operation with the German, Austrian, and Swiss ARIA groups(G), and the European Academy of Allergy and Clinical Immunology (EAACI)(H) Conclusion: The use of biologicals for the treatment of bronchial asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, and spontaneous urticaria should be continued as usual in patients without suspected infection or proven SARS-CoV-2 infection. Conclusion: The use of biologicals for the treatment of bronchial asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, and spontane-ous urticaria should be continued as usual in patients without suspected infection or proven SARS-CoV-2 infection. doi = 10.5414/alx02166e id = cord-267770-ik1ib3zb author = Koo, Hyun Jung title = RadioGraphics Update: Radiographic and CT Features of Viral Pneumonia date = 2020-06-05 keywords = CoV-2; SARS summary = doi = 10.1148/rg.2020200097 id = cord-323905-ayufx3wv author = Kort, N. P. title = Recommendations for resuming elective hip and knee arthroplasty in the setting of the SARS-CoV-2 pandemic: the European Hip Society and European Knee Associates Survey of Members date = 2020-08-18 keywords = CoV-2; SARS; arthroplasty summary = title: Recommendations for resuming elective hip and knee arthroplasty in the setting of the SARS-CoV-2 pandemic: the European Hip Society and European Knee Associates Survey of Members The April 2020 SARS-CoV-2 survey completed by EHS and EKA members in Europe has confirmed the impact of SARS-CoV-2: this pandemic has resulted in a tremendous reduction in primary hip and knee arthroplasty procedures as shown in the survey. The benefits of hip and knee arthroplasty should be carefully weighed against the risks of viral transmission and infection, complications and mortality in the mostly elderly population requiring joint arthroplasty Resuming elective hip and knee arthroplasty in the setting of the SARS-CoV-2 pandemic: pre-operative phase 1. Is there a need for -Modification or reorganization of hospital wards (patient density, bed density, medical and nursing stuff density, etc.)?417 (81) 70 (14) Resuming elective hip and knee arthroplasty in the setting of the SARS-CoV-2 pandemic: post-operative phase 1. doi = 10.1007/s00167-020-06212-0 id = cord-321624-z2mntwef author = Kowitdamrong, Ekasit title = Antibody responses to SARS-CoV-2 in patients with differing severities of coronavirus disease 2019 date = 2020-10-09 keywords = CoV-2; SARS summary = AIM: To investigate SARS-CoV-2 IgA and IgG antibodies in Thai patients with differing severities of COVID-19. The objective of this study was to investigate the response of IgA and IgG antibodies to SARS--CoV-2 in serial blood samples collected from a population of Thai patients with confirmed COVID-19, and the association of these responses with the severity of the illness. The second subgroup included 49 plasma samples collected from May 1 to May 31, 2020, from patients under investigation (PUI) for COVID-19 with RT-PCR results that were negative for SARS-CoV-2. In the present study, 30% of COVID-19 patients developed positive IgA antibodies very early, within 3 days after the onset of symptoms. In the present study, 20% of the patients with mild symptoms did not develop any IgG antibodies specific to COVID-19, even after 2 weeks after the onset of symptoms. doi = 10.1371/journal.pone.0240502 id = cord-333703-1ku3jc9s author = Kraus, Aurora title = A zebrafish model for COVID-19 recapitulates olfactory and cardiovascular pathophysiologies caused by SARS-CoV-2 date = 2020-11-08 keywords = ACE2; COVID-19; CoV-2; RBD; SARS; figure; zebrafish summary = Exposure of larvae to SARS-CoV-2 Spike (S) receptor binding domain (RBD) recombinant protein was sufficient to elevate larval heart rate and treatment with captopril, an ACE inhibitor, reverted this effect. In mice and humans, ace2 expression is detected in 121 sustentacular cells, olfactory stem cells known as horizontal and globose basal cells in the 122 olfactory epithelium, and vascular cells (pericytes) in the olfactory bulb (Brann et al., 2020 The present study reports for the first time that zebrafish larvae exposed to SARS-CoV-2 appear 134 to mount innate immune responses that resemble cytokine responses of mild COVID-19 patients. There are copious amounts of immune cells in the teleost olfactory organ ( Intranasal delivery of SARS-CoV-2 S RBD induces inflammatory responses and 318 widespread loss of olfactory receptor expression in adult zebrafish olfactory organ 319 320 doi = 10.1101/2020.11.06.368191 id = cord-024317-w1ep0wq8 author = Ku, Zhiqiang title = Antibody therapies for the treatment of COVID-19 date = 2020-04-30 keywords = COVID-19; CoV-2; SARS summary = Here, we discuss some of the most active areas of developing strategies to treat COVID-19, focusing on approaches to generate neutralizing antibodies against SARS-CoV-2 for prophylactic and therapeutic treatment of COVID-19. SIGNIFICANCE: Development of SARS-CoV-2 neutralizing antibodies with the desired efficacy and safety profile is a critical part of the toolbox of therapies for the treatment of COVID-19. The spike protein of SARS-CoV-2 plays an essential role in virus entry into host cells and is a primary target of neutralizing antibodies 5, 9 (Figures 1C,D) . Two MERS-CoV neutralizing mAbs, G2 and 7D10, target the S1-NTD region and function by blocking spike protein interaction with the host receptor DPP4 47, 48 . In the monkey study, researchers found that rhesus macaques infected with SARS-CoV-2 through the intratracheal route had mild illness, and their lungs showed signs of pneumonia similar to those in humans with COVID-19 58 . doi = 10.1093/abt/tbaa007 id = cord-256146-d599uera author = Kuiken, Thijs title = Newly discovered coronavirus as the primary cause of severe acute respiratory syndrome date = 2003-07-26 keywords = CoV; PCR; SARS; macaque summary = METHODS: We tested clinical and postmortem samples from 436 SARS patients in six countries for infection with SARSCoV, human metapneumovirus, and other respiratory pathogens. SARS-CoV was detected in pneumonic areas by virus isolation and RT-PCR, and was localised to alveolar epithelial cells and syncytia by immunohistochemistry and transmission electron microscopy. . Serial dilutions of the SARS-CoV virus stock and SARS-CoV-infected Vero cells from patient 5688 were made and tested with the NP and polymerase-specific RT-PCRs. Samples from the respiratory tract (nasal swabs, pharyngeal swabs, postmortem trachea, and lung samples) were also monitored for influenza A and B virus, respiratory syncytial virus A and B, rhinovirus, coronavirus (OC43 and 229E), and human metapneumovirus with use of essentially the same RT-PCR methods but with specific primers. Virological examinations of nasal and pharyngeal swabs, and tracheal and lung samples from all four macaques by RT-PCR for influenza A and B virus, respiratory syncytial virus A and B, rhinovirus, coronavirus (OC43 and 229E) and human metapneumovirus were negative. doi = 10.1016/s0140-6736(03)13967-0 id = cord-353392-rqeultbq author = Kumar, Govindarajan Venkat title = A short review on antibody therapy for COVID-19 date = 2020-04-20 keywords = CoV-2; SARS summary = Abstract The beginning of the novel SARS-CoV-2 human coronavirus in Wuhan, China, has triggered a worldwide respiratory disease outbreak (COVID-19). The third outbreak of severe illness caused by the novel SARS-CoV-2 coronavirus (COVID-19) that emerged in the Wuhan city, China, is pandemic and spread to more than 200 countries [5, 6, 7] . Based on the previous studies and reports in treating other coronaviruses such as SARS and MERS, the early administration of convalescent plasma from patients that contains raised antibodies can possibly reduce the spreading of infection and mortality [19, 20, 21, 22] . reported that the convalescent plasma transfusion may be beneficial in the treatment of critically ill patients with SARS-CoV-2 infections. After getting approval from the ethical committee, Shenzhen, Third People''s Hospital, they administrated convalescent plasma containing neutralizing antibodies to 5 critically ill patients with SARS-CoV-2. doi = 10.1016/j.nmni.2020.100682 id = cord-275565-xerr4vki author = Kumar, Manish title = Decay of SARS-CoV-2 RNA along the wastewater treatment outfitted with Upflow Anaerobic Sludge Blanket (UASB) system evaluated through two sample concentration techniques date = 2020-09-15 keywords = CoV-2; RNA; SARS summary = For the first time, we present, i) an account of decay in the genetic material loading of SARS-CoV-2 during Upflow Anaerobic Sludge Blanket (UASB) treatment of wastewater, and ii) comparative evaluation of polyethylene glycol (PEG), and filtration as virus concentration methods from wastewater for the quantification of SARS-CoV-2 genes. Thus, there still remains questions pertaining to: i) capability of conventional WWTPs to reduce the abundance of SARS-CoV-2 RNA, ii) better understanding of the protocol, virus J o u r n a l P r e -p r o o f Journal Pre-proof precipitation through PEG and filtration which one is better methods for concentrating the samples before RNA isolation. Appraising the genetic loading reduction through Upflow Anaerobic Sludge Blanket (UASB) systems, and iii) Comparing the performances between PEG and filtration as virus concentration methods in terms of SARS-CoV-2 RNA sensitivity and inhibition removal. doi = 10.1016/j.scitotenv.2020.142329 id = cord-296986-8fuj072z author = Kumar, Manish title = A chronicle of SARS-CoV-2: Part-I - Epidemiology, diagnosis, prognosis, transmission and treatment date = 2020-05-15 keywords = COVID-19; China; CoV-2; SARS summary = The review explicitly covers the aspects like genome and pedigree of SARS-CoV-2; epidemiology, prognosis, pathogenesis, symptoms and diagnosis of COVID-19 in order to catalog the right information on transmission route, and influence of environmental factors on virus transmissions, for the robust understanding of right strategical steps for proper COVID-19 management. We have explicitly highlighted several useful information and facts like: i) No established relationship between progression of SARS-CoV-2 with temperature, humidity and/or both, ii) The underlying mechanism of SARS-CoV-2 is not fully understood, iii) Respiratory droplet size determines drop and airborne-based transmission, iv) Prognosis of COVID-19 can be done by its effects on various body organs, v) Infection can be stopped by restricting the binding of S protein and AE2, vi) Hydroxychloroquine is believed to be better than chloroquine for COVID-19, vii) Ivermectin with Vero-hSLAM cells is able to reduce infection by ~5000 time within 2 days, and viii) Nafamostat mesylate can inhibit SARS-CoV-2 S protein-initiated membrane fusion. Outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): increased transmission beyond China-fourth update doi = 10.1016/j.scitotenv.2020.139278 id = cord-320935-3n157yl4 author = Kumar, Manish title = Making Waves Perspectives of Modelling and Monitoring of SARS-CoV-2 in Aquatic Environment for COVID-19 Pandemic date = 2020-09-12 keywords = COVID-19; CoV-2; RNA; SARS; virus summary = This paper aims to collate information on recent developments on WBE in monitoring the trend of community-scale SARS-CoV-2 prevalence as well as models to predict virus spread and transmission among populations. While several studies have identified the presence of SARS-CoV-2 in the faecal matter of corona-infected patients [35, 36] , there is a growing concern on the transmission of the virus through water treatment plants (WTPs) and WWTPs. Several studies also detected the genetic material of the virus in raw wastewater across the globe [22, 26, 27] . These studies provided enough excellent reasons for modelling the spread of 2019-nCoV with the external environmental conditions, assuming that the cases of infection will decrease through secondary infection routes due to the inactivation of the virus on different surfaces; however, the possibility of transmission via direct contact remains unchanged. doi = 10.1007/s40726-020-00161-5 id = cord-252389-xrdbmosj author = Kumar, Mukesh title = Neurological manifestations and comorbidity associated with COVID-19: an overview date = 2020-10-14 keywords = CNS; COVID-19; CoV-2; SARS summary = In this article, we have reviewed the neurological characteristic features of COVID-19 patients, latent neurotropic mechanisms of SARS-CoV-2 involvement in the comorbidity associated with CNS disorders, and neurological manifestations associated with COVID-19. Therefore, exploring the neurologic manifestations associated with COVID-19 is urgently required for better understanding the SARS-CoV-2 brain infections, inhibiting the additional spread and treating patients affected by this pandemic. The neuronal cells infected with virus, immune systems (microphase, T cells, and monocytes) triggered, and inflammatory system activated leads to cytokine storm, oxidative stress, and associated neurological manifestations neuroinvasiveness of SARS-CoV-2 [11, 35] . In a recent review [51] , authors have categorized the reported neurological findings related to COVID-19 into three categories: a) Central (headache, dizziness, impaired consciousness, acute cerebrovascular disease, ataxia, seizures, and special senses) b) Peripheral (hypogeusia, hyposmia) c) Musculoskeletal (ischemic or hemorrhagic) Apart from the above, increasing evidence indicated that coronaviruses may invade the CNS, causing neurological disorders. doi = 10.1007/s10072-020-04823-6 id = cord-311214-eqwxkwqa author = Kumar, Roshan title = Comparative Genomic Analysis of Rapidly Evolving SARS-CoV-2 Viruses Reveal Mosaic Pattern of Phylogeographical Distribution date = 2020-04-16 keywords = CoV-2; SARS; USA summary = Through the construction of SARS-CoV-2-human interactome, we further revealed that multiple host proteins (PHB, PPP1CA, TGF-β, SOCS3, STAT3, JAK1/2, SMAD3, BCL2, CAV1 & SPECC1) are manipulated by the viral proteins (nsp2, PL-PRO, N-protein, ORF7a, M-S-ORF3a complex, nsp7-nsp8-nsp9-RdRp complex) for mediating host immune evasion. A manually annotated reference database was generated using the Genbank 128 file of Severe acute respiratory syndrome coronavirus 2 isolate-SARS-CoV-129 2/SH01/human/2020/CHN (Accession number: MT121215) and open reading frames (ORFs) 130 were predicted against the formatted database using prokka (-gcode 1) [22] . All these isolates 189 were found to harbor 9 open reading frames coding for ORF1a (13218 bp) and ORF1b (7788 190 bp) polyproteins, surface glycoprotein or S-protein (3822 bp), ORF3a protein (828 bp Our analysis revealed that strains of human infecting SARS-CoV-2 are novel and highly 201 identical (>99.9%). In this study, the analysis was 358 performed on the genomes of the novel SARS-CoV-2 isolates recently reported from different 359 countries to understand viral pathogenesis. doi = 10.1101/2020.03.25.006213 id = cord-277841-7sp8ftbc author = Kumari, Pratibha title = Potential diagnostics and therapeutic approaches in COVID-19 date = 2020-08-12 keywords = COVID-19; CoV-2; RNA; SARS; detection summary = Molecular diagnostic tests target the detection of any of the following markers such as the specific region of the viral genome, certain enzyme, RNA-dependent RNA polymerase, the structural proteins such as surface spike glycoprotein, nucleocapsid protein, envelope protein, or membrane protein of SARS-CoV-2. COVID-19 is a contagious disease, caused by a novel severe acute respiratory syndrome Coronavirus (SARS-CoV-2). In this article, we evaluated literature for reports informing various diagnostic methods, potential antiviral chemical therapeutics, and effective treatment strategies towards clinical management of COVID-19 patients. Molecular diagnostic methods target to detect either specific regions of the viral genome or RNA-dependent RNA polymerase (RdRP) and/or structural proteins of SARS-CoV-2 (Table 1) . Like most immunological diagnostic protocols, Enzyme-Linked Immunosorbent Assay (ELISA) for COVID-19 detection uses IgM and IgG antibody against nucleocapsid (N) and receptor binding domain spike proteins (S) of SARS-CoV-2. Table 2: Primers and probes for targeting SARS-Cov-2 genes in an RT-PCR test for COVID-19 diagnosis. doi = 10.1016/j.cca.2020.08.013 id = cord-293578-yu2i0u2h author = Kusadasi, Nuray title = A Pathophysiological Perspective on the SARS-CoV-2 Coagulopathy date = 2020-08-10 keywords = CoV-2; FXII; SARS summary = The potential role of plasma kallikrein in case of SARS-CoV-2 infection may be summarized as (1) the activation of FXII with the end-product thrombin (coagulation system) (2) the generation of bradykinin with subsequent vascular permeability and leakage (kallikrein-kinin system), (3) the activation of the renin-angiotensin system through conversion of renin from pre-renin leading to a pro-inflammatory state through increased angiotensin 1 receptor activation and (4) the activation of C5, in part through activation of C1 via FXII and in part through activation of C3 via plasmin (complement system). 54, 55 Since prekallikrein is seen as a potential regulator in the fibrin clot formation through FXII activation and is involved in the pathogenesis of thrombosis, there might be an important role for controlling the hypercoagulable state of the patients infected with SARS-CoV-2 as a therapeutic target. Taken together, all these mechanisms may contribute to the complex hypercoagulable state of the critically ill patients infected with SARS-CoV-2 having severe hypoxia and ongoing endothelial activation. doi = 10.1097/hs9.0000000000000457 id = cord-104500-m0kfom0x author = Kyriakopoulos, Anthony M. title = The Potential Role of Super Spread Events in SARS-COV-2 Pandemic; a Narrative Review date = 2020-09-21 keywords = COV-2; COVID-19; Coronavirus; MERS; SARS; SSE summary = A comprehensive search was conducted among literature available in multiple electronic sources to find articles that addressed the "potential role of SSEs on severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) pandemic" and were published before 20(th) of August 2020. Specific screening strategies within potential super spreading host groups can also help to efficiently manage severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) epidemics, in contrast to the partially effective general restriction measures. However, the respective potential impact of SSEs on SARS-COV-2 outbreak is composed and presented in the current review, thereby implying the warranted effort required for effective SSE preventive strategies, which may lead to overt global community health benefits. Following this initial selection stage, further screening was performed by all reviewers, using the previously described search items to identify parameters determining the global impact of COVID-19 due to SSEs. Identified parameters included the global impact of immunity and vaccination, the holy cup and religion transmission, and the austerity caused by COVID-19 and other coronavirus epidemics due to restrictions applied. doi = nan id = cord-332080-923jpec0 author = Lai, Chih-Cheng title = In vitro diagnostics of coronavirus disease 2019: technologies and application date = 2020-06-05 keywords = CoV-2; SARS summary = Abstract Laboratory-based diagnostic measures including virological and serological tests are essential for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, serological tests cannot confirm SARS-CoV-2, and results will be false-negative when antibody concentrations fall below detection limits. (Hangzhou Bigfish Bio-tech Co., Ltd., Zhejiang, China) was recently registered 127 as a CE-IVD for detecting SARS-CoV-2 ORF-1ab and N genes in 128 nasopharyngeal swabs, sputum, and BAL fluids. The 145 performance of the Xpress SARS-CoV-2 test was clinically evaluated in 146 patients with respiratory illnesses from whom contrived nasopharyngeal swab 147 samples were collected into viral transport media. Serological tests that can detect SARS-CoV-2 IgG-IgM antibodies are simpler 248 than rRT-PCR, and do not require complicated equipment and protocols 249 (Table 3) . During the previous SARS 251 epidemic, the IgM antibody was the first line of defense during viral infections 252 and was detectable in blood samples from patients after 3 -6 days. Dynamics of 617 anti-SARS-Cov-2 IgM and IgG antibodies among COVID-19 patients doi = 10.1016/j.jmii.2020.05.016 id = cord-267782-4pjfnund author = Lan, Fan-Yun title = Association between SARS-CoV-2 infection, exposure risk and mental health among a cohort of essential retail workers in the USA date = 2020-10-30 keywords = COVID-19; CoV-2; SARS summary = doi = 10.1136/oemed-2020-106774 id = cord-326017-qw4qynqv author = Laskar, Partha title = “Tomorrow Never Dies”: Recent Advances in Diagnosis, Treatment, and Prevention Modalities against Coronavirus (COVID-19) amid Controversies date = 2020-08-06 keywords = COVID-19; China; CoV-2; Coronavirus; PCR; RNA; SARS; disease; patient summary = Considering this, we have summarized diverse research areas covering the current known biological properties of SARS-CoV-2, diagnostic tools for detection, therapeutic measurements for possible treatment, and prevention techniques to stop further spreading of this pandemic. Considering this, we have summarized diverse research areas covering the current known biological properties of SARS-CoV-2, diagnostic tools for detection, therapeutic measurements for possible treatment, and prevention techniques to stop further spreading of this pandemic. Overall, real-time RT-PCR based method enables developing a high-throughput testing for rapid, on-demand, low-cost, reliable, quantitative detection technique against COVID-19 in clinical settings [39] . Another newly developed method, SARS-CoV-2 DNA Endonuclease-Targeted CRISPR Trans Reporter (DETECTR), was found to perform simultaneous reverse transcription and isothermal amplification by (i) RT-LAMP for RNA extracted (for nasopharyngeal or oropharyngeal swabs), (ii) Cas12 detection of predefined coronavirus sequences, and (iii) cleavage of a reporter molecule confirms, which detects the virus [56] . doi = 10.3390/diseases8030030 id = cord-270533-s2d3q4ob author = Lau, Yu-Lung title = SARS: future research and vaccine date = 2004-11-05 keywords = CoV; SARS; severe summary = Severe acute respiratory syndrome (SARS), a newly emerged infectious disease of humans in the 21st century, appeared in Guangdong Province in Southern China in November 2002 and spread to 26 countries on five continents along international air travel routes, causing large scale outbreaks in Hong Kong, Singapore and Toronto in early 2003. This novel CoV has satisfied Koch''s postulates for causation by its consistent isolation from SARS patients, viral isolation, reproduction of disease in non-human primates after inoculation and the presence of specific antibody response against the virus in both patients and experimentally infected primates 8 . Indeed, sporadic reemergence of cases have been reported in Guangdong Province as well as from research laboratories Summary Severe acute respiratory syndrome (SARS) is a new infectious disease of the 21st century that has pandemic potential. The high morbidity and mortality of this potentially pandemic infection demands a rapid research response to develop effective antiviral treatment and vaccine. doi = 10.1016/j.prrv.2004.07.005 id = cord-296602-19noki6p author = Law, Helen KW title = Toll-like receptors, chemokine receptors and death receptor ligands responses in SARS coronavirus infected human monocyte derived dendritic cells date = 2009-06-08 keywords = CoV; SARS; TRAIL summary = In this study, we focussed on the gene expression of toll-like receptors (TLRs), chemokine receptors (CCRs) and death receptor ligands in SARS-CoV infected DCs. We also compared adult and cord blood (CB) DCs to find a possible explanation for the age-dependent severity of SARS. There was also strong induction of TNF-related apoptosis-inducing ligand (TRAIL), but not Fas ligand gene expression in SARS-CoV infected DCs. Interestingly, the expressions of most genes studied were higher in CB DCs than adult DCs. CONCLUSION: The upregulation of chemokines and CCRs may facilitate DC migration from the infection site to the lymph nodes, whereas the increase of TRAIL may induce lymphocyte apoptosis. Interestingly, the SARS-CoV infected DCs showed low expression of antiviral cytokines (IFN-α, IFN-β, IFN-γ and IL-12p40), moderate upregulation of proinflammatory cytokines (TNF-α and IL-6) but significant upregulation of inflammatory chemokines (macrophage inflammatory protein (MIP)-1α/CCL3, regulated upon activation, normal T cell expressed and secreted (RANTES)/CCL-5, interferon-inducible protein of 10 kD (IP-10)/CXCL10 and monocyte chemotactic protein (MCP)-1/CCL2. doi = 10.1186/1471-2172-10-35 id = cord-304418-k9owyolj author = Le Maréchal, M. title = COVID-19 in clinical practice: a narrative synthesis date = 2020-09-29 keywords = COVID-19; China; CoV-2; SARS; Wuhan; patient summary = Plasmatic detection of SARS-CoV-2 has been reported but only with low viral titers, and mainly in clinically severe cases [44] ; bloodstream infectivity has yet to be demonstrated. The first large clinical trial published on LPV/RTV on SARS-CoV-2 compared 99 patients receiving the antiviral vs 100 receiving SoC alone [124] ; there was no difference between the 2 groups regarding the primary end point (time to improvement) (15 vs 16 days, p=0.09). Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China Severity or Risk of Death in Patients with Hypertension Hospitalized for Coronavirus Disease 2019 (COVID-19) Infection in Wuhan, China doi = 10.1016/j.medmal.2020.09.012 id = cord-324557-4u8dja0n author = Leblanc, Jean‐François title = Risk of Transmission of Severe Acute Respiratory Syndrome Coronavirus‐2 by Transfusion: A Literature Review date = 2020-08-15 keywords = COVID-19; CoV-2; SARS summary = Complementary searches have identified reports demonstrating that the correlation between the presence of viral RNA in a biological sample and infectivity requires a minimal RNA load, which is rarely, if at all observed, in blood components. More specifically, PubMed was interrogated with a series of queries aimed at identifying references that relate to COVID-19/SARS-CoV-2 and the detection of viral genomic material in blood, plasma, or serum. From this screen, 23 references reporting any data or stating any information on the detection of SARS-CoV-2 genomic material in human blood, plasma, or serum, were selected ( Table 2) . An exhaustive search strategy led to the identification of 23 references reporting data on the detection of SARS-CoV-2 genomic material in blood components (Table 2) . doi = 10.1111/trf.16056 id = cord-279105-e2zjxjox author = Lee, Cheryl Yi-Pin title = Serological Approaches for COVID-19: Epidemiologic Perspective on Surveillance and Control date = 2020-04-24 keywords = CoV-2; SARS; antibody summary = With the limitations of qRT-PCR, immunoassays may offer another FIGURE 2 | Schematic illustration on the window period of detection for either viral RNA or antibodies in SARS-CoV-2-infected individuals. However, interestingly, one study demonstrated that longitudinal profiling of both antibodies in a population of 63 COVID-19 patients showed no specific chronological order in terms of IgM and IgG seroconversion (10) , which was also observed in patients infected with SARS-CoV and another human coronavirus, Middle East Respiratory Syndrome coronavirus (MERS-CoV) (22, 23) . These findings on SARS-CoV-2-specific antibodies seroconversion against the S viral protein suggest the importance to test for both IgM and IgG antibodies to confirm a positive infection. With the availability of immunoassays utilizing various coronavirus structural proteins, the use of more than one different antigen-based serological approach may be essential to establish a true positive SARS-CoV-2 infection. doi = 10.3389/fimmu.2020.00879 id = cord-265366-vmuqbpkk author = Leibowitz, Jill title = Comparison of Clinical and Epidemiologic Characteristics of Young Febrile Infants with and without SARS-CoV-2 Infection date = 2020-10-09 keywords = CoV-2; SARS; infant summary = 7, 8, 9, 10, 11, 12, 13 The largest case series to date describes 18 infants younger than 90 days of age who tested positive for SARS-CoV-2, 14 of whom were febrile. 9 The objective of this study was to compare the clinical and demographic characteristics and hospital course of febrile infants who presented to Cohen Children''s Medical Center (CCMC) during March and April of 2020, the time period of peak COVID-19 incidence in our region, to febrile infants treated in CCMC during March and April of previous years. The key findings of our study are that during the peak of the COVID-19 pandemic in New York, SARS-CoV-2 was the predominant pathogen identified among febrile infants younger than 57 days of age, and the disease was self-limited in all infants with COVID-19. 26 Infants with COVID-19 presented with lethargy and feeding difficulty more with SARS-CoV-2 infection among infants younger than 90 days of age. doi = 10.1016/j.jpeds.2020.10.002 id = cord-346777-zmmnn9b2 author = Lester, Sandra title = Middle East respiratory coronavirus (MERS-CoV) spike (S) protein vesicular stomatitis virus pseudoparticle neutralization assays offer a reliable alternative to the conventional neutralization assay in human seroepidemiological studies date = 2019-09-11 keywords = CoV; MERS; VSV summary = title: Middle East respiratory coronavirus (MERS-CoV) spike (S) protein vesicular stomatitis virus pseudoparticle neutralization assays offer a reliable alternative to the conventional neutralization assay in human seroepidemiological studies The present work describes the generation and validation of S protein-bearing vesicular stomatitis virus (VSV) pseudotype particles (VSV-MERS-CoV-S) in which the VSV glycoprotein G gene has been replaced by the luciferase reporter gene, followed by the establishment of a pseudoparticle-based neutralization test to detect MERS-CoV neutralizing antibodies under BSL-2 conditions. These results demonstrate that the MERS-CoV-S protein pseudotyped VSV particle-based neutralization assay would serve as a safe, reliable and highly specific alternative method to detect MERS-CoV neutralizing antibodies to be used for future sero-epidemiological studies. A laboratory-confirmed SARS-CoV patient serum sample and a panel of human sera with confirmed high neutralizing antibody titres to human coronaviruses 229E, HKU1, OC43 and NL63 were used in this study to evaluate the VSV-MERS-CoV-S particle-based neutralization assay for potential cross-neutralization. doi = 10.1099/acmi.0.000057 id = cord-338205-sy91rnse author = Li, Chenxi title = Laboratory Diagnosis of Coronavirus Disease-2019 (COVID-19) date = 2020-07-02 keywords = COVID-19; CoV-2; PCR; SARS summary = With limited understanding of COVID-19, it is difficult to exclude SARS-CoV-2 infection based on a single negative PCR result, especially when testing was used for upper respiratory tract specimens. The study found that SARS-CoV-2 could be detected in all primer-probe sets applied in the qRT-PCR tests, but significant discrepancy was observed in the detection limit and the ability to identify negatives and positives with a lower viral load. Compared with the qRT-PCR kit, nested RT-PCR analysis showed higher sensitivity and specificity, indicating that it is more suitable for clinical application to detect SARS-CoV-2 in cases with low viral load. In cases where RT-PCR assays are negative and there is a strong epidemiological link to SARS-CoV-2 infection, paired serum samples (in the acute and convalescent-phase) could support diagnosis once validated serology tests are available with the initial samples collected in the first week of COVID-19 and the second collected after 2-4 weeks [28] . doi = 10.1016/j.cca.2020.06.045 id = cord-341254-xnj6slby author = Li, Hua title = A new and rapid approach for detecting COVID‐19 based on S1 protein fragments date = 2020-06-05 keywords = CoV-2; SARS summary = Based on it, the detection of IgM/IgG in blood became an optional approach to improve the diagnosis, especially for the COVID-19 patient with negative nucleic acid test result. 2. Colloidal gold-labeled mouse-antihuman lgM/lgG antibody was manufactured by SAIYA Hebei Biotechnology Co., Ltd. To obtain the well-performance antibody, the antibody was selected for functional test including the positive and negative coincidence rates, minimum test threshold, and accelerated stability. Due to only around 50% positive rate of SARS-CoV-2 nucleic acid test 8, 12 under various condition of sample collection and storage, viral infection regions, RNA extraction methods, the quality of nucleic acid detection kit, and so on, 13 detection of IgM/IgG became a powerful approach for the early diagnosis of COVID-19 and could help identify the patients with negative nucleic acid but with obvious clinical symptoms. Development and clinical application of a rapid IgM-IgG combined antibody test for SARS-CoV-2 infection diagnosis doi = 10.1002/ctm2.90 id = cord-298067-awo3smgp author = Li, Huanjie title = Transmission Routes Analysis of SARS-CoV-2: A Systematic Review and Case Report date = 2020-07-10 keywords = CoV-2; Jinan; SARS; patient summary = Through associating infection symptoms with the transmission routes of virus and the patient course of the disease, we expect to provide guidelines for clinical diagnosis and the basis for suppressing the spread of the virus and antiviral treatment. On February 1, 2020, respiratory samples of four patients were confirmed SARS-CoV-2 infections by real-time PCR in Jinan Central Hospital, Shandong province, China. Summarizing the published articles, including SARS-CoV and SARS-CoV-2, we combined with epidemiological and clinical data to analyze the possible routes of asymptomatic patients with virus infection in order to provide the basis for suppressing the spread of the virus, and antiviral treatment and advice for the protection of medical staff. The study found that the detection of SARS-CoV-2 nucleic acid positive in a few feces of patients with confirmed COVID-19 cases indicated the presence of a live virus. doi = 10.3389/fcell.2020.00618 id = cord-029547-9ei1ram3 author = Li, Jingwei title = The epidemiology and therapeutic options for the COVID-19 date = 2020-05-28 keywords = COVID-19; China; CoV-2; SARS; clinical; patient summary = According to the Diagnosis and Treatment Program of Novel Coronavirus Pneumonia, only a suspected case has one of the pieces of evidence of etiology or serology, such as positive nucleic acid, confirmation of gene sequencing, and virus specific antibody, to be confirmed to be COVID-19 patient, 55 and the suspected cases were identified by a comprehensive analysis of epidemiological history and clinical manifestations. 64 There have been tens of clinical trials to confirm the safety and efficiency of chloroquine in treating COVID-19 patients, and its mechanism can be described as interfering with the glycosylation of ACE2 or alkalizing the phagolysosome to inhibit viral replication, 65, 66 which prevents the SARS-Cov-2 entering the host cells. Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a randomized clinical trial doi = 10.1093/pcmedi/pbaa017 id = cord-253905-zknmfgsh author = Li, Xingguang title = Evolutionary history, potential intermediate animal host, and cross‐species analyses of SARS‐CoV‐2 date = 2020-03-11 keywords = CoV-2; SARS; figure summary = To investigate the evolutionary history of the recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in China, a total of 70 genomes of virus strains from China and elsewhere with sampling dates between 24 December 2019 and 3 February 2020 were analyzed. Homology plot analysis of "dataset_6" also revealed that BetaCoV/bat/Yunnan/ RaTG13/2013 was more similar to the SARS-CoV-2 virus than the coronavirus obtained from the two pangolin samples (SRR10168377 and SRR10168378), consistent with phylogenetic analysis ( Figure S5 ). 46, 47 Bayesian analyses with the tip-dating method using a strict clock as well as constant size coalescent tree prior indicated that SARS-CoV-2 is evolving at a rate of 1.24 × 10 −3 substitutions per site per year (Table 1 ), in accordance with our prior research 46, 47 and similar to that found for other human F I G U R E 4 Estimated maximum-clade-credibility tree of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using tip-dating method. doi = 10.1002/jmv.25731 id = cord-312664-tgpaidhp author = Liang, Julia title = Interaction of the prototypical α-ketoamide inhibitor with the SARS-CoV-2 main protease active site in silico: Molecular dynamic simulations highlight the stability of the ligand-protein complex date = 2020-05-28 keywords = CoV-2; SARS summary = title: Interaction of the prototypical α-ketoamide inhibitor with the SARS-CoV-2 main protease active site in silico: Molecular dynamic simulations highlight the stability of the ligand-protein complex The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes an illness known as COVID-19, which has been declared a global pandemic with over 2 million confirmed cases and 137,000 deaths in 185 countries and regions at the time of writing (16 April 2020), over a quarter of these cases being in the United States. Further, molecular dynamics simulations highlight the stability of the interaction of the α-ketoamide 13b ligand with the SARS-CoV-2 M(pro) (ΔG = -25.2 and -22.3 kcal/mol for protomers A and B). Here, we performed molecular docking and molecular dynamics simulations to further characterize the interaction of α-ketoamide 13b with the active site of the SARS-CoV-2 M pro . Here, we performed molecular docking and molecular dynamics simulations to further characterize the interaction of α-ketoamide 13b with the active site of the SARS-CoV-2 M pro . doi = 10.1016/j.compbiolchem.2020.107292 id = cord-274834-24v2b509 author = Lima, Rosiane title = Establishment of a pediatric COVID-19 biorepository: unique considerations and opportunities for studying the impact of the COVID-19 pandemic on children date = 2020-09-11 keywords = COVID-19; CoV-2; MIS; SARS; child summary = Although the impact of SARS-CoV-2 infection in children is less clinically apparent, collecting high-quality biospecimens from infants, children, and adolescents in a standardized manner during the COVID-19 pandemic is essential to establish a biologic understanding of the disease in the pediatric population. METHODS: A COVID-19 biospecimen collection study was implemented with strategic enrollment guidelines to include patients seen in urgent care clinics and hospital settings, neonates born to SARS-CoV-2 infected mothers, and asymptomatic children. Specific questions that must be addressed revolve around the role children play in viral transmission, differences in pediatric viral susceptibility and immune responses, which could guide potential therapies for adults, the impact of maternal SARS-CoV-2 infection on fetal development, and factors driving the development of severe hyperinflammatory shock and cardiac damage seen in Multisystem Inflammatory Syndrome in Children (MIS-C). In order to capture the full range of SARS-CoV-2 infection in the pediatric population, a COVID-19 biospecimen collection study was designed and implemented, including patients seen in urgent care clinics and hospital settings, neonates born to SARS-CoV-2-infected mothers, and asymptomatic children. doi = 10.1186/s12874-020-01110-y id = cord-276630-qci7khki author = Lima, William Gustavo title = The potential of drug repositioning as a short-term strategy for the control and treatment of COVID-19 (SARS-CoV-2): a systematic review date = 2020-06-08 keywords = COVID-19; CoV-2; SARS summary = Due to the evidence of the anti-SARS-CoV-2 activity of various clinically available agents, drug repositioning stands out as a promising strategy for a short-term response in the fight against the novel coronavirus. Only seven drugs (chloroquine, tetrandrine, umifenovir (arbidol), carrimycin, Table 1 Clinical evidence of potential candidates for drug repositioning against COVID-19 (SARS-CoV-2) *Lopinavir (400 mg) + ritonavir (100 mg), q12h, orally; associated with umifenovir (200 mg), q12h, orally. [14] reported that the use of arbidol in combination with lopinavir/ritonavir inhibits the aggravation of pneumonia caused by SARS-CoV-2 and promotes a virus-negative conversion in patients from China. Of these, only six drugs (lopinavir/ritonavir, umifenovir (arbidol), remdesivir, chloroquine, and hydroxychloroquine) have shown promising results in preclinical trials and have clinically lessened the symptoms of COVID-19. Although lopinavir/ ritonavir had low anti-SARS-CoV-2 activity, arbidol, remdesivir, and chloroquine/hydroxychloroquine showed promising effects against this coronavirus. doi = 10.1007/s00705-020-04693-5 id = cord-272603-nbosceoz author = Lin, Qiuyuan title = Microfluidic Immunoassays for Sensitive and Simultaneous Detection of IgG/IgM/Antigen of SARS-CoV-2 within 15 min date = 2020-07-02 keywords = CoV-2; SARS summary = Facing the emergence of this pandemic, we established a portable microfluidic immunoassay system for easy-to-use, sensitive, rapid (<15 min), multiple, and on-site detection of IgG/IgM/Antigen of SARS-CoV-2 simultaneously. This integrated method was successfully applied for detecting SARS-CoV-2 IgM and IgG antibodies in clinical human serum as well as SARS-CoV-2 antigen in pharyngeal swabs from 26 patients with COVID-19 infection and 28 uninfected people. 