# ent

id: cord-007237-8y7218oj
type: DISEASE
entity:
  human rhinoviruses paramyxoviruses coronaviruses and bocavirus during acute respiratory tract infections


id: cord-003115-y40knklf
type: DNA
entity:
  jiy222 sha 17bbe32558609da8c1aceab2b751383aa9c3c18b doc_id 3115 cord_uid y40knklf Plasmodium falciparum erythrocyte


id: cord-007009-4wbvdg1r
type: ORG
entity:
  Liang National Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and Prevention Beijing


id: cord-277735-a9gkath5
type: WORK_OF_ART
entity:
  Antibody Response of Patients with Severe Acute Respiratory Syndrome SARS Targets the Viral Nucleocapsid


id: cord-275863-qos9vu3r
type: DNA
entity:
  jir173 sha 3062cebd70447841d68c48fe83f0eb51b07a761d doc_id 275863 cord_uid qos9vu3r Dengue virus receptors


id: cord-275863-qos9vu3r
type: PROTEIN
entity:
  glycan antigen Lewis x A dendritic cell specific intercellular adhesion molecule 3 grabbing nonintegrin DC SIGN related protein


id: cord-007176-61e9obb3
type: WORK_OF_ART
entity:
  Viroses Causing Common Respiratory Infections in Man III Respiratory Syncytial Viroses and Coronavimses date


id: cord-000842-kff3gig0
type: DNA
entity:
  HA NA unique pool 38 peptides Supplementary Table 1 A HA conserved pool containing 1 divergent amino acid


id: cord-000842-kff3gig0
type: DISEASE
entity:
  influenza A H1N1 virus after vaccination with seasonal influenza vaccine In vitro and in vivo characterization of new swine origin


id: cord-000842-kff3gig0
type: DISEASE
entity:
  influenza A virus in humans Immune correlates of protection against influenza in the human challenge model Haemagglutination inhibiting antibody to influenza virus Discordance between antibody and T cell responses


id: cord-269383-1tyorrb0
type: ORG
entity:
  The Joint Chinese University of Hong Kong New Territories East Cluster Clinical Research Ethics Committee


id: cord-001764-njzyu4mv
type: CELL_LINE
entity:
  293T human embryonic kidney Huh7 human hepatoma U373 human glioblastoma HOS human osteosarcoma HeLa human cervix carcinoma RPE human retinal pigment epithelial EA hy human endothelial hybrid Raji human B cell Jurkat human T cell CEMx174 human T cell B cell hybrid


id: cord-261241-eqf6ame6
type: DISEASE
entity:
  influenza virus coronaviruses rhinoviruses human metapneumovirus respiratory syncytial virus parainfluenza viruses


id: cord-013049-7d436sqg
type: PROTEIN
entity:
  alkaline phosphatase conjugated isotype specific goat anti human immunoglobulin G IgG immunoglobulin M IgM


id: cord-013049-7d436sqg
type: ORG
entity:
  the Laboratory of Infectious Diseases National Institute of Allergy and Infectious Diseases Potential


id: cord-290277-ndfoppoq
type: ORG
entity:
  Interim Infection Prevention and Control Recommendations for Hospitalized Patients with Middle East Respiratory Syndrome Coronavirus


id: cord-288821-nalulzfo
type: DNA
entity:
  1b gene primers repSZ 1f 15973 5 GTGATGCATA TGCTAATTTG 3 repSZ 3r 16210 5 CTCTTGCAGGTAT AATCCTA 3 repSZ 2f 16012 5 TTGGTAAACAAAAGAT AACT 3


id: cord-288821-nalulzfo
type: CHEMICAL
entity:
  NM_006413 5 AGATT TGGACCTGCGAGCG 3 forward primer and 5 GAGCGG CTGTCTCCACAAGT 3 reverse primer Viral


id: cord-259004-plst2wno
type: EVENT
entity:
  Frequent Detection of Human Coronaviruses in Clinical Specimens from Patients with Respiratory Tract Infection


id: cord-285087-i3nz5bvs
type: TAXON
entity:
  human adenovirus HAdV human bocavirus HBoV human enterovirus HEV human parechovirus HPeV human metapneumovirus HMPV