26 To meet the challenge of the large epidemic, we describe the development of a point-of-care microfluidic platform integrating a homemade fluorescence detection analyzer ( Figure 1A ), SARS-CoV-2 diagnostic microchips ( Figure 1B) , and multiple immunoassays ( Figure 1C ) for detecting three biomarkers (IgG, IgM, and antigen). This robust microfluidic immunoassay system can provide a useful tool for SARS-CoV-2 diagnosis in public health laboratories as well as for timely screening potentially infected patients to monitor and prevent the epidemic owning to its capability of easy, fast, cost-effective, and point-of-care detection. doi = 10.1021/acs.analchem.0c01635 id = cord-270116-r2rnnsfh author = Lippi, Giuseppe title = Current laboratory diagnostics of coronavirus disease 2019 (COVID-19) date = 2020-05-11 keywords = COVID-19; CoV-2; SARS summary = As concerns serological testing, promising information can be garnered from preliminary investigations, showing that the vast majority of COVID-19 patients seem to develop a sustained immune response against the virus, characterized especially by emergence of anti-SARS-CoV-2 IgG and IgA, 1 to 2 weeks after the onset of fever and/or respiratory symptoms. Recent studies have also been published on the possibility to use rapid reverse transcription loop-mediated isothermal amplification (RT-LAMP) assays for SARS-CoV-2 detection, but additional evidence is needed at this point in time for validating their routine usage in COVID-19 diagnostics (38, 39) . As concerns serological testing, promising information can be garnered from preliminary investigations, showing that the vast majority of COVID-19 patients seem to develop a sustained immune response against the virus, characterized by emergence of anti-SARS-CoV-2 IgG and IgA, 1 to 2 weeks after the onset of fever and/or respiratory symptoms. doi = 10.23750/abm.v91i2.9548 id = cord-334773-yw2qgv13 author = Lisco, Giuseppe title = Hypothesized mechanisms explaining poor prognosis in type 2 diabetes patients with COVID-19: a review date = 2020-08-10 keywords = COVID-19; CoV-2; SARS; clinical; diabetes; patient summary = This concern has been further confirmed by the results of a cohort study among 85 fatal cases of COVID-19 in Wuhan, hence defining DM as a potentially harmful comorbidity predisposing to worse clinical course or death once SARS-CoV-2 infection occurred [49] . Different hypothesis should be considered for explaining this clinical phenomenon, including glucose control at baseline and during the infection course, pathophysiology and immune system response in SARS-CoV-2 infected patients with T2D, diabetes-related comorbidities and concomitant medications. In conclusion, diabetic patients especially elderly individuals and those with worse baseline glucose control may exhibit immune system dysregulation that predispose them to a less effective response against SARS-CoV-2 and to a dysfunctional inflammation that requires to be carefully monitored in confirmed cases of COVID-19, for preventing or avoiding a harmful progression of the disease. Immune response and systemic inflammation play a crucial role in SARS-CoV-2 infection, particularly in case of severe clinical course of the disease. doi = 10.1007/s12020-020-02444-9 id = cord-345371-pjbviagq author = Lisi, Lucia title = Approaching Coronavirus Disease 2019: mechanisms of action of repurposed drugs with potential activity against SARS-CoV-2 date = 2020-07-23 keywords = ACE2; COVID-19; CoV-2; RNA; SARS; clinical; patient; severe summary = The rationale for drug selection was mainly, though not exclusively, based either i) on the activity against other coronaviruses or RNA viruses in order to potentially hamper viral entry and replication in the epithelial cells of the airways, and/or ii) on the ability to modulate the excessive inflammatory reaction deriving from dysregulated host immune responses against the SARS-CoV-2. Here, we review the recently published literature on the pharmacological treatments used so far and/or undergoing evaluation in clinical trials, with focus on the biochemical mechanisms of action of repurposed or investigational drugs, classified as agents directly targeting the virus ( Figure 1 and Table 1 ) and those used to treat the respiratory distress and inflammation associated with the cytokine release syndrome ( Figure 2 and Table 2 ). doi = 10.1016/j.bcp.2020.114169 id = cord-277253-vy0mvzeb author = Liu, Hongbo title = Scutellaria baicalensis extract and baicalein inhibit replication of SARS-CoV-2 and its 3C-like protease in vitro date = 2020-04-11 keywords = CoV-2; SARS summary = title: Scutellaria baicalensis extract and baicalein inhibit replication of SARS-CoV-2 and its 3C-like protease in vitro We further identified four baicalein analogue compounds from other herbs that inhibit SARS-CoV-2 3CLpro activity at microM concentration. baicalensis has effective anti-SARS-CoV-2 activity and baicalein and analogue compounds are strong SARS-CoV-2 3CLpro inhibitors. Inspired by the previous studies, several covalent inhibitors were experimentally identified to inhibit the 3CL pro activity and viral replication of SARS-CoV-2, and some of the complex crystal structures were solved [14, 15] . baicalensis inhibits SARS-CoV-2 3CL pro activity and the most active ingredient baicalein exhibits an IC50 of 0.39 M. We also identified four baicalein analogue compounds from other herbs that inhibit SARS-CoV-2 3CL pro activity at microM concentration. baicalensis and tested its inhibitory activity against SARS-CoV-2 3CL pro . baicalensis extract at different concentrations on SARS-CoV-2 3CL pro activity were 6 shown in Figure 1A . doi = 10.1101/2020.04.10.035824 id = cord-353484-q7d0ysbo author = Liu, Xue title = COVID-19: Progress in diagnostics, therapy and vaccination date = 2020-06-19 keywords = COVID-19; CoV-2; Coronavirus; RNA; SARS; patient summary = Given the urgency of the outbreak, we focus here on recent advances in the diagnostics, treatment, and vaccine development for SARS-CoV-2 infection, helping to guide strategies to address the current COVID-19 pandemic. Another type of rapid diagnostic test (RDT) that detects the presence of viral antigens expressed by SARS-CoV-2 virus in a respiratory tract sample is of low complexity and may provide results typically within 30 minutes [68, 69] . Studies in Vero E6 cells have suggested that favipiravir can cripple the SARS-CoV-2 virus (EC50 = 61.88 μM) [88] , and patients with COVID-19 are being recruited in randomized trials to evaluate the efficacy of favipiravir plus other antivirals (e.g., ClinicalTrials.gov: ChiCTR2000029600, ChiCTR2000029544). As no specific therapeutic agents or vaccines are available for COVID-19, this therapy is the only strategy that is immediately available for use to prevent and treat a novel, emerging infectious disease such as SARS-CoV-2 infection [121, 122] . doi = 10.7150/thno.47987 id = cord-319194-ukuia48s author = Liò, Pietro title = Phylogenomics and bioinformatics of SARS-CoV date = 2004-02-04 keywords = CoV; RNA; SARS; s1b summary = Tracing the history of molecular changes in coronaviruses using phylogenetic methods can provide powerful insights into the patterns of modification to sequences that underlie alteration to selective pressure and molecular function in the SARS-CoV (severe acute respiratory syndrome coronavirus) genome. Tracing the history of molecular changes in coronaviruses using phylogenetic methods can provide powerful insights into the patterns of modification to sequences that underlie alteration to selective pressure and molecular function in the SARS-CoV (severe acute respiratory syndrome coronavirus) genome. Figure 1 shows the maximum likelihood tree produced using a set of homologous replicases from five SARS-CoV strains, 12 other coronaviruses representing both groups 1 and 2 of the genus [2, 3] , one torovirus (Breda virus) and one okavirus [yellow head (YH) virus], which were determined to most closely represent the consensus coronavirus sequence by a PSI-Blast search [12] . doi = 10.1016/j.tim.2004.01.005 id = cord-266987-ikt8r2o1 author = Loeffelholz, Michael J. title = Laboratory diagnosis of emerging human coronavirus infections – the state of the art date = 2020-03-30 keywords = China; CoV-2; MERS; SARS summary = doi = 10.1080/22221751.2020.1745095 id = cord-263481-w5ytp1q7 author = Lokman, Syed Mohammad title = Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: A computational biology approach date = 2020-06-02 keywords = CoV-2; RBD; SARS summary = MERS-CoV uses dipeptidyl peptidase-4 (DPP4) as entry receptor [11] whereas SARS-CoV and SARS-CoV-2 utilize ACE-2 (angiotensin converting enzyme-2) [12] , abundantly available in lung alveolar epithelial cells and enterocytes, suggesting S glycoprotein as a potential drug target to halt the entry of SARS-with remarkable properties like glutamine-rich 42 aa long exclusive molecular signature (DSQQTVGQQDGSEDNQTTTIQTIVEVQPQLEMELTPVVQTIE) in position 983-1024 of polyprotein 1ab (pp1ab) [16] , diversified receptor-binding domain (RBD), unique furin cleavage site (PRRAR↓SV) at S1/S2 boundary in S glycoprotein which could play roles in viral pathogenesis, diagnosis and treatment [17] . There is growing evidence that spike protein, a 1273 amino acid long glycoprotein having multiple domains, possibly plays a major role in SARS-CoV-2 pathogenesis. In this study, we have analyzed 320 genomic sequences of SARS-CoV-2 to identify mutations between the available genomes followed by the amino acid variations in the glycoprotein S to foresee their impact on the viral entry to host cell from structural biology viewpoint. doi = 10.1016/j.meegid.2020.104389 id = cord-343517-vf32wxkx author = Lokman, Syed Mohammad title = Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: a computational biology approach date = 2020-04-11 keywords = CoV-2; SARS; spike summary = However, SARS-CoV-2 has emerged with remarkable properties like glutamine-rich 42 aa long exclusive molecular signature (DSQQTVGQQDGSEDNQTTTIQTIVEVQPQLEMELTPVVQTIE) in position 983-1024 of polyprotein 1ab (pp1ab) [16] , diversified receptor-binding domain (RBD), unique furin cleavage site (PRRAR↓SV) at S1/S2 boundary in S glycoprotein which could play roles in viral pathogenesis, diagnosis and treatment [17] . There is growing evidence that spike protein, a 1273 amino acid long glycoprotein having multiple domains, possibly plays a major role in SARS-CoV-2 pathogenesis. In this study, we have analyzed 320 genomic sequences of SARS-CoV-2 to identify mutations between the available genomes followed by the amino acid variations in the glycoprotein S to foresee their impact on the viral entry to host cell from structural biology viewpoint. The evolutionary distances showed that all the SARS-CoV-2 spike proteins cluster in the same node of the phylogenetic tree confirming the sequences are similar to Refseq YP_009724390 (Fig. 2) . doi = 10.1101/2020.04.07.030924 id = cord-334313-v2syspu6 author = Long, S. Wesley title = Molecular Architecture of Early Dissemination and Evolution of the SARS-CoV-2 Virus in Metropolitan Houston, Texas date = 2020-05-03 keywords = CoV-2; Houston; SARS; covid-19 summary = We sequenced the genomes of 320 SARS-CoV-2 strains from COVID-19 patients in metropolitan Houston, Texas, an ethnically diverse region with seven million residents. We sequenced the genomes of 320 SARS-CoV-2 strains from COVID-19 patients in metropolitan Houston, Texas, an ethnically diverse region with seven million residents. To better understand the first phase of virus spread in metropolitan Houston, Texas, we sequenced the genomes of 320 SARS-CoV-2 strains recovered from COVID-19 patients early in the Houston viral arc. To better understand the first phase of virus spread in metropolitan Houston, Texas, we sequenced the genomes of 320 SARS-CoV-2 strains recovered from COVID-19 patients early in the Houston viral arc. Because in vitro resistance of SARS-CoV to remdesivir has been reported to be caused by either of two amino acid replacements in RdRp (Phe476Leu and Val553Leu), we interrogated our data for polymorphisms in the nsp12 gene. doi = 10.1101/2020.05.01.072652 id = cord-287658-c2lljdi7 author = Lopez-Rincon, Alejandro title = Classification and Specific Primer Design for Accurate Detection of SARS-CoV-2 Using Deep Learning date = 2020-09-10 keywords = CoV-2; RNA; SARS; sequence summary = doi = 10.1101/2020.03.13.990242 id = cord-314051-dr27bsvt author = Lother, Sylvain A. title = Preoperative SARS-CoV-2 screening: Can it really rule out COVID-19? date = 2020-06-23 keywords = CoV-2; PCR; SARS summary = If viral carriage is not detected by testing, patients may proceed with elective surgery whereby signs and symptoms of coronavirus disease (COVID-19) may arise in the postoperative period, leading to adverse outcomes. 3 While screening with RT-PCR may detect some presymptomatic preoperative patients, the window of diagnostic utility is small, and careful interpretation of negative and positive test results must be considered prior to altering the course of therapy. A positive RT-PCR result identifies a group of patients who may be infected with SARS-CoV-2 and should have elective surgeries delayed. Si la présence virale n''est pas dépistée par un test, les patients peuvent aller de l''avant avec leur chirurgie non urgente, à la suite de laquelle les signes et symptômes d''une atteinte au coronavirus (COVID-19) pourraient survenir en période postopératoire, entraînant des devenirs défavorables. doi = 10.1007/s12630-020-01746-w id = cord-297599-y4lu8m4k author = Luo, Hua title = Anti-COVID-19 drug screening: Frontier concepts and core technologies date = 2020-10-28 keywords = ACE2; COV-2; COVID-19; SARS; TCM; chinese summary = This paper thoroughly summarizes interdisciplinary notions and techniques, including disease model, biochip, network pharmacology, and molecular docking technology, etc., providing a reference for researchers in the screening of drugs for COVID-19 prevention and treatment. Some researchers are currently using mice as an animal model to test drugs and vaccines and to investigate the nature of the infection of SARS-CoV-2 [49] [50] [51] . In fact, in a study led by Qin Chuan on SARS, engineered mice that could express human ACE2 protein was successfully established, leading this Chinese team pioneered the establishment of a SARS-CoV-2 infected hACE2 transgenic mouse model [54] . For example, an effective and convenient novel mouse model in evaluating in vivo protective capacity of the SARS-CoV-2 vaccines was developed through stitching the human gene for ACE2 into an adenovirus by Perlman et al. doi = 10.1186/s13020-020-00393-z id = cord-336057-tj9qcuf8 author = Lv, Yantian title = No intrauterine vertical transmission in pregnancy with COVID-19: a case report date = 2020-08-05 keywords = COV-2; SARS summary = The data of status of pregnant women and neonates after infection of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) is limited. We report a case of pregnant woman in her third trimester with critical COVID-19, and amniotic fluid, umbilical cord blood, placenta, and neonatal gastric fluid were retained during cesarean section. Amniotic fluid, umbilical cord blood, placenta, and neonatal gastric fluid were collected during the operation and tested for the SARS-COV-2 nucleic acid, and the mother and infant were separated after the operation. In addition, not only SARS-COV-2 nucleic acid test results were negative in 4 times pharyngeal swabs, but also the anal swab, amniotic fluid, umbilical cord blood, placenta, and neonatal gastric fluid were negative. Li 9 also reported a 35-week pregnant woman with COVID-19, whose amniotic fluid, cord blood and placenta, breast milk samples as well as neonates swab SARS-COV-2 nucleic acid were all negative. doi = 10.1016/j.jiac.2020.07.015 id = cord-305587-xtqvtleb author = Ma, Cuiqing title = From SARS-CoV to SARS-CoV-2: safety and broad-spectrum are important for coronavirus vaccine development date = 2020-05-11 keywords = CoV; SARS summary = Identification and characterization of novel neutralizing epitopes in the 506 receptor-binding domain of SARS-CoV spike protein: revealing the critical antigenic determinants in inactivated 507 SARS-CoV vaccine Intranasal vaccination of recombinant adeno-associated virus 533 encoding receptor-binding domain of severe acute respiratory syndrome coronavirus (SARS-CoV) spike protein induces 534 strong mucosal immune responses and provides long-term protection against SARS-CoV infection Receptor-binding domain of SARS-CoV spike protein induces highly 556 potent neutralizing antibodies: implication for developing subunit vaccine Recombinant modified vaccinia virus Ankara expressing the spike glycoprotein of severe acute respiratory syndrome coronavirus induces protective neutralizing antibodies 613 primarily targeting the receptor binding region Receptor-binding domain of severe acute respiratory syndrome coronavirus 621 spike protein contains multiple conformation-dependent epitopes that induce highly potent neutralizing antibodies. Cross-neutralization of human and palm civet severe acute 636 respiratory syndrome coronaviruses by antibodies targeting the receptor-binding domain of spike protein doi = 10.1016/j.micinf.2020.05.004 id = cord-269289-6uog10j4 author = Mabillard, Holly title = Electrolyte Disturbances in SARS-CoV-2 Infection date = 2020-07-22 keywords = CoV-2; RAS; SARS; patient summary = These include additional respiratory complications (pulmonary fibrosis -reported in 21% of those hospitalised with SARS-CoV-2 9 months post-discharge in one study 3 ) 7 , cardiovascular complications (acute cardiac injury (7% 8 ), cardiomyopathy (1/3 patients 9 ), cardiac tamponade, heart failure, dysrhythmias (17% 8 ) and venous thromboembolic events (20% 10 )) 11 , neurological complications (myopathy, acute stroke (5.7% of those with severe infection 12 ), Guillain-Barre syndrome (0.4% hospitalised patients 11 ) and encephalopathy) 13 , acute liver and/or pancreatic injury (29% and 17% respectively in one cohort) 14 , cytokine storm syndrome, septic shock, DIC, diarrhoea, Kawasaki-like disease 14 and renal complications (acute tubular injury, rhabdomyolysis, proteinuria, secondary focal segmental glomerulosclerosis and possible renin-angiotensinaldosterone system activation) 15 . The study reported that the degree of hypokalaemia correlated with severity of SARS-CoV-2 symptoms and they suggested that hypokalaemia can be difficult to correct as seen in two patients because the renal potassium wasting persists until clinical recovery from the virus. doi = 10.12688/f1000research.24441.2 id = cord-009476-4emc4o6n author = Madani, Tariq A title = Case definition and management of patients with MERS coronavirus in Saudi Arabia date = 2014-09-22 keywords = CoV; MERS summary = 16 outbreak and prevent human-to-human and animalto-human transmission; an appropriate management algorithm, including best-practice guidelines for accurate diagnosis, infection control, intensive care, emergency medicine, and treatment; prioritise research related to the MERS-CoV outbreak such as case-control and cohort studies, seroprevalence studies, and clinical trials; and to eff ectively monitor outbreak control activities. 2 The new case defi nition (appendix) was developed based on reported health-care-associated MERS-CoV pneumonia (added as category 2 in the new case defi nition) and non-respiratory characteristics of patients with confi rmed infection who fi rst presented with acute febrile dengue-like illness with body aches, leucopenia, and thrombocytopenia (added as category 3). WHO Revised interim case defi nition for reporting to WHO-Middle East respiratory syndrome coronavirus (MERS-CoV): as of First confi rmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in the United States, updated information on the epidemiology of MERS-CoV infection, and guidance for the public, clinicians, and Public Health Authorities doi = 10.1016/s1473-3099(14)70918-1 id = cord-258312-3v5t4k8d author = Majachani, Nicole title = A Case of a Newborn Baby Girl Infected with SARS-CoV-2 Due to Transplacental Viral Transmission date = 2020-10-25 keywords = CoV-2; SARS summary = Patient: Female, 31-year-old Final Diagnosis: COVID-19 • SARS-CoV-2 Symptoms: Asymptomatic Medication:— Clinical Procedure: — Specialty: Pediatrics and Neonatology OBJECTIVE: Unusual clinical course BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly infectious virus and is responsible for the current pandemic. CASE REPORT: 31-year-old Hispanic woman in the final week of pregnancy developed mild respiratory symptoms of COVID-19 pneumonia and tested positive for SARS-CoV-2 infection. In response to the potential risks to both the mother and fetus, the American College of Obstetricians and Gynecologists, the American Academy of Pediatrics, and the Centers for Disease Control have developed guidelines which provide a framework for detecting infections early and preventing potential transmission of SARS-CoV-2. Although similar viruses like severe acute respiratory syndrome coronavirus 1 have not demonstrated the ability to cause fetal infection, SARS-CoV-2 is able to bind ACE2 with much higher affinity [11] , thus increasing the probability of transplacental transmission. doi = 10.12659/ajcr.925766 id = cord-292152-gmru83ac author = Makrinioti, Heidi title = Intussusception in two children with SARS-CoV-2 infection in children date = 2020-08-08 keywords = CoV-2; SARS summary = This report compares intussusception as likely associated with SARS-CoV-2 infection in infants that presented in Wuhan and London. Based on the data so far, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in children is shown to run a milder course with lower reported mortality rates (1, 2) . However, as the definition of suspected cases does not include presentations with gastrointestinal symptoms only, there is still no clear answer to the question "should we screen for SARS-CoV-2 infection in children who require admission to hospital with gastrointestinal symptoms?". In addition to the fact that most of the presentations of the infection in children are atypical, there is very recent evidence showing that the highest viral shedding is taking place 2 to 3 days before onset of symptoms (https://www.nature.com/articles/s41591-020-0869-5). This brief report describes two cases of intussusception in infants found to be positive with SARS-CoV-2. This report describes two infants with intussusception and SARS-CoV-2 infection. doi = 10.1093/jpids/piaa096 id = cord-255815-5d9bqji0 author = Malik, Ajamaluddin title = MERS‐CoV papain-like protease (PL(pro)): expression, purification, and spectroscopic/thermodynamic characterization date = 2017-05-30 keywords = CoV; MERS summary = An orthogonal technique based on intrinsic tryptophan fluorescence also showed that MERS-CoV PL(pro) undergoes a single thermal transition and unfolds via a pathway of two-state folding with a T (m) value of 51.4 °C. In a similar experiment, MERS-CoV PL pro was gradually heated from 20 to 80°C at a rate of 1°C/min during which tryptophan fluorescence was measured by exciting at 295 nm and collecting at 330 and 350 nm to obtain the temperature melting curve. Commonly, protein unfolding fluorescence spectra are characterized by a long wavelength shift ''''red-shift.'''' But some proteins, Fig. 2 a Sequence of C-terminal His-tagged MERS-CoV PL pro showing ten Tyr and five Trp residues, which are highlighted in green and blue, respectively. Our result showed that the band intensity of the supernatant samples incubated from 20 to 70°C was apparently unchanged (Fig. 5) , indicating Fig. 3 Thermally induced structural changes in MERS-CoV PL pro as monitored by the intrinsic tryptophan fluorescence spectroscopy. doi = 10.1007/s13205-017-0744-3 id = cord-335122-8s3bcyo8 author = Marshall, Steve title = COVID-19: What do we know? date = 2020-09-21 keywords = COVID-19; CoV-2; N95; SARS summary = 44, 45, [47] [48] [49] The amount of viable SARS-CoV-2 in droplet nuclei remains unclear, but in subjects infected with other respiratory viruses, such as influenza, experiments comparing coughing and breathing suggest an equivalent production of viral RNA and replication-competent virus, detected at close range (< 12 inches). 78 In situations where healthcare workers wearing personal protective equipment (PPE) attend to patients with COVID-19 and do not perform medical AGPs, direct airborne transmission of replicationcompetent SARS-CoV-2 has not been confirmed. 79 The results of hospital studies evaluating aerosolization of body fluids and respiratory droplets of SARS-CoV-1 infected patients generated during certain medical AGPs (tracheal intubation, non-invasive ventilation, bronchoscopy, etc.), suggest that airborne transmission of SARS-CoV-2 may be possible during these procedures. Currently there are no studies reporting airborne viable (replication-competent) SARS-CoV-2 virus J o u r n a l P r e -p r o o f in hospital settings where infected patients are cared for, but not subjected to medical AGPs, by healthcare workers wearing surgical masks. doi = 10.1016/j.ajodo.2020.08.010 id = cord-291436-cu5o8ipw author = Martínez-Hernández, Fernando title = Assessing the SARS-CoV-2 threat to wildlife: Potential risk to a broad range of mammals date = 2020-10-05 keywords = ACE2; CoV-2; SARS; TMPRSS2 summary = Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect animals, however, the whole range of potential hosts is still unknown. This work makes an assessment of wildlife susceptibility to SARS-CoV-2 by analyzing the similarities of Angiotensin Converting Enzyme 2 (ACE2) and Transmembrane Protease, Serine 2 (TMPRSS2) —both recognized as receptors and protease for coronavirus spike protein— and the genetic variation of the viral protein spike in the recognition sites. Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) is causing the biggest pandemic 52 of this century, and could potentially infect between 30 to 40% of the world''s populations (De 53 Soto et al., 2020) . Due to its high transmission rate and mortality, researches around the world 54 are trying to get some insight about its origin through the analysis of related-virus genes 55 sequences in humans and animals (Lu R et al., 2020) , and looking for Angiotensin-Converting 56 doi = 10.1016/j.pecon.2020.09.008 id = cord-318934-dxipu00r author = Matsuyama, Shutoku title = Enhancement of SARS-CoV Infection by Proteases date = 2006 keywords = CoV; SARS summary = Moreover, SARS-CoV entry from the cell surface mediated by proteases was a 100-fold more efficient infection than entry through endosomes. However, no S2 band was detected in SARS-CoV infected cells treated with proteases that failed to induce fusion. 3 stated that SARS-CoV is able to enter cells directly from their surface, if receptor-bound virus is treated with trypsin and other proteases that induce fusion. Treatment of VeroE6 cells with bafilomycin was shown to suppress SARS-CoV infection via the endosomal pathway to less than 1/100 (Fig. 2) . Pseudotype VSV bearing SARS-CoV S protein infection was also facilitated in bafilomycin-treated VeroE6 cells after treatment with proteases that induce fusion of SARS-CoV infected cells. These observations suggest that proteases that facilitate SARS-CoV entry from the cell surface support efficient SARS-CoV infection. Characterization of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spike glycoprotein-mediated viral entry doi = 10.1007/978-0-387-33012-9_42 id = cord-331193-33cyvidx author = Mawhinney, Jamie A title = Neurotropism of SARS-CoV-2: COVID-19 presenting with an acute manic episode date = 2020-06-14 keywords = COVID-19; CoV-2; SARS summary = Psychiatric assessment found features consistent with acute mania, and he was detained under the Mental Health Act. This case indicates the need to consider COVID-19 in a wider series of clinical presentations and to develop a validated assay for SARS-CoV-2 in the cerebrospinal fluid. Psychiatric assessment found features consistent with acute mania, and he was detained under the Mental Health Act. This case indicates the need to consider COVID-19 in a wider series of clinical presentations and to develop a validated assay for SARS-CoV-2 in the cerebrospinal fluid. [9] [10] [11] [12] This article outlines a case of COVID-19 presenting with an acute manic episode necessitating emergency intubation and discusses potential mechanisms for the development of neuropsychiatric disease. ► The neuroinvasive potential of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (neurotropism) has been reported, but the pathophysiology remains unclear with uncertainty over its long-term consequences. doi = 10.1136/bcr-2020-236123 id = cord-292742-mio4przi author = McAloose, Denise title = From People to Panthera: Natural SARS-CoV-2 Infection in Tigers and Lions at the Bronx Zoo date = 2020-10-13 keywords = CoV-2; Fig; PCR; SARS; Tiger; animal summary = KEYWORDS One Health, Panthera leo, Panthera tigris, SARS-CoV-2, in situ hybridization, lion, rRT-PCR, tiger, virus isolation, whole-genome sequencing, zoo, zoonotic infection C oronaviruses are a recognized cause of disease in humans and animals (1) . Subsequent to confirmation of SARS-CoV-2 infection in the animals, an epidemiologic investigation of zoo staff identified 10 zoo keepers and two managers who provided care for and had close (Յ1.8-m) but not direct contact with the tigers or lions between 16 March 2020 (the date on which the zoo was closed to the public due to the pandemic) and 27 March to 3 April 2020 (timeline of disease onset in the animals). Nine complete SARS-CoV-2 genome sequences (from four tigers, three lions, and two keepers) and eight full-length S gene sequences (from seven symptomatic animals and one asymptomatic animal) were generated directly from respiratory and/or fecal samples (Data Sets 3 and 4). doi = 10.1128/mbio.02220-20 id = cord-256737-ptjng78b author = McBride, Corrin E. title = Palmitoylation of SARS-CoV S protein is necessary for partitioning into detergent-resistant membranes and cell-cell fusion but not interaction with M protein date = 2010-09-01 keywords = CoV; SARS summary = The SARS-CoV spike (S) protein mediates virus entry by binding cellular receptors and inducing fusion between the viral envelope and the host cell membrane. Importantly, we show that SARS-CoV S palmitoylation is not necessary for efficient interaction with SARS-CoV M, which differs from published experiments for MHV (Thorp et al., 2006) and suggests a significant difference between the two viruses that may have important implications for virus assembly and infectivity. To determine if SARS-CoV S becomes palmitoylated in a pre-medial Golgi compartment, HEK293T cells exogenously expressing SARS-CoV S were labeled for 30 min with 35 S-methionine/ cysteine to measure total protein expression or 3 H-palmitic acid to measure palmitoylated protein. Although both SARS-CoV S and S PN were present at the cell surface, it is possible that there could be a difference in the amount of protein at the plasma membrane at steady state if palmitoylation affects a post-Golgi trafficking step. doi = 10.1016/j.virol.2010.05.031 id = cord-329010-n0mz098o author = McKee, Dwight L. title = Candidate drugs against SARS-CoV-2 and COVID-19 date = 2020-04-29 keywords = ACE2; COVID-19; CoV-2; MERS; SARS summary = Further, chloroquine and hydroxychloroquine, and off-label antiviral drugs, such as the nucleotide analogue remdesivir, HIV protease inhibitors lopinavir and ritonavir, broad-spectrum antiviral drugs arbidol and favipiravir as well as antiviral phytochemicals available to date may prevent spread of SARS-CoV-2 and morbidity and mortality of COVID-19 pandemic. Drugs that have recently been shown to target MERS-CoV in mice [15] , and to inhibit Ebola virus RdRP and SARS-CoV-2 proteases in humans, such as remdesivir and ritonavir/lopinavir, also constitute candidate drugs against SARS-CoV-2 and are now investigated for their therapeutic efficacy in COVID-19 patients in 2 international clinical trials (SOLIDARITY Trial and DisCoVeRy Trial). The emergence of the novel beta coronavirus SARS-CoV-2 from Wuhan, Hubei province, China in December 2019 rapidly led to a pandemic involving more than 2,500,000 infected persons and more proven drugs such as camostat mesilate which prevents virus host cell entry by inhibiting TMPRSS2 [8] , and chloroquine phosphate which inhibits terminal phosphorylation of ACE2, or hydroxychloroquine which is metabolized in vivo to chloroquine [44] . doi = 10.1016/j.phrs.2020.104859 id = cord-260048-yis26g81 author = McNamara, Ryan P. title = High-density amplicon sequencing identifies community spread and ongoing evolution of SARS-CoV-2 in the Southern United States date = 2020-10-20 keywords = CoV-2; SARS; U.S. summary = doi = 10.1016/j.celrep.2020.108352 id = cord-314445-4cb4a9r5 author = McNamara, Ryan P. title = High-density amplicon sequencing identifies community spread and ongoing evolution of SARS-CoV-2 in the Southern United States date = 2020-06-19 keywords = CoV-2; SARS; U.S. summary = This study contributes to the understanding of COVID-19 by providing an extensive set of genomes from a non-urban setting and further informs vaccine design by defining D614G as a dominant and emergent SARS-CoV-2 isolate in the U.S. The current COVID-19 pandemic is an urgent public health emergency with over 112,000 deaths in the United States (U.S.) alone. At a CP ≥35 most positive samples still yielded reads that mapped to the target genome 227 and thus allowed detection of SARS-CoV-2 sequences; however, the results were less consistent, 228 and coverage was more variable. In sum, this study generated exhaustive SNV information representing the introduction and 325 spread of SARS-CoV-2 across a suburban low-density area in the Southern U.S. All samples were 326 from symptomatic cases and the majority of genomes clustered with variants that predominate the 327 outbreak in the U.S., rather than Europe or China. doi = 10.1101/2020.06.19.161141 id = cord-281679-xmbnpawj author = Meekins, David A. title = Susceptibility of swine cells and domestic pigs to SARS-CoV-2 date = 2020-08-16 keywords = CoV-2; SARS; pig summary = In the current study, we determined the ability of SARS-CoV-2 to (i) replicate in porcine cell lines, (ii) establish infection in domestic pigs via experimental oral/intranasal/intratracheal inoculation, and (iii) transmit to co-housed naive sentinel pigs. These data indicate that although different porcine cell lines are permissive to SARS-CoV-2, five-week old pigs are not susceptible to infection via oral/intranasal/intratracheal challenge. Cats, hamsters, and ferrets are highly susceptible to SARS-CoV-2 infection, demonstrate varying clinical and pathological disease manifestations, readily transmit the virus to naïve animals, and mount a virusspecific immune response [22] [23] [24] [25] [26] [27] [28] . Pigs are therefore unlikely to play an important role in the COVID-19 pandemic as a virus reservoir or as a pre-clinical animal model to study SARS-CoV-2 pathogenesis or develop novel countermeasures. doi = 10.1101/2020.08.15.252395 id = cord-322129-uyswj4ow author = Melin, Amanda D. title = Comparative ACE2 variation and primate COVID-19 risk date = 2020-10-27 keywords = ACE2; CoV-2; SARS; Supplementary; site summary = Infection studies of rhesus monkeys, long-tailed macaques, and vervets as biomedical models have made it clear that at least some nonhuman primate species are permissive to SARS-CoV-2 infection and develop symptoms in response to infection that resemble those of humans following the development of COVID-19, including similar age-related effects [11] [12] [13] [14] [15] [16] . We assessed the variation at amino acid residues identified as critical for ACE2 recognition by the SARS-CoV-2 RBD and undertook an analysis of positive selection and protein modeling to gauge the potential for adaptive differences and the likely effects of protein variation. In particular, the twelve sites in the ACE2 protein that are critical for binding of the SARS-CoV-2 virus are invariant across the Catarrhini, which includes great apes, gibbons, and monkeys of Africa and Asia (Fig. 1) . doi = 10.1038/s42003-020-01370-w id = cord-296268-kb7fgfaq author = Mendonça, Luiza title = SARS-CoV-2 Assembly and Egress Pathway Revealed by Correlative Multi-modal Multi-scale Cryo-imaging date = 2020-11-05 keywords = CoV-2; SARS; SEM summary = Here, we investigated SARS-CoV-2 replication in Vero cells under the near-native frozen-hydrated condition using a unique correlative multi-modal, multi-scale cryo-imaging approach combining soft X-ray cryo-tomography and serial cryoFIB/SEM volume imaging of the entire SARS-CoV-2 infected cell with cryo-electron tomography (cryoET) of cellular lamellae and cell periphery, as well as structure determination of viral components by subtomogram averaging. Understanding the genome 27 replication, assembly and egress of SARS-CoV-2, a multistage process that involves different 28 cellular compartments and the activity of many viral and cellular proteins, is critically Krios to identify each individual infected cell (39.2 % for MOI of 0.1 and 45.4% for MOI 124 0.5) where cryoET tilt series were collected at the cell periphery. The grids were then 125 transferred to a FIB/SEM dualbeam instrument and the same infected cells were subjected to 126 either serial cryoFIB/SEM volume imaging (Zhu et al., 2021) or cryoFIB milling of cellular 127 lamellae where additional cryoET tilt series were collected (Sutton et al., 2020) . doi = 10.1101/2020.11.05.370239 id = cord-334220-sqvfr31q author = Messina, Francesco title = Looking for pathways related to COVID-19 phenotypes: Confirmation of pathogenic mechanisms by SARS-CoV-2 - Host interactome date = 2020-11-03 keywords = COVID-19; CoV-2; SARS; protein summary = The functional analysis for all proteins, linked to many aspects of COVID-19 pathogenesis, allows to identify the subcellular districts, where SARS-CoV-2 proteins seem to be distributed, while in each interactome built around one single viral protein, a different response was described, underlining as ORF8 and ORF3a modulated cardiovascular diseases and pro-inflammatory pathways, respectively. We identified possible host responses induced by specific proteins of SARS-CoV-2, underlining the important role of specific viral accessory proteins in pathogenic phenotypes of severe COVID-19 patients. In SFigure For KEGG database the gene enrichment analysis on interactomes of NS7b, ORF1a, ORF3a and ORF8 showed pathway clusters highly significant and consistent with possible pathogenic mechanisms, such as the activation of the complement and of the coagulative cascade, (29) and the TGF-β-dominated immune response (30) . We identified different host response induced by specific proteins of SARS-CoV-2, underlining the important role of ORF3a and ORF8 in phenotypes of severe COVID-19 patients. doi = 10.1101/2020.11.03.366666 id = cord-283966-eln8ljjj author = Meyer, Benjamin title = Antibodies against MERS Coronavirus in Dromedary Camels, United Arab Emirates, 2003 and 2013 date = 2014-04-17 keywords = CoV; MERS; serum summary = Dromedary camels from the United Arab Emirates were infected at high rates with MERS-CoV or a closely related, probably conspecific, virus long before the first human MERS cases. Animals from the Arabian Peninsula had high neutralizing serum activities overall and reciprocal antibody titers <320-1,280, which support recent infection with MERS-CoV or a highly related virus. Expanding upon these studies, we used in the present study a recombinant MERS-CoV spike protein immunofluroescence assay (rIFA) augmented by a validated protein microarray (10, 21) , followed by MERS-CoV-specific neutralization assay, to screen 651 dromedary serum samples from the United Arabian Emirates. In the tested panel of camel serum samples, vIFA titers corresponded well to titers determined by rIFA and generally equal to or higher than titers in the rIFA (Table 1) To confirm results from affinity assays with results from a functional test, we determined endpoint virus neutralization titers by using a microneutralization test against MERS-CoV and BCoV. doi = 10.3201/eid2004.131746 id = cord-274122-n9jnu2ah author = Mielech, Anna M. title = MERS-CoV papain-like protease has deISGylating and deubiquitinating activities date = 2014-02-01 keywords = CoV; MERS; SARS summary = Coronaviruses encode papain-like proteases (PLpro) that are often multifunctional enzymes with protease activity to process the viral replicase polyprotein and deubiquitinating (DUB)/deISGylating activity, which is hypothesized to modify the innate immune response to infection. Further, we compared the ability of MERS-CoV PLpro and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) PLpro to block innate immune signaling of proinflammatory cytokines. In this study, we demonstrate the deISGylating and deubiquitinating (DUB) activities of the papain-like protease from MERS-CoV, and provide new information on the potential role of coronavirus protease/DUBs to inhibit the innate immune response. Our results suggest that PLpro might contribute to the modulation of innate immune responses upon SARS-CoV and MERS-CoV infection, however, the exact mechanism and the role of coronavirus PLPs and their associated DUB and deISGylating activities in these processes remains to be determined. doi = 10.1016/j.virol.2013.11.040 id = cord-287847-rmhvc5n5 author = Miles, Brett A. title = Tracheostomy during SARS‐CoV‐2 pandemic: Recommendations from the New York Head and Neck Society date = 2020-04-20 keywords = CoV-2; SARS; tracheostomy summary = Patients with significant medical comorbidities, acute respiratory distress syndrome/severe respiratory failure and a low chance of recovery who are infected with SARS-CoV-2 should be carefully evaluated, and discussions with family members, consultants, institutional ethics committees and the treating team should focus on overall prognosis and goals of care prior to performing tracheostomy as a routine matter of care. Although there are limited data on the current pandemic to fully inform personal protective equipment (PPE) recommendations, performing tracheostomy in an actively infected SARS-CoV-2 patient is certainly a high-risk procedure for health care workers. Techniques to manage the acute airway with endotracheal intubation, video laryngoscope for example, should be utilized if possible to avoid emergent tracheostomy in SARS-CoV-2 patients due to the high risk of unsafe conditions and health care worker contaminations. • When clinically appropriate, delay of tracheostomy procedures is recommended to allow for reduced viral load and to decrease the risk of nosocomial infection to critical health care providers. doi = 10.1002/hed.26166 id = cord-266156-xmf4emln author = Miller, Tyler E. title = Clinical sensitivity and interpretation of PCR and serological COVID‐19 diagnostics for patients presenting to the hospital date = 2020-08-28 keywords = CoV-2; PCR; SARS; day summary = doi = 10.1096/fj.202001700rr id = cord-356166-fpno9zg5 author = Miyakawa, Kei title = Rapid quantitative screening assay for SARS-CoV-2 neutralizing antibodies using HiBiT-tagged virus-like particles date = 2020-09-15 keywords = CoV-2; SARS summary = title: Rapid quantitative screening assay for SARS-CoV-2 neutralizing antibodies using HiBiT-tagged virus-like particles However, a simple, convenient, rapid, and high-throughput test capable of directly detecting nAbs with high specificity, which could act as an ideal alternative to the neutralization assay, is yet to be developed (Ozcurumez et al., 2020) . In this report, we have developed a HiBiT-VLP-based neutralization test (hiVNT) that can readily detect SARS-CoV-2 nAbs ( Figure 1A ). We noticed a robust increase in NanoLuc activity when the LgBiT-expressing We next tested whether our newly developed hiVLP-SARS2 system could detect nAbs in the serum of COVID-19 patients. In this study, we established the hiVNT, a simple, high-throughput assay system for the quantitative and rapid determination of SARS-CoV-2 nAbs in the sera of individuals after recovery from symptomatic or subclinical COVID-19. Potent Neutralizing Antibodies against SARS-CoV-2 Identified by High-Throughput Single-Cell Sequencing of Convalescent Patients'' B Cells doi = 10.1093/jmcb/mjaa047 id = cord-275313-mfyff9ne author = Modjarrad, Kayvon title = Treatment strategies for Middle East respiratory syndrome coronavirus date = 2016-01-01 keywords = CoV; East; MERS; Middle summary = Most recently, Middle East respiratory syndrome coronavirus (MERS-CoV) has emerged as a novel cause of severe acute respiratory illness after first being identified in a Saudi Arabian patient in 2012 [2] . Much of the work to develop safe and effective MERS-CoV countermeasures has centred on vaccines, but the relatively low prevalence of the disease, the sporadic nature of the case clusters and the dearth of detailed knowledge on chains of transmission highlight the need for greater investments into the discovery of effective therapeutic and secondary prophylactic regimens for infected and exposed individuals. Feasibility, safety, clinical, and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol Towards the prophylactic and therapeutic use of human neutralizing monoclonal antibodies for Middle East respiratory syndrome coronavirus (MERS-CoV) Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection doi = nan id = cord-262786-otxpc46a author = Mohammadi, Soheil title = Understanding the Immunologic Characteristics of Neurologic Manifestations of SARS-CoV-2 and Potential Immunological Mechanisms date = 2020-09-01 keywords = CNS; COVID-19; CoV-2; IL-6; SARS summary = doi = 10.1007/s12035-020-02094-y id = cord-284068-sbon3aes author = Mok, Chee Keng title = Calcitriol, the active form of vitamin D, is a promising candidate for COVID-19 prophylaxis date = 2020-06-22 keywords = CoV-2; SARS summary = Validation assays to determine changes in infectious virus titres upon treatment was carried out by testing selected hit compounds in dose-dependent assays in Vero E6 to confirm the primary screen observation and also in the human hepatocarcinoma HuH7 cell line as the latter cell line expresses high levels of the ACE2 receptor (10) and supports replication of coronaviruses (11) . While recent data has shown that vitamin D levels are negatively associated with morbidity and mortality of COVID-19 cases (13, 14) , this is the first report of a direct inhibitory effect of calcitriol on SARS-CoV-2. The authors speculated that vitamin D supplementation could protect against SARS-CoV-2 infection and improve patient disease outcomes (16) , and our finding certainly provides credence to this hypothesis. Given the high transmissibility of SARS-CoV-2 globally (23), if these findings can be replicated in clinical trials, calcitriol may certainly prove to be an effective tool in the effort to control the pandemic while waiting for an effective vaccine to be rolled out globally. doi = 10.1101/2020.06.21.162396 id = cord-340516-9dfaqsv7 author = Moore, Anne C. title = Pre-clinical studies of a recombinant adenoviral mucosal vaccine to prevent SARS-CoV-2 infection date = 2020-09-06 keywords = CoV-2; SARS; vaccine summary = We demonstrate that, compared to expression of the S1 domain or a stabilized spike antigen, the full length, wild-type spike antigen induces significantly higher neutralizing antibodies in the periphery and in the lungs, when the vaccine is administered mucosally. Here, we report the induction of neutralizing antibody (Nab), IgG and IgA antibody responses, and T cell responses in mice following immunization of rAd vectors expressing one or more SARS-CoV-2 antigens. We have previously demonstrated that an oral, tableted rAd-based vaccine can induce protection against respiratory infection and shedding following influenza virus challenge 15 as well as intestinal immunity to norovirus antigens in humans 12 . In summary, these studies in mice represent our first step in creating a vaccine candidate, demonstrating the immunogenicity of the construct at even low vaccine doses and the elucidation of the full-length spike protein as a leading candidate antigen to induce T cell responses and superior systemic and mucosal neutralizing antibody. doi = 10.1101/2020.09.04.283853 id = cord-289407-8fje16z1 author = Moore, G. title = Detection of SARS-CoV-2 within the healthcare environment: a multicentre study conducted during the first wave of the COVID-19 outbreak in England date = 2020-09-25 keywords = CoV-2; RNA; SARS summary = Understanding how Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is spread within the hospital setting is essential if staff are to be adequately protected, effective infection control measures are to be implemented and nosocomial transmission is to be prevented. 6 Air samples taken during tracheostomy procedures, high flow nasal oxygen treatment, non-invasive ventilation and nebulisation have not contained SARS-CoV-2 RNA 7 and HCWs exposed to unrecognised COVID-19 patients undergoing similar high-risk AGPs have not become infected. . https://doi.org/10.1101/2020.09.24.20191411 doi: medRxiv preprint Several studies, utilising a range of air and surface sampling methods, have been carried out to determine the presence and prevalence of SARS-CoV-2 in the healthcare environment. [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] The detection of viral RNA in air samples differs with study with some reporting widespread airborne contamination 14, 18, 21 but many reporting low or non-detectable concentrations 13, 15, 16, 19 even in samples collected 10 cm from the face of positive patients. Detection of air and surface contamination by SARS-CoV-2 in hospital rooms of infected patients doi = 10.1101/2020.09.24.20191411 id = cord-292256-jp80u828 author = Moriguchi, Takeshi title = A first case of meningitis/encephalitis associated with SARS-Coronavirus-2 date = 2020-04-03 keywords = CoV-2; SARS summary = We report the first case of meningitis associated with SARS-CoV-2 who was brought in by ambulance due to a convulsion accompanied by unconsciousness. A brain MRI showed hyperintensity along the wall of right lateral ventricle and hyperintense signal changes in the right mesial temporal lobe and hippocampus, suggesting the possibility of SARS-CoV-2 meningitis. (Wang et al., 2020a,b) A preliminary report warned that SARS-CoV-2 could have neuroinvasive potential because some patients showed neurologic symptoms such as headache, nausea, and vomiting . This brief report describes the first case of the patient, which brought in by the ambulance due to a convulsion accompanied by unconsciousness, was diagnosed with aseptic encephalitis with SARS-CoV-2 RNA in cerebrospinal fluid. This case shows the neuroinvasive potential of the virus and that we cannot exclude SARS-CoV-2 infections even if the RT-PCR test for SARS-CoV-2 using the patient''s nasopharyngeal specimen is negative. doi = 10.1016/j.ijid.2020.03.062 id = cord-261566-fn08b0y2 author = Mudgal, Rajat title = Prospects for mucosal vaccine: shutting the door on SARS-CoV-2 date = 2020-09-15 keywords = CoV; CoV-2; MERS; SARS; mucosal; vaccine summary = doi = 10.1080/21645515.2020.1805992 id = cord-304073-f3iwclkm author = Mullick, Jhinuk Basu title = Animal Models to Study Emerging Technologies Against SARS-CoV-2 date = 2020-07-27 keywords = ACE2; CoV-2; SARS; human summary = Animal models are indispensable to understand these processes and develop and test emerging technologies; however, the mechanism of infection for SARS-CoV-2 requires certain similarities to humans that do not exist in common laboratory rodents. Here, we review important elements of viral infection, transmission, and clinical presentation reflected by various animal models readily available or being developed and studied for SARS-CoV-2 to help bioengineers evaluate appropriate preclinical models for their emerging technologies. Non-human primates, Syrian hamsters, ferrets, cats, and engineered chimeras mimic the human infection more closely and hold strong potential as animal models of SARS-CoV-2 infection and progression of resulting human disease. Overall, the studies show that the Syrian hamster is a useful animal model for SARS-CoV-2 infection especially to study viral replication, shedding, and transmission through the respiratory tract. In all studies, animals developed NAbs. Overall, the rhesus macaque model has been similar in many aspects to the human COVID-19 pathogenesis. doi = 10.1007/s12195-020-00638-9 id = cord-293988-f5gvwjyh author = Musso, Nicolò title = New SARS-CoV-2 Infection Detected in an Italian Pet Cat by RT-qPCR from Deep Pharyngeal Swab date = 2020-09-11 keywords = China; CoV-2; RNA; SARS summary = The pandemic respiratory disease COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan in December 2019 and then spread throughout the world; Italy was the most affected European country. In this study, a domestic cat with clear clinical signs of pneumonia, confirmed by Rx imaging, was found to be infected by SARS-CoV-2 using quantitative RT–qPCR from a nasal swab. The World Health Organization (WHO) declared COVID-19 disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as a worldwide pandemic [1] . As the cat''s pathology evolved rapidly and harmfully (the animal died in as little as three days), with clinical signs and rate of disease progression similar to human COVID-19 patients, and because previously published papers reported different cases of feline infection [10, [13] [14] [15] [16] , a nasal swab was collected in order to verify a possible infection with SARS-CoV-2. doi = 10.3390/pathogens9090746 id = cord-332448-5fz8ef4f author = Mutnal, M. B. title = Early trends for SARS-CoV-2 infection in central and north Texas and impact on other circulating respiratory viruses date = 2020-05-02 keywords = CoV-2; SARS summary = Testing for SARS-CoV-2 was performed by real-time RT-PCR assay and results were shared with State public health officials for immediate interventions. . https://doi.org/10.1101/2020.04.30.20086116 doi: medRxiv preprint of this study is to encourage other laboratories to consider an early start to testing during pandemics, share 74 initial trends in this part of the world and possible impact of SARS-CoV-2 on other seasonal respiratory 75 This report describes the early trends of SARS-CoV-2 infections in the central and north Texas, 76 USA and impact of epidemiological interventions that may have led to the decrease in the incidence of was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. BSWH laboratory provided test results data on both ambulatory and inpatient 275 population, and shared patient demographics with local public health officials. doi = 10.1101/2020.04.30.20086116 id = cord-287758-da11ypiy author = Mônica Vitalino de Almeida, Sinara title = COVID-19 therapy: what weapons do we bring into battle? date = 2020-09-10 keywords = ACE2; COVID-19; CoV-2; Coronavirus; FDA; FIG; MERS; RNA; SARS; drug; patient; viral summary = The increase in studies related to SARS-CoV-2 during the first semester in 2020 has allowed the rather speedy identification of promising therapeutic targets for both developing immunotherapies and producing/identifying antiviral drugs. 5, 64 So far, structural proteins and enzymes that participate actively in the process of viral replication are the most investigated targets for the development of molecules for anti-CoVs therapies (FIG. Based on results from previous studies as well, nelfinavir was considered a likely therapy for COVID-19 after its indication for clinical trials as a promising anti-SARS drug. 218 In addition to this well-known antitumor effect, imatinib has also shown in-vitro antiviral properties against several virus, such as infectious bronchitis virus (a viral model for studying the role of tyrosine kinase activity during CoV infection), by interfering with virus-cell fusion, 219 and other RNA viruses including coxsackie virus, 220 hepatitis C virus, 221 Ebola, 222 among others, mainly by blocking viral entry or egress from the host cell. doi = 10.1016/j.bmc.2020.115757 id = cord-309147-c3ikb81g author = Nadeem, Muhammad Shahid title = Origin, Potential Therapeutic Targets and Treatment for Coronavirus Disease (COVID-19) date = 2020-04-22 keywords = ACE2; COVID-19; CoV-2; SARS summary = According to available information, SARS-CoV-2 is inferred to be a recombinant virus that originated from bats and was transmitted to humans, possibly using the pangolin as the intermediate host. The interaction of the SARS-CoV-2 spike protein with the human ACE2 (angiotensin-converting enzyme 2) receptor, and its subsequent cleavage by serine protease and fusion, are the main events in the pathophysiology. The recent reports have suggested that SARS-CoV-2 is a modified coronavirus of bat origin [22, 32] , which came to humans as a result of zoonotic transmission [33, 34] . The receptor-binding domain (RBD) of pangolin-CoV has only a one amino acid difference with that of SARS-CoV-2; the infected pangolins exhibit pathological symptoms similar to humans suffering from COVID-19, and their blood circulating antibodies can react with the spike protein of SARS-CoV-2 [35, 36] . Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and corona virus disease-2019 (COVID-19): The epidemic and the challenges doi = 10.3390/pathogens9040307 id = cord-256217-fnjer0e0 author = Neri, Piergiorgio title = COVID-19 and the eye immunity: lesson learned from the past and possible new therapeutic insights date = 2020-04-20 keywords = COV-2; SARS summary = Corona virus represents nowadays the hot topic in the scientific world due to the outbreak of a novel serotype formerly named coronavirus disease (COVID)-19 and now identified as severe acute respiratory syndrome (SARS)-COV-2 [1] . Although ECOR was used to study retinal degeneration specifically, it might represent a possible experimental model for interesting speculations on how to approach severe SARS-COV-2 pulmonary complications. Looking at the ECOR model, it gives the impression that coronavirus creates two different phases: the first is represented by the primary infection which induces the triggering of the immune system, while the second phase is likely to be an autoimmune disease where the role of the severe postviral inflammation represents a severe occurrence worth of prompt intervention. Albeit it is true that anti-IL-6 receptor monoclonal antibody has given promising results for the control of severe SARS-COV-2 pneumonia, it is interesting to notice that retinal degeneration in ECOR is associated with an evident increase in TNF-alpha, as well as soluble TNFR2, inducing an anomaly of TNF-alpha signaling [12] . doi = 10.1007/s10792-020-01389-2 id = cord-302707-cap2rgf7 author = Ng, Dianna L. title = SARS-CoV-2 seroprevalence and neutralizing activity in donor and patient blood date = 2020-09-17 keywords = CoV-2; Fig; SARS; San summary = Here, we present data validating the use of the EUA authorized Abbott Architect SARS-CoV-2 IgG test for antibody detection in two populations in March 2020, a hospitalized COVID-19 patient cohort at a tertiary care hospital in San Francisco and a cohort of blood donors from the San Francisco Bay Area. These studies demonstrate that SARS-CoV-2 seroprevalence in the San Francisco Bay Area was very low, suggesting limited circulation of the virus in the community as of early March, and that IgG and IgM titers are predictive of neutralizing activity, with high positive percent agreement. To evaluate assay sensitivity, we assembled a cohort of 38 hospitalized patients and 5 outpatients at University of California, San Francisco (UCSF) Medical Center and the San Francisco Veterans Affairs (SFVA) Health Care System, all of whom received care at adult inpatient units or clinics and were real-time polymerase chain reaction (RT-PCR) positive for SARS-CoV-2 from nasopharyngeal and/or oropharyngeal swab testing ( Fig. 1a and Supplementary Table 1 ). doi = 10.1038/s41467-020-18468-8 id = cord-339762-lh8czr0a author = Ng, Dianna L. title = Clinicopathologic, Immunohistochemical, and Ultrastructural Findings of a Fatal Case of Middle East Respiratory Syndrome Coronavirus Infection in the United Arab Emirates, April 2014 date = 2016-03-31 keywords = CoV; East; MERS; SARS summary = title: Clinicopathologic, Immunohistochemical, and Ultrastructural Findings of a Fatal Case of Middle East Respiratory Syndrome Coronavirus Infection in the United Arab Emirates, April 2014 Middle East respiratory syndrome coronavirus (MERS-CoV) infection causes an acute respiratory illness and is associated with a high case fatality rate; however, the pathogenesis of severe and fatal MERS-CoV infection is unknown. Middle East respiratory syndrome coronavirus (MERS-CoV) infection causes an acute respiratory illness and is associated with a high case fatality rate; however, the pathogenesis of severe and fatal MERS-CoV infection is unknown. Middle East respiratory syndrome coronavirus (MERS-CoV) was initially isolated from a sputum specimen of a patient who died of respiratory and renal failure in Saudi Arabia in 2012. Although the pathogenesis of severe and fatal MERS-CoV infection is unknown, these postmortem findings provide critical insights, including evidence that pneumocytes are important targets, suggesting that direct cytopathic effects contribute to MERS-CoV respiratory symptoms. doi = 10.1016/j.ajpath.2015.10.024 id = cord-291523-4dtk1kyh author = Nguyen, Thanh Thi title = Origin of Novel Coronavirus (COVID-19): A Computational Biology Study using Artificial Intelligence date = 2020-07-01 keywords = CoV-2; Fig; SARS summary = Outcomes of a phylogenetic analysis suggest that the virus belongs to the genus Betacoronavirus, sub-genus Sarbecovirus, which includes many bat SARS-like CoVs and SARS CoVs. Another study in [5] confirms this finding by analysing genomes obtained from three adult patients admitted to a hospital in Wuhan on December 27, 2019. With the cut-off parameter C is set equal to 0.7, the hierarchical clustering algorithm separates the reference sequences into 6 clusters in which cluster "5" comprises all examined viruses of the Sarbecovirus sub-genus, including many SARS CoVs, bat SARS-like CoVs and pangolin CoVs (Fig. 7A) . With the results obtained in Fig. 7D (and also in the experiments with the DBSCAN method presented next), we support a hypothesis that bats or pangolins are the probable origin of SARS-CoV-2. In this Appendix, we first present results of the hierarchical clustering method applied to the dataset that combines Set 1 of reference sequences (Table 1 ) with all 334 SARS-CoV-2 sequences (see Fig. 9 ). doi = 10.1101/2020.05.12.091397 id = cord-293688-g6kag5ij author = Nora, Holtmann title = Assessment of SARS-CoV-2 in human semen - a cohort study date = 2020-05-29 keywords = CoV-2; SARS summary = OBJECTIVE: To investigate the presence of viral RNA in human semen of severe-acute-respiratory syndrome coronavirus 2 (SARS-CoV-2) recovered and positive patients and to evaluate its presence and relevance on semen parameters. SARS-CoV-2 RNA could not be detected in semen of recovered and acute COVID-19 positive males. SARS-CoV-2 RNA could neither be detected in semen samples from recovered nor from acute infected subjects. On another note, it is of interest, that although it was described before in the literature that viral infections have a negative impact on semen parameters like 306 volume, number of spermatozoa and motility we could not detect a negative influence of the SARS-CoV-2 infection in respect of the aforementioned sperm count parameters in recovered subjects with mild symptoms. We found no evidence of SARS-CoV-2 shedding in semen of recovered males or patients with an acute COVID-19 infection after a recovery time of 32,7 days on average. doi = 10.1016/j.fertnstert.2020.05.028 id = cord-303297-fiievwy7 author = Oberemok, Volodymyr V. title = SARS-CoV-2 will continue to circulate in the human population: an opinion from the point of view of the virus-host relationship date = 2020-04-30 keywords = COVID-19; CoV-2; SARS; virus summary = In this article, we will concentrate on the facts currently available about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has caused COVID-19 (coronavirus disease 2019) pandemic and try to predict its development and consequences based on the virus-host relationship. In addition, it seems that the virus is also more likely to affect the heart than any other similar viruses, so although pneumonia is often the main cause of death, cardiologists and infectionists, for example in Russia, are seeing infected patients whose worst symptoms are not respiratory, but cardiac and many people infected with COVID-19 are dying from heart attacks, as a possible complication of SARS-CoV-2 infection. Despite the initial reports stating that most of the laboratory-confirmed infected patients (27 of 41 cases) had links to the Wuhan seafood market where different animals, including bats, snakes, birds, pangolins, and other small mammals are normally traded within the market [6] , it is now obvious that the newly identified coronavirus SARS-CoV-2 is transmitted with enormous efficacy from human to human via respiratory droplets or close contact. doi = 10.1007/s00011-020-01352-y id = cord-348192-ibohbjfb author = Odih, Erkison E. title = Could Water and Sanitation Shortfalls Exacerbate SARS-CoV-2 Transmission Risks? date = 2020-06-09 keywords = CoV-2; SARS; transmission summary = Endemic and epidemic transmission of multiple feco-oral pathogens via this route continues to be documented in areas without safely managed sanitation, and, therefore, the risk of SARS-CoV-2 transmission needs to be evaluated, tracked, and forestalled in such settings. Furthermore, environmental surveillance of SARS-CoV-2 in wastewater and accumulated human waste, as well as efforts to mitigate the virus'' entry into unprotected household water sources, should be a priority part of the COVID-19 response in settings without safely managed sanitation for the duration of the pandemic. 3, 5, 6 Considerable concern has been expressed in the literature that the feco-oral transmission potential for SARS-CoV-2 places endoscopists, caregivers of diapered children who shed the virus, 7 and fecal transplant recipients 8 at high risk of contracting the infection. 20, 21 Although there are as yet no reports of transmission of SARS-CoV-2 via sewage or fecal matter in settings without safely managed sanitation, or recovery from household water, these examples demonstrate that feco-oral transmission by endemic pathogenic organisms is commonplace in these settings. doi = 10.4269/ajtmh.20-0462 id = cord-254916-y1rw9q11 author = Ogando, Natacha S. title = SARS-coronavirus-2 replication in Vero E6 cells: replication kinetics, rapid adaptation and cytopathology date = 2020-06-22 keywords = CoV-2; Fig; RNA; SARS; Vero; cell summary = doi = 10.1099/jgv.0.001453 id = cord-349682-kpg0vley author = Ojha, Probir Kumar title = Therapeutics for COVID-19: from computation to practices—where we are, where we are heading to date = 2020-09-02 keywords = ACE2; COVID-19; CoV-2; Fig; SARS; drug summary = For example, the broad-spectrum antiviral drug Arbidol recently entered the clinical trial for the treatment of SARS-CoV-2 which may act by inhibiting virus-host cell fusion, thus preventing the viral entry into host cells against influenza virus [37] [38] [39] . Smith and Smith [22] analyzed 8000 small drug molecules and natural products (SWEETLEAD library database) employing restrained temperature replica-exchange MD simulations combining virtual screening through the ensemble docking to identify the effective drug for COVID-19 which might stop the virus by two ways: (a) disrupting S protein and ACE2 receptor interface stability; or (b) by troubling the capability of the S protein to recognize Table 2 Pharmacological safety data of selected potential drug candidates [11, 12, 14, 34, 38, 39, 43-45, 57-59, 64, 69, 70, 89] Drug Dose Drug-drug interaction Toxicity Chloroquine phosphate (Aralen) [11, 12, 14, 43, 89] This is a genetically engineered vaccine candidate with the replicationdefective adenovirus type 5 as the vector to express SARS-CoV-2 spike protein. doi = 10.1007/s11030-020-10134-x id = cord-308110-cco3aq4n author = Okamoto, Mika title = The chemokine receptor antagonist cenicriviroc inhibits the replication of SARS-CoV-2 in vitro date = 2020-07-30 keywords = CVC; CoV-2; SARS summary = In this study, CVC was examined for its inhibitory effect on the replication of SARS-CoV-2, the causative agent of COVID-19, in cell cultures and found to be a selective inhibitor of the virus. The 50% effective concentrations of CVC were 19.0 and 2.9 μM in the assays based on the inhibition of virus-induced cell destruction and viral RNA levels in culture supernatants of the infected cells, respectively. Considering the fact that the regulation of excessive immune activation is required to treat COVID-19 patients at the late stage of the disease, CVC should be further pursued for its potential in the treatment of SARS-CoV-2 infection. Since not only the inhibition of viral replication but also the control of excessive immune activation is mandatory to save COVID-19 patients at the late stage of the disease, CVC should be further pursued for its potential in the treatment of SARS-CoV-2 infection. doi = 10.1016/j.antiviral.2020.104902 id = cord-332948-h297ukuu author = Olotu, Fisayo A. title = Leaving no stone unturned: Allosteric targeting of SARS-CoV-2 Spike protein at putative druggable sites disrupts human angiotensin-converting enzyme interactions at the receptor binding domain. date = 2020-10-16 keywords = CoV-2; RBD; SARS; protein; site summary = authors: Olotu, Fisayo A.; Omolabi, Kehinde F.; Soliman, Mahmoud E.S. title: Leaving no stone unturned: Allosteric targeting of SARS-CoV-2 Spike protein at putative druggable sites disrupts human angiotensin-converting enzyme interactions at the receptor binding domain. 30 Identification of other functional (allosteric) sites on the prefusion S protein could present another dynamic and effective approach of preventing SARS-CoV-2 infectivity relative to its interaction with the host cell ACE2 and proteases. 53 Relatively, this study was implemented to (i) identify potential druggable sites across the S1 and S2 domains of the SARS-CoV-2 S protein other than the RBD-hACE2 interface (ii) perform high-throughput (virtual) screening of ~1500 FDA approved drugs against the most druggable site(s) (iii) investigate the binding dynamics and interaction mechanisms of the compounds and their consequential effects on the S-protein RBD-ACE2 complex. We believe this systematic study will be able to provide structural and molecular insights into possible allosteric sites on SARS-CoV-2 S protein suitable for selective targeting and structureComputational methodologies doi = 10.1016/j.imu.2020.100451 id = cord-255997-oer5lxxr author = Onodi, Fanny title = SARS-CoV-2 induces activation and diversification of human plasmacytoid pre-dendritic cells date = 2020-07-10 keywords = CoV-2; Fig; IFN; SARS summary = Here, we have studied the interaction of isolated primary SARS-CoV-2 viral strains with human plasmacytoid pre-dendritic cells (pDC), a key player in antiviral immunity. Importantly, all major aspects of SARS-CoV-2-induced pDC activation were inhibited by hydroxychloroquine, including P2and P3-pDC differentiation, the expression of maturation markers, and the production of interferon-α and inflammatory cytokines. Interestingly, pDC responded to SARS-CoV-2 by a complete activation program, including diversification into effector subsets, production of type I and type III IFN, as well as inflammatory cytokines. We also showed that hydroxychloroquine, an antimalarial drug proposed for treatment of COVID-19 patients (Das et al., 2020; Mahévas et al., 2020) , inhibits SARS-CoV-2-induced pDC activation and IFN production in a dose-dependent manner. Following 24 hours of culture, we found that HCQ inhibited pDC diversification in response to SARS-CoV-2, which is similar to the decrease observed with Flu, used as a positive control ( Fig 4A) . doi = 10.1101/2020.07.10.197343 id = cord-318316-9unfl966 author = Ortega, Joseph T. title = Understanding Severe Acute Respiratory Syndrome Coronavirus 2 Replication to Design Efficient Drug Combination Therapies date = 2020-10-23 keywords = COVID-19; CoV-2; SARS summary = SUMMARY: This review focused on the basic principles of virology and pharmacology to understand the importance of early stages of virus-cell interaction as therapeutic targets and other main processes vital for SARS-CoV-2 replication. Furthermore, we focused on describing the main targets associated with SARS-CoV-2 antiviral therapy and the rationale of drug combinations for efficiently suppressing viral replication. Another early target evaluated against SARS-CoV-2 is a cellular protease related to the priming of the spike protein (S), which exposes the fusion motive and allows the release of viral RNA into the cytosol. HCQ, hydroxychloroquine; RdRp, RNA-dependent RNA polymerase; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TMPRSS2, transmembrane serine protease 2; ORF, open reading frame. Favipiravir, another antiviral agent with broad activity against other RNA viruses by inhibiting the RdRp, halting viral replication, was evaluated against SARS-CoV-2, showing effects in vitro and in vivo [43] [44] [45] . doi = 10.1159/000512141 id = cord-286683-mettlmhz author = Ortiz-Prado, Esteban title = Clinical, molecular and epidemiological characterization of the SARS-CoV2 virus and the Coronavirus disease 2019 (COVID-19), a comprehensive literature review date = 2020-05-30 keywords = COVID-19; China; CoV-2; Coronavirus; MERS; SARS; Wuhan; infection; patient; severe summary = Interestingly, the increased amounts of proinflammatory cytokines in serum associated with pulmonary inflammation and extensive lung damage described both in SARS [59] and MERS diseases [60] were also reported in the early study of 41 patients with COVID-19 in Wuhan [41] . A recently published case report of a patient with mild-to-moderate COVID-19 revealed the presence of an increased activated CD4+ T cells and CD8+ T cells, antibody-secreting cells (ASCs), follicular helper T cells (TFH cells), and anti-SARS-CoV-2 IgM and IgG antibodies, suggesting that both cellular and humoral responses are important in containing the virus and inhibiting severe pathology [82] . Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: Retrospective case series doi = 10.1016/j.diagmicrobio.2020.115094 id = cord-262119-s6hc7fxs author = Ostaszewski, Marek title = COVID-19 Disease Map, a computational knowledge repository of SARS-CoV-2 virus-host interaction mechanisms date = 2020-10-27 keywords = ACE2; COVID-19; CoV-2; Coronavirus; Disease; Map; SARS; SBML; cell; pathway; protein summary = title: COVID-19 Disease Map, a computational knowledge repository of SARS-CoV-2 virus-host interaction mechanisms The molecular pathophysiology that links SARS-CoV-2 infection to the clinical manifestations and course of COVID-19 is complex and spans multiple biological pathways, cell types and organs [2, 3] . With this goal in mind, we initiated a collaborative effort involving over 230 biocurators, domain experts, modelers and data analysts from 120 institutions in 30 countries to develop the COVID-19 Disease Map, an open-access collection of curated computational diagrams and models of molecular mechanisms implicated in the disease [4] . The COVID-19 Disease Map diagrams, available in layout-aware systems biology formats and integrated with external repositories, are available in several formats allowing a range of computational analyses, including network analysis and Boolean, kinetic or multiscale simulations. COVID-19 Disease Map, building a computational repository of SARS-CoV-2 virus-host interaction mechanisms doi = 10.1101/2020.10.26.356014 id = cord-302382-eifh95zm author = Owji, Hajar title = Immunotherapeutic approaches to curtail COVID-19 date = 2020-08-21 keywords = ACE2; COVID-19; CoV-2; SARS; antibody; cell; immune; patient summary = Active immunization through vaccines, interferon administration, passive immunotherapy by convalescent plasma or synthesized monoclonal and polyclonal antibodies, as well as immunomodulatory drugs, are different immunotherapeutic approaches that will be mentioned in this review. Nevertheless, the similarity of severe respiratory failure induced by SARS-CoV-2 to acute respiratory distress syndrome (ARDS) and the deterioration of patients'' conditions in around a week following the first symptoms implicate the role of immunity dysregulation in COVID-19 profile [6] . Subsequently, plasma transfusion was recommended as a safe and effective way for the prevention or treatment of the Ebola virus in 2014 and also several other severe viral infections, including MERS, SARS-CoV, and avian influenza A [35, 36] . CP extracted from the SARS-COV-2 survivors may be a promising approach for the protection of COVID-19 patients with antibody deficiency before the development of an effective vaccine [44] . doi = 10.1016/j.intimp.2020.106924 id = cord-328395-2cakgmsj author = Oxford, Alexandra E. title = Endothelial Cell Contributions to COVID-19 date = 2020-09-25 keywords = ACE2; COVID-19; CoV-2; SARS; cell; endothelial summary = Recent reports suggest that SARS-CoV-2, unlike other related viruses, infects and replicates within endothelial cells, which may explain a significant portion of the observed clinical pathology. This review will focus on the concept of endothelial cell infection and dysfunction as an active driver of COVID-19, which begins as a respiratory illness, with vascular pathology contributing significantly to the most negative patient outcomes. Endothelial cell infection that proceeds via ACE2 shows how SARS-CoV-2 can replicate into a wide range of cells, which may explain some of the clinical symptoms found in COVID-19 patients. Thus far, we have discussed the viral mechanisms of SARS-CoV-2 and resultant COVID-19 sequelae as they relate to endotheliitis and endothelial cell infection mediated by viral spike protein-ACE2 interaction. The successful use of anti-interleukin drugs to treat the inflammatory symptoms seen in severe COVID-19 would have marked effects on endothelial pathology as these cells are highly responsive to cytokine signaling [59] . doi = 10.3390/pathogens9100785 id = cord-278370-fuu20ae7 author = Palao, M. title = Multiple Sclerosis following SARS-CoV-2 infection date = 2020-07-07 keywords = CoV-2; SARS summary = However, available information about demyelinating complications of the central nervous system (CNS) is limited with only one report of acute disseminated encephalomyelitis (ADEM) in a severe COVID-19 patient being published to date 5 and a single case of meningo-encephalitis 6 , the latter with the presence of SARS-CoV-2 in the cerebrospinal fluid (CSF) confirmed by PCR. As viral infections have been linked to the development of demyelinating diseases 7 it would be interesting to know if this relationship also exists in the case of SARS-CoV-2. We present a case of first presentation of demyelinating disease in the form of optic neuritis following SARS-CoV-2 infection. In our case, the patient presented symptoms attributed to COVID-19 infection (anosmia and dysgeusia) prior to the visual manifestations. In this case, SARS-CoV-2 may have acted as a precipitating factor rather than multiple sclerosis being a direct consequence of the infection. doi = 10.1016/j.msard.2020.102377 id = cord-301730-flv5lnv8 author = Pandey, Anamika title = Natural Plant Products: A Less Focused Aspect for the COVID-19 Viral Outbreak date = 2020-10-15 keywords = COVID-19; CoV; MERS; SARS summary = Despite the previous positive reports of plant-based medications, no successful clinical trials of phyto-anti-COVID drugs could be conducted to date. Medicinal plant extracts have been reported to impede the replication of several viruses including human immunodeficiency virus (HIV), hepatitis B virus (HBV), poxvirus, severe acute respiratory syndrome (SARS) virus, and herpes simplex virus type 2 (HSV-2) (Vermani and Garg, 2002; Kotwal et al., 2005; Huang et al., 2006) . Different researchers are investigating diverse plant forms based on ethnopharmacological data to find effective anti-CoV drugs with novel action mechanisms especially targeting viral replication. Moreover, creating an effective phyto-anti-COVID drug during this pandemic may provide an idea on the duration and the strategy required for the development of potent plant-based therapeutics in case of such random viral outbreaks (Figure 1) . doi = 10.3389/fpls.2020.568890 id = cord-318164-6rqi17oz author = Paoli, D. title = Sperm cryopreservation during the SARS-CoV-2 pandemic date = 2020-10-10 keywords = CoV-2; RNA; SARS summary = This study therefore aimed to analyze the safety of sperm cryopreservation for cancer patients after the onset of the pandemic in Italy, through assessment of the risk of SARS-CoV-2 exposure and viral RNA testing of semen samples. CONCLUSION: This preliminary assessment suggests that a thorough evaluation (especially in the setting of a multidisciplinary team) and molecular confirmation of the absence of SARS-CoV-2 in seminal fluid from asymptomatic cancer patients may assist in ensuring the safety of sperm cryopreservation. This study thus aimed to evaluate the safety of sperm cryopreservation of cancer patients referred to our sperm bank after the onset of the pandemic in Italy through the assessment of the risk of SARS-CoV-2 exposure and, in selected volunteers, viral RNA testing of semen samples. This was further confirmed by testing seminal fluid samples from 10 asymptomatic cancer patients for SARS-CoV-2 RNA. doi = 10.1007/s40618-020-01438-8 id = cord-339859-anatn295 author = Paret, Michal title = SARS-CoV-2 infection (COVID-19) in febrile infants without respiratory distress date = 2020-04-17 keywords = CoV-2; SARS summary = title: SARS-CoV-2 infection (COVID-19) in febrile infants without respiratory distress We report two cases of SARS-CoV-2 infection (COVID-19) in infants presenting with fever in the absence of respiratory distress who required hospitalization for evaluation of possible invasive bacterial infections. The diagnoses resulted from routine isolation and real-time RT-PCR-based testing for SARS-CoV-2 for febrile infants in an outbreak setting. [2] [3] [4] Even in the setting of asymptomatic or mildly symptomatic infection, children may represent a source of SARS-CoV-2 spread in community or hospital settings, so understanding the spectrum of COVID-19 illness in infants, particularly regarding conditions that result in hospitalization, is crucial to establishment of effective infection control interventions. Vital signs and pertinent laboratory findings appear in the A real-time RT-PCR assay performed at the New York State Department of Health detected SARS-CoV-2 RNA in the patient''s NP sample. doi = 10.1093/cid/ciaa452 id = cord-278522-e4qa19o6 author = Park, Se Yoon title = Persistent severe acute respiratory syndrome coronavirus 2 detection after resolution of coronavirus disease 2019-associated symptoms/signs date = 2020-06-19 keywords = CoV-2; SARS summary = There are limited data on the duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in respiratory specimens after resolution of coronavirus disease 2019 (COVID-19)-associated symptoms/signs. Persistent severe acute respiratory syndrome coronavirus 2 detection after resolution of coronavirus disease 2019-associated symptoms/signs Se Yoon Park 1 , Soon Gyu Yun 2 , Jeong Won Shin 2 , Bo Young Lee 3 , Hyo-Ju Son 1 , Seungjae Lee 1 , Eunjung Lee 1 , and Tae Hyong Kim 1 Since the first case of coronavirus disease 2019 (COVID-19) was reported in Wuhan, China in December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than three million people in 211 countries. Few studies have investigated the duration of SARS-CoV-2 detection during the patients'' recovery phase after resolution of COVID-19-associated symptoms/signs. SARS-CoV-2 shedding continued for about 4 weeks after resolution of COVID-19-associated symptoms/signs, with the longest period being 48 days. In conclusion, we found that SARS-CoV-2 virus shedding can persist for more than three weeks after resolution of COVID-19-associated symptoms/signs. doi = 10.3904/kjim.2020.203 id = cord-274396-l611eisi author = Park, Su-Jin title = Antiviral Efficacies of FDA-Approved Drugs against SARS-CoV-2 Infection in Ferrets date = 2020-05-22 keywords = CoV-2; PBS; SARS; group summary = While the lopinavir-ritonavir-, hydroxychloroquine sulfate-, or emtricitabine-tenofovir-treated group exhibited lower overall clinical scores than the phosphate-buffered saline (PBS)-treated control group, the virus titers in nasal washes, stool specimens, and respiratory tissues were similar between all three antiviral-candidate-treated groups and the PBS-treated control group. Compared to the PBS-treated control group, azathioprine-immunosuppressed ferrets exhibited a longer period of clinical illness, higher virus titers in nasal turbinate, delayed virus clearance, and significantly lower serum neutralization (SN) antibody titers. In order to determine the antiviral efficacies of lopinavir-ritonavir, hydroxychloroquine (HCQ) sulfate, or emtricitabine-tenofovir for treatment of SARS-CoV-2 infection, SARS-CoV-2 antibody-free ferrets (10/group) were inoculated with 10 5.8 50% tissue culture infective doses (TCID 50 )/ml of an NMC-nCoV02 strain through the intranasal (i.n.) route ( Fig. 1 ). Therefore, although clinical symptoms were attenuated in ferret groups treated with antiviral candidates, we also evaluated virus titers in respiratory and gastrointestinal tracts using nasal washes and stool samples, respectively, from SARS-CoV-2-infected ferrets. doi = 10.1128/mbio.01114-20 id = cord-268540-wrjzr3ws author = Park, You Jeong title = Fighting the War Against COVID-19 via Cell-Based Regenerative Medicine: Lessons Learned from 1918 Spanish Flu and Other Previous Pandemics date = 2020-08-13 keywords = ACE2; COVID-19; Cov-2; SARS; cell; patient; spanish; virus summary = A potential target for drug development for COVID-19 also involves inhibition of ACE2, the host cell receptor for the S protein of SARS-CoV-2 that is primed by TMPRSS2 protease and may prevent the entry of the virus. As previously described, the intermolecular interaction between the viral SP and human ACE2 Phase II CAStem cells will be intravenously injected into patients with or without acute respiratory distress syndrome (ARDS) induced by COVID-19. Phase II Patients with acute respiratory distress syndrome caused by COVID-19 will be treated with intravenous UC-MSCs at a dose 1 million xKg. Patient improvement will be evaluated over three weeks, along with the assessment of the immune profile, investigating the stem cells'' effect on the cytokine storm. The similarities in systemic multi-organ complications between H7N9 and Sars-Cov-2 infections, along with direct evidence of the benefits of MSCs transplantation for COVID-19, further supports the potential of stem cells as an effective treatment [138] . doi = 10.1007/s12015-020-10026-5 id = cord-339665-nwwutduy author = Patel, Ami title = Intradermal-delivered DNA vaccine provides anamnestic protection in a rhesus macaque SARS-CoV-2 challenge model date = 2020-07-29 keywords = COVID-19; CoV-2; SARS summary = Prior work with the related coronaviruses, SARS-CoV and MERS-CoV, delineated that the Spike protein of these viruses was an important target for development of neutralizing antibodies, and in animal viral challenges vaccine targeted immunity (reviewed in (Du et al., 2009; Roper and Rehm, 2009; Thanh Le et al., 2020) (Liu et al., 2018; Muthumani et al., 2015; van Doremalen et al., 2020a) . These memory titers were comparable to those observed in other reported protection studies in macaques performed at the acute phase of the vaccine-induced immune response (Gao et al., 2020; van Doremalen et al., 2020b; Yu et al., 2020) and those reported in the sera of convalescent patients (Ni et al., 2020; Robbiani et al., 2020) . Our study and other published reports show that DNA vaccination with candidates targeting the full-length SARS-CoV-2 spike protein likely increase the availability of T cell immunodominant epitopes leading to a broader and more potent immune response, compared to partial domains and truncated immunogens. doi = 10.1101/2020.07.28.225649 id = cord-271781-cfv0ta10 author = Patel, Kishan P. title = Transmission of SARS-CoV-2: an update of current literature date = 2020-07-07 keywords = COVID-19; CoV-2; RNA; SARS summary = To date, many studies have discussed that the rationale behind its transmission potential is that viral RNA has unexpectedly been detected in multiple bodily fluids, with some samples having remained positive for extended periods of time. In this evidence-based comprehensive review, we discuss various potential routes of transmission of SARS-CoV-2—respiratory/droplet, indirect, fecal-oral, vertical, sexual, and ocular. Additionally, studies have noted that its fecal-oral transmission potential may lie in the fact that prolonged viral shedding can occur in fecal matter-one case reported an asymptomatic COVID-19 patient experiencing viral detection in the stool for up to 42 days, while nasopharyngeal sampling was negative [31] . To oppose, in a retrospective review of nine COVID-19 pregnant mothers who underwent cesarean section, six patients had samples of amniotic fluid, cord blood, neonatal throat swab, and breastmilk samples tested for SARS-CoV-2, and all were negative [43] . doi = 10.1007/s10096-020-03961-1 id = cord-342383-ckswlo9o author = Pawlowski, C. title = Exploratory analysis of immunization records highlights decreased SARS-CoV-2 rates in individuals with recent non-COVID-19 vaccinations date = 2020-07-28 keywords = CoV-2; PCR; SARS summary = Furthermore, age, race/ethnicity, and blood group stratified analyses reveal significantly lower SARS-CoV-2 rate among black individuals who have taken the PCV13 vaccine, with relative risk of 0.45 at the 5 year time horizon (n: 653, 95% CI: (0.32, 0.64), p-value: 6.9e-05). Given this study population, we assess the rates of SARS-CoV-2 infection among individuals who did and did not receive one of 18 vaccines in the past 1, 2, and 5 years relative to the date of PCR testing. In Figure 6 , we present the results from the tipping point analysis on the statistically significant associations between vaccination and reduced rates of SARS-CoV-2 infection in the overall study population. For example, for the polio vaccine at the 1 year time horizon, an unobserved confounder with a relative risk of 2.78 which is prevalent in 17.8% of the vaccinated cohort and 0% of the unvaccinated cohort could explain the differences in SARS-CoV-2 infection rates that we observe in the data. doi = 10.1101/2020.07.27.20161976 id = cord-262266-m0fjt483 author = Peddu, Vikas title = Metagenomic analysis reveals clinical SARS-CoV-2 infection and bacterial or viral superinfection and colonization date = 2020-05-07 keywords = CoV-2; SARS summary = METHODS: To evaluate metagenomic approaches in the context of the current SARS-CoV-2 epidemic, laboratory-confirmed positive and negative samples from Seattle, Washington were evaluated by metagenomic sequencing, with comparison to a 2019 reference genomic database created before the emergence of SARS-CoV-2. A subset of samples also showed superinfection or colonization with human parainfluenza virus 3 or Moraxella species, highlighting the need to test directly for SARS-CoV-2 as opposed to ruling out an infection using a viral respiratory panel. Eight unique patient samples consisting of six positive and two negative cases of suspected SARS-CoV-2 were sequenced using RNA extracted for a qRT-PCR diagnostic assay. Despite our reference database not containing any SARS-CoV-2 genomes, the six samples that were positive for SARS-CoV-2 by qRT-PCR had reads classified to Table 2) . Phylogenetic analysis revealed that the six SARS-CoV-2 sequences found cluster within two clades representing the Washington state and European outbreaks. doi = 10.1093/clinchem/hvaa106 id = cord-311847-2czqs84q author = Pennisi, Manuela title = SARS-CoV-2 and the Nervous System: From Clinical Features to Molecular Mechanisms date = 2020-07-31 keywords = ACE2; CNS; COVID-19; CoV-2; Coronavirus; SARS; patient summary = Increasing evidence suggests that Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2) can also invade the central nervous system (CNS). Although there are limitations in the epidemiological studies carried on COVID-19, as well as limited case records for determining the actual incidence of these complications, some patients reported neurological symptoms, but clinical findings and pathogenic features have not yet systematically addressed. The aims of this review are i) to summarize the available information on the relationship between CoVs and the nervous system, ii) to identify the potential targets and routes of entry of SARS-CoV-2 into the nervous system, and iii) to describe the range of the neurological features reported to date in patients with COVID-19 and the proposed pathogenic mechanisms. Indeed, no axonal transport of SARS-CoV-2 to the brain has been demonstrated in the hamster model during the first two weeks after infection [89] , and no viral accumulation or persistence has been reported in cerebral olfactory regions of autopsy material from patients with COVID-19 [90] . doi = 10.3390/ijms21155475 id = cord-293274-ysr1l557 author = Perisé-Barrios, Ana Judith title = Humoral response to SARS-CoV-2 by healthy and sick dogs during COVID-19 pandemic in Spain date = 2020-09-22 keywords = CoV-2; SARS; dog summary = Infection of animals with SARS-CoV-2 are being reported during last months, and also an increase of severe lung pathologies in domestic dogs has been detected by veterinarians in Spain. Infection of animals with SARS-CoV-2 are being reported during last months, and also an increase of severe lung pathologies in domestic dogs has been detected by veterinarians in Spain. Here we report that despite detecting dogs with IgG α-SARS-CoV-2, we never obtained a positive RT-qPCR, not even in dogs with severe pulmonary disease; suggesting that even in the case of a canine infection transmission would be unlikely. Here we report that despite detecting dogs with IgG α-SARS-CoV-2, we never obtained a positive RT-qPCR, not even in dogs with severe pulmonary disease; suggesting that even in the case of a canine infection transmission would be unlikely. doi = 10.1101/2020.09.22.308023 id = cord-150183-zzzyewjb author = Phillips, J. C. title = Synchronized Attachment and the Darwinian Evolution of Coronaviruses CoV-1 and CoV-2 date = 2020-08-27 keywords = CoV-2; protein summary = These are (CoV-1 site numbering from Uniprot P59594): 546Gln to Leu; 556 and 561Ser to Ala; and 568Ser to Leu. The differences associated with each of these mutations are hydropathically large (~50-100 in the MZ scale [4] ; all 20 amino acids span a range from most hydrophilic to most hydrophobic of 170). The central hydrophilic level set, absent from CoV-1 and present in CoV-2, is our main result ( There is an excellent review of the principles of self-organized criticality in living matter [3] . Some readers may be interested in the connections between hydropathic scaling theory of proteins and the more general synchronization of complex networks. Now that we are in the genomic age, with a very large sequence data base available for many proteins and many species, the discovery of these 20 fractals [5, 13] opens a new biophysics field of accurate thermodynamic analysis of small but medically important evolutionary differences. doi = nan id = cord-351169-y91fdf66 author = Phillips, Lia title = Successful management of SARS-CoV-2 acute respiratory distress syndrome and newly diagnosed acute lymphoblastic leukemia date = 2020-09-14 keywords = CoV-2; SARS summary = Corticosteroid can be given safely to patients with SARS-CoV-2 presenting with acute respiratory distress syndrome and ALL. Although recommendations are emerging for the general management of oncology patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 1,2 there is little experience in patients with newly diagnosed acute lymphoblastic leukemia (ALL). Providers may have concern about initiating multiagent chemotherapy in patients with SARS-CoV-2, particularly corticosteroids, which are an essential part of induction regimens, but raise the theoretical possibility of delayed viral clearance. We describe our experience of successfully initiating therapy for an adolescent diagnosed with ALL, while managing severe SARS-CoV-2 infection marked by respiratory failure, systemic inflammation, and autoimmune hemolytic anemia (AIHA). 