id: cord-003171-z22ekgtv
type: DISEASE
entity:
  influenza A H1N1 2009 virus where are we Complex patterns of human antisera reactivity to novel 2009


id: cord-279311-msh9wvsh
type: PROTEIN
entity:
  human monoclonal anti CD3 fluorescein isothiocyanate FITC anti CD4 phycoerythrin PE anti CD8 allophycocyanin APC anti CD19 PE anti CD16 APC


id: cord-299835-92karhpl
type: DISEASE
entity:
  influenza A H5N1 Hong Kong Seroepidemiology of human enterovirus 71 World Health Organization Global surveillance for severe acute respiratory syndrome SARS


id: cord-299149-lc2dxvxz
type: ORG
entity:
  the National University of Singapore s ethics review committee National University of Singapore Institutional Review Board


id: cord-299149-lc2dxvxz
type: DISEASE
entity:
  influenza B virus human parainfluenza virus hPIV types 1 4 and respiratory syncytial virus RSV RSV A


id: cord-261472-qcu73sdu
type: ORG
entity:
  Cleavage and Serum Reactivity of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein date 2004


id: cord-007013-tlvgyzft
type: PROTEIN
entity:
  IFN interferon IL 1 interleukin 1 IL 6 interleukin 6 IL 8 interleukin 8 IL 10 interleukin 10 IL 12p40 interleukin 12p40 IL 17 interleukin 17 MCP 1 monocyte chemoattractant protein 1 TNF


id: cord-007013-tlvgyzft
type: GGP
entity:
  IFN interferon IL 1 interleukin 1 IL 6 interleukin 6 IL 8 interleukin 8 IL 10 interleukin 10 IL 12p40 interleukin 12p40 IL 17 interleukin 17 MCP 1 monocyte chemoattractant protein 1 TNF α tumor necrosis factor α


id: cord-307918-8y89p11a
type: DISEASE
entity:
  respiratory syncytial virus RSV adenovirus rhinovirus parainfluenza virus PIV 1 3 human metapneumovirus coronavirus CoV


id: cord-296197-ohfhnpma
type: PROTEIN
entity:
  Leishmania species L donovani L amazonensis L infantum L braziliensis L peruviana L guyanensis L panamensis L mexicana L major L lainsoni L tropica


id: cord-309786-8zyf9e3k
type: DNA
entity:
  jiz408 sha 5113521b5a193540f5783167133b6eef32259c98 doc_id 309786 cord_uid 8zyf9e3k BACKGROUND Respiratory syncytial virus RSV


id: cord-309786-8zyf9e3k
type: PERSON
entity:
  Peter L Buchholz Ursula J title Safety and Immunogenicity of the Respiratory Syncytial Virus Vaccine RSV


id: cord-313000-as507p4t
type: CELL_LINE
entity:
  Sao Paulo Sao Paulo Brazil Dr Atul Humar Mount Sinai Hospital Toronto Canada and Dr Ian Mackay Royal Children s Hospital Queensland Australia We also thank George Gallucci Brian Holloway Xiaoyan Lu and Karen McCaustland CDC Atlanta Georgia for technical assistance Pongpun Sawatwong Thailand Ministry of Public Health US CDC Collaboration


id: cord-312552-udky2ko7
type: CELL_LINE
entity:
  UNICEF United Nations Development Programme UNDP World Bank World Health Organization WHO Special Programme for Research and Training in Tropical Diseases TDR


id: cord-312552-udky2ko7
type: ORG
entity:
  the UNICEF United Nations Development Programme UNDP World Bank World Health Organization WHO Special Programme for Research and Training in Tropical Diseases


id: cord-312552-udky2ko7
type: ORG
entity:
  The International Bank for Reconstruction and Development The World Bank World Health Organization Global


id: cord-313344-rqvi2ksc
type: DISEASE
entity:
  gastrointestinal tract heart kidney lung lymph nodes skeletal muscle liver and spleen 14 Gastrointestinal complaints