1, 2 In this case, intensive remission induction chemotherapy was initially delayed due to concern for potential worsening of SARS-CoV-2 disease by exacerbating the patient''s already immunocompromised state in the setting of ALL. doi = 10.1182/bloodadvances.2020002745 id = cord-308945-i2agpvhk author = Phipps, William S title = SARS-CoV-2 Antibody Responses Do Not Predict COVID-19 Disease Severity date = 2020-07-15 keywords = CoV-2; PCR; SARS summary = METHODS: A total of 967 subjects were tested for IgG antibodies reactive to SARS-CoV-2, including 172 suspected cases of SARS-CoV-2, 656 plasma samples from healthy donors, 49 sera from patients with rheumatic disease, and 90 specimens from individuals positive for polymerase chain reaction (PCR)–based respiratory viral panel. Long et al 8 have described a variable antiviral IgM and IgG immune response to SARS-CoV-2 infection in a Chinese population in which seroconversion in a group of 285 patients from 3 hospitals showed IgG positivity for all cases beyond 17 to 19 days. The goals of this study were to ascertain key performance metrics of analytical specificity and cross-reactivity for a SARS-CoV-2 IgG serologic assay, perform a detailed cross-sectional and serial assessment of IgG and IgM antibody responses in suspected COVID-19 patients, and determine their relation to disease severity. SARS-CoV-2 IgG antibody results agreed with the PCR-negative samples for 96 of 97 (99%) of cases, including 55 instances of patients with new or acute-on-chronic symptoms suspicious for COVID-19 and with known time of onset. doi = 10.1093/ajcp/aqaa123 id = cord-261718-zqoggwnk author = Pietschmann, Jan title = Brief Communication: Magnetic Immuno-Detection of SARS-CoV-2 specific Antibodies date = 2020-06-03 keywords = CoV-2; SARS summary = Available point-of-care diagnostic systems as lateral flow assays have high potential for fast and easy on-site antibody testing but are lacking specificity, sensitivity or possibility for quantitative measurements. Here, a new point-of-care approach for SARS-CoV-2 specific antibody detection in human serum based on magnetic immuno-detection is described and compared to standard ELISA. For magnetic immuno-detection, immunofiltration columns were coated with a SARS-CoV-2 spike protein peptide. After addition of 176 biotinylated GaR and subsequent labelling with streptavidin-AP, the ELISA plate was read out at 177 405 nm and obtained measuring values were used to generate calibration curves for SARS-CoV-2 178 specific antibody concentrations in PBS (Fig 1, black curve) and in human serum samples (Fig 1, red 179 curve). Same calibration measurements employing dilutions of SARS-CoV-2 specific antibody were 211 done with our PoC MInD-based setup (Fig 2 and 3) . Comparable to laboratory-based ELISA, the same 212 dilutions of SARS-CoV-2 spike protein peptide specific antibody in PBS-buffer (Fig 3, black doi = 10.1101/2020.06.02.131102 id = cord-262958-tmp6yxlv author = Pinto, Dora title = Structural and functional analysis of a potent sarbecovirus neutralizing antibody date = 2020-04-09 keywords = CoV-2; S309; SARS summary = doi = 10.1101/2020.04.07.023903 id = cord-193133-puqcbf8t author = Piplani, Sakshi title = In silico comparison of spike protein-ACE2 binding affinities across species; significance for the possible origin of the SARS-CoV-2 virus date = 2020-05-13 keywords = ACE2; CoV-2; SARS; protein summary = The devastating impact of the COVID19 pandemic caused by SARS coronavirus 2 (SARSCoV2) has raised important questions on the origins of this virus, the mechanisms of any zoonotic transfer from exotic animals to humans, whether companion animals or those used for commercial purposes can act as reservoirs for infection, and the reasons for the large variations in susceptibilities across animal species. Here we show how computational chemistry methods from structure-based drug design can be used to determine the relative binding affinities of the SARS-CoV-2 spike protein for its receptor, angiotensin converting enzyme (ACE)-2, a critical initiating event for SARS-CoV-2 infection, across multiple common and exotic animal species. 31, 32 Molecular docking was performed on the homology modelled SARS-CoV-2 spike protein with human and animal ACE2 proteins. The molecular dynamics simulation of complexes of SARS-CoV-2 spike protein and ACE2 receptors of various species were performed for 100ns. doi = nan id = cord-346960-3empldlo author = Plebani, M. title = Analytical and clinical performances of five immunoassays for the detection of SARS-CoV-2 antibodies in comparison with neutralization activity date = 2020-08-04 keywords = CoV-2; SARS summary = In 184 serum samples from 130 COVID-19 patients and 54 SARS-CoV-2 negative subjects, the analytical and clinical performances of four commercially available chemiluminescent assays (Abbott SARS-Cov-2 IgG, Roche Elecsys anti-SARS-CoV-2, Ortho SARS-CoV-2 total and IgG) and one enzyme-linked immunosorbent assay (Diesse ENZY-WELL SARS-CoV-2 IgG) were evaluated and compared with the neutralization activity achieved using the plaque reduction neutralization test (PRNT). On limiting the analysis to samples collected 12 days after onset of symptoms, the sensitivity of all assays increased, the highest value (95.2%) being obtained with VITRO Anti-SARS-CoV-2 Total and Architect SARS-CoV-2 IgG. 54 SARS-CoV-2 negative subjects (33 healthcare workers, 21 autoimmune patients, 8 pregnant women) were included in the study ( Moreover, Liaison SARS-CoV-2 S1/S2 IgG (Diasorin, Sallugia-VC, Italy), ENZY-Well SARS-CoV-2 IgA and IgM were evaluated for the correlation with the neutralization results. . To provide insight on neutralization activity compared with immunoassays results, PRNT assay was performed on 52 samples from SARS-CoV-2 positive subjects. doi = 10.1101/2020.08.01.20166546 id = cord-298669-g2up0cfi author = Pollock, David D title = Viral CpG deficiency provides no evidence that dogs were intermediate hosts for SARS-CoV-2 date = 2020-07-13 keywords = CoV-2; SARS; Xia summary = Nevertheless, the evolutionary reasons for low GC content are still debated in even exceptionally well-studied systems with unquestioned animal origins (2020) points out, the mammalian zinc finger antiviral protein (ZAP) binds to CpG dinucleotides in viral RNA genomes and inhibits viral replication and mediates viral degradation (Ficarelli et al., 2020; Ficarelli et al., 2019; Meagher et al., 2019; Takata et al., 2017) . Despite this, Xia (2020) speculated that low viral genomic CpG levels in SARS-CoV-2 required evolutionary time in a previous host species and tissue that more actively selected for CpG depletion than do bats. In addition to being unsupported by positive evidence, Xia''s (2020) hypothesis for dogs as intermediate hosts of ancestral viruses giving rise to SARS-CoV-2 requires an unlikely history of cross-species viral transmission (see Fig. 2 for potential hypotheses) for which there is no evidence. doi = 10.1093/molbev/msaa178 id = cord-310017-c8rd714a author = Popa, Alexandra title = Mutational dynamics and transmission properties of SARS-CoV-2 superspreading events in Austria date = 2020-07-17 keywords = CoV-2; Fig; SARS; austrian; mutation summary = Moreover, we combined our deep viral genome sequencing data with epidemiologically identified chains of transmissions and family clusters together with biomathematical analyses to study genetic bottlenecks and the dynamics of genome evolution of SARS-CoV-2. We assembled SARS-CoV-2 genome sequences, constructed phylogenies and identified low 15 frequency mutations based on high-quality sequencing results with >5 million reads per sample and >80% of mapped viral reads (Fig. S2A-B) . Our pipeline was validated by experimental controls involving sample titration and technical sample replicates ( Fig. S2CTo investigate the link between local outbreaks in Austria and the global pandemic, we 20 performed phylogenetic analysis of 305 SARS-CoV-2 genomes from the Austrian cases (>96% genome coverage, >80% aligned viral reads) and 7,695 global genomes from the GISAID database (Fig. 1B, Table S1 ). 7 Dynamics of low frequency and fixed mutations in clusters Next, we sought to gain insights into the fundamental processes of SARS-CoV-2 infection by integrative analysis of viral genomes. doi = 10.1101/2020.07.15.204339 id = cord-258914-g6pv8zz9 author = Proud, Pamela C. title = Prophylactic intranasal administration of a TLR2 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model date = 2020-09-25 keywords = CoV-2; SARS summary = title: Prophylactic intranasal administration of a TLR2 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model We show that prophylactic intra-nasal administration of the TLR2/6 agonist INNA-051 in a SARS-CoV-2 ferret infection model effectively reduces levels of viral RNA in the nose and throat. The results of our study support clinical development of a therapy based on prophylactic TLR2/6 innate immune activation in the URT to reduce SARS-CoV-2 transmission and provide protection against COVID-19. The TLRs are key microbe-recognition receptors with a crucial role in 97 activation of host defence and protection from infections and therefore attractive drug 98 targets against infectious diseases [12] [13] [14] To determine whether TLR2/6 agonists are also active against SARS-CoV-2, we used In life samples were taken at days 1, 3, 5, 7, 10 and 12, with scheduled culls at days 137 3 (n=6) and end of study days 12-14 (n=18) (Fig 1A) . doi = 10.1101/2020.09.25.309914 id = cord-288731-x2cwyvb7 author = Puenpa, Jiratchaya title = Molecular epidemiology of the first wave of severe acute respiratory syndrome coronavirus 2 infection in Thailand in 2020 date = 2020-10-06 keywords = CoV-2; March; SARS; Thailand summary = In the current study associations between SARS-CoV-2 gene variation and exposure history during the first wave of the outbreak in Thailand between January and May 2020 were investigated. In Thailand the Ministry of Public Health reported the first laboratory-confirmed case of SARS-CoV-2 in a 61-year-old Chinese traveller who had arrived from Wuhan on 12 January 2020. Based on the genome sequences available in GIASID, nucleotide variation in four regions of the SARS-CoV-2 genome was used to conduct viral tracking and identify sites of origin of outbreaks in Thailand. One sample in the current study collected in January 2020 was closely related to the SARS-CoV-2 strain circulating in China at that time identified as type L. A new cohort of imported cases identified in May 2020 included a group of migrant workers in the southern part of Thailand 24 with type G2 SARS-CoV-2. doi = 10.1038/s41598-020-73554-7 id = cord-335155-x9az3twa author = Qi, Zhen title = Phylogeny of SARS-CoV as inferred from complete genome comparison date = 2003 keywords = CoV; SARS summary = SARS-CoV, as the pathogeny of severe acute respiratory syndrome (SARS), is a mystery that the origin of the virus is still unknown even a few isolates of the virus were completely sequenced. To explore the genesis of SARS-CoV, the FDOD method previously developed by us was applied to comparing complete genomes from 12 SARS-CoV isolates to those from 12 previously identified coronaviruses and an unrooted phylogenetic tree was constructed. Differently, from the topology of the phylogenetic tree we found that SARS-CoV is more close to group 1 within genus coronavirus. To date, genomes from 12 SARS-CoV isolates and 12 previously identified coronaviruses have been completely sequenced. The unrooted phylogenetic tree was constructed for genomes from 12 SARS-CoV isolates and that from 12 previously identified coronviruses (Fig. 1) . Comparative full-length genome sequence analysis of 14 SARS coronavirus isolates and common mutations associated with putative origins of infection A complete sequence and comparative analysis of a SARS-associated virus (Isolate BJOI) doi = 10.1007/bf03183930 id = cord-343827-jo61t3m0 author = Qian, Qun title = Direct evidence of active SARS-CoV-2 replication in the intestine date = 2020-07-08 keywords = CoV-2; SARS summary = We investigated the presence of virions and pathological changes in surgical rectal tissues of a clinically confirmed COVID-19 patient with rectal adenocarcinoma. RNA of SARS-CoV-2 was detected in surgically resected rectal specimens, but not in samples collected on 37 day after discharge. Notably, coincidence with rectal tissues of surgical specimens tested nucleic acid positive for SARS-CoV-2, typical coronavirus virions in rectal tissue were observed under electron microscopy. Notably, fecal samples remained positive for SARS-CoV-2 RNA nearly 5 weeks after the viral clearance from the upper respiratory tract in COVID-19 patients [8] . To clarify the above questions, we performed a retrospective study to detect the presence of SARS-CoV-2 virions and determine the pathological changes in rectal tissues of this patient. Samples of rectal tissues, succus entericus and intestinal mucosa of ileostomy, and rectal mucosa were tested for SARS-CoV-2 nucleic acid using qRT-PCR. doi = 10.1093/cid/ciaa925 id = cord-290792-ggcz1zfw author = Qutob, N. title = Seroprevalence of SARS-CoV-2 in Palestine: a cross-sectional seroepidemiological study date = 2020-09-01 keywords = CoV-2; SARS summary = doi = 10.1101/2020.08.28.20180083 id = cord-329190-kv9n2qj3 author = Rabaan, Ali A. title = A review of candidate therapies for Middle East respiratory syndrome from a molecular perspective date = 2017-09-01 keywords = CoV; East; IFN; MERS; Middle; SARS summary = The current therapies have mainly been adapted from severe acute respiratory syndrome (SARS-CoV) treatments, including broad-spectrum antibiotics, corticosteroids, interferons, ribavirin, lopinavir–ritonavir or mycophenolate mofetil, and have not been subject to well-organized clinical trials. The Medline database was searched using combinations and variations of terms, including ''Middle East respiratory syndrome coronavirus'', ''MERS-CoV'', ''SARS'', ''therapy'', ''molecular'', ''vaccine'', ''prophylactic'', ''S protein'', ''DPP4'', ''heptad repeat'', ''protease'', ''inhibitor'', ''anti-viral'', ''broad-spectrum'', ''interferon'', ''convalescent plasma'', ''lopinavir ritonavir'', ''antibodies'', ''antiviral peptides'' and ''live attenuated viruses''. A position paper on the evidence base for specific MERS-CoV therapies, published by Public Health England (PHE) and the World Health Organization-International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC-WHO), suggested that benefit was likely to exceed risk for convalescent plasma, lopinavir-ritonavir, IFNs and monoclonal/polyclonal antibodies, while, by contrast, for ribavirin monotherapy and corticosteroids it was considered that the risks would outweigh the benefits [42] . doi = 10.1099/jmm.0.000565 id = cord-275252-4e3cn50u author = Rad SM, Ali Hosseini title = Implications of SARS-CoV-2 mutations for genomic RNA structure and host microRNA targeting date = 2020-05-16 keywords = CoV-2; RNA; SARS; mutation summary = In addition to amino acid changes, mutations could affect RNA secondary structure critical to viral life cycle, or interfere with sequences targeted by host miRNAs. We have analysed subsets of genomes from SARS-CoV-2 isolates from around the globe and show that several mutations introduce changes in Watson-Crick pairing, with resultant changes in predicted secondary structure. The impact of these and further mutations on secondary structures, miRNA targets or potential splice sites offers a new context in which to view future SARS-CoV-2 evolution, and a potential platform for engineered viral attenuation and antigen presentation. A common primary focus of mutational analysis of emerging viruses is the alteration in amino acid sequence of viral proteins that may provide enhanced or new functions for virus replication, immune avoidance, or spread. However, the potential of these mutations to impact upon RNA structure and miRNA recognition provides a basis for ongoing monitoring of viral evolution at these sites in the SARS-CoV-2 genome. doi = 10.1101/2020.05.15.098947 id = cord-311114-ggcpsjk8 author = Radhakrishnan, Chandni title = Initial insights into the genetic epidemiology of SARS-CoV-2 isolates from Kerala suggest local spread from limited introductions date = 2020-09-09 keywords = CoV-2; India; Kerala; SARS summary = The rapid increase in the COVID-19 cases in the state of Kerala has necessitated the understanding of the genetic epidemiology of circulating virus, evolution, and mutations in SARS-CoV-2. The analysis identified 166 unique high-quality variants encompassing 4 novel variants and 89 new variants identified for the first time in SARS-CoV-2 samples isolated from India. Phylogenetic and haplotype analysis revealed that the circulating population of the virus was dominated (94.6% of genomes) by three distinct introductions followed by local spread, apart from identifying polytomies suggesting recent outbreaks. Further analysis of the functional variants revealed two variants in the S gene of the virus reportedly associated with increased infectivity and 5 variants that mapped to five primer/probe binding sites that could potentially compromise the efficacy of RT-PCR detection. In our analysis, we mapped the SARS-CoV-2 genetic variants obtained from Kerala genomes to the 132 primer or probes sequence and calculated the melting temperature (Tm) of the mutant with the wild type sequence. doi = 10.1101/2020.09.09.289892 id = cord-334564-bqh9jkds author = Raony, Ícaro title = Psycho-Neuroendocrine-Immune Interactions in COVID-19: Potential Impacts on Mental Health date = 2020-05-27 keywords = COVID-19; CoV-2; HPA; IL-6; SARS; severe summary = Since COVID-19 is associated with increased levels of pro-inflammatory cytokines (8) , an immune signature shared with several psychiatric disorders, we propose how the relationship between SARS-CoV-2/host can possibly impair interactions between the immune, nervous and endocrine systems, leading to psychiatric symptoms. Several studies have demonstrated psychiatric manifestations in patients with MERS or SARS during the acute phase, such as increased stress levels, impaired memory, symptoms of depression, anxiety, PTSD, psychoses, and suicidal behavior (28) (29) (30) (31) (32) (33) . If the increase in cytokine levels and the manifestation of psychiatric symptoms are related to the severity of the symptoms of SARS-CoV infection, the "cytokine storm" might also be related to the "mental health thunderstorms" seen in patients with COVID-19? Similar to possible mechanisms involved in the impacts of SARS-CoV-2 infection on mental health, social isolation may also be associated with dysfunctional psycho-neuroendocrine-immune interactions, which in turn can contribute to the development or the worsening of psychiatric disturbances (Figure 2) . doi = 10.3389/fimmu.2020.01170 id = cord-323093-u3ozc9ry author = Rathnayake, Athri D. title = 3C-like protease inhibitors block coronavirus replication in vitro and improve survival in MERS-CoV–infected mice date = 2020-08-19 keywords = CoV; Fig; MERS; SARS; compound summary = After we observed that treatment with compound 6j resulted in the survival of MERS MA -CoV-infected hDPP4-KI mice, we conducted another study by delaying treatment initiation until 3 dpi. This nucleoside analog was originally developed as an antiviral drug against Ebola virus and has been shown to be effective against both MERS-CoV and SARS-CoV in cell culture assays and in animal models of coronavirus infection (23) (24) (25) (26) . Prophylactic treatment or early therapeutic treatment of infected mice with remdesivir reduced MERS-CoV-or SARS-CoV-mediated weight loss and decreased lung virus titers and lung injury scores compared to those of vehicle-treated animals (23, 26) . The goal of this study was to evaluate the efficacy of 3CLpro inhibitors against human coronaviruses, including SARS-CoV-2, in a FRET enzyme assay and cell culture assays, as well as in a mouse model of MERS-CoV infection. doi = 10.1126/scitranslmed.abc5332 id = cord-336150-l8w7xk0b author = Rathore, Jitendra Singh title = Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a newly emerged pathogen: an overview date = 2020-08-25 keywords = ACE2; CoV-2; MERS; RBD; SARS summary = The essential surface glycoprotein of SARS-CoV-2 known as spike (S) protein, essential for host cell receptor binding, showed only 72% similarity with SARS-CoV at the nucleotide level. Comparative genome analysis of RaTG13, a virus from a Rhinolophusaffinis (i.e. horseshoe) bat sampled from Yunnan province in China in 2013, with SARS-CoV-2, showed that SARS-CoV-2 has 96% similarity at the nucleotide sequence level . Later, it was found that the disease was caused by a virus designated as a novel human coronavirus, MERS-CoV, phylogenetic data showed that it belonged to lineage C of the Betacoronavirusgenus and was highly similar to bat coronaviruses HKU4 (Tylonycterispachypus) and HKU5 (Pipistrelluspipistrellus; Lau et al. When cell lines over-expressed the transmembrane protein ''angiotensin-converting enzyme 2'' (ACE2) from humans, bats, pig or civet cats and were infected with SARS-CoV-2, results showed that they became hypersensitized to infection, thus indicating that ACE2 is a SARS-CoV-2 receptor . Recently, neutralizing monoclonal antibodies and nanobodies against the RBD domain of S protein showed protection against SARS-CoV and MERS-CoV (Du et al. doi = 10.1093/femspd/ftaa042 id = cord-350557-7i7122zi author = Rawlings, Stephen A title = No Evidence of SARS-CoV-2 Seminal Shedding Despite SARS-CoV-2 Persistence in the Upper Respiratory Tract date = 2020-08-07 keywords = CoV-2; SARS summary = We evaluated the presence and level of SARS-CoV-2 RNA in semen, nasal secretion, and saliva collected after confirmed infection. SARS-CoV-2 RNA was not detected in semen 6–17 days after the onset of symptoms despite concomitant shedding in oral secretions. Here, we evaluated the presence and level of SARS-CoV-2 in paired semen, nasal secretion, and saliva samples collected in the short and medium term after confirmed SARS-CoV-2 symptomatic infections. Before enrollment, 5/6 participants tested positive for SARS-CoV-2 RNA on NP swab samples collected within 1-3 days following the onset of symptoms. Upon enrollment in the study, the diagnosis of active SARS-CoV-2 infection was confirmed by positive PCR on NP swab on day 6 post-symptom onset. We found no evidence of SARS-CoV-2 in semen collected 6-17 days after the onset of symptoms despite all men having concomitant shedding of virus in oral secretions up to 792 copies/µL. doi = 10.1093/ofid/ofaa325 id = cord-254446-yxqbe1dj author = Ren, Yunzhao R. title = A Comprehensive Updated Review on SARS‐CoV‐2 and COVID‐19 date = 2020-05-29 keywords = COVID-19; China; CoV-2; Coronavirus; Disease; SARS; patient summary = The disease name -COVID-19‖ and the associated virus name -SARS-CoV-2‖ were coined by the World Health Organization (WHO) and the Coronavirus Study Group of the International Committee on Virus Taxonomy, respectively, on February 11 1, 2 . Interestingly, pharyngeal swab viral nucleic acid screening results of 2,510 patients between January 23 and February 25 from a hospital fever clinic in Hunan Province (a neighboring province of Hubei) demonstrated that the positive rate of SARS-CoV-2 (1.3%) was lower than that of Influenza A (2.3%) and Influenza B (3.3%) 42 . Clinical characteristics of fatal and recovered cases of coronavirus disease 2019 (COVID-19) in Wuhan, China: a retrospective study Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial doi = 10.1002/jcph.1673 id = cord-313505-2lr4xara author = Resende, Paola Cristina title = Genomic surveillance of SARS-CoV-2 reveals community transmission of a major lineage during the early pandemic phase in Brazil date = 2020-06-18 keywords = CoV-2; SARS summary = title: Genomic surveillance of SARS-CoV-2 reveals community transmission of a major lineage during the early pandemic phase in Brazil Phylogenetic analyses revealed multiple introductions of SARS-CoV-2 in Brazil and the community transmission of a major B.1.1 lineage defined by two amino acid substitutions in the Nucleocapsid and ORF6. Introduction 59 COVID-19, the disease caused by Severe Acute Respiratory Syndrome Coronavirus-2 60 (SARS-CoV-2), is leading to high rates of acute respiratory syndrome, hospitalization, and death 61 genomes (> 10% of ambiguous positions), we obtained a final dataset of 7,674 sequences. The prevalence of the sub-clade 211 B.1.1 in our sample (92%) was much higher than that observed in other Brazilian sequences 212 available in GISAID (36%) (Fig. 1C) phylogenetic tree, consistent with the hypothesis of multiple independent introductions (Fig. 2) (Fig. 2) . Revealing COVID-19 Transmission by SARS-CoV-2 Genome 410 Sequencing and Agent Based Modelling. doi = 10.1101/2020.06.17.158006 id = cord-346539-kxnrf5g5 author = Riggioni, Carmen title = A compendium answering 150 questions on COVID‐19 and SARS‐CoV‐2 date = 2020-06-14 keywords = ACE2; COVID-19; CoV-2; SARS; cell; clinical; figure; infection; patient; respiratory; severe summary = This paper answers pressing questions, formulated by young clinicians and scientists, on SARS‐CoV‐2, COVID‐19 and allergy, focusing on the following topics: virology, immunology, diagnosis, management of patients with allergic disease and asthma, treatment, clinical trials, drug discovery, vaccine development and epidemiology. The first cases of the coronavirus disease 2019 (COVID19) , caused by the novel severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), were reported in China in December 2019 1 and rapidly led to pandemic. 40, 41 A seroconversion study in COVID-19 patients has found and association between disease severity and SARS-CoV-2-specific IgA levels. Mesenchymal stem cell therapy may potentiate the low IFN-I and -III levels and moderate IFN-stimulated gene response reported in SARS-CoV-2-infected ferrets and COVID-19 patients. Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial doi = 10.1111/all.14449 id = cord-291397-look6ddt author = Roberto, Palumbo title = Current treatment of COVID-19 in renal patients: hope or hype? date = 2020-09-28 keywords = COVID-19; CoV-2; HCL; SARS; patient summary = Given the lack of specific therapy about the ongoing SARS-CoV-2 infection, we conducted a brief review to summarize the mechanism of action and the potentially side effects of the treatment currently available, focusing on the effects of the drugs on renal disease at different stages in terms of therapeutic management and survival. A randomized clinical trial, handled by a Chinese group, suggested that in hospitalized adult patients with severe infection, no benefit was observed with lopinavir/ritonavir beyond standard care in terms of time to clinical improvement, reduction of mortality and safety (side effects and discontinuation of treatment) [29, 30] . Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a randomized clinical trial doi = 10.1007/s11739-020-02510-0 id = cord-314451-mqnqjn0c author = Roberts, Anjeanette title = A Mouse-Adapted SARS-Coronavirus Causes Disease and Mortality in BALB/c Mice date = 2007-01-12 keywords = BALB; CoV; MA15; SARS; TCID; Urbani summary = To generate a model that satisfies these criteria, we have serially passaged SARS-CoV in the respiratory tract of young BALB/c mice, resulting in a lethal virus that causes dosedependent weight loss and mortality associated with higher viral titers in the respiratory tract than are seen with the wildtype virus and with histopathologic findings of severe pulmonary disease. Northern blot analysis of RNA from infected Vero E6 cells indicated that genomic vRNA and viral mRNA and all eight sub-genomic mRNAs were present in similar ratios for the recombinant viruses and MA15 virus as for SARS-CoV (Urbani) ( Figure 2A ). In order to evaluate whether changes in tissue tropism or levels of viral replication could contribute to the lethal phenotype of the MA15 virus, viral titers in lungs, spleen, liver, and brain of BALB/c mice were determined at various time points following intranasal inoculation with SARS-CoV (Urbani) or MA15. doi = 10.1371/journal.ppat.0030005 id = cord-321901-zpi7uis1 author = Roberts, Anjeanette title = Animal models and antibody assays for evaluating candidate SARS vaccines: Summary of a technical meeting 25–26 August 2005, London, UK date = 2006-11-30 keywords = CoV; SARS; animal; antibody; vaccine summary = Scientists at the WHO Technical Meeting on Animal Models and Antibody Assays for Evaluating Candidate SARS Vaccines held on 25-26 August 2005 in South Mimms, UK, discussed many aspects of research pertaining to the use of animal models in vaccine development including available animal models, suitability of the various models, correlates of protection, critical components of potential vaccines, and the potential for disease enhancement in vaccinated animals following exposure to SARS-CoV. It may actually be worthwhile to enhance the virulence of a SARS-CoV isolate by serial passages in an animal model to produce a challenge virus stock for vaccine studies that would elicit more reproducible disease in the animals. Although none of the studies to date have shown enhanced respiratory disease following SARS-CoV challenge in previously immunized animals, further studies in this area are warranted in view of some of the available in vitro data. Development and characterization of a severe acute respiratory syndrome-associated coronavirus-neutralizing human monoclonal antibody that provides effective immunoprophylaxis in mice doi = 10.1016/j.vaccine.2006.07.009 id = cord-347706-r0rs3ls1 author = Roberts, Anjeanette title = Animal Models for Sars date = 2006 keywords = BALB; CoV; SARS summary = Mice that recover from infection develop a neutralizing antibody response and are protected from subsequent challenge; antibody alone is sufficient to protect mice from replication of SARS-CoV in the lower respiratory tract and NK, NK-T, T, and B cells are not required for viral clearance. 13, 13b CoV disease, with weight loss and pneumonitis that begins with acute bronchiolitis and In summary, SARS-CoV replicates efficiently in the respiratory tract of young viremia occurs 1 to 2 days following infection and virus is detected in the liver and spleen in hamsters. As seen with the other animal models, the course of infection in experimentally infected nonhuman primates is short, with a rapid peak in viral replication and clearance of virus from the lungs by days 4 to 7 in different species. Development and characterization of a severe acute respiratory syndrome-associated coronavirus-neutralizing human monoclonal antibody that provides effective immunoprophylaxis in mice doi = 10.1007/978-0-387-33012-9_83 id = cord-309633-1cd74xdl author = Rogers, Julia H. title = Characteristics of COVID-19 in Homeless Shelters: A Community-Based Surveillance Study date = 2020-09-15 keywords = CoV-2; SARS; shelter summary = MEASUREMENTS: The primary outcome measure was test positivity rate of SARS-CoV-2 infection at shelters, determined by dividing the number of positive cases by the total number of participant encounters, regardless of symptoms. CONCLUSION: Active surveillance and surge testing were used to detect multiple cases of asymptomatic and symptomatic SARS-CoV-2 infection in homeless shelters. Surge testing was initiated on 30 March 2020 (and continued through 24 April) in collaboration with Public Health-Seattle & King County''s Communicable Disease Epidemiology Team to conduct contact tracing at 6 shelters where cases of SARS-CoV-2 were previously detected ( Figure 2 ). We calculated the test positivity rate of SARS-CoV-2 infection at shelters by dividing the number of positive cases by the total number of participant encounters in the study period. Overall, 2% of participant encounters involved positive SARS-CoV-2 results, with most cases detected through surge testing events. doi = 10.7326/m20-3799 id = cord-287501-7it4kh0e author = Roh, Changhyun title = A facile inhibitor screening of SARS coronavirus N protein using nanoparticle-based RNA oligonucleotide date = 2012-05-03 keywords = CoV; RNA; SARS summary = We have previously shown that quantum dots (QDs)-conjugated RNA oligonucleotide is sensitive to the specific recognition of the SARS-associated coronavirus (SARS-CoV) nucleocapsid (N) protein. Among the polyphenolic compounds examined, (−)-catechin gallate and (−)-gallocatechin gallate demonstrated a remarkable inhibition activity on SARS-CoV N protein. 33 In this study, we report a novel approach for the inhibitor screening of SARS-CoV N protein using a quantum dots (QDs)-conjugated oligonucleotide system with wide applicability for facile and sensitive imaging analysis on a biochip. To the best of our knowledge, this is the first report on the inhibition effects of (-)-catechin gallate and (-)-gallocatechin gallate on SARS-CoV N protein using an optical nanoparticle-based RNA oligonucleotide platform. Among the polyphenolic compounds screened, (-)-catechin gallate and (-)-gallocatechin gallate showed high anti-SARS-CoV N protein activity. At a concentration of 0.05 µg mL -1 , (-)-catechin gallate and (-)-gallocatechin gallate showed more than 40% inhibition activity on a QDs-RNA oligonucleotide biochip platform. doi = 10.2147/ijn.s31379 id = cord-350992-l6l24pco author = Roldan, Eugenia Quiros title = The possible mechanisms of action of 4-aminoquinolines (chloroquine/hydroxychloroquine) against Sars-Cov-2 infection (COVID-19): A role for iron homeostasis? date = 2020-05-13 keywords = COVID-19; Cov-2; HCQ; Sars; iron summary = Here we review what is currently known on the mechanisms of action of CQ and HCQ as anti-viral, anti-inflammatory and anti-thrombotic drugs and discuss the up-to-date experimental evidence on the potential mechanisms of action of CQ/HCQ in Sars-Cov2 infection and the current clinical knowledge on their efficacy in the treatment of COVID-19 patients. We also propose a different insight into some of CQ and HCQ effects, suggesting a potential role of iron homeostasis in Sars-Cov-2 disease (COVID-19), similarly to several other human viral infections [2] [3] [4] . The search strategy was to use different search terms alone and in any combination, such as "Sars-Cov-2 disease", "COVID-19", "Sars-Cov-2", "coronavirus", "clinical trial", "treatment", "drug", "chloroquine", "hydroxychloroquine", "iron", "virus", "viral entry", "viral spread", "anti-viral activity", "infection", "inflammation", "immunity", "innate immunity", "cytokine", "IL-6", "TNF-", "IL-1", "adaptive immunity", "thrombosis", "in vitro". doi = 10.1016/j.phrs.2020.104904 id = cord-278618-7tu5c7m1 author = Romano-Bertrand, Sara title = Sustainability of SARS-CoV-2 in aerosols: Should we worry about airborne transmission? date = 2020-06-12 keywords = CoV-2; SARS summary = This is based on previous knowledge [1] and the doctrine that: a patient positive for SARS-CoV-2 is contagious by respiratory secretions (>10μm in size) that disseminate only on short distance (<1m); SARS-CoV-2 carried on large droplets settles onto local surfaces and is not stable in the air; SARS-CoV-2 aerosol dispersion is possible during AGPs which extensively expose HCWs and therefore HCWs need to wear a respirator for a higher respiratory protection during AGPs. However, an experimental study of van Doremalen et al, [2] assessed the sustainability of SARS-CoV-2 in aerosols (<5μm at 65% of hygrometry (expressed in %RH for relative humidity)) performed using a high-powered machine that does not reflect normal cough conditions (https://www.who.int/publications-detail/modes-of-transmission-of-virus-causing-covid-19-implicationsfor-ipc-precaution-recommendations). They showed that SARS-CoV-2 remained viable and infective at least 3 hours in aerosols, which opened the debate on SARS-CoV-2 transmission through longdistance aerosols (>1m), and questioned the appropriateness of respiratory protection for HCWs. An individual who is well, emits 10 to 10 4 particles per liter of expired air, including 95% of <1μm-size particles [3] . doi = 10.1016/j.jhin.2020.06.018 id = cord-356009-emn2w8if author = Roshandel, M. R. title = What Specimen Urologists Should Be Most Concerned About ? A Systematic Review and Meta-Analysis date = 2020-10-13 keywords = COVID-19; CoV-2; RNA; SARS summary = Conclusions: Our review concludes that not only the SARS-CoV-2 can be excreted in the urine in eight ?percent of patients but also its incidence may have associations with the severity of the ?systemic disease, ICU admission, and fatality rates. The searches included medical subject headings (MeSH) and keywords for SARS-CoV-2, COVID, Corona, together with shedding, persistence, urine, urinary, specimen, viral load, or RNA body fluids. We completed the data abstraction process using created forms to record study characteristics, clinical data, and laboratory data including study year and design, country of study origin, total initial population size, test type for disease diagnosis, test type for samples (urine/stool/rectal swab/blood), patients age (including mean and range), number of positive and total patients and/or (wherever applicable) number of positive and total specimens collected for each test category, disease severity, ICU admission, and fatality rate. doi = 10.1101/2020.10.08.20209544 id = cord-309289-vm0k7hfx author = Rothan, Hussin A. title = The FDA- approved gold drug Auranofin inhibits novel coronavirus (SARS-COV-2) replication and attenuates inflammation in human cells date = 2020-04-14 keywords = COV-2; SARS summary = title: The FDAapproved gold drug Auranofin inhibits novel coronavirus (SARS-COV-2) replication and attenuates inflammation in human cells These data indicate that auranofin could be a useful drug to limit SARS-CoV-2 infection and associated lung injury due to its anti-viral, anti-inflammatory and anti-ROS properties. Herein, we report that the FDA-approved gold drug, auranofin, inhibits SARS-COV-2 replication in human cells at low micro molar concentration. Herein, we report that the FDA-approved gold drug, auranofin, inhibits SARS-COV-2 replication in human cells at low micro molar concentration. These data indicate that auranofin could be a useful drug to limit SARS-CoV-2 infection and associated lung injury due to its anti-viral, antiinflammatory and anti-ROS properties. We investigated the anti-viral activity of auranofin against SARS-CoV-2 and its effect on virus-induced inflammation in human cells. These data indicate that auranofin could be a useful drug to limit SARS-CoV-2 infection and associated lung injury. doi = 10.1101/2020.04.14.041228 id = cord-262276-5nue46dm author = Roussel, Yanis title = SARS-CoV-2: fear versus data date = 2020-03-19 keywords = CoV-2; SARS summary = The first, severe acute respiratory syndrome (SARS) coronavirus, had very little impact on global morbidity and mortality, with more than 80 0 0 recognized cases and 774 deaths [15 , 16] . Among the Organisation for Economic Co-operation and Development (OECD) countries, 7476 patients have tested positive for SARS-CoV-2, with 96 deaths (mortality rate 1.3%) ( Table 3 ). In France, 191 people have tested positive for SARS-CoV-2, with three deaths (mortality rate 1.6%). If the extrapolation of deaths in AP-HM hospitals is correct, in metropolitan France, this would represent 543/0.8 * 100 = 67 875 cases of patients hospitalized with a respiratory infection with common coronaviruses in 2 months, which is almost as many cases as for SARS-CoV-2 worldwide. Epidemiology and clinical characteristics of human coronaviruses OC43, 229E, NL63, and HKU1: a study of hospitalized children with acute respiratory tract infection in Guangzhou, China doi = 10.1016/j.ijantimicag.2020.105947 id = cord-029813-o2uzcuai author = Rusconi, Stefano title = COVID-19: studying the global pandemic – foreword date = 2020-07-27 keywords = CoV-2; SARS; covid-19 summary = This special issue of Future Virology contains nine articles on diverse aspects of the COVID-19 pandemic and its causative agent, SARS-CoV-2. The topics range from basic virology on coronavirus evolution and replication to identification of repurposed therapeutics for clinical testing to public health issues including the conundrums of asymptomatic viral transmission and risks to homeless populations. The Commentary by Parvez [1] briefly reviews the detection of SARS-CoV-2 RNA in fecal samples, including its persistence, and the finding of gastrointestinal complaints in a minority of hospitalized patients. While it is clear that this phytochemical has multiple pharmacological activities, as reviewed previously [10] , this in silico report does not provide biologic data on rutin''s possible effects in SARS-CoV-2 infection. Detection of relatively high SARS-CoV-2 RNA loads in upper respiratory tract samples has been reported in both presymptomatic (late incubation period) and truly asymptomatic infected persons. Transmission and clinical characteristics of asymptomatic patients with SARS-CoV-2 infection doi = 10.2217/fvl-2020-0211 id = cord-158628-71n1tgrw author = Russo, Giulia title = In Silico Trial to test COVID-19 candidate vaccines: a case study with UISS platform date = 2020-05-05 keywords = CoV-2; SARS; UISS; cell summary = Recently, specific findings about the genome sequencing of SARS-CoV-2 in different countries where cases of infection were registered, revealed its relative intrinsic genomic variability, its virus dynamics and the related host response mechanisms, unveiling interesting knowledge useful for the formulation of innovative strategies for preventive vaccination. Specifically, SARS-CoV-2 sequencing along with its relative intrinsic genomic variability [10] , the presence of minority variants generated during SARS-CoV-2 replication [11] , the involved cellular factors that favors SARS-CoV-2 cell entry [12] , the timing in which viral load peaks (during the first week of illness), its gradual decline (over the second week) and the increasing of both IgG and IgM antibodies (around day 10 after symptom onset) represent some of the relevant insights so far delineated and considered by research community about SARS-CoV-2 virus [13] . UISS is an immune system simulation platform that was designed to be applied to several and different scenarios, especially to carry on in silico trials to predict the efficacy of a specific prophylactic or therapeutic vaccine against a particular disease. doi = nan id = cord-344714-0cam9ipf author = Russo, Maria title = Roles of flavonoids against coronavirus infection date = 2020-07-28 keywords = 3CL; ACE2; COVID-19; CoV; RNA; SARS summary = Here, we reviewed the capacity of well-known (e.g. quercetin, baicalin, luteolin, hesperetin, gallocatechin gallate, epigallocatechin gallate) and uncommon (e.g. scutellarein, amentoflavone, papyriflavonol A) flavonoids, secondary metabolites widely present in plant tissues with antioxidant and anti-microbial functions, to inhibit key proteins involved in coronavirus infective cycle, such as PL(pro), 3CL(pro), NTPase/helicase. Inhibition of TMPRSS2 and Furin protease activities can be considered an interesting therapeutic option against coronavirus infection, especially COVID-19, allowing the block and/or prevention of SARS-CoV-2 infection, as recently reported [28] . Based on these observations, it is not surprising that molecular docking approach, summarized in Fig. 3 , supports the role of flavonoids in the inhibition of SARS-CoV 3CL pro by binding His41 and Cys145 of the catalytic site and other active site residues (e.g., Met49, Gly143, His163, His164, Glu166, Pro168, and Gln89), stimulating their validation by in vitro and in vivo studies. doi = 10.1016/j.cbi.2020.109211 id = cord-286269-vrjyj2y1 author = Sagheb, Setareh title = Two seriously ill neonates born to mothers with COVID-19 pneumonia- a case report date = 2020-09-21 keywords = COV-2; COVID-19; SARS summary = doi = 10.1186/s13052-020-00897-2 id = cord-337089-ksh62ni0 author = Salajegheh Tazerji, Sina title = Transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to animals: an updated review date = 2020-09-21 keywords = COVID-19; CoV-2; MERS; SARS summary = In addition to the considerable COVID-19 cases, hospitalizations, and deaths in humans, several cases of SARS-CoV-2 infections in animal hosts (dog, cat, tiger, lion, and mink) have been reported. Therefore, this study aimed to gather information about the reported cases of COVID-19 transmission in animals through a literary review of works published in scientific journals and perform genomic and phylogenetic analyses of SARS-CoV-2 isolated from animal hosts. However, based on recently published findings, other authors hypothesized that an immunological cross-protection between SARS-CoV-2 and canine respiratory coronavirus (CRCoV) exists due to the high homology between the spike protein epitopes of the two taxonomicallyrelated coronaviruses [21] . The objective of the present study was to gather, present, and discuss information on the reported cases of COVID-19 in animals focusing on the virus transmission cases in pets and perform genomic and phylogenetic analyses of SARS-CoV-2 isolated from animal hosts. doi = 10.1186/s12967-020-02534-2 id = cord-335652-v98gv5uf author = Salazar, Cecilia title = Multiple introductions, regional spread and local differentiation during the first week of COVID-19 epidemic in Montevideo, Uruguay date = 2020-05-10 keywords = CoV-2; SARS; Uruguay summary = Methods We performed whole-genome sequencing of 10 SARS-CoV-2 from patients diagnosed during the first week (March 16th to 19th) of COVID-19 outbreak in Uruguay. Our analysis set the bases for future genomic epidemiology studies to understand the dynamics of SARS-CoV-2 in Uruguay and the Latin America and the Caribbean region. This global health emergency has deployed international efforts to apply genomic epidemiology to track the spread of SARS-CoV-2 in real time. The recent development of targeted sequencing protocols by the ARTIC Network [3] , open sharing of genomic data through the GISAID (www.gisaid.org) database and straightforward bioinformatic tools for viral phylogenomics [4] , provides the opportunity to reconstruct global spatio-temporal dynamics of the COVID-19 pandemic with unprecedented comprehensiveness and resolution. We therefore aimed to characterize the spatio-temporal dynamics of SARS-CoV-2 by sequencing around 10% of cases occurred during the first week of outbreak in Montevideo, allowing us to identify transmission patterns, geographic origins and genetic variation among local strains. doi = 10.1101/2020.05.09.086223 id = cord-332595-874tpi09 author = Salehi, Najmeh title = Profiling of Initial Available SARS-CoV-2 Sequences from Iranian Related COVID-19 Patients date = 2020-09-08 keywords = CoV-2; SARS summary = To this purpose, SARS-CoV-2 full genome sequence profiling of 20 patients in Iran and different countries that already had a travel history to Iran or contacts with Iranian cases were provided from the GISAID database. The bioinformatics analysis showed 44 different nucleotide mutations that caused 26 nonsynonymous mutations in protein sequences with regard to the reference full genome of the SARS-CoV-2 sequence (NC_045512.2). On the other hand, nineteen sequences of the full genome sequence of SARS-CoV-2 on the GISAID database from patients in different countries that had a travel history to Iran or contacts with Iranian cases were retrieved from the database. In this study, the full genome sequences of SARS-CoV-2 from the 20 Iranian related COVID-19 patients were profiled in detail. B. The nucleotide and protein mutations, the number of mutation events in data from the 20 Iranian related patients, the entropy values of these mutations in all 3927 SARS-CoV-2 sequences, and the corresponded proteins are depicted. doi = 10.22074/cellj.2020.7524 id = cord-273451-xnce010o author = Salisbury-Afshar, Elizabeth M. title = Vulnerable Populations: Weathering the Pandemic Storm date = 2020-04-22 keywords = CoV-2; SARS summary = Yet, even with awareness that all individuals deserve access to services, and that supporting marginalized populations will slow the spread of SARS-CoV-2, resource limitations will demand difficult allocation determinations. 3 Many individuals experiencing homelessness with SARS-CoV-2 will not meet hospitalization criteria and will be discharged into the general population. 11 In response to SARS-CoV-2, the Substance Abuse and Mental Health Services Administration has developed emergency regulations to support medication for opioid use disorder via telehealth, 12 and temporarily waived the requirement for in-person physical exam to be able to initiate buprenorphine. These often forgotten populations-people incarcerated, homeless, or using drugs-are likely to experience higher risk of exposure to SARS-CoV-2 because of their social circumstances. Planning should incorporate dedicated efforts, funding, and policies/guidelines specific to individuals who experience homelessness, are incarcerated, or are coping with substance use disorders both because these populations deserve care and services, and because not doing so poses great risk to the broader community. doi = 10.1016/j.amepre.2020.04.002 id = cord-267134-5gz2dotn author = Sallenave, Jean-Michel title = Innate Immune Signaling and Proteolytic Pathways in the Resolution or Exacerbation of SARS-CoV-2 in Covid-19: Key Therapeutic Targets? date = 2020-05-28 keywords = ACE2; CoV; SARS; cell; virus summary = doi = 10.3389/fimmu.2020.01229 id = cord-025119-201ac32t author = Salman, Saad title = Virtual screening of immunomodulatory medicinal compounds as promising anti-SARS-COV-2 inhibitors date = 2020-05-21 keywords = COV-2; SARS; compound summary = Results: Out of more than 300 medicinal compounds, only six compounds: arzanol, ferulic acid, genistein, resveratrol, rosmanol and thymohydroquinone showed significant interaction with the SARS viral proteins by forming hydrogen bonds with the active site residues with low binding energy. Here, we analyzed different medicinal compounds using a virtual screening method to obtain promising inhibitors for these viral proteins that could be further utilized for SARS-COV-2 treatment. More than 300 medicinal compounds with immunomodulatory and antiviral activity were added to the Raccoon2 plugin of Autodock vina to perform virtual screening to obtain promising inhibitors for SARS-COV-2 proteins. This study aimed to obtain novel drug candidates that have the capability to interact with the active site of all of these viral proteins and should possess efficient pharmacokinetic profile with low toxicity to ensure safety during administration. • Docking interaction of immunomodulatory medicinal compounds library filtered six promising medicinal compounds against severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) viral proteins. doi = 10.2217/fvl-2020-0079 id = cord-340049-6rqmc89u author = Salvatori, Giovanni title = SARS-CoV-2 SPIKE PROTEIN: an optimal immunological target for vaccines date = 2020-06-03 keywords = CoV-2; SARS summary = Evidence of the key role played by the S protein in counteracting coronavirus infection came from studies on human-neutralizing antibodies from rare memory B cells of individuals infected with SARS-CoV [2] or MERS-CoV [3] . Journal of Translational Medicine antibody responses, and vigorously neutralized SARS-CoV-2 S-mediated entry into cells, thus further encouraging the use of this molecular target for vaccination and immunotherapies [4] . Given the above and that the coronavirus S glycoprotein is surface-exposed and mediates entry into host cells by interacting with angiotensin-converting enzyme 2 (ACE2), it rapidly became the main target of neutralizing antibodies and the focus of therapeutic and vaccine design. Several companies and research institutes have started developing a vaccine that has the SARS-CoV-2 protein S as its target (see Table 1 ), although the various vaccination strategies show a differing ability to induce in the host both an antibody-mediated humoral response and a cell response mediated by CD4 or CD8 T lymphocytes in preclinical models. doi = 10.1186/s12967-020-02392-y id = cord-334550-xb0alubj author = Samaddar, Arghadip title = The Enigma of Low COVID-19 Fatality Rate in India date = 2020-07-28 keywords = BCG; CoV-2; SARS; covid-19; indian summary = These include some ongoing mutations that can alter the virulence of the circulating SARS-CoV-2 strains, host factors like innate immunity, genetic diversity in immune responses, epigenetic factors, genetic polymorphisms of ACE2 receptors, micro RNAs and universal BCG vaccination, and environmental factors like high temperature and humidity which may alter the viability and transmissibility of the strain. Researchers from Translational Bioinformatics Group at International Center for Genetic Engineering and Biotechnology (ICGEB) in collaboration with the Department of Biochemistry, Jamia Hamdard, New Delhi, India, performed an integrated mutational analysis of SARS-CoV-2 genomes from different geographical locations, including India, Italy, United States, Nepal and Wuhan, and observed a novel mutation in S protein (A930V, 24351C>T) of the Indian strain, which was absent in other strains (Sardar et al., 2020) . While this apparent protection among Indians is largely attributed to non-heritable influences as discussed earlier, a safe and effective vaccine against SARS-CoV-2 can reduce disease severity, control transmission, and prevent future infections across all populations. doi = 10.3389/fgene.2020.00854 id = cord-259229-e8m8m4ut author = Samidurai, Arun title = Cardiovascular Complications Associated with COVID-19 and Potential Therapeutic Strategies date = 2020-09-16 keywords = ACE2; COVID-19; China; CoV-2; Coronavirus; SARS; Wuhan; patient summary = doi = 10.3390/ijms21186790 id = cord-289588-n61gz7pi author = Samudrala, Pavan Kumar title = Virology, pathogenesis, diagnosis and in-line treatment of COVID-19 date = 2020-07-17 keywords = COVID-19; CoV-2; Coronavirus; SARS summary = Literature reported a significant mutation in receptor binding sites and membrane proteins of the previous SARS-CoV to turned as SARS-CoV-2 virus, responsible for most dreadful pandemic COVID-19. As far as safety is a major concern, 424 Gilead Sciences announced phase III clinical trial of remdesivir to prove its safety and 425 efficacy in COVID-19 infection (Keown, 16 .03.2020). Epidemiology, causes, clinical manifestation and 687 diagnosis, prevention and control of coronavirus disease (COVID-19) during the early 688 outbreak period: a scoping review First known person-to-784 person transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 785 the USA Clinical 803 features of patients infected with 2019 novel coronavirus in Wuhan SARS-CoV-2 (COVID-19) Vaccine Development and Production: An 817 Severe acute respiratory 845 syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The 846 epidemic and the challenges Unique epidemiological and clinical features 949 of the emerging 2019 novel coronavirus pneumonia (COVID-19) implicate special control 950 measures doi = 10.1016/j.ejphar.2020.173375 id = cord-293691-ewerquin author = Sauerhering, Lucie title = Cyclophilin Inhibitors Restrict Middle East Respiratory Syndrome Coronavirus Via Interferon λ In Vitro And In Mice date = 2020-07-02 keywords = CoV; East; MERS; figure summary = RATIONALE: While severe coronavirus infections, including Middle East respiratory syndrome coronavirus (MERS-CoV) cause lung injury with high mortality rates, protective treatment strategies are not approved for clinical use. METHODS: Calu-3 cells and primary human alveolar epithelial cells (hAEC) were infected with MERS-CoV and treated with CsA or ALV or inhibitors targeting cyclophilin inhibitor-regulated molecules including Calcineurin, NFAT, or MAP kinases. To address the previously proposed antiviral activity of CsA in clinically relevant cells, we infected the human bronchial epithelial cell line Calu-3 and primary human alveolar epithelial cells (hAEC) with MERS-CoV and analyzed intracellular viral RNA and infectious particle release in presence of DMSO or CsA ( Figure 1 ). Our data demonstrated that silencing of IRF1 but not treatment by control siRNA lead to a significant increase in MERS-CoV released viral particles in CsA-treated cells ( Figure 6A , B). doi = 10.1183/13993003.01826-2019 id = cord-024133-zv0ysi8m author = Saxena, Shailendra K. title = Current Insight into the Novel Coronavirus Disease 2019 (COVID-19) date = 2020-04-30 keywords = COVID-19; CoV-2; SARS summary = On 11 March 2020, the World Health Organization (WHO) declared severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a pandemic that causes novel coronavirus disease 2019 (COVID-19) (World Health Organization 2020a). In addition, the scientific fraternity worldwide has been continuously working on COVID-19 from the beginning by publishing the genome and developing highly specific diagnostic tools for the detection of SARS-CoV-2 infection. There is no specific treatment available for SARS-CoV-2 and the current treatment relies on supportive care of the infected patients (Centre for Disease Control and Prevention 2020b). Fig. 1.3 Steps needed to be taken by COVID-19 patients in order to prevent the spread of SARS-CoV-2 infection Interim guidelines for collecting, handling, and testing clinical specimens from persons for coronavirus disease 2019 (COVID-19). Centre for Disease Control and Prevention (2020b) Interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19). doi = 10.1007/978-981-15-4814-7_1 id = cord-309474-9h9w46eq author = Schiaffini, Riccardo title = School and pre-school children with type 1 diabetes during covid-19 quarantine: the synergic effect of parental care and technology date = 2020-07-03 keywords = cov; diabetes; t1d summary = We compared insulin and CGM data (TIR, TBR and TAR) of two periods: PRE-COV and IN-COV, in which children have transitioned from normal school attendance to the exclusive care of their parents. This is a real-life, retrospective, observational study aimed at evaluating how constant parental care compared to spending time outside home affected glycemic control in pre-school and school children with T1D utilizing Tandem Basal IQ system before and during the quarantine period due to pandemic COVID-19 infection. Our observational real-life study confirms the positive effect of parental care in T1D very young children and that, though new technologies can potentially improve diabetes outcomes also in this sub-population, maintenance of a good glucose control remains largely dependent on family competence and education 10. doi = 10.1016/j.diabres.2020.108302 id = cord-124012-5zxkd2jy author = Schwab, Patrick title = predCOVID-19: A Systematic Study of Clinical Predictive Models for Coronavirus Disease 2019 date = 2020-05-17 keywords = CoV-2; ICU; SARS summary = Here, we study clinical predictive models that estimate, using machine learning and based on routinely collected clinical data, which patients are likely to receive a positive SARS-CoV-2 test, require hospitalisation or intensive care. In addition, [48] performed a cohort study for clinical and laboratory predictors of COVID-19 related inhospital mortality that identified baseline neutrophil count, age Fig. 2 : The presented multistage machine-learning pipeline consists of preprocessing (light purple) the input data x, developing multiple candidate models using the given dataset (orange), selecting the best candidate model for evaluation (blue), and evaluating the selected best model''s outputsŷ. Owing to the recent emergence of SARS-CoV-2, there currently exists, to the best of our knowledge, no prior systematic study on clinical predictive models that predict likelihood of a positive SARS-CoV-2 test, hospital and intensive care unit admission from clinical, demographic and blood analysis data that accounts for the missingness that is characteristic for the clinical setting. doi = nan id = cord-284867-p4jgyusp author = Schöler, Lara title = A Novel In-Cell ELISA Assay Allows Rapid and Automated Quantification of SARS-CoV-2 to Analyze Neutralizing Antibodies and Antiviral Compounds date = 2020-10-09 keywords = CoV-2; SARS; figure summary = Altogether, the SARS-CoV-2 icELISA test allows rapid (<48 h in total, read-out in seconds) and automated quantification of virus infection in cell culture to evaluate the efficacy of NAbs and antiviral drugs using reagents and equipment present in most routine diagnostics departments. The fact that the infection and the resulting icELISA signal were neutralized by NAbs present in immune sera indicated that the fast and automated icELISA format is applicable for icNTs. Although most SARS-CoV-2 NTs have not been formally validated and certified, classic plaque reduction neutralization tests (PRNT) are currently considered to represent the gold standard for the detection of SARS-CoV-2-specific NAbs. Various commercially available IgM, IgA, and IgG ELISAs have been compared to PRNTs [e.g., (30) ]. Given the excellent signal-to-noise ratio between infected and uninfected cells, the test was applicable to quantify the efficacy of antiviral compounds, here shown for IFNb, and SARS-CoV-2-specific NAbs present in immune sera. doi = 10.3389/fimmu.2020.573526 id = cord-324919-ciamusjs author = Scialo, Filippo title = ACE2: The Major Cell Entry Receptor for SARS-CoV-2 date = 2020-11-10 keywords = ACE2; COVID-19; CoV-2; SARS summary = Since the beginning of the COVID-19 pandemic, hypertension and diabetes have been correlated with higher risk of mortality, and initial reports speculated that angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs), which are commonly used therapeutic agents for these conditions, would up-regulate ACE2 expression, thus increasing the risk of severe illness [37] . Binding of S1 subunit of the Spike protein of SARS-CoV-2 to the ACE2 receptor triggers the cleavage of ACE2 by ADAM17/tumor necrosis factorconverting enzyme (TACE) at the ectodomain sites [41] and a soluble form that retains its catalytic activity (sACE2) is produced [42] . ACE2 shedding can be stimulated by proinflammatory cytokines such as IL-1β and tumor necrosis factor (TNF)-α, and endotoxin [47] that could result in a positive effect reducing SARS-CoV-2 entry, but at the same time, may cause an increase in AngII and further activation of the AngII/AT1R axis worsening inflammation (discussed below) (Fig. 1) . Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2) doi = 10.1007/s00408-020-00408-4 id = cord-284589-j1609xlu author = Sedova, Mayya title = Coronavirus3D: 3D structural visualization of COVID-19 genomic divergence date = 2020-05-29 keywords = CoV-2; SARS summary = RESULTS: Coronavirus3D website integrates data on the SARS-CoV-2 virus mutations with information about 3D structures of its proteins, allowing users to visually analyze the mutations in their 3D context. At the same time, with the exception of the spike protein mutations, there are no publicly available resources that provide analysis for all the other structurally characterized regions of the SARS-CoV-2 proteins. For commercial re-use, please contact journals.permissions@oup.com MN908947.3), with information on boundaries of the predicted proteins, currently available SARS-CoV-2 structures and a histogram of the aminoacid mutation frequency. The first of the lower level panels (Figure 1b) provides interactive visualization of the selected structure or model, with an option for coloring the chain according to the mutation frequency. The Coronavirus3D server was designed to provide users with information and tools to carry out their own analysis of how mutations in the SARS-CoV-2 proteins may affect their 3D-structures and their functions. doi = 10.1093/bioinformatics/btaa550 id = cord-309418-dx6e0lri author = Segalés, Joaquim title = Detection of SARS-CoV-2 in a cat owned by a COVID-19−affected patient in Spain date = 2020-10-06 keywords = COVID-19; CoV-2; SARS summary = Several models for SARS-CoV-2 infection have been so far developed in animals, including Egyptian fruit bat, ferret, golden Syrian hamster, cat, humanized angiotensin-converting enzyme 2 (ACE2) transgenic mice (hACE2 mice), and some nonhuman primate species (3) (4) (5) (6) (7) (8) . The clinical condition was finally attributed to a feline hypertrophic cardiomyopathy, but the animal was also infected by SARS-CoV-2. The detection of SARS-CoV-2 RNA in several samples of C1, all of them with Ct values over 30 (low viral load), and presence of antibodies (neutralizing and nonneutralizing) in both C1 and C2, indicated both animals suffered from a productive viral infection, probably linked to the exposure of the cats to COVID-19−affected owners. These experimental results, together with the few reports on SARS-CoV-2 detection in domestic cats and wild felids, indicate that felines are susceptible to infection by the novel coronavirus. doi = 10.1073/pnas.2010817117 id = cord-315085-rucfowvv author = Sekulic, Miroslav title = Molecular Detection of SARS-CoV-2 Infection in FFPE Samples and Histopathologic Findings in Fatal SARS-CoV-2 Cases date = 2020-05-26 keywords = CoV-2; FFPE; RNA; SARS; lung summary = In this study we report postmortem findings and detection and sequencing of SARS-CoV-2 viral RNA from formalin-fixed paraffinembedded (FFPE) samples of multiple organs collected in 2 patients with antemortem detection of SARS-CoV-2. The patient''s medical history was otherwise notable for dementia, radiologic evidence of a left lung mass (managed with hospice care), coronary artery disease (status post coronary artery bypass grafting), atrial fibrillation (biventricular pacemaker implanted), congestive heart failure, peripheral artery disease (status post iliac stenting), diabetes mellitus, hypertension, dyslipidemia, chronic kidney disease, gout, smoking, cerebrovascular accidents, and urinary tract infections. On day 1 after admission, ❚Image 2❚ (Case 1) Postmortem microscopic examination of the lungs showed diffuse alveolar damage characterized by hyaline membrane formation (A, ×100) and scattered squamous metaplasia of distal airways (B, ×100) on a background of emphysematous changes. doi = 10.1093/ajcp/aqaa091 id = cord-342756-rgm9ffpk author = Senger, Mario Roberto title = COVID-19: molecular targets, drug repurposing and new avenues for drug discovery date = 2020-10-02 keywords = ACE2; COVID-19; CoV-2; Fig; MERS; RNA; SARS; clinical; drug; protein summary = Here, we aimed at presenting a critical view of ongoing drug repurposing efforts for COVID-19 as well as discussing opportunities for development of new treatments based on current knowledge of the mechanism of infection and potential targets within. In the following topic, we will review SARS-CoV-2 structure and mechanism of infection in order to discuss molecular targets from the virus or its human host that are being considered for drug repurposing and perhaps future development of new drugs. (128) Its role as a functional receptor of SARS-CoV-2 S protein in host cells makes this protein a potential drug target to treat COVID-19. (138) TMPRSS2 has a major role in SARS-CoV-2 cell entry and replication, and thus represents an interesting therapeutic target since its inhibitors could potentially block virus infection in its initial stages. (199) A robust preclinical drug discovery pipeline comprising in vitro, and in vivo models of SARS-CoV-2 infection is particularly important to identify new antivirals for human COVID-19 treatment. doi = 10.1590/0074-02760200254 id = cord-268483-joiajgs4 author = Shah, Vibhuti Kumar title = Overview of Immune Response During SARS-CoV-2 Infection: Lessons From the Past date = 2020-08-07 keywords = COVID-19; CoV-2; MERS; SARS; cell; coronavirus summary = As there are no specific treatments available for this novel coronavirus, numerous small molecular drugs that are being used for the treatment of diseases like SARS, MERS, HIV, ebola, malaria, and tuberculosis are being given to COVID-19 patients, and clinical trials for many such drugs have already begun. An ELISA-based time kinetics study to detect the COVID-19 specific humoral immune response showed that the patients produced IgM and IgG antibodies that did not cross-react with other human coronaviruses except SARS-CoV. A case study on pediatric patients reports that 5 out of 6 children showed a protective humoral response, with neutralizing IgG and IgM antibodies targeting the N and S-RBD proteins of SARS-CoV-2 (65) . T cell responses are required for protection from clinical disease and for virus clearance in severe acute respiratory syndrome coronavirus-infected mice doi = 10.3389/fimmu.2020.01949 id = cord-331472-kd4uxcve author = Shahid, Zainab title = COVID‐19 and Older Adults: What We Know date = 2020-04-20 keywords = COVID-19; CoV-2; SARS summary = Studies have shown that this virus causes worse outcomes and a higher mortality rate in older adults and those with comorbidities such as hypertension, cardiovascular disease, diabetes, chronic respiratory disease, and chronic kidney disease (CKD). 5 The Centers for Disease Control and Prevention (CDC) reported that although individuals older than age 65 comprise 17% of the total population in the United States, they make up 31% of COVID-19 infections, 45% of hospitalizations, 53% of intensive care unit admissions, and 80% of deaths caused by this infection. 15, 16 These symptoms are also common in older adults; one study on 21 critically ill patients with SARS-CoV-2 infection, with a mean age of 70 years, found that the most common presenting symptoms were shortness of breath (76%), fever (52%), and cough (48%). 19 One study on 46 fatal cases of SARS-CoV-2, in which 84% of patients were older than age 60, found that diabetes is likely associated with increased mortality. doi = 10.1111/jgs.16472 id = cord-314669-lvibjx97 author = Shang, Guifang title = Theoretically estimated risk of severe acute respiratory syndrome transmission through blood transfusion during an epidemic in Shenzhen, Guangdong, China in 2003 date = 2007-11-26 keywords = CoV; SARS; Shenzhen summary = title: Theoretically estimated risk of severe acute respiratory syndrome transmission through blood transfusion during an epidemic in Shenzhen, Guangdong, China in 2003 STUDY DESIGN AND METHODS: Case onset dates from the 2003 Shenzhen SARS epidemic and investigational results from Taiwan on viremia in humans are used to estimate the number of cases that were viremic throughout the epidemic. RESULTS: Based on data from Shenzhen, Hongkong and Taiwan, the maximum and mean risk (per million) of SARS-CoV transmission from donors in Shenzhen were estimated as 23.57 (95% CI: 6.83–47.69) and 14.11 (95% CI: 11.00–17.22), respectively. Theoretically estimated risk of severe acute respiratory syndrome transmission through blood transfusion during an epidemic in Shenzhen, Guangdong, China in 2003 Then, using this information and information on the asymptomatic or subclinical SARS-CoV infection-to-clinically confirmed SARS ratio (R), the proportion of infected individuals who remain asymptomatic (A), and the population size, we estimated the risk of SARS-CoV transmission by transfusion from a unit of blood donated at time t during the epidemic. doi = 10.1016/j.transci.2007.09.004 id = cord-305856-xt3zxajf author = Shanmugam, Chandrakumar title = COVID-2019 – A comprehensive pathology insight date = 2020-09-18 keywords = COVID-19; China; CoV-2; SARS; acute summary = Corona virus disease-2019 (COVID-19) caused by severe acute respiratory syndrome corona virus-2 (SARS CoV-2), a highly contagious single stranded RNA virus genetically related to SARS CoV. Pathologically, the lungs show either mild congestion and alveolar exudation or acute respiratory distress syndrome (ARDS) with hyaline membrane or histopathology of acute fibrinous organizing pneumonia (AFOP) that parallels disease severity. The current pandemic of corona virus disease-2019 (COVID-19) caused by severe acute respiratory syndrome corona virus-2 (SARS CoV-2) led to complete lockdown in many countries contributing to major socio-economic crisis and irreparable recession, globally. [22, 31, 32, 33] Similar to SARS CoV, a recent study reported non-O blood group specifically group A had higher infection and death rates due to COVID-19 owing to absence of protective anti-A IgM antibodies. Pulmonary pathology of early phase 2019 novel coronavirus (COVID-19) pneumonia in two patients with lung cancer The clinical pathology of severe acute respiratory syndrome (SARS): a report from China doi = 10.1016/j.prp.2020.153222 id = cord-268388-kkhuzf3p author = Sharif-Yakan, Ahmad title = Emergence of MERS-CoV in the Middle East: Origins, Transmission, Treatment, and Perspectives date = 2014-12-04 keywords = CoV; MERS; respiratory summary = Two years have passed since the initial description of the Middle East respiratory syndrome coronavirus (MERS-CoV), yet the epidemic is far from being controlled. First reported in 2012 [1] , Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel coronavirus and the first lineage 2C Betacoronavirus known to infect humans [2] . Middle east respiratory syndrome coronavirus (MERS-CoV) RNA and neutralising antibodies in milk collected according to local customs from dromedary camels, qatar Middle east respiratory syndrome coronavirus (MERS-CoV) in dromedary camels Epidemiological, demographic, and clinical characteristics of 47 cases of middle east respiratory syndrome coronavirus disease from saudi arabia: A descriptive study Clinical features and viral diagnosis of two cases of infection with middle east respiratory syndrome coronavirus: A report of nosocomial transmission Clinical features and virological analysis of a case of middle east respiratory syndrome coronavirus infection Ribavirin and interferon therapy in patients infected with the middle east respiratory syndrome coronavirus: An observational study doi = 10.1371/journal.ppat.1004457 id = cord-324480-7u5lh4jx author = Sharma, A. title = Structural stability of SARS-CoV-2 degrades with temperature date = 2020-10-14 keywords = CoV-2; SARS summary = Here we have used atomic force microscopy to examine the structural stability of individual SARS-CoV-2 virus like particles at different temperatures. This is consistent with other existing non-mechanistic studies of viral infectivity, provides a single particle perspective on viral seasonality, and strengthens the case for a resurgence of COVID-19 in winter. However an understanding of how SARS-CoV-2 survives different environmental conditions is still incomplete and mechanisms of virus particle degradation are poorly mapped out. A key challenge in studying SARS-CoV-2 is the extreme level of threat associated with the live virus and the resultant need for high safety standards for such work. Here we used this technology to study the stability of the viral envelope and associated proteins (M, E, and S) under different environmental conditions. Environmental stability of SARS-CoV-2 on different types of surfaces under indoor and seasonal climate conditions doi = 10.1101/2020.10.12.336818 id = cord-033551-eojpkxz9 author = Shekh, Shamasoddin title = In silico allicin induced S-thioallylation of SARS-CoV-2 main protease date = 2020-09-16 keywords = CoV-2; SARS summary = In the current report, using virtual screening methods, reactive sulfur species allicin is subjecting for covalent docking at the active site of SARS-CoV-2 M(pro) using PX-12 as a benchmark reference compound. Figure 1a shows the structure of SARS-CoV-2 M pro with free cysteine thiols and active site dyad residues. Figure 2b shows the formation of cysteine allyl disulfide at the Cys-145 residue of SARS-CoV-2 M pro after covalent docking with allicin. Figure 4b and c show the formation of cysteine allyl disulfide at Cys-85 and Cys-156 residue of SARS-CoV-2 M pro after covalent docking with allyl sulfenic acid. Table-S2 provides a summary of covalent docking of allicin/PX-12/allyl sulfenic acid at cysteine thiols of four different co-crystal structures of SARS-CoV-2 M pro . Figure 5b shows the sulfur mediated hydrogen bonding by the sulfur of allyl disulfide formed after covalent docking of allicin at the active site of SARS-CoV-2 M pro . doi = 10.1080/17415993.2020.1817457 id = cord-325966-0g7a9s5z author = Shih, Hsin-I. title = Fighting COVID-19: a quick review of diagnoses, therapies, and vaccines date = 2020-05-30 keywords = BCG; COVID-19; CoV-2; RNA; SARS; vaccine summary = Some candidate drugs targeting different levels and stages of human responses against COVID-19 such as cell membrane fusion, RNA-dependent RNA polymerase, viral protease inhibitor, interleukin 6 blocker, and convalescent plasma may improve the clinical outcomes of critical COVID-19 patients. However, these clinical, laboratory, and imaging findings are nonspecific and cannot differentiate COVID-19 from other viral respiratory infections; viral diagnostic methods specific for SARS-CoV-2 should be applied for disease confirmation. An open-label study published in 2004 suggested, by comparison with a control group that received only ribavirin, that the addition of lopinavir-ritonavir (400 mg and 100 mg, respectively) to ribavirin reduced the risk of adverse clinical outcomes (acute respiratory distress syndrome or death) and viral load among patients with SARS [29] . Some available candidate drugs targeting different levels of human responses to COVID-19, such as cell membrane fusion, RNA-dependent RNA polymerase, viral protease inhibitor, IL-6 blocker and convalescent plasma, may improve the clinical outcomes of critical COVID-19 patients. doi = 10.1016/j.bj.2020.05.021 id = cord-254636-3lr008th author = Shishir, Tushar Ahmed title = In silico comparative genomics of SARS-CoV-2 to determine the source and diversity of the pathogen in Bangladesh date = 2020-08-16 keywords = Bangladesh; CoV-2; SARS summary = We conducted comparative analysis of publicly available whole-genome sequences of 64 SARS-CoV-2 isolates in Bangladesh and 371 isolates from another 27 countries to predict possible transmission routes of COVID19 to Bangladesh and genomic variations among the viruses. Compared to the ancestral SARS-CoV-2 sequence reported from China, the isolates in Bangladesh had a total of 180 mutations in the coding region of the genome, and 110 of these were missense. We conducted comparative analysis of publicly available genome sequences of SARS-CoV-2 from 27 countries to predict the origin of viruses in Bangladesh by studying a time-4 resolved phylogenetic relationship. Later, we analyzed the variants present in different isolates of Bangladesh to understand the pattern of mutations in relation to the ancestral Wuhan strain, find unique mutations, and possible effect of these mutations on the stability of encoded proteins, and selection pressure on genes. doi = 10.1101/2020.07.20.212563 id = cord-308342-ycdok8fc author = Shutler, J. title = Risk of SARS-CoV-2 infection from contaminated water systems date = 2020-06-20 keywords = CoV-2; SARS; water summary = Collectively this evidence suggests that SARS-CoV-2 virus can survive 45 within water and the viral loads within untreated sewage effluent are likely high in countries 46 of high infection rates, a portion of which is viable virus, and therefore water contaminated 47 We note that adenoviruses are 122 known to be particularly resilient, and therefore likely to represent an upper estimate, but 123 also that our selected range is consistent with the 10 -3 value used elsewhere for assessing 124 viral risk in water systems (eg 14 ), including one assessment for SARS CoV-2 transmission 125 risk to wastewater workers 18 . Collectively this means that if a drinking water source 156 was to become infected with SARS-CoV-2 the standard virus removal and disinfection 157 approaches of ultraviolet exposure and chlorination may not reduce the virus below 158 detectable limits. doi = 10.1101/2020.06.17.20133504 id = cord-339344-qd73h1ie author = Simon, David title = Patients with immune-mediated inflammatory diseases receiving cytokine inhibitors have low prevalence of SARS-CoV-2 seroconversion date = 2020-07-24 keywords = COVID-19; CoV-2; IMID; SARS summary = To test whether differences in social exposure between the groups account for the low prevalence of SARS-CoV-2 IgG responses in IMID patients treated with cytokine inhibitors, we assessed exposure risk variables (contact with persons with a respiratory infection, presence at workplace outside home, travel to risk areas) of IMID patient groups and control groups. The low seroprevalence of SARS-CoV-2 in anti-cytokine treated IMIDs could have two principle explanations: While (i) the four groups were recruited in the same region, (ii) the HC control group having the highest prevalence for SARS-CoV-2 IgG was in direct contact with the IMID patients and (iii) all participants were exposed to similar detailed information regarding social behavior during the outbreak of the COVID-19 pandemic in Germany, IMID patients may have followed an even more stringent exposure prophylaxis than healthy individuals. doi = 10.1038/s41467-020-17703-6 id = cord-290290-wyx9ib7s author = Sinegubova, Maria V. title = High-level expression of the monomeric SARS-CoV-2 S protein RBD 320-537 in stably transfected CHO cells by the EEF1A1-based plasmid vector date = 2020-11-05 keywords = CHO; CoV-2; RBD; SARS; cell; protein summary = title: High-level expression of the monomeric SARS-CoV-2 S protein RBD 320-537 in stably transfected CHO cells by the EEF1A1-based plasmid vector Based on the previously developed p1.1 vector, containing the regulatory sequences of the Eukaryotic translation elongation factor 1 alpha gene (EEF1A1) from Chinese hamster, we created two expression constructs encoding SARS-CoV-2 RBD with C-terminal c-myc and polyhistidine tags. Previously we have developed the plasmid vector p1.1, containing large fragments of non-coding DNA from the EEF1A1 gene of the Chinese hamster and fragment of the Epstein-Barr virus long terminal repeat concatemer [21] and employed it for unusually high-level expression of various proteins in CHO cells, including blood clotting factors VIII [22] , IX [23] , and heterodimeric follicle-stimulating hormone [24] . We have proposed that SARS-CoV-2 RBD, suitable for in vitro diagnostics use, may be expressed in large quantities by stably transfected CHO cells, bearing the EEF1A1-based plasmid. doi = 10.1101/2020.11.04.368092 id = cord-319241-div9rzax author = Singh, Bhuchitra title = Severe Acute Respiratory Syndrome‐Corona Virus‐2 (SARS‐CoV‐2) and its Effect on Gametogenesis and Early Pregnancy date = 2020-09-23 keywords = ACE2; COVID-19; CoV-2; SARS summary = There is also evidence of significant placental pathology in SARS‐CoV‐2 infection, but it is unclear what effects there may be for early pregnancy, though available data suggest less severe effects compared to other respiratory virus outbreaks. We searched for articles that contained information related to SARS-CoV-2 and reproductive tissues (ovaries, testes), gametes, placentation, and early pregnancy in humans. Our search phrases included: "severe acute respiratory syndrome coronavirus 2", "2019 ncov", "sarscov 2", "SARS-Cov-2", "pregnancy", "gravidity", "abortion", "germ cells", "oocytes", "gametes", "embryonic structures", "embryo", "fertility", "testes", "miscarriage"(See Appendix 1 for completed list of databases search strategy and Figure 1 for PRISMA table). Specifically, 10 women with severe COVID-19 were tested or SARS-CoV-2 