id: cord-306983-6w2fvtfy
type: DNA
entity:
  primer F 5 ATCCAGGTGAGACTGGGAGAGC ACA 3 nucleotide nt 222 246 and reverse primer R 5 GTAGACCTTGGTGTAGACTCCAGGC 3 nt 692 716


id: cord-275355-4izc5jxs
type: ORG
entity:
  the Netherlands World Health Organization International Avian Influenza Investigation Team Vietnam Lack


id: cord-275355-4izc5jxs
type: DISEASE
entity:
  influenza A H5N1 Hong Kong Atypical avian influenza H5N1 Avian influenza H5N1 and healthcare workers World Health Organization


id: cord-007375-hqmyund4
type: DNA
entity:
  Ϫ238 5 AAATCAGTCAGTGGCCCAGAA 3 5 TCATTCAACCAGC GGAAAACT 3 5 FAM CTCCCTGCTCCGATT MGB 3 and 5 VIC CTCCCTGCTCTGATT MGB 3


id: cord-007375-hqmyund4
type: DNA
entity:
  Ϫ308 5 GAAATGGAGGCAATAGGTTTTGAG 3 5 GTAGGACCCT GGAGGCTGAAC 3 5 FAM CCGTCCCCATGCC MGB 3 and 5 VIC CCGTCCTCATGCC MGB 3 for IL 10 Ϫ592 5 AGCTGAAGAGGTGGAAACATGTG 3 5 CAAGCAGCCC Differences


id: cord-297432-2edncbgn
type: ORG
entity:
  Henrik Ullum Capital Region Blood Bank Department of Clinical Immunology Rigshospitalet Copenhagen University Hospital


id: cord-300019-8vxqr3mc
type: GGP
entity:
  HMPV OR 9 8 95 CI 2 3 41 0 AFE 90 AdV OR not available AFE approximately 100 RV OR 7 1 95 CI 3 7 13 6 AFE 86 and CoV OR 2 8 95 CI 2 0 4 1 AFE


id: cord-287210-sars5dmi
type: DNA
entity:
  primer Reverse primer pol LPW1465 5 GTTCAAGTGTCGCTGTTCA 3 LPW1822 5 CTATCATTATCACAATCCACAG 3 LPW1467 5 GGGTATGAAGTATCATCCTA 3 LPW1825 5 GATAATCCCAACCCATAAGAAC 3 LPW1826 5 CATCTTATAAAGGATGTTGAC 3 LPW1829 5 ACAAACAACACATGCACCTACAC 3 S LPW1830 5 TTGCCTATTATTTTACAAGGT 3 LPW1864 5 ACACTACCTATAACTATAGTAC 3 LPW1832 5 TATGTTAATAAWACTTTGTATAGTG 3 LPW1866 5 TACAATTGACAAGAACTAGAAG 3 LPW1836 5 GATTTGCARTTGGGCAGTTCTGG 3 LPW1868 5 CCATTAGAATCATACAAAAGAT 3 LPW1840 5 GGTATTTTTAAAGAAGTTTCTGC 3 LPW1870 5 AGCTTCAACAAAACCWACATCTG 3 LPW1844 5 TAGGTYCACAMTGYGGTTCTTC 3 LPW1872 5 AMCCTTGYTTAGGTGCAATACCT 3 LPW1848 5 TTAAAACTGTYTTAGTAAGTCC 3 LPW1874 5 TAGTAAAACTAGTTAYAACACC 3 N LPW1887 5 TAGTGGTATGGATACTGCCTTGT 3 LPW1890 5 GCTTTAACATTTCAGMATTACCA 3 LPW1891 5 CAGTGTTTTGGTAAAAGAGGACC 3 LPW1892 5 TACCACCTAGTGTCGAATTAGG 3


id: cord-007026-ejv0gidp
type: TAXON
entity:
  virus parainfluenza 1 4 virus respiratory syncytial virus metapneumovirus rhinovirus enterovirus human coronavirus OC43 and 229E NL63 adenovirus


id: cord-324001-m7ys95z7
type: DISEASE
entity:
  H1N1 strain A Brevig Mission 1918 The proliferation response was measured by adding 5 bromo 2 deoxyuridine BrdU