in vaginal fluid, with all samples negative for virus [48] . Another study performed during the 2002-2003 SARS pandemic showed that 4 of 7 (57%) pregnant women infected with SARS-CoV had a spontaneous miscarriage in the first trimester of pregnancy [55] , though notably no viral inclusion bodies or particles were detected in the products of conception. doi = 10.1111/aji.13351 id = cord-268476-3lxsh1zz author = Skoog, Hunter title = Tracheotomy in the SARS‐CoV‐2 pandemic date = 2020-04-29 keywords = CoV-2; SARS summary = The severe acute respiratory syndrome (SARS)‐CoV‐2 pandemic continues to produce a large number of patients with chronic respiratory failure and ventilator dependence. The severe acute respiratory syndrome (SARS)-CoV-2 pandemic continues to produce a large number of patients with chronic respiratory failure and ventilator dependence. Our priorities in establishing these guidelines included: optimal patient care, protection of medical personnel, minimizing further spread of the virus and preservation of important resources (ICU beds, ventilators, and PPE). Due to the paucity of data regarding the current SARS-CoV-2 epidemic, the literature from the SARS epidemic of In Canada, 43% of cases occurred in health care workers as a result of AGPs. 1,2 One instance involved a difficult intubation of a patient who was under investigation for SARS. There are multiple reports 3,4 of safely performing tracheotomy on patients with SARS without infecting health care workers. doi = 10.1002/hed.26214 id = cord-029112-u507i0t0 author = Smith, Keisha title = A Phase 3 Open-label, Randomized, Controlled Study to Evaluate the Efficacy and Safety of Intravenously Administered Ravulizumab Compared with Best Supportive Care in Patients with COVID-19 Severe Pneumonia, Acute Lung Injury, or Acute Respiratory Distress Syndrome: A structured summary of a study protocol for a randomised controlled trial date = 2020-07-13 keywords = ALXN1210-COV-305; Alexion; Amendment; BSC; Investigator; SAE; day; patient; study summary = doi = 10.1186/s13063-020-04548-z id = cord-033780-184e64tr author = Smith, Rasheid title = Implications of current and future approaches to coronavirus disease 2019 testing date = 2020-10-13 keywords = COVID-19; CoV-2; SARS summary = The current reality is that SARS-CoV-2 is a highly transmissible airborne disease with a broad presentation of symptoms and leaves lasting damage in severe cases, and for which there is a scarcity of effective medications to treat it. Using the cycle threshold value in this manner only informs as to the presence of the virus and may not reveal disease progression, severity and viral load in the sample; and as such the results are largely qualitative despite the inherent quantitative nature of real-time RT-PCR [27] . Nevertheless, initial studies have demonstrated that chest CT imaging is more accurate than RT-PCR at detecting SARS-CoV-2 patients [32] with 97.2% versus 83% in the early stages of infection [33] . Immunoassays (antibody serum tests), such as enzyme-linked immunosorbent assays (ELISAs), are used to detect the presence of serum antibodies (either IgA, IgG or IgM) to viral proteins and can indicate when a person has developed an immune response to SARS-CoV-2. Rapid detection of COVID-19 causative virus (SARS-CoV-2) in human nasopharyngeal swab specimens using field-effect transistor-based biosensor doi = 10.2217/fvl-2020-0318 id = cord-341287-i1hyk962 author = Smith, Trevor R. F. title = Immunogenicity of a DNA vaccine candidate for COVID-19 date = 2020-05-20 keywords = ACE2; CoV-2; Fig; INO-4800; SARS; dna summary = Following immunization of mice and guinea pigs with INO-4800 we measure antigen-specific T cell responses, functional antibodies which neutralize the SARS-CoV-2 infection and block Spike protein binding to the ACE2 receptor, and biodistribution of SARS-CoV-2 targeting antibodies to the lungs. In subjects immunized with INO-4700 (MERS-CoV S protein DNA vaccine) durable neutralizing antibodies (nAbs) and T cell immune responses were measured, and a seroconversion rate of 96% was observed and immunity was followed for 60 weeks in most study volunteers 9 . We followed the induction of immunity by the selected immunogen in mice and guinea pigs, measuring SARS-CoV-2 S protein-specific antibody levels in serum and in the lung fluid, and antibody functionality through competitive inhibition of ACE2 binding, pseudovirus and live virus neutralization. In summary, humoral immunogenicity testing in both mice and guinea pigs revealed the COVID-19 vaccine candidate, INO-4800, was capable of eliciting functional blocking antibody responses to SARS-CoV-2 spike protein. doi = 10.1038/s41467-020-16505-0 id = cord-262045-r2iqpmmc author = Smits, Saskia L. title = Reliable typing of MERS-CoV variants with a small genome fragment date = 2014-12-15 keywords = CoV; MERS summary = RESULTS: A reverse-transcription PCR assay for MERS-CoV targeting a 615 bp spike fragment provides a phylogenetic clustering of MERS-CoV variants comparable to that of full-length genomes. In addition, the MERS-CoV variant typing assay was performed on camel samples from a slaughterhouse in Qatar [13] and sequences for 14 MERS-CoV positive animals with cycle threshold values ranging from 12.9 to 32.2 as determined by UpE real time RT-PCR [17, 18] were obtained (Fig. 2) . Subsequent analyses revealed a region in the open reading frame that encodes the spike protein with a number of positions in which nucleotide variation occurs between MERS-CoV variants with a strong phylogenetic signal regarding previously identified clusters of viruses based on full-length MERS-CoV genomes. Middle East respiratory syndrome coronavirus quasispecies that include homologues of human isolates revealed through whole-genome analysis and virus cultured from dromedary camels in Saudi Arabia doi = 10.1016/j.jcv.2014.12.006 id = cord-259603-bh198xgl author = Snijder, E.J. title = The Nonstructural Proteins Directing Coronavirus RNA Synthesis and Processing date = 2016-09-14 keywords = CoV; Fig; MHV; RNA; SARS; ZBD; protein summary = Reverse-genetics studies targeting specific residues in SARS-CoV nsp7 confirmed the protein''s importance for virus replication (Subissi et al., 2014b) , although the impact of single point mutations was smaller than anticipated on the basis of the biochemical characterization of the RNA-binding properties of nsp7-containing protein complexes in vitro (see later). The large number of viral subunits in these complexes (Subissi et al., 2014a) , the likely requirement for host factors (van Hemert et al., 2008) , and the concept of RNA synthesis occurring in a dedicated microenvironment in the infected cell (Knoops et al., 2008; V''Kovski et al., 2015) complicate the straightforward characterization of the CoV RdRp. To reconstitute the enzyme''s activities in vitro, purified recombinant nsp12 is a key reagent but, for many years, such studies were hampered by poor nsp12 expression in Escherichia coli. doi = 10.1016/bs.aivir.2016.08.008 id = cord-350903-nwagvvc5 author = Softic, Laurent title = Inhibition of SARS-CoV-2 Infection by the Cyclophilin Inhibitor Alisporivir (Debio 025) date = 2020-06-23 keywords = CoV-2; SARS summary = Alisporivir reduced SARS-CoV-2 RNA production in a dose-dependent manner in Vero E6 cells, with a 50% effective concentration (EC(50)) of 0.46 ± 0.04 μM. For instance, chloroquine has been shown to bear potent antiviral properties against SARS-CoV-2 in vitro, and several clinical trials are under way to assess its efficacy in patients with COVID-19. Cyclosporine A (CsA), a potent cyclophilin inhibitor, blocks the replication of various coronaviruses in vitro, including HCoV-229E, HCoV-NL63, FPIV, mouse hepatitis virus (MHV), avian infectious bronchitis virus, and SARS-CoV (5, (8) (9) (10) . The antiviral effectiveness of increasing concentrations of alisporivir was measured in Vero E6 cells infected with a clinical isolate of SARS-CoV-2 at a multiplicity of infection (MOI) of 0.02 (Fig. 1A) . These results justify rapidly conducting a proof-of-concept phase 2 trial to assess the antiviral properties and the effect of alisporivir on COVID-19 clinical outcomes in infected patients. doi = 10.1128/aac.00876-20 id = cord-338544-eph89g47 author = Spuntarelli, Valerio title = COVID-19: is it just a lung disease? A case-based review date = 2020-07-28 keywords = COV-2; COVID-19; SARS summary = COVID-19 pandemic reached 3.78 million confirmed reported cases worldwide, and it is generally associated to the acronym that precedes its name: severe acute respiratory syndrome (SARS). A prospective study investigating left ventricular performance in 46 patients with severe acute respiratory syndrome showed subclinical diastolic impairment without systolic involvement [3] . Pathological findings of COVID-19 associated with acute respiratory distress syndrome showed few interstitial mononuclear inflammatory infiltrates, but no other substantial damage in the heart tissue [7] . A case report highlights myocarditis as a complication associated with COVID-19, even without symptoms and signs of interstitial pneumonia in an otherwise healthy 53-year-old white woman [8] . The authors concluded that the presence of the characteristic features of symmetric, multifocal lesions with thalamic involvement suggests that this is a case of acute necrotizing hemorrhagic encephalopathy associated with COVID-19. Guillain Barre syndrome associated with COVID-19 infection: a case report doi = 10.1007/s42399-020-00418-6 id = cord-331429-mh2hd5fe author = Srikantiah, Padmini title = SARS Clinical Features, United States, 2003 date = 2005-01-17 keywords = CoV; SARS summary = We compared the clinical features of 8 U.S. case-patients with laboratory-confirmed severe acute respiratory syndrome (SARS) to 65 controls who tested negative for SARS coronavirus (SARS-CoV) infection. Shortness of breath, vomiting, diarrhea, progressive bilateral infiltrates on chest radiograph, and need for supplemental oxygen were significantly associated with confirmed SARS-CoV infection. Case-patients with laboratory-confirmed SARS were compared to a convenience sample of persons who met the clinical and epidemiologic criteria for suspected or probable SARS but subsequently tested negative for SARS-CoV infection. Controls had negative findings on all testing performed for SARS-CoV, including the absence of antibody against the virus in convalescent-phase serum samples obtained >21 days after onset of symptoms. Over the course of their illness, findings suggestive of a lower respiratory tract infection developed in all 8 patients with laboratory-confirmed SARS; these findings included dyspnea (n = 8), rales (n = 5), and hypoxia (n = 5) (Table 1) . doi = 10.3201/eid1101.040585 id = cord-329493-ueqlhgn0 author = Stadler, Konrad title = SARS — beginning to understand a new virus date = 2003 keywords = CoV; RNA; SARS; protein; virus summary = A new infectious disease, known as severe acute respiratory syndrome (SARS), appeared in the Guangdong province of southern China in 2002. When Thiel and colleagues 20 isolated one genomic and eight subgenomic RNAs from the FRA strain and sequenced their 5′ ends, they identified a conserved sequence (5′ACGAAC3′) that was located in coronaviruses: S, spike protein; E, envelope protein; M, membrane glycoprotein; and N, nucleocapsid protein. Alternatively, these antigens could be delivered by DNA immunization by Figure 6 | The S1 domain of SARS-CoV spike is structurally related to group 2 coronaviruses. Schematic representation of cysteine positions in the S1 domains of group 1, 2 and 3 coronaviruses, compared with the SARS-CoV spike protein. The complete genome sequence of a SARS-CoV isolate (FRA) and experimental data on its key RNA elements and protein functions are described. Comparative full-length genome sequence analysis of 14 SARS coronavirus isolates and common mutations associated with putative origins of infection doi = 10.1038/nrmicro775 id = cord-303741-1ou0cy5k author = Stafstrom, Carl E. title = COVID-19: Neurological Considerations in Neonates and Children date = 2020-09-10 keywords = CNS; COVID-19; CoV-2; SARS; child; infection summary = An especially apropos case demonstrated maternal viremia, placental infection shown by immunohistochemistry, and high placental viral load with subsequent neonatal viremia, implying transplacental transfer of SARS-CoV-2 from pregnant mother to fetus [24] ; this newborn presented with neurological symptoms as discussed in Section 3. The lack of unequivocal reports of SARS-CoV-2 being recovered from the CSF of individuals affected with presumed neurological involvement nor in brain tissue from the limited number of autopsied cases strengthens the possibility that the virus does not often directly cause the symptoms but rather, that the neurological sequelae are secondary to hypoxia, cytokine involvement, or some other non-direct mechanism (see Section 6). Finally, 4 of 27 children with COVID-19 associated MIS-C developed new neurologic symptoms including encephalopathy, headache, weakness, ataxia, and dysarthria [81] ; two patients had lumbar punctures and CSF was negative for SARS-CoV-2 in both. doi = 10.3390/children7090133 id = cord-275690-83nrzfon author = Stanifer, Megan L. title = Critical role of type III interferon in controlling SARS-CoV-2 infection, replication and spread in primary human intestinal epithelial cells date = 2020-04-24 keywords = CoV-2; Fig; IFN; SARS summary = title: Critical role of type III interferon in controlling SARS-CoV-2 infection, replication and spread in primary human intestinal epithelial cells Our results demonstrate that human intestinal epithelial cells fully support SARS-CoV-2 infection, replication and production of infectious de-novo virus particles. Importantly, and in agreement with the results observed in cells depleted of the type III IFN receptor, this increase in infectivity was also associated with an increase in infectious denovo virus particle production ( Fig. 3G ). All together, these results strongly support a model where the type III IFN mediated signaling controls SARS-CoV-2 infection in human intestinal epithelial cells. All together these results show that human colon organoids can support SARS-CoV-2 infection, replication and spread and that the type III IFN response plays a critical role in controlling virus replication. doi = 10.1101/2020.04.24.059667 id = cord-290796-x9xqqcj6 author = Stefanelli, P. title = Longevity of seropositivity and neutralizing titers among SARS-CoV-2 infected individuals after 4 months from baseline: a population-based study in the province of Trento date = 2020-11-13 keywords = CoV-2; SARS summary = All individuals above ten years of age resident in 5 municipalities of the Autonomous Province of Trento, northern Italy, who resulted IgG positive for anti-SARS-CoV-2 nucleocapsid (NC) antibodies in a serosurvey conducted on May 2020 were retested after 4 months. The duration of protection against infection with common human coronaviruses appears to be rather short 2, 3 , and there are studies showing declines in IgG antibodies against SARS-CoV-2 among both symptomatic and asymptomatic individuals 4, 5 . In order to evaluate the persistence of SARS-CoV-2 antibodies, we repeated a serosurvey in five municipalities of the Autonomous Province (AP) of Trento, Italy, recruiting those individuals who had resulted positive in a large population-based seroprevalence study conducted 4 months before 14 . The analyser automatically calculates SARS-CoV-2 NC IgG antibody concentration expressed as an is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint doi = 10.1101/2020.11.11.20229062 id = cord-353209-qkhfp66l author = Steiner, Daniel J. title = Array-based analysis of SARS-CoV-2, other coronaviruses, and influenza antibodies in convalescent COVID-19 patients date = 2020-06-16 keywords = CoV-2; SARS; air summary = We report a multiplex label-free antigen microarray on the Arrayed Imaging Reflectometry (AIR) platform for detection of antibodies to SARS-CoV-2, SARS-CoV-1, MERS, three circulating coronavirus strains (HKU1, 229E, OC43) and three strains of influenza. Aminereactive substrates for fabrication of AIR arrays were provided by Adarza BioSystems, Inc. For ELISA assays, SARS-CoV-2 full-length spike and RBD were produced in-house using a mammalian expression system, 20,21 as was influenza A/H1N1/California 2009 hemagglutinin. To that end, we have presented preliminary data on a 15-plex array on the AIR platform, developed in response to the need to study SARS-CoV-2 but incorporating antigens for other coronaviruses and influenza. Responses to SARS-CoV-2 antigens on the array effectively discriminated between serum samples from uninfected and COVID-19 convalescent subjects, with generally good correlation to ELISA data. doi = 10.1101/2020.06.15.153064 id = cord-342796-f7n8sxbu author = Stowe, J. title = Interactions between SARS-CoV-2 and Influenza and the impact of coinfection on disease severity: A test negative design date = 2020-09-18 keywords = CoV-2; SARS; influenza summary = Findings: The risk of testing positive for SARS-CoV-2 was 68% lower among influenza positive cases, suggesting possible pathogenic competition between the two viruses. The odds of ventilator use or death and ICU admission or death was greatest among coinfection patients showing strong evidence of an interaction effect compared to SARS-CoV-2/influenza acting independently. Severity and risk of death among individuals with a coinfection: The mortality rate among individuals with a SARS-CoV-2 and influenza coinfection and those with SARS-CoV-2 infection who tested negative for influenza was calculated by dividing the number of deaths by the total number of individuals tested by age group. We also found strong evidence that coinfection with influenza and SARS-CoV-2 was associated with an increased risk of death or severe disease and that this appears to be beyond the additive effect of the two viruses acting independently. doi = 10.1101/2020.09.18.20189647 id = cord-266348-tbr2ynx0 author = Stroemer, A. title = Diagnostic accuracy of six commercial SARS-CoV-2 IgG/total antibody assays and identification of SARS-CoV-2 neutralizing antibodies in convalescent sera date = 2020-06-17 keywords = CoV-2; SARS summary = Here, we compare the diagnostic accuracy of six commercially available SARS-CoV-2 IgG (Abbott SARS-CoV-2 IgG; Diasorin Liaison SARS-CoV-2 S1/2 IgG; Epitope EDI Novel Coronavirus COVID-19 IgG ELISA Kit; Euroimmun Anti-SARS-CoV-2 ELISA (IgG); Mikrogen recomWell SARS-CoV-2 IgG) or total SARS-CoV-2 antibody assays (Roche Elecsys Anti-SARS-CoV-2). The majority of assay results were confirmed in a laboratory-developed plaque reduction neutralization test and by a SARS-CoV-2 IgG-specific line assay including measurement of generally low IgG avidities (Mikrogen recomLine Coronavirus IgG [Aviditaet], prototype). Out 132 of the remaining 34 samples, only one serum (#20; Figure 1 ) which was obtained ten days after a positive 133 RT-PCR was tested negative for SARS-CoV-2 IgG/total antibodies in the six assays. Six of them -including three family members of a 153 confirmed COVID-19 case (#22; Figure 1 ) -were classified SARS-CoV-2 IgG/total antibody positive by the 154 majority of the tests. doi = 10.1101/2020.06.15.20131672 id = cord-291710-ixun0c8g author = Su, Haixia title = Discovery of baicalin and baicalein as novel, natural product inhibitors of SARS-CoV-2 3CL protease in vitro date = 2020-04-14 keywords = CoV-2; SARS; baicalein summary = A crystal structure of SARS-CoV-2 3CLpro in complex with baicalein, the first non-covalent, non-peptidomimetic small-molecule inhibitor, was also determined, revealing a unique binding mode of this natural product with the protease. To validate the binding of baicalin and baicalein with SARS-CoV-2 3CLpro and exclude the suspicion of being the pan-assay interference compounds (PAINS) (15) , their binding affinities with the protease were measured by isothermal titration calorimetry (ITC), widely known as an invaluable tool used to determine thermodynamic parameters of protein-ligand interactions such as Kd (Fig. 1, A and B ; Table 1 ). Moreover, the ITC profiles in combination with their chemical structures suggest that baicalin and baicalein act as noncovalent inhibitors of SARS-CoV-2 3CLpro with a high ligand binding efficiency. The mode of action of baicalein and the structural determinants associated with its binding with SARS-CoV-2 3CLpro were further explored using X-ray protein crystallography. doi = 10.1101/2020.04.13.038687 id = cord-312305-ll29frwc author = Sun, Shihui title = Characterization and structural basis of a lethal mouse-adapted SARS-CoV-2 date = 2020-11-11 keywords = COVID-19; CoV-2; Fig; SARS; mouse summary = Herein, we generated and characterized a novel mouse-adapted SARS-CoV-2 strain named MASCp36 that causes acute respiratory symptoms and mortality in standard laboratory mice. We further characterized the in vivo replication dynamics of MASCp6 in both young and aged mice, and the results from qRT-PCR showed that high levels of SARS-CoV-2 subgenomic RNAs were persistent in the lung and tracheas till 4 day post infection (dpi) in aged mice (Fig. 1E) . The skewed age distribution of COVID-19 disease was reproduced in the MASCp36 infected mouse model where more severe symptoms were observed in aged mice when compared to young mice. In addition to the age-related skewed distribution of COVID-19, gender-related differences in distribution of COVID-19 disease is also recapitulated in this MASCp36 infected mouse model with increased susceptibility and enhanced pathogenicity observed in male mice when compared to their female counterparts. doi = 10.1101/2020.11.10.377333 id = cord-352909-s11tpfoq author = Sun, Zhiping title = Survival of SARS-COV-2 under liquid medium, dry filter paper and acidic conditions date = 2020-08-14 keywords = COV-2; SARS summary = Survival of SARS-COV-2 under liquid medium, dry filter paper and acidic conditions Zhiping Sun 1 , Xia Cai 1 , Chenjian Gu 2 , Rong Zhang 2 , Wendong Han 1 , Yun Qian 1 , Yuyan Wang 2 , Wei Xu 2 , Yang Wu 2 , Xunjia Cheng 2 , Zhenghong Yuan 2 , Youhua Xie 2 and Di Qu 1, 2 Dear Editor, The pneumonia caused by a novel coronavirus was first reported in December 2019 in Wuhan of China, and since then has become a pandemic 1, 2 . Here, we first investigated the infectivity of SARS-COV-2 using a plaque-purified strain nCoV-SH01 isolated from a patient in Shanghai (GenBank MT121215) 6 , studied subsequently its stability in liquid medium, on dry filter paper, and under acidic condition (pH2.2) at RT. doi = 10.1038/s41421-020-00191-9 id = cord-268718-tt07cwrf author = Tan, Heng Wee title = Angiotensin‐converting enzyme 2: The old door for new severe acute respiratory syndrome coronavirus 2 infection date = 2020-06-30 keywords = ACE2; COVID-19; CoV-2; RNA; SARS summary = 54 Virus infectivity study has indicated that the SARS-CoV-2 is able to utilize ACE2 of human, Chinese horseshoe bats, civet, and pig but was not able to use mouse ACE2. The roles of ACE2 expression in SARS-CoV-2 pathogenesis and human COVID-19 susceptibility are largely unknown. B, ACE2 expression in lung cancer patients with different smoking histories analyzed using similar methods as described previously 106 other symptoms in addition to respiratory symptoms, suggesting that SARS-CoV-2 could perhaps infect other organs (Figure 3 ). 118 In addition to sputum, SARS-CoV-2 RNA has been detected in the stools of a COVID-19 patient, 119 F I G U R E 3 Tissue distribution of angiotensin-converting enzyme 2 (ACE2) expression and potential COVID-19 susceptibility. Expression of elevated levels of proinflammatory cytokines in SARS-CoV-infected ACE2 + cells in SARS patients: relation to the acute lung injury and pathogenesis of SARS doi = 10.1002/rmv.2122 id = cord-322051-89wgv100 author = Tanasa, Ingrid Andrada title = Anosmia and ageusia associated with coronavirus infection (COVID-19) - what is known? date = 2020-05-28 keywords = CoV-2; SARS; olfactory summary = This study summarizes the existing data regarding the association of anosmia and ageusia with the SARS-CoV-2 infection. In a retrospective observational study, Klopfenstein et al (20) reported that 54 patients (47%) with confirmed SARS-CoV-2 infection developed anosmia, 4.4 (±1.9) days after infection onset, and that was the third symptom to manifest in 38% (22/52) of the cases. Some authors reported three mechanisms for anosmia in COVID-19 patients: i) local infection of support cells and vascular pericytes in the nose and olfactory bulb that may affect the function of bipolar neurons or mitral cells; ii) damage to support cells in the sensory epithelium that may indirectly influence the signaling pathway from sensory neurons to the brain; and iii) damage to sustentacular cells and Bowman''s gland cells that could lead to diffuse morphological damage to the olfactory sensory epithelium and altering of smell perception (28, 29) . Further research is needed to demonstrate the association between anosmia and ageusia with SARS-CoV-2 infection, the clinical manifestations determined by variants of ACE2 receptor, and recovery rates of olfactory and gustative dysfunction, and specific treatment protocols of these manifestations. doi = 10.3892/etm.2020.8808 id = cord-269275-b7xxk48t author = Tang, Xiaojia title = Neurological manifestations in COVID-19 and its possible mechanism date = 2020-09-27 keywords = COVID-19; China; CoV-2; SARS; patient summary = SARS-CoV-2 has been reported to be associated with Guillain-Barré syndrome, rhabdomyolysis, acute cerebrovascular disease, central nervous system infections and other neurological diseases. Four formal reports have described neurological problems in SARS patients, including polyneuropathy [35] , myopathy and rhabdomyolysis [36] , large artery ischemic stroke [37] and central nervous system infections [38] . In a study by Mao et al., 214 patients diagnosed with COVID-19 were enrolled, and six (2.80%) of them developed acute cerebrovascular disease (five cases of ischemic stroke and one case of cerebral hemorrhage). Strokes are not uncommon in critically ill patients with multiple comorbidities, so SARS-CoV-2 infections in humans may increase the risk of stroke. Since some COVID-19 patients have complained of headaches, nausea etc, care providers should be alert for central nervous system infections caused by SARS-CoV-2 if such patients also exhibit symptoms such as a fever, epilepsy and disturbances of consciousness. doi = 10.18632/aging.103732 id = cord-015503-j99cgsjt author = Tang, Xiaolu title = On the origin and continuing evolution of SARS-CoV-2 date = 2020-03-03 keywords = CoV-2; SARS; type summary = Although we found only 4% variability in genomic nucleotides between SARS-CoV-2 and a bat SARS-related coronavirus (SARSr-CoV; RaTG13), the difference at neutral sites was 17%, suggesting the divergence between the two viruses is much larger than previously estimated. Our results suggest that the development of new variations in functional sites in the receptor-binding domain (RBD) of the spike seen in SARS-CoV-2 and viruses from pangolin SARSr-CoVs are likely caused by mutations and natural selection besides recombination. Population genetic analyses of 103 SARS-CoV-2 genomes indicated that these viruses evolved into two major types (designated L and S), that are well defined by two different SNPs that show nearly complete linkage across the viral strains sequenced to date. Further, the genomic sequences of SARS-CoV-2 viruses isolated from a number of patients share sequence identity higher than 99.9%, suggesting a very recent host shift into humans [1] [2] [3] . doi = 10.1093/nsr/nwaa036 id = cord-274841-rcdoewwv author = Tay, Matthew Zirui title = The trinity of COVID-19: immunity, inflammation and intervention date = 2020-04-28 keywords = ACE2; COVID-19; CoV-2; SARS summary = Monoclonal antibodies targeting the When severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects cells expressing the surface receptors angiotensin-converting enzyme 2 (ACE2) and TMPRSS2, the active replication and release of the virus cause the host cell to undergo pyroptosis and release damageassociated molecular patterns, including ATP, nucleic acids and ASC oligomers. While there are no clinical trials specifically testing these drugs against COVID-19 at the time of writing, when camostat mesylate was tested on SARS-CoV-2 isolated from a patient, it prevented entry of the virus into lung cells 44, 50 . Severe acute respiratory syndrome coronavirus (SARS-CoV) infection inhibition using spike protein heptad repeat-derived peptides T cell responses are required for protection from clinical disease and for virus clearance in severe acute respiratory syndrome coronavirus-infected mice Neutralizing antibodies in patients with severe acute respiratory syndrome-associated Nature reviews | Immunology coronavirus infection doi = 10.1038/s41577-020-0311-8 id = cord-350352-wgppovfx author = Temmam, Sarah title = Absence of SARS-CoV-2 infection in cats and dogs in close contact with a cluster of COVID-19 patients in a veterinary campus date = 2020-08-29 keywords = CoV-2; SARS; cat summary = In this cross-sectional study, we tested the antibody response in a cluster of 21 domestic pets (9 cats and 12 dogs) living in close contact with their owners (belonging to a veterinary community of 20 students) in which two students tested positive for COVID-19 and several others (n = 11/18) consecutively showed clinical signs (fever, cough, anosmia, etc.) compatible with COVID-19 infection. We investigated the presence of SARS-CoV-2 infection of domestic cats (n = 9) and dogs (n = 12) living in close contact with a cluster of French veterinary students, their owners (n = 18), whose median age was 23 years (21-28 years). Although based on a small cluster of 21 domestic pets, our cross-sectional study based on the antibody response one month after exposure to the index case points to J o u r n a l P r e -p r o o f Journal Pre-proof undetectable interspecific transmission of the SARS-CoV-2 virus between COVID-19 patients and domestic dogs or cats under natural exposure conditions. doi = 10.1016/j.onehlt.2020.100164 id = cord-325324-kh2aal5n author = Teng, Shaolei title = ACE2 Enhance Viral Infection or Viral Infection Aggravate the Underlying Diseases date = 2020-08-06 keywords = ACE2; COVID-19; CoV-2; SARS summary = SARS-CoV-2 spike protein (S) is cleaved by the human furin enzyme to generate S1, which binds to the host receptor, ACE-2. It is possible that the released free spike or the cleaved S1 protein in the blood might bind to cellular membrane ACE2 of heart, artery and alveolar lung cells to block the conversion of Angiotensin II to Ang-(1-7) and/or Angiotensin I to Ang-(1-9), which is consistent with a previous experimental result on SARS-CoV-1 (59) . Therefore, our hypothesis, as shown in the right side of Fig. 1 as "Viral aggravating existing diseases", is that comorbidities in COVID-19 patients are aggravated by the infection of SARS-CoV-2 to causes higher fatalities because the viral S protein interacts with ACE2 to inhibit ACE2 function. The claims that COVID-19 disproportionately affects the individuals of minority groups and aged people are not only supported by reported data but also by our hypothesis that SARS-CoV-2 infection generates spike protein that interacts with ACE2 to either exhaust ACE2 or inhibit ACE2 function or both so that the comorbidities are aggravated (Figure 1 ). doi = 10.1016/j.csbj.2020.08.002 id = cord-345929-z7yfegr5 author = Thakur, Suman S. title = Proteomics and Its Application in Pandemic Diseases date = 2020-11-06 keywords = COVID-19; CoV-2; SARS summary = found that the antimalarial drug metaquine and anti-HIV antiretroviral saquinavir interact with four SARS-CoV-2 receptors, including Nsp9 replicase, main protease (Mpro), NSP15 endoribonuclease, and spike protein (S protein), interacting with human ACE2; therefore, they may be repurposed for COVID-19 treatment. Furthermore, Maffucci and Contini used an in silico approach to find drug candidates against the main proteinase and spike protein of SARS-CoV-2. suggested that the antigenic peptides generated from the S1 spike glycoprotein of SARS-CoV-2 using aminopeptidases ERAP1, ERAP2, and IRAP might be helpful in selecting better epitopes for immunogenic studies and the design of a vaccine for COVID-19. Interestingly, a computational method was used to find an allosteric site on the SARS-CoV-2 spike protein by Di Paola et al., as its detection would weaken the spike−ACE2 interaction and thereby reduce the viral infection. doi = 10.1021/acs.jproteome.0c00824 id = cord-321166-nvphu1fm author = Thomson, Emma C. title = The circulating SARS-CoV-2 spike variant N439K maintains fitness while evading antibody-mediated immunity date = 2020-11-05 keywords = CoV-2; N439; RBD; RBM; SARS; d614; figure summary = We find that the N439K mutation is associated with a similar clinical spectrum of disease and slightly higher viral loads in vivo compared with isolates with the wild-type N439 residue, and that it results in immune escape from polyclonal sera from a proportion of recovered individuals and a panel of neutralizing mAbs. N439K provides a sentinel example of immune escape, indicating that RBM variants must be evaluated when considering vaccines and the therapeutic or prophylactic use of mAbs. Long term control of the pandemic will require systematic monitoring of immune escape variants and selection of strategies that address the variants circulating in targeted populations. Fitness of this variant, N439K, was demonstrated by repeated emergence by convergent evolution, spread to multiple countries and significant representation in the SARS-CoV-2 sequence databases, the fact that the N439K RBD retains a high affinity interaction with the hACE2 receptor, efficient viral replication in cultured cells, and no disease attenuation in a large cohort of infected individuals. doi = 10.1101/2020.11.04.355842 id = cord-297842-hkr1wm3k author = Tilley, Kimberly title = A Cross-Sectional Study Examining the Seroprevalence of Severe Acute Respiratory Syndrome Coronavirus 2 Antibodies in a University Student Population date = 2020-10-15 keywords = CoV-2; SARS; student summary = PURPOSE: The aim of the study was to determine the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in a university student population. METHODS: This was a cross-sectional survey study based on the World Health Organization population-based seroepidemiological investigational protocol for SARS-CoV-2 conducted between April 29, 2020, and May 8, 2020, examining SARS-CoV-2 antibody prevalence among 790 university students in Los Angeles, CA. With the goal of having the sample distributions match distributions in the population, these strata were selected based on internal university data, indicating that females are more likely to participate in health-related research projects compared with males, and fewer undergraduates (36.4%) spent the end of the Spring 2020 semester in Los Angeles relative to graduate students (76.5%). Seroprevalence of SARS-CoV-2 antibodies in a Los Angeles university student population as of May 8, 2020, was estimated to be 4.0%. doi = 10.1016/j.jadohealth.2020.09.001 id = cord-337430-c2vdnml7 author = Timpka, Toomas title = Sports Health During the SARS-Cov-2 Pandemic date = 2020-05-02 keywords = Cov-2; SARS; covid-19 summary = In December 2019, the Chinese city of Wuhan reported an outbreak of SARS-Cov-2 (severe acute respiratory syndrome coronavirus-2) infection that causes the Covid-19 disease, an atypical pneumonia [1] . The national public health agencies choose social distancing regulations based on an overall assessment of how critical certain activities are for society as a whole and whether motivation to comply with the rules can be assumed. During the SARS-Cov-2 pandemic, effectively all population-level interventions include the recommendation that social contacts with the elderly, and especially the senior elderly, are to be reduced to an absolute minimum. Sports organisations should develop a pandemic response strategy that addresses the needs of its athletes and coaches, while complying with the regulations and recommendations issued by the government and national public health agency. The temporary frameworks for organised sports practice and competitions must be developed based on the social distancing and quarantine protocols activated during the pandemic. doi = 10.1007/s40279-020-01288-7 id = cord-325614-e9hnhzfg author = Todorov, German title = A Possible Path towards Rapid Development of Live-Attenuated SARS-CoV-2 Vaccines: Plunging into the Natural Pool date = 2020-10-14 keywords = CoV-2; SARS; attenuated summary = Our proposed approach is based on screening for, identifying, analyzing and selecting naturally attenuated yet highly immunogenic SARS-CoV-2 strains, which may lead to a shorter cycle of vaccine development, as well as higher vaccine effectiveness. The proposed approach is based on screening for, identifying, analyzing and selecting naturally attenuated yet highly immunogenic SARS-CoV-2 strains, potentially leading to a more rapid cycle of vaccine development, as well as higher vaccine effectiveness. If the candidate attenuated SARS-CoV-2 strain is easily transmissible, we would need to evaluate whether a live-attenuated virus that causes a very mild form of infection but is easy to transmit can be considered sufficiently safe for use as a vaccine, or whether it needs to be further attenuated in the lab, which could slow down the development of the vaccine. All in all, at present there are too many unknowns to predict how much screening of suitable individuals in high-risk subpopulations will be required to find naturally-evolved candidate strains for the development of live-attenuated vaccines. doi = 10.3390/biom10101438 id = cord-252049-rgdynmla author = Tomar, Sakshi title = Ligand-induced Dimerization of Middle East Respiratory Syndrome (MERS) Coronavirus nsp5 Protease (3CL(pro)): IMPLICATIONS FOR nsp5 REGULATION AND THE DEVELOPMENT OF ANTIVIRALS date = 2015-06-08 keywords = 3CL; CoV; Fig; MERS; SARS; pro summary = All coronaviruses, including the recently emerged Middle East respiratory syndrome coronavirus (MERS-CoV) from the β-CoV subgroup, require the proteolytic activity of the nsp5 protease (also known as 3C-like protease, 3CL(pro)) during virus replication, making it a high value target for the development of anti-coronavirus therapeutics. Therefore, we determined the dependence of the enzymatic activity of MERS-CoV 3CL pro on the total enzyme concentration and compared it with other 3CL pro enzymes from HKU4, HKU5, and SARS coronaviruses (Fig. 2) . The kinetic data for all four 3CL pro enzymes, MERS-CoV, HKU4-CoV, HKU5-CoV, and SARS-CoV, fit well to this model, and the resulting values for the monomer-dimer equilibrium dissociation constant, K d , and apparent turnover number, k cat , for each enzyme are provided in Table 2 . Compound 11 also forms two direct and one water-mediated hydrogen bond interactions with amino acids in the MERS-CoV 3CL pro active site (Fig. 6E) . doi = 10.1074/jbc.m115.651463 id = cord-289535-srrfr1es author = Tregoning, J. S. title = Vaccines for COVID‐19 date = 2020-10-18 keywords = COVID-19; CoV-2; MERS; RNA; SARS; dna; phase; vaccine summary = One concern with vaccine development for SARS-CoV-2 is that the immune response can cause disease, often in the act of clearing the infection. Preclinical animal studies have demonstrated that DNA vaccines encoding the M, N, 3a or S proteins of the SARS-CoV-1 virus could elicit immune responses [180] [181] [182] . The S protein is the target of the only SARS-CoV-1 DNA vaccine to progress to Phase I clinical trial, delivered by bio-injector, and it was safe and induced neutralizing antibody responses [183] . T cell responses are required for protection from clinical disease and for virus clearance in severe acute respiratory syndrome coronavirus-infected mice Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals A SARS DNA vaccine induces neutralizing antibody and cellular immune responses in healthy adults in a Phase I clinical trial doi = 10.1111/cei.13517 id = cord-289716-nleql08z author = Tsitsilonis, Ourania E. title = Seroprevalence of Antibodies against SARS-CoV-2 among the Personnel and Students of the National and Kapodistrian University of Athens, Greece: A Preliminary Report date = 2020-09-21 keywords = CoV-2; NKUA; SARS summary = Due to early implementation of public health measures, Greece had low number of SARS-CoV-2 infections and COVID-19 severe incidents in hospitalized patients. Although focused on the specific population of NKUA members, our study shows that the prevalence of anti-SARS-CoV-2 Igs for the period June–July 2020 remained low and provides knowledge of public health importance for the NKUA members. According to the manufacturer''s package insert, Elecsys ® Anti-SARS-CoV-2 exhibits high overall clinical specificity of 99.81% with no cross-reactivity to the common cold coronaviruses; clinical sensitivity, determined by testing a total of 204 samples from 69 symptomatic patients with a PCR-confirmed SARS-CoV-2 infection, is 100% for samples collected ≥14 days after PCR confirmation in this collective; these values were verified in our study by measuring 25 RT-qPCR SARS-CoV-2 positive and 25 negative samples. doi = 10.3390/life10090214 id = cord-280068-rszu1c48 author = Twomey, Julianne D. title = COVID-19 update: The race to therapeutic development date = 2020-10-24 keywords = ACE2; COVID-19; CoV-2; SARS summary = We highlight two major lines of therapeutic strategies for COVID-19 treatment: 1) repurposing the existing drugs for use in COVID-19 patients, such as antiviral medications (e.g., remdesivir) and immunomodulators (e.g., dexamethasone) which were previously approved for other disease conditions, and 2) novel biological products that are designed to target specific molecules that are involved in SARS-COV-2 viral entry, including neutralizing antibodies against the spike protein of SARS-COV-2, such as REGN-COV2 (an antibody cocktail) and LY-COV555, as well as recombinant human soluble ACE2 protein to counteract SARS-COV-2 binding to the transmembrane ACE2 receptor in target cells. The current review highlights the potential therapeutic strategies for the treatment of COVID-19, including small molecule drugs and therapeutic proteins to target the SARS-CoV-2 viral entry, viral amplification or the host immune responses. doi = 10.1016/j.drup.2020.100733 id = cord-338436-0z828org author = Tzou, Philip L. title = Coronavirus Antiviral Research Database (CoV-RDB): An Online Database Designed to Facilitate Comparisons between Candidate Anti-Coronavirus Compounds date = 2020-09-09 keywords = COVID-19; CoV-2; MERS; SARS; cell; compound summary = Results: As of August 2020, the Coronavirus Antiviral Research Database (CoV-RDB; covdb.stanford.edu) contained over 2800 cell culture, entry assay, and biochemical experiments, 259 animal model studies, and 73 clinical studies from over 400 published papers. Figure 4 displays EC 50 values for many of the directly acting antiviral compounds currently in clinical trials for the treatment of COVID-19 including six polymerase inhibitors (remdesivir, EIDD-2801, favipiravir, ribavirin, galidesivir, and sofosbuvir), three HIV-1 protease inhibitors (lopinavir, atazanavir, and darunavir), and three entry inhibitors (receptor binding monoclonal antibodies, soluble recombinant human ACE2, and umifenovir). Viruses 2020, 12, x FOR PEER REVIEW 11 of 22 Table 4 describes a set of the most promising compounds for the treatment of SARS-CoV-2 based on the following criteria: (i) act by a validated direct or indirect antiviral mechanism, (ii) display submicromolar activity in vitro and/or inhibitory activity in an animal model, and (iii) have a record of safety and favorable pharmacokinetics in human subjects. doi = 10.3390/v12091006 id = cord-349643-jtx7ni9b author = Uyeki, Timothy M. title = Development of Medical Countermeasures to Middle East Respiratory Syndrome Coronavirus date = 2016-07-17 keywords = CoV; East; MERS; Middle summary = Preclinical development of and research on potential Middle East respiratory syndrome coronavirus (MERS-CoV) medical countermeasures remain preliminary; advancements are needed before most countermeasures are ready to be tested in human clinical trials. Research priorities include standardization of animal models and virus stocks for studying disease pathogenesis and efficacy of medical countermeasures; development of MERS-CoV diagnostics; improved access to nonhuman primates to support preclinical research; studies to better understand and control MERS-CoV disease, including vaccination studies in camels; and development of a standardized clinical trial protocol. F rom September 2012 through April 27, 2016, a total of 1,728 laboratory-confirmed Middle East respiratory syndrome coronavirus (MERS-CoV) infections, leading to 624 deaths (36% case-fatality proportion), had been reported to the World Health Organization (WHO) (1) . Prophylaxis with a Middle East respiratory syndrome coronavirus (MERS-CoV)-specific human monoclonal antibody protects rabbits from MERS-CoV infection doi = 10.3201/eid2207.160022 id = cord-274802-7ioiwsd8 author = Varghese, Praveen Mathews title = Host-pathogen interaction in COVID-19: Pathogenesis, potential therapeutics and vaccination strategies date = 2020-08-19 keywords = COVID-19; China; CoV-2; Coronavirus; SARS; Syndrome; acute; cell; clinical; patient; severe; study summary = Proteomic and transcriptomic studies on bronchoalveolar lavage (BAL) samples from COVID-19 patients have also revealed considerable insights into the expression of SARS-CoV-2 receptors, co-receptors, immune responses, as well as risk factors for severe disease e.g. age and co-morbidities. Furthermore, treatment with a recombinant C5a antibody on 2 male COVID-19 patients aged 54 and 67 years showed significant benefit in suppressing complement hyperactivation, which contributes to the excessive immune response causing aggravated inflammatory lung injury, a hallmark of SARS-CoV-2 pathogenesis and lethality (242) . Consistent with endothelial injury, the significantly elevated levels of von Willebrand factor found in the patient with severe COVID-19 has led to the idea that the infection of the ACE2 expressing endothelium by SARS-CoV-2 induces injury and activates the complement , which sets up a feedback loop that maintains a state of inflammation (243, (268) (269) (270) . Initial clinical studies in China involving 100 SARS-CoV-2 infected patients, who were treated with Chloroquine, showed amelioration of pneumonia, shortened disease progression, increased resolution of lung lesions on CT, and a better virus-negative conversion (313, 314) . doi = 10.1016/j.imbio.2020.152008 id = cord-265322-3854ddb9 author = Vavougios, George D. title = A data-driven hypothesis on the epigenetic dysregulation of host metabolism by SARS coronaviral infection: potential implications for the SARS-CoV-2 modus operandi date = 2020-04-23 keywords = CoV-2; SARS summary = Based on both structural and syndromic similarities with SARS-CoV, a hypothesis is formed on SARS-CoV-2 potential to affect the host''s metabolism as part of its lifecycle. In the literature, SARS-CoV has been known to cause de novo diabetes by ACE2-dependent uptake on pancreatic isle cells, and furthermore dysregulate lipid autophagy in favor of the viral lifecycle. Their study provided the foundation for a hypothesis put forth by Fang and colleagues indicating that diabetic and hypertensive patients exposed to ACE2 inhibitors may be at an increased risk of more severe COVID-19 (7) . In another study, SARS-CoV was shown to cause diabetes by ACE2-dependent infection of pancreatic isle cells (10) . Future studies should determine SARS-CoV-2 interaction and effect on the human transcriptome, further identifying drug targets using pharmacogenomic enrichment analyses. Natural small molecules as inhibitors of coronavirus lipid-dependent attachment to host cells: a possible strategy for reducing SARS-COV-2 infectivity? doi = 10.1016/j.mehy.2020.109759 id = cord-309876-l0xginsa author = Vena, Antonio title = Prevalence of Antibodies to SARS-CoV-2 in Italian Adults and Associated Risk Factors date = 2020-08-27 keywords = CoV-2; SARS summary = A generalized estimating equations model showed that the main risk factors associated with SARS-CoV-2 seroprevalence were the following: an occupational exposure to the virus [Odd ratio (OR) = 2.36; 95% CI 1.59–3.50, p = 0.001], being a long-term care facility resident (OR = 4.53; 95% CI 3.19–6.45, p = 0.001), and reporting previous symptoms of influenza-like illness (OR = 4.86; 95% CI 3.75–6.30, p = 0.001) or loss of sense of smell or taste (OR = 41.00; 95% CI 18.94–88.71, p = 0.001). In the present observational study performed on a large sample of subject in northern Italy, we found the following: (1) the overall seroprevalence of anti-SARS-CoV-2 antibodies (IgG and/or IgM) was 11.0%; (2) occupational exposure to the virus, long-term care facility residency, as well as previous symptoms of influenza-like illness or loss of sense of smell or taste were independently associated with anti-SARS-CoV-2 positivity. doi = 10.3390/jcm9092780 id = cord-280821-kc0ut4oy author = Venturini, Elisabetta title = Treatment of children with COVID-19: position paper of the Italian Society of Pediatric Infectious Disease date = 2020-09-24 keywords = COVID-19; Cov-2; SARS; day; patient summary = The Italian Society of Pediatric Infectious Diseases steering and scientific committee developed a position paper on treatment of children with COVID-19, reviewing the current literature on this topic and providing indications based on the available literature data. Currently, American guidelines on COVID-19 treatment published in May 2020, recommend both in children and adults to use lopinavir/ritonavir only in the context of clinical trials, given the lack of effectiveness reported now in literature [9, 12] . The latest Chinese guidelines on SARS-Cov-2 pneumoniae do not recommend the use of a specific antiviral for the treatment of COVID-19, and nevertheless include lopinavir/ritonavir among the available therapeutic options for hospitalized patients [29] . In May 2020, following an assessment of the emergency use authorization criteria and available scientific evidence, the FDA issued an emergency use authorization allowing for the administration of remdesivir intravenously by health care providers for the treatment of COVID-19 suspected or laboratoryconfirmed in adults and pediatric patients hospitalized with severe disease [34] . doi = 10.1186/s13052-020-00900-w id = cord-316702-dj2fo8sn author = Vignesh, Ramachandran title = Is Herd Immunity Against SARS-CoV-2 a Silver Lining? date = 2020-09-30 keywords = COVID-19; CoV-2; SARS summary = Since many studies from different geographical locations are documenting preexisting immunity to SARS-CoV-2, it will be important to define specificities of these T and B cell immune response carefully to assess their association with COVID-19 disease severity. This preexisting cross-reactive T and B cell immunity to SARS-CoV-2 may have wide implications as this could explain differential clinical outcomes in COVID-19 patients, disease severity, vaccine development, and important in accessing herd immunity for SARS-CoV-2 viral infection/COVID-19 disease. Several studies have provided strong evidence for the importance of SARS-CoV-2 specific CTLs, and T helper cells in mild and moderate patients compared to severe COVID-19 disease (27, 28, (31) (32) (33) . Several studies have provided strong evidence for the importance of SARS-CoV-2specific neutralizing antibodies in association with less disease severity in COVID-19 patients (38, 39) . A recent modelling study has estimated that about one in five individuals worldwide would be at increased risk of severe COVID-19, upon infection with SARS-CoV-2, owing to the underlying conditions. doi = 10.3389/fimmu.2020.586781 id = cord-281281-knelqmzx author = Villas-Boas, Gustavo R. title = The New Coronavirus (SARS-CoV-2): A Comprehensive Review on Immunity and the Application of Bioinformatics and Molecular Modeling to the Discovery of Potential Anti-SARS-CoV-2 Agents date = 2020-09-07 keywords = ACE2; COVID-19; China; CoV-2; RNA; SARS; figure; virus summary = doi = 10.3390/molecules25184086 id = cord-296426-upwsdgso author = Virmani, Sarthak title = Identifying a Kidney Transplant Recipient COVID Phenotype to Aid Test Utilization in the Setting of Limited Testing Availability - Does One Exist? date = 2020-06-20 keywords = COVID-19; CoV-2; SARS summary = While it is true that other non-novel viruses tend to cause more severe disease in immunocompromised patients [1] , no conclusive data is available to suggest an increased susceptibility or severity of SARS-Cov-2 infection in immunosuppressed kidney transplant recipients (KTRs). This was a single center, retrospective chart review performed as a QAPI project to assess similarities in kidney transplant recipients who tested positive for SARS-CoV-2 as compared to those who tested negative, and guide testing recommendations in the setting of limited testing availability during the COVID-19 pandemic. We did not observe any significant association between patient gender, level of education, or history of diabetes on the SARS-CoV-2 test result. Our cohort of KTRs showed no significant difference in ALC between patients who tested positive and negative for SARS-CoV-2 (Table 3 ). Though statistically significant in our small patient cohort, larger studies of KTRs with COVID-19 disease and a history of BKV will be required to confirm and better understand this association. doi = 10.1016/j.transproceed.2020.05.033 id = cord-253665-1dn3ek34 author = Vishnubalaji, Radhakrishnan title = Protein Coding and Long Noncoding RNA (lncRNA) Transcriptional Landscape in SARS-CoV-2 Infected Bronchial Epithelial Cells Highlight a Role for Interferon and Inflammatory Response date = 2020-07-07 keywords = CoV-2; SARS; covid-19; figure; nhbe summary = Coronavirus disease 2019 , caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was declared a global pandemic by the World Health Organization (WHO) on Phenomenal changes in ncRNA expression are also seen within host cells, which can play a major role in respiratory virus pathogenesis, with long non-coding RNAs (lncRNAs) exhibiting higher tissue specificity than coding genes [30] . Disease and function analysis on the differentially expressed genes revealed the most significant enrichment in pathways related to reactive oxygen species, induction of apoptosis and necrosis, as well as activation of neutrophils in SARS-CoV-2 infected NHBE cells (Figure 3a,b) . The top ten activated upstream regulator networks (CST5, IFNG, IFNL1, IFNA2, SPI1, RNY3, PRL, TGM2 , miR-122 and miR-122-5p) in lung tissue derived from COVID-19 patient based on transcriptome and IPA analyses, revealed the enrichment of functions related to immune system associated JAK-STAT cascade, type 1 interferon receptor binding, cytokine receptor binding, and MHC 1 biosynthesis (Figure 6a and Supplementary Table S10 ). doi = 10.3390/genes11070760 id = cord-332778-rf47ptj6 author = Vivarelli, Silvia title = Cancer Management during COVID-19 Pandemic: Is Immune Checkpoint Inhibitors-Based Immunotherapy Harmful or Beneficial? date = 2020-08-10 keywords = COVID-19; CoV-2; SARS; cancer; patient summary = It was demonstrated that cancer patients have an increased risk of developing a worse symptomatology upon severe acute respiratory syndrome associated coronavirus-2 (SARS-CoV-2) infection, often leading to hospitalization and intensive care. Given their immune-compromised status, cancer patients infected by SARS-CoV-2 might be at a higher risk of developing severe and critical consequences upon COVID-19, including ARDS, septic shock and acute myocardial infarction [29] [30] [31] . Nevertheless, cancer patients, when infected by SARS-CoV-2 might develop more severe outcomes, if anti-cancer treatments induce a weakening of the host immune health [38] . Since the beginning of this pandemic, nine independent clinical studies have been published about the risks possibly related to SARS-CoV-2 infection in patients with cancer. In line with this concept, three additional independent clinical studies are currently enrolling non-cancer COVID-19 patients to test the efficacy of administering ICIs to reshape the impaired immune system of SARS-CoV-2 infected individuals (i.e., NCT04268537; NCT04356508 and NCT04413838). doi = 10.3390/cancers12082237 id = cord-304306-rxjahqwh author = Vlachakis, Dimitrios title = Molecular mechanisms of the novel coronavirus SARS-CoV-2 and potential anti-COVID19 pharmacological targets since the outbreak of the pandemic date = 2020-10-08 keywords = COVID-19; CoV-2; RNA; SARS; protein summary = The currently available antiviral option for hospitalized patients is remdesivir, which may inhibit the replication process by targeting the RdRp. Previously proposed treatments for hospitalized patients included hydroxychloroquine, which thought to disrupt virus endocytosis, and lopinavir/ritonavir, which thought to inhibit SARs-CoV-2 main protease (Astuti and Ysrafil, 2020; Magro, 2020) . Silibilin is predicted to have a dual activity against SARS-CoV-2 infection; silibilin can potentially reduce viral replication activity by targeting NSP12 as a remdesivir-like inhibitor, and modulate inflammatory responses by direct inhibition of STAT3 (BoschBarrera et al., 2020) . A recombinant form of the human ACE2 protein was synthesized as a therapeutic treatment for COVID-19, functioning as a decoy for SARS-CoV-2 and essentially preventing the virus from binding to the cell surface ACE2 (Schuster et al., 2010) . Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response doi = 10.1016/j.fct.2020.111805 id = cord-348301-bk80pps9 author = Wahl, Angela title = Acute SARS-CoV-2 Infection is Highly Cytopathic, Elicits a Robust Innate Immune Response and is Efficiently Prevented by EIDD-2801 date = 2020-09-24 keywords = CoV-2; Fig; SARS; human summary = Here, we used a single experimental platform based on human lung-only mice (LoM) to demonstrate efficient in vivo replication of all recently emerged human coronaviruses (SARS-CoV, MERS-CoV, SARS-CoV-2) and two highly relevant endogenous pre-pandemic SARS-like bat coronaviruses. Further detailed analysis of pandemic SARS-CoV-2 in vivo infection of LoM human lung tissue showed predominant infection of human lung epithelial cells, including type II pneumocytes present in alveoli and ciliated airway cells. Human lung tissues of LoM were inoculated with SARS-CoV-2 and titers of replication competent virus determined 2, 6, and 14 days post-exposure (Fig. 1c , Extended Data Table 2 ). Collectively, our results indicate that LoM re ect the pathogenic effects in icted by SARS-CoV-2 on the human lung and demonstrate their utility as a single in vivo platform to evaluate and compare the replication and pathogenesis of past, present, and future pre-emergent, epidemic, and pandemic coronaviruses accelerating the development and testing of pre-exposure prophylaxis agents such as EIDD-2801. doi = 10.21203/rs.3.rs-80404/v1 id = cord-262328-q7mt0xve author = Wajnberg, Ania title = Humoral response and PCR positivity in patients with COVID-19 in the New York City region, USA: an observational study date = 2020-09-25 keywords = CoV-2; PCR; SARS summary = In this observational study, we ran an outreach programme in the New York City (NY, USA) area, including parts of Connecticut and New Jersey, to identify people who had recovered from SARS-CoV-2 infection for nasopharyngeal PCR (cobas 6800; Roche Diagnostics, Indianapolis, IN, USA) and serum IgG titre measurement (ELISA; Icahn School of Medicine at Mount Sinai, New York, NY, USA). We did not find reports of ELISA antibody assays as large as this one from areas with major COVID-19 hotspots, and found mixed and growing reports of IgG response to and PCR positivity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) over time. In the 584 participants for whom both nasopharyngeal PCR testing and serum antibody testing was available, SARS-CoV-2 RNA was detected in 249 (43%) at a median of 20 days (IQR 18-23) from symptom onset and 12 days (9-14) from symptom resolution. doi = 10.1016/s2666-5247(20)30120-8 id = cord-351115-dy81dtnk author = Wang, Chen title = Identification of evolutionarily stable sites across the SARS-CoV-2 proteome date = 2020-10-20 keywords = CoV-2; RNA; SARS; site summary = This study addresses both by utilizing evolutionary information from SARS-CoV-2 sequence and structural data to search for actionable functional sites for each protein in the SARS-CoV-2 genome. Here we systematically suggest potential drug target sites for most SARS-CoV-2 proteins based on evolutionary information. This relative ranking re ects the variation entropy of each sequence position within and across the branches of an associated phylogenetic tree, revealing evolutionary pressure points that correspond to functional and structural determinants, and the protein sites at which they often cluster (30) . As in our approach to discover ET drug sites, we combined ET residue ranking information with sequencing data from SARS-CoV-2 isolates to arrive at linear peptides along the proteome that are evolutionarily important and also show little variation in the current outbreak ( Figure S6 , Dataset S5). The data include, for example, multiple sequence alignments, precalculated ET ranks, and predicted epitopes (both linear and structural) for all SARS-CoV-2 proteins. doi = 10.21203/rs.3.rs-95030/v1 id = cord-294212-nlekz39f author = Wang, Dongliang title = Immunoinformatic Analysis of T- and B-Cell Epitopes for SARS-CoV-2 Vaccine Design date = 2020-07-03 keywords = CoV-2; HLA; SARS summary = Linear B-cell epitopes of the SARS-CoV-2 S protein were predicted by BepiPred 2.0 in IEDB (BepiPred 2.0., Immune Epitope Database and Analysis Resource, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA) with a threshold of 0.55 (corresponding specificity > 0.817 and sensitivity < 0.292), and only the epitopes with more than 8 residues were considered for subsequent antigenicity analysis. Discontinuous B-cell epitopes were predicted via the DiscoTope 2.0 server tool in IEDB with a default threshold of −3.7 (corresponding specificity > 0.75 and sensitivity < 0.47), based on the 3-dimensional (3D) structures of the SARS-CoV-2 S protein (PDB ID: 6VYB, B chain) and the SARS-CoV-2 S protein RBD (PDB ID: 6M0J, B chain). It is worth noting that one epitope ( 786 QILPDPLKPTKRSFIEDLLFNKVTLA 811 ) located in the S2 subunit of the SARS-CoV S protein is an important linear B-cell epitope capable of eliciting the production of a neutralizing antibody (NAb) identified in patients who recovered from SARS-CoV infection (Table S2 ) [13] . doi = 10.3390/vaccines8030355 id = cord-254469-7q6xi2xx author = Wang, Fuzhou title = An Evidence Based Perspective on mRNA-SARS-CoV-2 Vaccine Development date = 2020-05-05 keywords = COVID-19; CoV-2; SARS; vaccine summary = In March 2020, the first phase I clinical trial of a novel lipid nanoparticle (LNP)-encapsulated mRNA-based vaccine, mRNA-1273, which encodes the spike protein (S protein) of SARS-CoV-2, began in the United States (US). However, on March 16 2020, the first phase I clinical trial of a novel lipid nanoparticle (LNP)-encapsulated mRNA-based vaccine, mRNA-1273, which encodes the spike protein (S protein) of SARS-CoV-2, began in the United States (US), conducted by Moderna and the Vaccine Research Center (VRC) of the National Institute of Allergy and Infectious Diseases (NIAID) [12, 13] . Although mRNA vaccines are commencing human clinical trials, due to the rapid global spread of this new viral pandemic, it may not be possible to develop a safe and effective vaccine for SARS-CoV-2 in time to prevent the increasing number of deaths due to this novel RNA virus. doi = 10.12659/msm.924700 id = cord-271505-eot38721 author = Wang, Hongliang title = Molecular pathogenesis of severe acute respiratory syndrome date = 2006-09-28 keywords = ACE2; CoV; SARS; SIGN summary = demonstrated that the angiotensin-converting enzyme 2 (ACE2) is a functional cellular receptor of SARS-CoV, by using coimmunoprecipitation of the virus glycoprotein (S1) with lysates from cells that are susceptible to virus infection (Vero E6 cells) followed by mass spectrometry analysis [7] . In the case of SARS, apoptosis was observed in patients'' lung epithelial cells; thus, SARS-CoV induced apoptosis would certainly have a deleterious pathogenic role, leading to severe tissue damage [26] . This model system allowed us to avoid possible secondary effects resulting from viral replication or infections in vivo and to directly test whether SARS-CoV spike protein might adversely affect acute lung injury through modulation of ACE2. SARS-CoV infection or spike protein treatment can down-regulate the expression of ACE2, and thus aggravate lung injury. Nabel, pH-dependent entry of severe acute respiratory syndrome coronavirus is mediated by the spike glycoprotein and enhanced by dendritic cell transfer through DC-SIGN doi = 10.1016/j.micinf.2006.06.012 id = cord-260508-z11exbyu author = Wang, Hongru title = Synonymous mutations and the molecular evolution of SARS-Cov-2 origins date = 2020-10-12 keywords = CoV-2; GD410721; SARS summary = doi = 10.1101/2020.04.20.052019 id = cord-034354-4xu97je3 author = Wang, Hongye title = SARS-CoV-2 Proteome Microarray for Mapping COVID-19 Antibody Interactions at Amino Acid Resolution date = 2020-10-21 keywords = CoV-2; SARS; figure summary = The first landscape of B-cell epitopes for SARS-CoV-2 IgM and IgG antibodies in the serum of 10 coronavirus disease of 2019 (COVID-19) patients with early infection is also constructed. Using the SARS-CoV-2 proteome microarray, we screened IgM and IgG antibodies in the serum of 10 COVID-19 patients who were in the early stage of infection (days of symptoms onset, 3.0 ± 5.92) (Supporting Information, Table S2 ) to construct a landscape of humoral responses to the SARS-CoV-2 proteome (Figure 2 ). Sixty-one (61) IgG and IgM antibody epitopes were identified in seven SARS-CoV-2 proteins (M, N, S, Orf1ab, Orf3a, Orf7a, and Orf8) with a Z-score higher than 3 in at least one COVID-19 patient (Table 1) . Furthermore, we constructed the first landscape of B-cell epitopes of serum IgM and IgG antibodies, representing the comprehensive antibody response of COVID-19 patients to SARS-CoV-2 infection (Figures 2−4) . doi = 10.1021/acscentsci.0c00742 id = cord-296362-9vi8xwu7 author = Wang, Jian-Min title = Construction of a non-infectious SARS coronavirus replicon for application in drug screening and analysis of viral protein function date = 2008-09-12 keywords = CoV; SARS summary = title: Construction of a non-infectious SARS coronavirus replicon for application in drug screening and analysis of viral protein function Based on the infectious cDNA clone of rSARS-CoV-DE, in which the E gene has been deleted, a safe non-infectious replicon was constructed by replacing the S gene with the enhanced green fluorescent protein (eGFP) gene. Based on the infectious cDNA clone of rSARS-CoV-DE, in which the E gene has been deleted, a safe non-infectious replicon was constructed by replacing the S gene with the enhanced green fluorescent protein (eGFP) gene. For in-depth study of functions of different viral proteins and regulatory sequence elements by reverse genetics, full-length infectious cDNA clones have been established using various techniques including bacterial artificial chromosome (BAC) vector [23] [24] [25] and SARS-CoV replicon cell lines [26] , which can also be used for antiviral drug screening. Construction of a severe acute respiratory syndrome coronavirus infectious cDNA clone and a replicon to study coronavirus RNA synthesis doi = 10.1016/j.bbrc.2008.06.129 id = cord-258881-74aijckl author = Wang, Maomao title = Case Report: One Case of Coronavirus Desease 2019(COVID-19) in Patient Co-nfected by HIV With a Low CD4+ T Cell Count date = 2020-04-23 keywords = Cov-2 summary = Abstract The ongoing outbreak of COVID-19 that began in Wuhan, China has become an emergency of international concern When thousands of peolple were infected around the world.We report a case infected by SARS-Cov-2 and HIV simultaneously,which showed a longer course of disease and slower generation of specific antibody. Here we report a patient infected by SARS-Cov-2 , who had a relatively long course of disease with unstable state. Then eight markers of infectious diseases was checked and the result showed that abtibodies to HIV and syphilis were positive .Then the patient was transferred to specialty hospital for further treatment on March 8. People are generally susceptible to SARS-Cov-2 infection, especially the elderly patients and those with underlying diseases [2] . The author suggested that SARS-Cov-2 might damage lymphocytes, especially T lymphocytes, and the immune system was impaired during the period of disease [2] . In conclusion, we report the clinical features of a patient infected by SARS-Cov-2 and HIV. doi = 10.1016/j.ijid.2020.04.060 id = cord-297332-rzf0cw1x author = Wang, Qidi title = Immunodominant SARS Coronavirus Epitopes in Humans Elicited both Enhancing and Neutralizing Effects on Infection in Non-human Primates date = 2016-04-11 keywords = ADE; CoV; DPI; SARS; USA; figure summary = 15 Other observations include evidence of ADE reported here for the first time induced by an inactivated SARS-CoV vaccine in rhesus macaques ( Figure 1 ) and by antisera from SARS patients (Table S1) , as well as ADE in other coronavirus infections. Herein, we discovered that a peptide of the viral sequence simultaneously elicits the antibodies of disparate functions in protection and enhancement against SARS-CoV infection by the studies with host Vero E6 cells in vitro and in non-human primates. In contrast, the immunized monkeys in the Vac3 group had a strongly increased ability to control SARS-CoV infection in association with induction of high levels of anti-S 604−625 antibodies ( Figure 7E ). 44 This study demonstrates for the first time that an antibody (mAb43-3-14) targeting a specific linear epitope (S 597−603 ) of the SARS-CoV spike protein can mediate enhancement of virus infection both in vitro and in non-human primates via an epitope sequence-dependent mechanism. doi = 10.1021/acsinfecdis.6b00006 id = cord-193489-u6ewlh16 author = Wang, Rui title = Decoding SARS-CoV-2 transmission, evolution and ramification on COVID-19 diagnosis, vaccine, and medicine date = 2020-04-29 keywords = CoV-2; SARS; SNP; protein summary = Based on the genotyping of 6156 genome samples collected up to April 24, 2020, we report that SARS-CoV-2 has had 4459 alarmingly mutations which can be clustered into five subtypes. Genetic identification and characterization of the geographic distribution, intercontinental evolution, and global trends of SARS-CoV-2 is the most efficient approach for studying COVID-19 genomic epidemiology and offer the molecular foundation for region-specific SARS-CoV-2 vaccine design, drug discovery, and diagnostic development [10] . We use K-means methods to cluster SARS-CoV-2 mutations, which provides the updated molecular information for the region-specific design of vaccines, drugs, and diagnoses. Table 5 presents the statistics of single mutations on various SARS-CoV-2 proteins that occurred in the recorded genomes between January 5, 2020, and April 24, 2020. Specifically, nucleocapsid protein has both the highest number of mutations per residues of 0.56 and the highest h-index of 27, suggesting that it is the most non-conservative protein in SARS-CoV-2 genomes. doi = nan id = cord-296250-7ln7p715 author = Wang, Sheng-Fan title = The pharmacological development of direct acting agents for emerging needed therapy against severe acute respiratory syndrome coronavirus-2 date = 2020-05-20 keywords = ACE2; CoV-2; RNA; SARS summary = Increasing evidence showed potential therapeutic agents directly acting against SARS-CoV-2 virus, such as interferon, RNA-dependent RNA polymerase inhibitors, protease inhibitors, viral entry blockers, neuraminidase inhibitor, vaccine, antibody agent targeting the SARS-CoV-2 RNA genome, natural killer cells, and nucleocytoplasmic trafficking inhibitor. Increasing evidence reveals potential therapeutic agents acting directly against SARS-CoV-2, such as interferon (IFN), RdRp inhibitors, protease inhibitors, coronaviral protease inhibitor, viral entry blocker, neuraminidase inhibitor, vaccine, antibody, agent targeting the SARS-CoV-2 RNA genome, natural killer cells, and nucleocytoplasmic trafficking inhibitors. The novel specific anti-SARS-CoV-2 agents might comprise inhibitors interfering with the viral replication cycle, antibody targeting the host receptor and virus S protein, and inhibitors of host cellular proteases involved in the virus endocytosis pathway. 33, 34 Moreover, evidence showed that diarylheptanoids, the natural products derived from Japanese alder (Alnus japonica), can inhibit the papain-like protease and restore the host innate immunity response against SARS-CoV through maintaining the function of IFNs. 31 Therefore, specific coronaviral proteases might be good candidate targets for developing new drugs to fight COVID-19. doi = 10.1097/jcma.0000000000000353 id = cord-354394-zojhdnlu author = Wang, Wei-Kung title = Detection of SARS-associated Coronavirus in Throat Wash and Saliva in Early Diagnosis date = 2004-07-17 keywords = CoV; RNA; SARS summary = We examined oral specimens, including throat wash and saliva, and found large amounts of SARS-CoV RNA in both throat wash (9.58 x 10(2) to 5.93 x 10(6) copies/mL) and saliva (7.08 x 10(3) to 6.38 x 10(8) copies/mL) from all specimens of 17 consecutive probable SARS case-patients, supporting the possibility of transmission through oral droplets. This finding, with the high detection rate a median of 4 days after disease onset and before the development of lung lesions in four patients, suggests that throat wash and saliva should be included in sample collection guidelines for SARS diagnosis. Using a quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) assay and fractionation experiment, we investigated the load of SARS-CoV in these samples and different components of the throat wash. As shown in Table 1 , SARS-CoV RNA was detected in the cell-associated component of the throat wash from all 16 specimens examined. doi = 10.3201/eid1007.031113 id = cord-282142-76jr4p7n author = Wang, Yun title = Potential Effect of COVID-19 on Maternal and Infant Outcome: Lesson From SARS date = 2020-08-07 keywords = COVID-19; CoV-2; SARS; infection summary = Pregnant women are susceptible to respiratory pathogens and the development of severe pneumonia, suggesting the urgent need to assess the potential maternal and infant outcome of pregnancy with COVID-19. Therefore, the effect of SARS-CoV-2 infection on maternal and infant outcomes needs to be explored, especially the intrauterine vertical transmission potential of COVID-19. SARS-CoV infection during pregnancy was associated with a risk of adverse maternal and neonatal complications, including intrauterine growth restriction, preterm delivery, spontaneous miscarriage, severe maternal illnesses, such as, admission to the intensive care unit (ICU), renal failure, and disseminated intravascular coagulopathy, and death (4, 6, 13, (42) (43) (44) (45) (46) . The samples of amniotic fluid, cord blood, neonatal throat swab, and breastmilk samples from six patients tested negative for SARS-CoV-2 (5), suggesting no intrauterine vertical transmission of SARS-CoV-2 in the nine pregnant COVID-19 patients. doi = 10.3389/fped.2020.00511 id = cord-333326-n9ifhw5s author = Wardell, Hanna title = Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Febrile Neonates date = 2020-07-09 keywords = COVID-19; CoV-2; SARS summary = Most severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in pediatric patients are mild or asymptomatic. We report a case series of 4 full-term neonates hospitalized with fever and found to have SARS-CoV-2 infection with a spectrum of illness severities. Herein we present a case series of 4 full-term neonates who were hospitalized with fever and found to be infected with SARS-CoV-2. Due to the concern for end-organ involvement with possibly evolving acute myocardial injury as well as a supplemental oxygen requirement, the patient was initiated on therapy with remdesivir on inpatient day 4 via an expanded-access program from the manufacturer after approval from the US Food and Drug Administration and local institutional review board, with informed consent. In this report, we present 4 febrile neonates hospitalized with SARS-CoV-2 infection with favorable outcomes. SARS-CoV-2 infection (COVID-19) in febrile infants without respiratory distress doi = 10.1093/jpids/piaa084 id = cord-317786-iv1br2oj author = Waterfield, T. title = Seroprevalence of SARS-CoV-2 antibodies in children - A prospective multicentre cohort study. date = 2020-09-02 keywords = CoV-2; SARS; September summary = Discussion In this study children demonstrated similar antibody titres in response to SARS-CoV-2 irrespective of age. The objective of this study was to report the presence, and titres, of SARS-CoV-2 antibodies in healthy children of healthcare workers across the UK and to report the symptomatology of infection including the asymptomatic rate. This multicentre observational prospective cohort study was designed to determine the seroprevalence of SARS-CoV-2 antibodies in healthy children, and report the symptomatology of infection. Participants and their parents provided information at enrollment relating to age, sex, previous health and potential predictors of SARS-CoV-2 infection including; known contact with individuals with COVID-19, contact with individuals who have been symptomatic and/or self-isolating and results of any diagnostic testing such as RT-qPCR testing/antibody testing. Seroprevalence of SARS-CoV-2 antibodies in children of healthcare workers-A prospective multicentre cohort study protocol -Accepted for publication doi = 10.1101/2020.08.31.20183095 id = cord-326706-75mjs6vm author = Waterfield, Thomas title = Seroprevalence of SARS-CoV-2 antibodies in children: a prospective multicentre cohort study date = 2020-11-10 keywords = CoV-2; SARS summary = Following multivariable analysis four independent variables were identified as significantly associated with SARS-CoV-2 seropositivity: known infected household contact OR=10.9 (95% CI 6.1 to 19.6); fatigue OR=16.8 (95% CI 5.5 to 51.9); gastrointestinal symptoms OR=6.6 (95% CI 3.0 to 13.8); and changes in sense of smell or taste OR=10.0 (95% CI 2.4 to 11.4). The objective of this study was to report the presence, and titres, of SARS-CoV-2 antibodies in healthy children of healthcare workers across the UK and to report the symptomatology of infection including the asymptomatic rate. This multicentre observational prospective cohort study was designed to determine the seroprevalence of SARS-CoV-2 antibodies in healthy children, and report the symptomatology of infection. 26 Participants and their parents provided information at enrolment relating to age, sex, previous health and potential predictors of SARS-CoV-2 seropositivity including; known contact with individuals with COVID-19, contact with individuals who have been symptomatic and/or self-isolating and results of any diagnostic testing such as RT-qPCR testing/ antibody testing. doi = 10.1136/archdischild-2020-320558 id = cord-258595-bk35vxlr author = Westhaus, Sandra title = Detection of SARS-CoV-2 in raw and treated wastewater in Germany – Suitability for COVID-19 surveillance and potential transmission risks date = 2020-08-18 keywords = CoV-2; RNA; SARS; wastewater summary = Inoculation of differentiated Caco-2 cells for ten days with purified and concentrated wastewater (P2, P5, P11, and P12) did not result in the production of infectious SARS-CoV-2 particles (data not shown), which suggests that treated sewage appears to be non-infectious even though viral RNA fragments can be detected. Inter-comparing these nine catchment areas, we plotted the estimated cumulative and the acute prevalence against the measured SARS-CoV-2 load (Figure 8 ), the latter calculated from RT-qPCR measured M-gene copy concentration ( Figure 4 ) and the actual wastewater flow Q actual on the day of sampling (Table 2) . In contrast, plotting the incidence against SARS-CoV-2 concentration did not yield a conclusive correlation (not shown), likely because the precision of the qPCR employed was not sufficient to discriminate relatively minor differences in the incidence prevailing in the studied catchment areas at the time of sampling, ranging from 30 to 174 cases per 100,000 residents (less than an order of magnitude, Figure 8C and D). doi = 10.1016/j.scitotenv.2020.141750 id = cord-264031-0y7xbgun author = Wierbowski, Shayne D. title = A 3D Structural Interactome to Explore the Impact of Evolutionary Divergence, Population Variation, and Small-molecule Drugs on SARS-CoV-2-Human Protein-Protein Interactions date = 2020-10-13 keywords = CoV-2; SARS; human; interface; protein summary = title: A 3D Structural Interactome to Explore the Impact of Evolutionary Divergence, Population Variation, and Small-molecule Drugs on SARS-CoV-2-Human Protein-Protein Interactions This resource includes docked structures for all interactions with protein structures, enrichment analysis of variation along interfaces, predicted ΔΔG between SARS-CoV and SARS-CoV-2 variants for each interaction, predicted impact of natural human population variation on binding affinity, and a further prioritized set of drug repurposing candidates predicted to overlap with protein interfaces†. Further, we explore the utility of our interactome modeling approach in identifying key 99 interactions undergoing evolution along viral protein interfaces, highlighting population variants on 100 human interfaces that could modulate the strength of viral-host interactions to confer protection from or 101 susceptibility to COVID-19, and prioritizing drug candidates predicted to bind competitively at viral-102 human interaction interfaces. doi = 10.1101/2020.10.13.308676 id = cord-264968-ctx39vhi author = Woo, Patrick CY title = Relative rates of non-pneumonic SARS coronavirus infection and SARS coronavirus pneumonia date = 2004-03-13 keywords = CoV; ELISA; SARS summary = doi = 10.1016/s0140-6736(04)15729-2 id = cord-327997-noqbcxua author = Wu, Kevin E. title = RNA-GPS Predicts SARS-CoV-2 RNA Residency to Host Mitochondria and Nucleolus date = 2020-06-20 keywords = CoV-2; GPS; RNA; SARS; figure summary = We predict the SARS-CoV-2 RNA genome and sgRNAs to be enriched towards the host mitochondrial matrix and nucleolus, and that the 5'' and 3'' viral untranslated regions contain the strongest, most distinct localization signals. As previously discussed, since much of the APEX-seq mitochondrial data used to train RNA-GPS actually consists of nuclear-encoded transcripts likely picked up as the APEX-COX4 fusion protein is transported to the mitochondria, we hypothesize that our predicted mitochondrial residency is alluding to similarity in localization pathways, rather than localization destination. To further validate the robustness of these results, we also trained a different predictive algorithm (a recurrent neural network, see STAR Methods for additional details) on the APEX-seq data and performed a similar set of experiments, comparing SARS-CoV-2 dominant subcellular residency predictions to human and coronavirus baselines ( Figure S3A /B). doi = 10.1016/j.cels.2020.06.008 id = cord-354824-7fdcu2f0 author = Wu, Renyi title = An Update on Current Therapeutic Drugs Treating COVID-19 date = 2020-05-11 keywords = COVID-19; China; CoV-2; RNA; SARS; patient; treatment summary = Evolving research and clinical data regarding the virologic SARS-CoV-2 suggest a potential list of repurposed drugs with appropriate pharmacological effects and therapeutic efficacies in treating COVID-19 patients. This estimated 20% of patients developing more severe disease with SARS-CoV-2 infection are most likely due to genetics, epigenetics, and or other factors, with dampened innate immune response to fight the virus coupled with enhanced viral load leading to cytokine storm, severe inflammatory/oxidative stress response, and severe lung injury secondary to ARDS. Chloroquine can inhibit the entry of SARS-CoV-2 and prevent virus-cell fusion by interfering with glycosylation of ACE2 receptor and its binding with spike protein, suggesting that chloroquine treatment might be more effective in the early stage of infection, before COVID-19 reduces ACE2 expression and activity [30, 38, 39] . Chloroquine diphosphate in two different dosages as adjunctive therapy of hospitalized patients with severe respiratory syndrome in the context of coronavirus (SARS-CoV-2) infection: Preliminary safety results of a randomized, doubleblinded, phase IIb clinical trial (CloroCovid-19 Study) doi = 10.1007/s40495-020-00216-7 id = cord-271243-8cfyen86 author = Xiao, Y. title = Pathological Changes in Masked Palm Civets Experimentally Infected by Severe Acute Respiratory Syndrome (SARS) Coronavirus date = 2008-05-31 keywords = CoV; SARS summary = title: Pathological Changes in Masked Palm Civets Experimentally Infected by Severe Acute Respiratory Syndrome (SARS) Coronavirus Summary Masked palm civets are highly susceptible to infection with the severe acute respiratory syndrome coronavirus (SARS-CoV). The present study describes the spectrum of histopathological changes in the lung, spleen, lymph node, liver, small intestine, kidney and cerebrum of civets infected experimentally with SARS-CoV. One animal from each group was sacrificed at 3, 13, 23, 34 and 35 days post-infection (dpi), and lung, spleen, lymph node, small intestine, kidney, trachea, cerebrum, pancreas, sex glands, stomach and heart were collected from each animal. In summary, the data presented in this study further corroborate previous findings (Wu et al., 2005) in demonstrating that civets are more susceptible to SARS-CoV infection than other animals, as implied by their clinical symptoms, pathological changes and virus distribution within tissues. doi = 10.1016/j.jcpa.2007.12.005 id = cord-321918-9jwma2y6 author = Xiu, Siyu title = Inhibitors of SARS-CoV-2 Entry: Current and Future Opportunities date = 2020-06-15 keywords = ACE2; CoV; CoV-2; MERS; RBD; SARS summary = The spike protein can be divided into two domains; S1 is responsible for angiotensin-converting enzyme II(ACE2) recognition, the recently identified host cell receptor, and S2 mediates membrane fusion (Figure 2 ). 98 99 On the basis of this approach, they identified two small molecules, TGG (12, Table 4 ) and luteolin (13) , that can bind avidly to the SARS-CoV S2 protein and inhibit viral entry of SARS-CoV into Vero E6 cells with IC 50 values of 4.5 and 10.6 μM, respectively. 