id: cord-327673-3uem0e22
type: PROTEIN
entity:
  antibodies anti CD3 HIT3a anti T cell receptor TCR g9 B3 anti TCR d2 B6 anti NKG2D 1D11 anti TRAIL RIK


id: cord-327673-3uem0e22
type: DISEASE
entity:
  human immunodeficiency virus hepatitis B virus herpes simplex virus vaccinia virus human cytomegalovirus


id: cord-332303-0bbw64p5
type: WORK_OF_ART
entity:
  The Influence of Simulated Sunlight on the Inactivation of Influenza Virus in Aerosols Stability of Middle East


id: cord-332303-0bbw64p5
type: ORG
entity:
  Standard Practice for Evaluation of Effectiveness of Decontamination Procedures for Surfaces When Challenged with Droplets


id: cord-320764-p4ydngag
type: ORG
entity:
  the Centers for Disease Control and Prevention s Global Disease Detection International Emerging Infections Program


id: cord-329392-fufattj8
type: ORG
entity:
  SARS CoV 2 Specific Antibody Detection for Seroepidemiology A Multiplex Analysis Approach Accounting for Accurate Seroprevalence


id: cord-333429-bq7kfpby
type: ORG
entity:
  The National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial Study Group Comparative


id: cord-345727-bcxkycjh
type: DISEASE
entity:
  human adenovirus coronavirus parainfluenza virus 1 2 3 rhinovirus A B C respiratory syncytial virus A B bocavirus 1 2 3 4


id: cord-338776-2wa30218
type: ORG
entity:
  the Supplementary Table Flow Cytometry Analysis Immunofluorescence Staining and Western Blot Immunostaining


id: cord-344954-gpb25fga
type: PROTEIN
entity:
  Transgenic Human Dipeptidyl Peptidase 4 Mouse Model date 2019 11 15 journal J Infect Dis DOI 10 1093 infdis jiz137 sha b5f25901015340a5312e3c9f6b4fc7b1a6744df9 doc_id 344954


id: cord-321132-xdpb3ukt
type: DNA
entity:
  jit438 sha 82ad77b161e31fb733c63e3ebe5067c938d43d40 doc_id 321132 cord_uid xdpb3ukt Hepatitis E virus HEV


id: cord-352526-t8odetzw
type: ORG
entity:
  Autoimmune Diseases Cardiovascular Diseases Familial Primary Pulmonary Hypertension Hypertension Hypertension Pulmonary


id: cord-352526-t8odetzw
type: ORG
entity:
  Cardiovascular Diseases Familial Primary Pulmonary Hypertension Hypertension Pulmonary and Hypertension


id: cord-352526-t8odetzw
type: DISEASE
entity:
  Autoimmune Diseases Cardiovascular Diseases Familial Primary Pulmonary Hypertension Hypertension Hypertension


id: cord-351776-otx5qwyu
type: DISEASE
entity:
  chronic obstructive pulmonary disease obstructive sleep apnea hypopnea syndrome ischemic or valvular heart disease


id: cord-353495-c3s5n5vo
type: DISEASE
entity:
  oropharyngeal nasal turbinates and cloacal swab samples and analyzed using primers specific for the hCoV EMC RdRp gene Viral RNA


id: cord-351571-gwtkrt5u
type: DNA
entity:
  jis476 sha 476068f3966199a6b182892dfeb8d217a66589c3 doc_id 351571 cord_uid gwtkrt5u Human rhinovirus


id: cord-346411-d2re00r9
type: DNA
entity:
  HMPV 9 positive pairs 33 N P and 11 P N HRV 44 positive pairs 7 N P and 27 P N PIV2 2 positive pairs 50 N P and


id: cord-346411-d2re00r9
type: FAC
entity:
  the Upper Respiratory Tract for Infection of the Lower Respiratory Tract With Hematopoietic Stem Cell Transplantation


# bib

id: cord-000842-kff3gig0
author: Nayak, Jennifer L.
date: 2013-01-15
txt: ./txt/cord-000842-kff3gig0.txt
cache: ./cache/cord-000842-kff3gig0.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3532833/
doi: 10.1093/infdis/jis684
summary:
  Knowledge of the relationship between CD4 + T cells and the development of a neutralizing antibody response following administration of TIV is even more limited, with the few studies addressing this question failing to find a correlation between these parameters [12, 20] , except when an adjuvanted influenza A virus subtype H5N1 vaccine was used [29] . In this study, we used an experimental approach designed to maximally detect antigen-specific CD4 + T cells by using cytokine enzyme-linked immunosorbent spot (ELISPOT) assays with pools of overlapping synthetic peptides as recall antigens to quantify responses to conserved and novel epitopes following vaccination of adults with monovalent inactivated A (H1N1)pdm09 vaccine. We conclude from this that expansion of CD4 + T cells rather than the baseline number of influenza virus-reactive cells correlates with and predicts the development of a neutralizing antibody response following A (H1N1)pdm09 vaccination, a result that is consistent with the idea that CD4 + T-cell help may limit the antibody response to pandemic influenza vaccines.

title:
  CD4(+) T-Cell Expansion Predicts Neutralizing Antibody Responses to Monovalent, Inactivated 2009 Pandemic Influenza A(H1N1) Virus Subtype H1N1 Vaccine

abstract:
  Background. The ability of influenza vaccines to elicit CD4(+) T cells and the relationship between induction of CD4(+) T cells and vaccine-induced neutralizing antibody responses has been controversial. The emergence of swine-origin 2009 pandemic influenza A virus subtype H1N1 (A[H1N1]pdm09) provided a unique opportunity to examine responses to an influenza vaccine composed of both novel and previously encountered antigens and to probe the relationship between B-cell and T-cell responses to vaccination. Methods. We tracked CD4(+) T-cell and antibody responses of human subjects vaccinated with monovalent subunit A(H1N1)pdm09 vaccine. The specificity and magnitude of the CD4(+) T-cell response was evaluated using cytokine enzyme-linked immunosorbent spot assays in conjugation with peptide pools representing distinct influenza virus proteins. Results. Our studies revealed that vaccination induced readily detectable CD4(+) T cells specific for conserved portions of hemagglutinin (HA) and the internal viral proteins. Interestingly, expansion of HA-specific CD4(+) T cells was most tightly correlated with the antibody response. Conclusions. These results indicate that CD4(+) T-cell expansion may be a limiting factor in development of neutralizing antibody responses to pandemic influenza vaccines and suggest that approaches to facilitate CD4(+) T-cell recruitment may increase the neutralizing antibody produced in response to vaccines against novel influenza strains.


id: cord-001401-f29y8vh5
title: Multiyear Persistence of 2 Pandemic A/H1N1 Influenza Virus Lineages in West Africa
author: Nelson, Martha I.
date: 2014-07-01
txt: ./txt/cord-001401-f29y8vh5.txt
cache: ./cache/cord-001401-f29y8vh5.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162001/
doi: 10.1093/infdis/jiu047
summary:
  Increased genetic sequencing of African A/H1N1 pandemic influenza viruses during 2009-2013 revealed multiyear persistence of 2 viral lineages within West Africa, raising questions about the roles of reduced air traffic and the asynchrony of seasonal influenza epidemics among West African countries in the evolution of independent lineages. Increased genetic sequencing of African A/H1N1 pandemic influenza viruses during 2009-2013 revealed multiyear persistence of 2 viral lineages within West Africa, raising questions about the roles of reduced air traffic and the asynchrony of seasonal influenza epidemics among West African countries in the evolution of independent lineages. To elucidate the evolution of influenza viruses in Africa, we conducted a large-scale phylogenetic analysis of global pH1N1 influenza virus diversity during 2009-2013, including 299 pH1N1 HA sequences collected in 18 African countries. Our analysis identified 2 well-supported clades of pH1N1 viruses that each persisted for >1.5 years in West Africa, highlighting the need to further understand the ecology and evolution of IAVs in this understudied and relatively geographically isolated region.