113 A high-throughput screen (HTS) of a 1000-compound library that resulted in the identification of MDL28170 (17 , Table 4 ) by Bates et al., and in an antiviral activity assay, 17 specifically inhibited cathepsin L-mediated substrate cleavage and blocked SARS-CoV viral entry, with an IC 50 value of 2.5 nM and EC 50 value in the range of 100 nM. doi = 10.1021/acs.jmedchem.0c00502 id = cord-338973-73a7uvyz author = Xu, Jiabao title = Systematic Comparison of Two Animal-to-Human Transmitted Human Coronaviruses: SARS-CoV-2 and SARS-CoV date = 2020-02-22 keywords = COVID-19; China; CoV-2; MERS; SARS summary = After the outbreak of the severe acute respiratory syndrome (SARS) in the world in 2003, human coronaviruses (HCoVs) have been reported as pathogens that cause severe symptoms in respiratory tract infections. Recently, a new emerged HCoV isolated from the respiratory epithelium of unexplained pneumonia patients in the Wuhan seafood market caused a major disease outbreak and has been named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The source of unexplained pneumonia was first discovered in Wuhan in Dec, 2019, and SARS-CoV-2, a new coronavirus, was isolated from the respiratory epithelium of patients. Hong Kong scholars found that, compared with ribavirin alone, patients treated with lopinavir/ritonavir and ribavirin had lower risk of acute respiratory distress syndrome (ARDS) or death caused by SARS-CoV [76, 77] . A high-resolution crystal structure of SARS-CoV-2 coronavirus 3CL hydrolase (Mpro) was announced after the outbreak of COVID-19 in the world [80] , and human coronaviruses (HCoVs) have been treated as severe pathogens in respiratory tract infections. doi = 10.3390/v12020244 id = cord-348821-2u6ki9dv author = Xu, Ping title = Clinical Characteristics of Two Human to Human Transmitted Coronaviruses: Corona Virus Disease 2019 versus Middle East Respiratory Syndrome Coronavirus. date = 2020-03-10 keywords = COV; East; MERS summary = The aim of this study, therefore, is to perform a systematic review to compare epidemiological, clinical and laboratory features of COVID-19 and MERS-COV population. Thus, the purpose of this study is to perform a systematic review of epidemiological, clinical and laboratory characteristics of patients infected by COVID-19 or MERS-COV disease, and to compare COVID-19 and MERS-COV in the context of their incubation, laboratory features, admission rate of intensive cure unit (ICU) and rate of discharge and fatality, which will provide a comprehensive reference for clinical physicians in treatment of coronavirus diseases. https://doi.org/10.1101/2020.03.08.20032821 doi: medRxiv preprint 5 The study that met following criteria were included: (1) reporting clinical characteristics of COVID-19 or MERS-COV disease, (2) minimum sample size of five, (3) confirmed COVID-19 or MERS-COV disease, (4) English literature. Clinical predictors of mortality of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection: A cohort study Clinical outcomes among hospital patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection doi = 10.1101/2020.03.08.20032821 id = cord-306373-61snvddh author = Xu, Xiao-Wei title = Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series date = 2020-02-19 keywords = Cov-2; SARS; Wuhan summary = OBJECTIVE: To study the clinical characteristics of patients in Zhejiang province, China, infected with the 2019 severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) responsible for coronavirus disease 2019 (covid-2019). Since the outbreak of covid-19, strict precautionary measures have been implemented in Zhejiang province, including the creation of fever clinics that exclusively receive patients with suspected SARS-Cov-2 infection, defined as presenting with a fever or any respiratory symptoms, including dry cough, and especially in those with a history of travel to Wuhan or exposure to infected people within two weeks before the onset of illness since January 2020. The incubation period was defined as the time from exposure to the onset of illness, which was estimated among patients who could provide the exact date of close contact with individuals from Wuhan with confirmed or suspected SARS-Cov-2 infection. doi = 10.1136/bmj.m606 id = cord-032222-i6gfp4me author = Xue, Ling title = A quick look at the latest developments in the COVID-19 pandemic date = 2020-09-10 keywords = COVID-19; CoV-2; SARS summary = Later, the Coronavirus Study Group of the International Committee on Taxonomy of Viruses formally named this virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a novel coronavirus, and an effective vaccine has yet to be developed. 51 A recombinant adenovirus type 5 vector vaccine, developed by Chen Wei''s team, showed good safety and immunogenicity in a phase I clinical trial, rapidly inducing both humoral and T-cell responses against SARS-CoV-2 in most participants. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia doi = 10.1177/0300060520943802 id = cord-352562-qfb478sf author = Yamamoto, Lidia title = SARS-CoV-2 infections with emphasis on pediatric patients: a narrative review date = 2020-09-04 keywords = ACE2; COVID-19; CoV-2; PCR; SARS summary = In the section devoted to the specific laboratory diagnosis of COVID-19, the most used RT-PCR protocols were described and some studies on the serological diagnosis with IgA, IgM and IgG detection were detailed, including the use of rapid immunochromatographic assays and discussing the ideal period after the onset of symptoms to perform each type of test. They identified 191 cases in hospitalized patients younger than 21 years of age, reported by hospitals in the New York State with the diagnosis of Kawasaki disease, toxic shock syndrome, myocarditis, and suspected multisystem inflammatory syndrome associated with COVID-19 in children (MIS-C). The laboratory diagnosis of COVID-19 are based on the detection of viral RNA by real time amplifications (RT-PCR) 40 or the detection of antibodies (immunoglobulins) anti-SARS-CoV-2 from the classes IgM, IgA and IgG, produced by the host''s immune system. Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection in children and adolescents: a systematic review doi = 10.1590/s1678-9946202062065 id = cord-267887-ntwvquqz author = Yang, Ren title = Development and effectiveness of Pseudotyped SARS-CoV-2 system as determined by neutralizing efficiency and entry inhibition test in vitro date = 2020-08-21 keywords = CoV-2; SARS summary = title: Development and effectiveness of Pseudotyped SARS-CoV-2 system as determined by neutralizing efficiency and entry inhibition test in vitro Previously, researchers had developed a pseudotyped virus system for SARS-CoV and MERS-CoV, based on HIV-1 core, bearing virus spike protein. Furthermore, the neutralization results for ppSARS-2 were consistent with those of live SARS-CoV-2 and determined using the serum samples from convalescent patients. In conclusion, we have developed an easily accessible and reliable tool for studying the neutralizing efficiency of antibodies against SARS-CoV-2 and the entry process of the virus in a BSL-2 laboratory. Development and optimization of a sensitive pseudovirus-based assay for HIV-1 neutralizing antibodies detection using A3R5 cells A safe and convenient pseudovirus-based inhibition assay to detect neutralizing antibodies and screen for viral entry inhibitors against the novel human coronavirus MERS-CoV Neutralization of SARS-CoV-2 spike pseudotyped virus by recombinant ACE2-Ig doi = 10.1016/j.bsheal.2020.08.004 id = cord-327690-di7hfghi author = Yang, Xiaobo title = Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study date = 2020-02-24 keywords = CoV-2; SARS; patient summary = title: Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study METHODS: In this single-centered, retrospective, observational study, we enrolled 52 critically ill adult patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) of Wuhan Jin Yin-tan hospital (Wuhan, China) between late December, 2019, and Jan 26, 2020. In this study, we investigated critically ill patients with confirmed SARS-CoV-2 pneumonia who were admitted to Wuhan Jin Yin-tan hospital. The baseline SARS-CoV-2-associated morbidity and mortality data from this study will be of considerable value for the early identification of individuals who are at risk of becoming critically ill and who are most likely to benefit from intensive care treatment. During the outbreak of SARS-CoV-2 infection, the number of critically ill patients exceeded the capacity of ICUs. Therefore, two provisional ICUs were urgently established in Jin Yin-tan hospital and hence most mechanical ventilator settings and recordings were not recorded, except records of positive end-expiratory pressure in some cases. doi = 10.1016/s2213-2600(20)30079-5 id = cord-351525-306syrrn author = Yang, Yong-Le title = Broad Cross-Species Infection of Cultured Cells by Bat HKU2-Related Swine Acute Diarrhea Syndrome Coronavirus and Identification of Its Replication in Murine Dendritic Cells In Vivo Highlight Its Potential for Diverse Interspecies Transmission date = 2019-11-26 keywords = CoV; Fig; SADS; Vero; cell summary = title: Broad Cross-Species Infection of Cultured Cells by Bat HKU2-Related Swine Acute Diarrhea Syndrome Coronavirus and Identification of Its Replication in Murine Dendritic Cells In Vivo Highlight Its Potential for Diverse Interspecies Transmission We first demonstrated that SADS-CoV possesses a broad species tropism and is able to infect cell lines from diverse species, including bats, mice, rats, gerbils, hamsters, pigs, chickens, nonhuman primates, and humans. As a brief summary of the results, 21 of the 24 cell lines showed significant susceptibility to SADS-CoV infection, defined by efficient viral replication, antigen expression, and the appearance of cytopathic effect (CPE). As some cells did not display CPE after SADS-CoV infection, all cell lines were subsequently tested for viral M protein expression by immunofluorescence assay (IFA) Fig. 1) , revealing the same range as seen by CPE in the different cell lines (data not shown). doi = 10.1128/jvi.01448-19 id = cord-253457-gawn4s9g author = Yau, Kevin title = COVID-19 Outbreak in an Urban Hemodialysis Unit date = 2020-07-15 keywords = CoV-2; SARS summary = Patients with SARS-CoV-2 infection including asymptomatic individuals were treated with droplet and contact precautions until confirmation of negative SARS-CoV-2 RT-PCR testing. Nasopharyngeal swabs were performed by physicians, nurse practitioners, and staff from the hospital''s COVID-19 Assessment Centre under droplet and contact precautions in the hemodialysis unit with curtains drawn around the dialysis station at which the patient was being swabbed. At the time of testing, six (55%) patients and six (55%) staff positive for SARS-CoV-2 were asymptomatic. Patients with confirmed SARS-CoV-2 infection including asymptomatic individuals were dialyzed in a dedicated room separate from the main hemodialysis unit for the duration of their infection and maintained on droplet and contact precautions. Five hemodialysis staff were allowed to return to work following symptom resolution and documentation of two negative SARS-CoV-2 nasopharyngeal swabs performed 14 days from symptom onset. Infection control authorities concluded that SARS-CoV-2 transmission during an outbreak at the St. Michael''s Hospital hemodialysis unit was likely to have originated from two index cases. doi = 10.1053/j.ajkd.2020.07.001 id = cord-353704-lfndq85x author = Ye, Zi-Wei title = Zoonotic origins of human coronaviruses date = 2020-03-15 keywords = CoV; CoV-2; MERS; NL63; SARS summary = In contrast, SARS-CoV, MERS-CoV and the newly-identified SARS-CoV-2 are highly pathogenic, causing severe lower respiratory tract infection in relatively more patients with a higher chance to develop acute respiratory distress syndrome (ARDS) and extrapulmonary manifestations. The 2019 novel HCoV (2019-nCoV), which has subsequently been renamed SARS-CoV-2, is the causative agent of the ongoing epidemic of coronavirus disease 2019 (COVID19) , which has claimed more than 3,120 lives and infected more than 91,000 people as of March 3, 2020 [19] . All these four communityacquired HCoVs have been well adapted to humans and are generally less likely to mutate to cause highly pathogenic diseases, though accidents did occur for unknown reasons as in the rare case of a more virulent subtype of HCoV-NL63, which has recently been reported to cause severe lower respiratory tract infection in China [38] . Alternatively, whereas bat alpha-CoVs serve as the gene pool of HCoV-229E, alpacas and dromedary camels might serve as intermediate hosts that transmit viruses to humans, exactly as in the case of MERS-CoV [69] . doi = 10.7150/ijbs.45472 id = cord-253844-y6xdcf20 author = Yesudhas, Dhanusha title = COVID-19 outbreak: history, mechanism, transmission, structural studies and therapeutics date = 2020-09-04 keywords = ACE2; CoV-2; SARS; human; protein; receptor summary = In SARS-CoV-2 infection, intrinsically disordered regions are observed at the interface of the spike protein and ACE2 receptor, providing a shape complementarity to the complex. SUMMARY: The overall history and mechanism of entry of SARS-CoV-2 along with structural study of spike-ACE2 complex provide insights to understand disease pathogenesis and development of vaccines and drugs. The sequence similarity between SARS-CoV-2 and SARS-CoV spike proteins explains the possibility of binding to the same receptor angiotensin converting enzyme 2 (ACE2) in the host cell [14] . In this review, we discuss the history of coronaviruses in both humans and animals, their transmissions, mechanism of host cell entry and the structural studies, explaining active and inactive receptor binding of spike protein and the key residues playing an important role in the receptor binding. During viral infection, spike protein (~ 1300 amino acid residues) is cleaved by host proteases into receptor binding subunit S1 and membrane fusion subunit S2. doi = 10.1007/s15010-020-01516-2 id = cord-289598-t8upoq9a author = Yoon, Jane C title = COVID-19 Prevalence among People Experiencing Homelessness and Homelessness Service Staff during Early Community Transmission in Atlanta, Georgia, April–May 2020 date = 2020-09-08 keywords = CoV-2; PEH; SARS summary = BACKGROUND: In response to reported COVID-19 outbreaks among people experiencing homelessness (PEH) in other U.S. cities, we conducted multiple, proactive, facility-wide testing events for PEH living sheltered and unsheltered and homelessness service staff in Atlanta, Georgia. We describe SARS-CoV-2 prevalence and associated symptoms and review shelter infection prevention and control (IPC) policies METHODS: PEH and staff were tested for SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR) during April 7–May 6, 2020. Risk of SARS-CoV-2 infection, the virus that causes COVID-19, may be higher among people experiencing homelessness (PEH) because of challenges in preventing respiratory disease transmission in congregate shelter settings. Our finding of decreased prevalence in four shelters during repeat testing is consistent with reports from skilled nursing facilities and correctional facilities, supporting the use of universal (facility-wide) testing for early identification and isolation of those with positive SARS-CoV-2 as a strategy to interrupt transmission in congregate settings [23] [24] [25] . doi = 10.1093/cid/ciaa1340 id = cord-282058-it0ojdk3 author = Yu, Yuanqiang title = Coronavirus Disease 2019 (COVID-19) in Neonates and Children From China: A Review date = 2020-05-15 keywords = COVID-19; China; CoV-2; SARS; Wuhan summary = References for this review were identified through searches of PubMed for articles published from January 1, 2003, to May 1, 2020, by use of the terms "coronavirus, " "neonate, " "children, " "COVID19, " and "SARS-CoV-2." Relevant articles published between 2003 and 2020 were identified through searches in the authors'' personal files. The World Health Organization (WHO) subsequently named the novel coronavirus pneumonia Coronavirus Disease 2019 (COVID-19) and named the virus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The World Health Organization (WHO) subsequently named the novel coronavirus pneumonia Coronavirus Disease 2019 (COVID-19) and named the virus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The symptoms of COVID-19 appear to be less severe in infants and children than in adult patients, similar to the SARS-CoV infection (15) (16) (17) . Of the 34 pregnant women who were confirmed with the SARS-CoV-2 infection in multiple hospitals in Wuhan, including one pregnant woman with a negative nucleic acid test result, 30 had a fever and 16 had a cough (54) (55) (56) (57) . doi = 10.3389/fped.2020.00287 id = cord-342902-y1v8wzxq author = Yuan, Shuofeng title = Clofazimine is a broad-spectrum coronavirus inhibitor that antagonizes SARS-CoV-2 replication in primary human cell culture and hamsters date = 2020-10-07 keywords = COVID-19; CoV-2; RNA; SARS; clofazimine; figure summary = Here, we show that clofazimine, an anti-leprosy drug with a favorable safety and pharmacokinetics profile, possesses pan-coronaviral inhibitory activity, and can antagonize SARS-CoV-2 replication in multiple in vitro systems, including the human embryonic stem cell-derived cardiomyocytes and ex vivo lung cultures. In a hamster model of SARS-CoV-2 pathogenesis, prophylactic or therapeutic administration of clofazimine significantly reduced viral load in the lung and fecal viral shedding, and also prevented cytokine storm associated with viral infection. Since clofazimine is orally bioavailable and has a comparatively low manufacturing cost, it is an attractive clinical candidate for outpatient treatment and remdesivir-based combinatorial therapy for hospitalized COVID-19 patients, particularly in developing countries. We found that co-application of clofazimine and remdesivir impacts SARS-CoV-2 replication in a manner that extends beyond the additive combinatorial activity predicted by the Bliss independence model (maximal Bliss Synergy Score of 44.28; Figure 5a , Extended Data Figure 2) , and indicates these two drugs harbor a synergistic antiviral relationship. doi = 10.21203/rs.3.rs-86169/v1 id = cord-258268-7ypq0t3d author = Zanin, Luca title = SARS-CoV-2 can induce brain and spine demyelinating lesions date = 2020-05-04 keywords = CoV-2; SARS summary = On January 24, 2020, a new virus named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been identified, quickly gaining worldwide attention [21] . Similarly to other Coronavirus, SARS-CoV-2 can attack the olfactory bulb and then affect the central nervous system (CNS) through the olfactory tract in the early stages of infection [5] . Neurological impairment and demyelinating reaction appear as complications in case of severe Coronavirus Disease 2019 (COVID-19) [10] . Our patient showed symptoms consistent with a neurological involvement consequent to SARS-CoV-2 infection. In SARS-CoV-2 infection, neurological impairment was observed only in case of severe COVID-19 [10] . SARS-CoV-2 was not detected in the CSF probably because the neurological damage was sustained by a delayed immune response that occurred after the viremia. Sudden neurological impairment with seizures in COVID-19 patients may be sustained by CNS involvement and demyelinating lesions. Neurologic features in severe SARS-CoV-2 infection doi = 10.1007/s00701-020-04374-x id = cord-338243-njkhwkwk author = Zhang, Dayi title = Potential spreading risks and disinfection challenges of medical wastewater by the presence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) viral RNA in septic tanks of Fangcang Hospital date = 2020-06-23 keywords = CoV-2; SARS summary = title: Potential spreading risks and disinfection challenges of medical wastewater by the presence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) viral RNA in septic tanks of Fangcang Hospital In this study, we evaluated the presence of SARS-CoV-2 viral RNA in septic tanks of Wuchang Cabin Hospital and found a striking high level of (0.5–18.7) × 103 copies/L after disinfection with sodium hypochlorite. In septic tanks, disinfection achieved free chlorine > 6.5 mg/L for 1.5 hours when the dosage of sodium hypochlorite was 800 g/m 3 , meeting well with the guideline for emergency treatment of medical sewage containing SARS-CoV-2 suggested by China CDC. Septic tanks can behave as a long-term source J o u r n a l P r e -p r o o f to release SARS-CoV-2 viral RNA into waters when disinfection is not sufficient and challenges public health via potentially spreading viruses in drainage pipelines. doi = 10.1016/j.scitotenv.2020.140445 id = cord-293082-fw7deem8 author = Zhang, Guangzhi title = Animal coronaviruses and SARS‐CoV‐2 date = 2020-08-16 keywords = CoV-2; Coronavirus; SARS summary = As of April 7, just four months since its first outbreak, more 48 than 3.4 million confirmed cases and 238,000 deaths have been recorded in 215 countries, areas, 49 and territories, and moreover it seems that severe acute respiratory syndrome coronavirus 2 50 (SARS-CoV-2) that causes COVID-19 will probably continue to circulate around the globe 51 (https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports/). The health 52 authorities and governments of affected countries have paid attention to current pandemic and 53 have taken immediate measures to block COVID-19 transmission, including utilization of personal 54 protective equipment, quarantine, epidemiological investigation, isolation, clinical data analysis 55 and sharing, public health education, maintaining social distance, the creation of diagnostics, 56 therapeutics, and vaccines, etc (Xiao and Torok 2020) . Human Kidney is a Target for Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection SARS-CoV-2 Spike protein variant D614G increases infectivity and retains sensitivity to antibodies that target the receptor binding domain doi = 10.1111/tbed.13791 id = cord-294831-pem059zk author = Zhang, Ling-Pu title = Focus on a 2019-novel coronavirus (SARS-CoV-2) date = 2020-06-11 keywords = COVID-19; China; CoV-2; MERS; SARS summary = A report of five patients in a family cluster who traveled to Wuhan and were infected with SARS-CoV-2 was the first report directly illustrating that the virus is capable of person-to-person transmission in hospital and family settings [23] . Xiao and colleagues showed that 53.42% of 73 hospitalized COVID-19 patients had SARS-CoV-2 RNA in stool specimens, and the duration time of positive stool results ranged from 1 to 12 days [27] . In a study published in The Lancet, 41 of 41 patients who were identified as positive for SARS-CoV-2 infection presented with pneumonia and abnormal chest computed tomography (CT) [6] . An article reported in Science shows that SARS-CoV-2 can replicate in the upper respiratory tract of ferrets, indicating that ferrets represent an ideal animal model for evaluating antiviral drugs or vaccine candidates against COVID-19 [64] . Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan doi = 10.2217/fmb-2020-0063 id = cord-261075-wqtxhiy8 author = Zhang, Meng title = The nervous system——a new territory being explored of SARS-CoV-2 date = 2020-10-28 keywords = ACE2; COVID-19; CoV-2; SARS summary = However, there is growing evidence that SARS-CoV-2 can result in a broad spectrum of neurologic diseases (6) (7) (8) (9) , which is not surprising, as neurological manifestations have been reported in other respiratory viral infections, including coronavirus, but the nervous system manifestations of COVID-19 are more common and disabling, raising the worldwide concerns about its potential long-term complications to humans (10, 11) . In particular, we focused on its neurological manifestations and specific pathogenesis, as well as its comparison with other viral respiratory infections.Finally, we further summarized the significance of the neuroinvasion and the follow-up issues that need to be paid attention to by scientists, so as to help neurologists understand the influence of SARS-CoV-2 on nervous system better and promote the accurate diagnosis and efficient treatment of COVID-19. doi = 10.1016/j.jocn.2020.10.056 id = cord-254968-czrgzyr3 author = Zhang, Qiang title = A serological survey of SARS-CoV-2 in cat in Wuhan date = 2020-09-17 keywords = CoV-2; SARS; Wuhan summary = Here, we investigated the infection of SARS-CoV-2 in cats during COVID-19 outbreak in Wuhan by serological detection methods. Our data demonstrated that SARS-CoV-2 has infected cats in Wuhan during the outbreak and described serum antibody dynamics in cats, providing an important reference for clinical treatment and prevention of COVID-19. Here, we investigated the serological prevalence of SARS-CoV-2 in cats by an indirect ELISA and virus neutralization tests (VNT), and monitored the serum antibody dynamics of cats infected SARS-CoV-2, providing a basis for further understanding the infection of SARS-CoV-2 in cats. In this study, we detected the presence of SARS-CoV-2 antibodies in cats in Wuhan during the COVID-19 outbreak with ELISA, VNT and western blot. Virus neutralization test and Western blot assay of cat serum samples for SARS-CoV-2 (A) Cat#14, Cat#15 and Cat#4 sera were 3-fold serially diluted and mixed with SARS-CoV-2; after incubated at 37°C for 1 h, the mixture was used to infect Vero E6 cells, and replaced with semi-solid media 1 h later. doi = 10.1080/22221751.2020.1817796 id = cord-316126-j51dik7f author = Zhang, X. Sophie title = SARS-CoV-2 and Health Care Worker Protection in Low-Risk Settings: a Review of Modes of Transmission and a Novel Airborne Model Involving Inhalable Particles date = 2020-10-28 keywords = COVID-19; CoV-2; N95; PPE; SARS; mask; study; transmission summary = title: SARS-CoV-2 and Health Care Worker Protection in Low-Risk Settings: a Review of Modes of Transmission and a Novel Airborne Model Involving Inhalable Particles Since the beginning of the COVID-19 pandemic, there has been intense debate over SARS-CoV-2''s mode of transmission and appropriate personal protective equipment for health care workers in low-risk settings. This review attempts to summarize current cumulative data on SARS-CoV-2''s modes of transmission and identify gaps in research while offering preliminary answers to the question on everyone''s mind: is the airborne route significant and should we modify our COVID-19 PPE recommendations for frontline workers in low-risk settings? Given that substantial disagreement persists on the importance of natural aerosol generation by COVID-19 patients, and consequently, the necessary level of respiratory protection in non-AGP contexts, our review will focus on transmission and PPE in low-risk health care settings. doi = 10.1128/cmr.00184-20 id = cord-343528-5283jsnu author = Zhang, Zhao title = Evolutionary Dynamics of MERS-CoV: Potential Recombination, Positive Selection and Transmission date = 2016-05-04 keywords = CoV; Fig; MERS summary = Our analyses show: 1) 28 potential recombinant sequences were detected and they can be classified into seven potential recombinant types; 2) The spike (S) protein of MERS-CoV was under strong positive selection when MERS-CoV transmitted from their natural host to human; 3) Six out of nine positive selection sites detected in spike (S) protein are located in its receptor-binding domain which is in direct contact with host cells; 4) MERS-CoV frequently transmitted back and forth between human and camel after it had acquired the human-camel infection capability. Together, these results suggest that potential recombination events might have happened frequently during MERS-CoV''s evolutionary history and the positive selection sites in MERS-CoV''s S protein might enable it to infect human. In order to study the temporal and spatial pattern of MERS-CoV transmission, a maximum clade credibility (MCC) tree was constructed using MERS-CoV whole genome sequences without recombinant strains (Fig. 3c) . The amino acid sites under positive selection in MERS-CoV S protein, especially those in its receptor binding domain, might have facilitated its cross-species transmission from animal host to human. All authors reviewed the manuscript. doi = 10.1038/srep25049 id = cord-347767-aq9niccc author = Zhao, Jie title = Yidu-toxicity blocking lung decoction ameliorates inflammation in severe pneumonia of SARS-COV-2 patients with Yidu-toxicity blocking lung syndrome by eliminating IL-6 and TNF-a date = 2020-06-19 keywords = CD4; COV-2; IL-6; SARS summary = The present study investigates the differences in inflammatory agents alterations, immune function, and leukocyte differential count evaluation in severe pneumonia of SARS-COV-2 patients with Yidu-toxicity blocking lung syndrome after the recommended Chinese medicine prescription of Yidu-toxicity blocking lung decoction. A total of 40 patients with yidu-toxicity blocking lung syndrome, diagnosed as severe pneumonia of SARS-COV-2 following the latest Chinese national recommendations for the diagnosis and treatment of pneumonia caused by SARS-COV-2 (the 5th edition), were recruited. To characterize the effect of herbal medicine, immune function, and inflammatory agents, levels of white blood cells were detected for all patients according to the manufacturer''s instructions at the beginning and at the end of the two weeks. In conclusion, our study suggests that the 5th edition recommendation''s CM prescription, can be safely used in the treatment of severe pneumonia of SARS-COV-2 with yidu-toxicity blocking lung syndrome. doi = 10.1016/j.biopha.2020.110436 id = cord-321358-plxz5mkg author = Zheng, Jun title = SARS-CoV-2: an Emerging Coronavirus that Causes a Global Threat date = 2020-03-15 keywords = China; CoV-2; SARS; Wuhan summary = An ongoing outbreak of pneumonia caused by a novel coronavirus, currently designated as the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), was reported recently. In this review, we summarize the key events occurred during the early stage of SARS-CoV-2 outbreak, the basic characteristics of the pathogen, the signs and symptoms of the infected patients as well as the possible transmission pathways of the virus. CoVs have been identified in both avian hosts and various mammals, including bat, camels, dogs and masked palm civets, and are previously regarded as pathogens that only cause mild diseases in the immunocompetent people until the emergence of the coronavirus causing severe acute respiratory syndrome (SARS-CoV) in late of 2002 [3] [4] [5] [6] . doi = 10.7150/ijbs.45053 id = cord-290904-ngvhk0qy author = Zheng, Zhiqiang title = Monoclonal antibodies for the S2 subunit of spike of SARS-CoV-1 cross-react with the newly-emerged SARS-CoV-2 date = 2020-07-16 keywords = CoV-2; SARS; protein summary = In this study, we aim to verify if the sequence of the immunogen used to generate mAb 1A9, as well as three other mAbs, is conserved in different coronaviruses and if these mAbs bind to the S protein of SARS-CoV-2 expressed in mammalian cell lines. IF analysis performed on transiently transfected COS-7 cells showed binding of the four mAbs to this S protein fragment of SARS-CoV-2 ( Figure 2B ). Utility of monoclonal antibody 1A9 for detection of S protein in a sandwich ELISA format and in SARS-CoV-2 infected cells Based on indirect ELISA data, mAb 1A9 has the strongest binding to S protein when compared with the other three mAbs. Hence, a sandwich ELISA was performed to determine if it can be paired with the human mAb CR3022 which is known to bind to the S1 subunit of SARS-CoV-2. doi = 10.2807/1560-7917.es.2020.25.28.2000291 id = cord-214854-ck61ja2t author = Zhong, Jing title = Rapid and sensitive detection of SARS-CoV-2 with functionalized magnetic nanoparticles date = 2020-10-08 keywords = CoV-2; SARS summary = Homogeneous biosensing based on magnetic nanoparticles (MNPs) is one of the most promising approaches for rapid and highly sensitive detection of biomolecules. This paper proposes an approach for rapid and sensitive detection of SARS-CoV-2 with functionalized MNPs via the measurement of their magnetic response in an ac magnetic field. Homogeneous biosensing based on magnetic nanoparticles (MNPs) is one of the most promising approaches for rapid and sensitive detection of specific biomolecules, e.g. protein, DNA/RNA and virus. demonstrated the feasibility of wash-free, sensitive and specific assays for the detection of different viruses, e.g. orchid and influenza viruses, with antibody-functionalized MNPs by measuring the reduction in the ac susceptibility in mixed-frequency ac magnetic fields [23] [24] [25] . All these approaches have demonstrated that MNP-based homogeneous biosensing is a wash-free and mix-and-measure approach for rapid and sensitive detection of specific biomolecules. doi = nan id = cord-294363-bv6xa8v8 author = Zhou, Hong title = Potential Therapeutic Targets and Promising Drugs for Combating SARS‐CoV‐2 date = 2020-05-05 keywords = ACE2; China; CoV-2; RNA; SARS summary = Several studies demonstrated angiotensin converting enzyme 2 (ACE2) as an important therapeutic target of SARS-CoV-2 entry and infection, and many potential targets were subsequently proposed, such as the spike (S) protein and transmembrane serine protease 2 (TMPRSS2). Therefore, accelerating research for potential therapeutic target confirmation, promising drug discovery, and clinical verification development will speed up efforts to combat SARS-CoV-2. In addition to inhibiting the virus directly, ASOs are also expected to target the disease-related proteins involved in the inflammatory cytokine storm process, which could be considered a promising therapeutic strategy for combating SARS-CoV-2 . Although many strategies have been used to block the attachment, entry, replication and release processes to inhibit SARS-CoV-2 infection, how to prevent viral evasion from host immune responses and virus-induced cytopathic effects is considered one of the most urgent problems that need to be solved in SARS-CoV-2-induced pneumonia-associated respiratory syndrome (PARS) patients. doi = 10.1111/bph.15092 id = cord-302584-fwdpzv85 author = Zhu, Ying title = Isolation of Virus from a SARS Patient and Genome-wide Analysis of Genetic Mutations Related to Pathogenesis and Epidemiology from 47 SARS-CoV Isolates date = 2005-01-01 keywords = CoV; SARS; WHU summary = title: Isolation of Virus from a SARS Patient and Genome-wide Analysis of Genetic Mutations Related to Pathogenesis and Epidemiology from 47 SARS-CoV Isolates Despite the fact that the SARS-CoV can cause an atypical and fatal form of pneumonia, the genome structure, gene expression pattern, and protein profiles of the virus are similar to those of other conventional coronaviruses [17] , which are only responsible for mild respiratory tract infections in a wide range of animals including humans, pigs, cows, mice, cats, and birds [10, 19] . In this report, we described the isolation of a new SARS-CoV strain (WHU) from a patient in Hubei Province, China during the late period of SARS outbreak. Comparative study of genetic characterization and nucleotide variation of all known SARS-CoV offers insights into understanding functions of the viral genes and revealing the evolution trends of the virus. doi = 10.1007/s11262-004-4586-9 id = cord-268561-vq1uhj5i author = da Silva, Severino Jefferson Ribeiro title = Clinical and Laboratory Diagnosis of SARS-CoV-2, the Virus Causing COVID-19 date = 2020-08-04 keywords = COVID-19; China; CoV-2; Coronavirus; Disease; SARS; patient summary = 11 The causative agent was identified as a novel CoV, eventually named SARS-CoV-2, and the respiratory syndrome associated with the infection was designated as coronavirus disease-2019 (COVID-19) by the World Health Organization (WHO). In direct tests, the clinical sample is examined directly for the presence of particles, virus antigens, or viral nucleic acids, whereas indirect methods detect the serological response against the infection (Figure 2 ). 11 Culture-based methods for SARS-CoV-2 detection have been used in research and public health laboratories in different parts of the world, but virus isolation is not recommended as a routine diagnostic procedure because it has low sensitivity, it is time-consuming, and it requires BSL-3 containment. 11 In addition to unequivocally confirming the diagnosis of a SARS-CoV-2 infection, regular sequencing of a percentage of patient samples from clinical cases can be used to monitor changes in the viral genome over time and trace transmission patterns. doi = 10.1021/acsinfecdis.0c00274 id = cord-260729-b12v3c8c author = de Lang, Anna title = Functional Genomics Highlights Differential Induction of Antiviral Pathways in the Lungs of SARS-CoV–Infected Macaques date = 2007-08-10 keywords = CoV; IFN; SARS; lung; stat1 summary = As opposed to many in vitro experiments, SARS-CoV induced a wide range of type I interferons (IFNs) and nuclear translocation of phosphorylated signal transducer and activator of transcription 1 in the lungs of macaques. In order to elucidate early host responses during the acute phase of SARS-CoV infection, we infected cynomolgus macaques with SARS-CoV and used macaque-specific microarrays and real-time (RT)-PCR techniques to study host gene expression profiles. In this study, we simultaneously examined virus replication and host-response gene expression profiles in macaque lungs during the acute phase of SARS to gain more insight into the early events that take place after SARS-CoV infection. In order to visualize the host response in the lungs of SARS-CoV-infected macaques, IFN-b production and translocation of phosphorylated STAT1 was studied using immunohistochemistry. The expression of IFN-b, which strongly correlated to the amount of virus present, continued throughout day 4 and was confirmed using immunohistochemistry; IFN-b-positive cells could be detected in the lungs of the SARS-CoV-infected macaques. doi = 10.1371/journal.ppat.0030112 id = cord-332992-8rmqg4rf author = de Vries, A. A. F. title = SARS-CoV-2/COVID-19: a primer for cardiologists date = 2020-07-15 keywords = COVID-19; CoV-2; RNA; SARS; cell; patient; virus summary = Although SARS-CoV-2 particles/components have been detected in, for example, endothelial cells, the digestive tract and the liver, not all extrarespiratory manifestations of COVID-19 are necessarily caused by direct viral injury but may also be the consequence of the hypoxaemia, (hyper)inflammatory response, neuroendocrine imbalance and other pathophysiological changes induced by the airway infection [43] . Factors that may contribute to the thrombophilia observed in severely ill COVID-19 patients include the following: (1) a disturbed balance between pro-and anticoagulant activities due to excessive production of proinflammatory cytokines, activation of complement, formation of neutrophil extracellular traps and activation of platelets; (2) inflammation-related endothelial activation; (3) death of SARS-CoV-2-infected endothelial cells; (4) endothelial dysfunction caused by unbalanced angiotensin IIangiotensin II type-1 receptor signalling; (5) formation of prothrombotic antiphospholipid antibodies; (6) immobility-associated reduction of blood flow; (7) hypoxia due to respiratory impairment resulting from SARS-CoV-2-induced lung injury [79] [80] [81] . doi = 10.1007/s12471-020-01475-1 id = cord-319877-izn315hb author = de Wit, Emmie title = SARS and MERS: recent insights into emerging coronaviruses date = 2016-06-27 keywords = CoV; East; MERS; Middle; SARS; respiratory summary = Scientific advancements since the 2002–2003 severe acute respiratory syndrome coronavirus (SARS-CoV) pandemic allowed for rapid progress in our understanding of the epidemiology and pathogenesis of MERS-CoV and the development of therapeutics. The downregulation of ACE2 results in the excessive production of angiotensin II by the related enzyme ACE, and it has been suggested that the stimulation of type 1a angiotensin II receptor and Middle East respiratory syndrome coronavirus (MERS-CoV) encode two large polyproteins, pp1a and pp1ab, which are proteolytically cleaved into 16 non-structural proteins (nsps), including papain-like protease (PLpro), 3C-like protease (3CLpro), RNA-dependent RNA polymerase (RdRp), helicase (Hel) and exonuclease (ExoN). Both severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) have developed mechanisms to interfere with these signalling pathways, as shown; these subversion strategies involve both structural proteins (membrane (M) and nucleocapsid (N)) and non-structural proteins (nsp1, nsp3b, nsp4a, nsp4b, nsp5, nsp6 and papain-like protease (PLpro); indicated in the figure by just their nsp numbers and letters). doi = 10.1038/nrmicro.2016.81 id = cord-353293-vjdwh19x author = nan title = Post-COVID-19 global health strategies: the need for an interdisciplinary approach date = 2020-06-11 keywords = COVID-19; CoV-2; SARS; patient summary = Gemelli IRCSS (Rome, Italy) has set up a multidisciplinary healthcare service called "Post-COVID-19 Day Hospital." The specialist assessments offered to patients are outlined in the following sections. Furthermore, the important role of geriatrician acting as a care manager of patients who suffered COVID-19 disease is described. A respiratory follow-up is of pivotal importance to evaluate lung function, alveolar-arterial gas exchange, and exercise tolerance in recovered non-infective COVID-19 patients [5] . In this Post-COVID-19 Day Hospital, internal medicine and geriatric specialists are integrated with infectious disease physicians, pneumologists, immuno-rheumatologists, and other specialists into the management of the SARS-CoV-2 infection. As a whole, the post-acute care service at the Fondazione Policlinico Gemelli aims at expanding the knowledge of COVID-19 and its impact on health status and care needs as well as at promoting healthcare strategies to treat and prevent the clinical consequence of SARS-CoV-2 infection across different organs and systems. doi = 10.1007/s40520-020-01616-x id = cord-310507-5h6egve4 author = van Doorn, Amarylle S. title = Systematic review with meta‐analysis: SARS‐CoV‐2 stool testing and the potential for faecal‐oral transmission date = 2020-08-27 keywords = COVID-19; CoV-2; SARS summary = Since December 2019, the world has been dealing with the outbreak of the novel Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) leading to Corona Virus Disease 2019 (COVID-19) that emerged in Wuhan, China. However, there is a growing body of studies in which SARS-CoV-2 RNA was detected in stool samples (including anal swabs) from COVID-19 patients. 11, 15, 16 This study aims to (1) critically assess the clinical relevance of testing stool samples and anal swabs and (2) provide a critical overview of the available literature regarding the faecal-oral transmission of SARS-CoV-2. We collected the following data from the eligible original articles: study design, geographic location, study period, number of patients, age, types of tested specimens, number of tested specimens, methods of the performed tests, duration and prevalence of positive test results in different specimens, disease severity, gastrointestinal symptoms, endoscopic results, specific evidence supporting faecal-oral transmission and remarkable patient/population characteristics. doi = 10.1111/apt.16036 id = cord-328175-4i3cz20j author = van Doremalen, Neeltje title = Efficacy of antibody-based therapies against Middle East respiratory syndrome coronavirus (MERS-CoV) in common marmosets date = 2017-07-31 keywords = CoV; MERS summary = Abstract Cases of Middle East respiratory syndrome coronavirus (MERS-CoV) continue to be identified and with a lack of effective clinical treatment and no preventative strategies, treatment using convalescent plasma or monoclonal antibodies (mAbs) is a potential quick route to an intervention. Here we assess the effect of treatment with marmoset-derived hyperimmune plasma as well as the human mAb m336 on disease outcome in the recently developed marmoset MERS-CoV infection model, which recapitulates severe respiratory disease (Falzarano et al., 2014) . Viral loads in lung tissues from hyperimmune plasma-treated compared to control animals were found to be significantly lower using a onetailed unpaired Student''s t-test (average of 4.0  10 4 and 1.2  10 6 TCID 50 equivalent/gram, respectively, p-value ¼ 0.008). In this study, hyperimmune plasma treatment of marmosets inoculated with MERS-CoV resulted in a small (0.5e1 log) but significant reduction in respiratory tract viral loads, as well as reduced disease severity such as observed with radiographs, compared to marmosets treated with non-convalescent plasma or PBS. doi = 10.1016/j.antiviral.2017.03.025 id = cord-265329-bsypo08l author = van Dorp, Lucy title = Emergence of genomic diversity and recurrent mutations in SARS-CoV-2 date = 2020-05-05 keywords = CoV-2; SARS; figure; genome summary = Three sites in Orf1ab in the regions encoding Nsp6, Nsp11, Nsp13, and one in the Spike protein are characterised by a particularly large number of recurrent mutations (>15 events) which may signpost convergent evolution and are of particular interest in the context of adaptation of SARS-CoV-2 to the human host. The extraordinary availability of genomic data during the COVID-19 pandemic has been made possible thanks to a tremendous effort by hundreds of researchers globally depositing SARS-CoV-2 assemblies (Table S1 ) and the proliferation of close to real time data visualisation and analysis tools including NextStrain (https://nextstrain.org) and CoV-GLUE (http://cov-glue.cvr.gla.ac.uk). In this work we use this data to analyse the genomic diversity that has emerged in the global population of SARS-CoV-2 since the beginning of the COVID-19 pandemic, based on a download of 7710 assemblies. The genomic diversity of the global SARS-CoV-2 population being recapitulated in multiple countries points to extensive worldwide transmission of COVID-19, likely from extremely early on in the pandemic. doi = 10.1016/j.meegid.2020.104351