abstract:
  Our understanding of the global ecology of influenza viruses is impeded by historically low levels of viral surveillance in Africa. Increased genetic sequencing of African A/H1N1 pandemic influenza viruses during 2009–2013 revealed multiyear persistence of 2 viral lineages within West Africa, raising questions about the roles of reduced air traffic and the asynchrony of seasonal influenza epidemics among West African countries in the evolution of independent lineages. The potential for novel influenza virus lineages to evolve within Africa warrants intensified influenza surveillance in Africa and other understudied areas.


id: cord-001764-njzyu4mv
title: Comparative Analysis of Host Cell Entry of Ebola Virus From Sierra Leone, 2014, and Zaire, 1976
author: Hofmann-Winkler, Heike
date: 2015-10-01
txt: ./txt/cord-001764-njzyu4mv.txt
cache: ./cache/cord-001764-njzyu4mv.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4564534/
doi: 10.1093/infdis/jiv101
summary:
  Here, we show that the GPs of the EBOVs circulating in 1976 and 2014 transduce the same spectrum of target cells, use the same cellular factors for host cell entry, and are comparably susceptible to blockade by antiviral interferon-induced transmembrane proteins and neutralizing antibody KZ52. However, EBOV-GP 2014 was less susceptible than EBOV-GP 1976 to blockade by a third inhibitor, CatL ( Figure 3B ), which inhibits catB and catL activity to similar extents [40] , suggesting subtle differences in the protease dependence of these GPs. HIV-derived particles rapidly lose infectivity when stored at room temperature [41] , and this loss might be due to inactivation of the viral envelope protein. Comparably Inhibited by IFITM Proteins and Neutralizing Antibody KZ52 IFITM proteins 1, 2, and 3 inhibit cellular entry of EBOV [42] and several other viral pathogens [42, 43] and might reduce EBOV amplification in the infected host, raising the question of whether viruses circulating in 2014 are less susceptible to IFITM protein inhibition than those responsible for the 1976 outbreak in Zaire.

abstract:
  The ongoing Ebola virus (EBOV) disease (EVD) epidemic in Western Africa is the largest EVD outbreak recorded to date and requires the rapid development and deployment of antiviral measures. The viral glycoprotein (GP) facilitates host cell entry and, jointly with cellular interaction partners, constitutes a potential target for antiviral intervention. However, it is unknown whether the GPs of the currently and previously circulating EBOVs use the same mechanisms for cellular entry and are thus susceptible to inhibition by the same antivirals and cellular defenses. Here, we show that the GPs of the EBOVs circulating in 1976 and 2014 transduce the same spectrum of target cells, use the same cellular factors for host cell entry, and are comparably susceptible to blockade by antiviral interferon-induced transmembrane proteins and neutralizing antibody KZ52. Thus, the viruses responsible for the ongoing EVD epidemic should be fully susceptible to established antiviral strategies targeting GP and cellular entry factors.


id: cord-002333-90f9vr0a
author: Madan, Anuradha
date: 2016-12-01
txt: ./txt/cord-002333-90f9vr0a.txt
cache: ./cache/cord-002333-90f9vr0a.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5144728/
doi: 10.1093/infdis/jiw414
summary:
  The coprimary immunogenicity objective determined whether adjuvanted vaccines elicited an immune response against the vaccine-homologous virus, 21 days after the second vaccine dose per US and European licensure criteria in the per-protocol cohort (n = 389). The coprimary immunogenicity objective was to evaluate whether the adjuvanted A/Shanghai/2/2013 (H7N9) vaccines elicited an immune response against the vaccine-homologous virus that met US CBER and European Committee for Medicinal Products for Human Use (CHMP) immunogenicity targets at day 42 (21 days after the second vaccine dose). In a sub-analysis of the homologous immune response by age, the adjuvanted vaccine was immunogenic in both age groups, with SPRs ≥80.0% in participants 41-64 years of age, despite lower GMTs (Table 3 ). The results of this phase I/II randomized, placebo-controlled trial showed that 2 doses of the H7N9 AS03-adjuvanted vaccine elicited a robust immune response in healthy adults up to 64 years of age, with an acceptable safety profile.

title:
  Immunogenicity and Safety of an AS03-Adjuvanted H7N9 Pandemic Influenza Vaccine in a Randomized Trial in Healthy Adults

abstract:
  Background. Almost 700 cases of human infection with avian influenza A/H7N9 have been reported since 2013. Pandemic preparedness strategies include H7N9 vaccine development. Methods. We evaluated an inactivated H7N9 vaccine in an observer-blind study in healthy adults aged 18–64 years. Participants (420) were randomized to receive 1 of 4 AS03-adjuvanted vaccines (low or medium dose of hemagglutinin with AS03(A) or AS03(B)), one nonadjuvanted vaccine, or placebo. The coprimary immunogenicity objective determined whether adjuvanted vaccines elicited an immune response against the vaccine-homologous virus, 21 days after the second vaccine dose per US and European licensure criteria in the per-protocol cohort (n = 389). Results. All adjuvanted vaccines met regulatory acceptance criteria. In groups receiving adjuvanted formulations, seroconversion rates were ≥85.7%, seroprotection rates ≥91.1%, and geometric mean titers ≥92.9% versus 23.2%, 28.6%, and 17.2 for the nonadjuvanted vaccine. The AS03 adjuvant enhanced immune response at antigen-sparing doses. Injection site pain occurred more frequently with adjuvanted vaccines (in ≤98.3% of vaccinees) than with the nonadjuvanted vaccine (40.7%) or placebo (20.0%). None of the 20 serious adverse events reported were related to vaccination. Conclusions. Two doses of AS03-adjuvanted H7N9 vaccine were well tolerated and induced a robust antibody response at antigen-sparing doses in healthy adults. Clinical Trials Registration. NCT01999842.


id: cord-002921-i5jxn1vj
title: Pandemic Zika: A Formidable Challenge to Medicine and Public Health
author: Morens, David M
date: 2017-12-15
txt: ./txt/cord-002921-i5jxn1vj.txt
cache: ./cache/cord-002921-i5jxn1vj.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5853239/
doi: 10.1093/infdis/jix383
abstract: nan
summary:
  Because of the pandemic''s uniqueness and the insidious ability of Zika virus to harm unborn children, the pandemic has captured the attention of infectious disease researchers and practitioners of clinical and public health medicine around the world, as well as the attention of allied colleagues working in entomology, vector control, informatics, teratology, immunology, and a host of other disciplines [3] [4] [5] . Furthermore, some studies have suggested that preexisting flavivirus immunity (eg, from prior dengue virus infection) might potentiate Zika [16] via antibody-dependent infection enhancement in some circumstances [17] , while other research has countered this view [18] . As with most flaviviruses, small-animal models of Zika virus infection and disease have been problematic, but considerable progress has nonetheless been made, including important new information bearing on teratogenicity and vaccine design strategy [20] . Evolutionary enhancement of Zika virus infectivity in Aedes aegypti mosquitoes


id: cord-002926-7ereip3x
author: Yoon, Sun-Woo
date: 2018-02-01
txt: ./txt/cord-002926-7ereip3x.txt
cache: ./cache/cord-002926-7ereip3x.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5853788/
doi: 10.1093/infdis/jix328
summary:
  title: Dysregulated T-Helper Type 1 (Th1):Th2 Cytokine Profile and Poor Immune Response in Pregnant Ferrets Infected With 2009 Pandemic Influenza A(H1N1) Virus This model predicts that the poorer outcome for pregnant women during the A(H1N1)pdm09 pandemic was due to an elevated level of viral replication and to a cytokine imbalance that led to a less effective immune response. This model predicts that the poorer outcome for pregnant women during the A(H1N1)pdm09 pandemic was due to an elevated level of viral replication and to a cytokine imbalance that led to a less effective immune response. To determine whether a similar phenotype is present in pregnant ferrets, we measured the expression levels of inflammatory cytokines and chemokines by quantitative real-time polymerase chain reaction in the trachea (representative of the upper respiratory tract), lungs (representative of the lower respiratory tract), and bronchoalveolar lavage to evaluate responses in resident or infiltrating immune cells lining the airways [6] of pregnant and nonpregnant animals following infection.

title:
  Dysregulated T-Helper Type 1 (Th1):Th2 Cytokine Profile and Poor Immune Response in Pregnant Ferrets Infected With 2009 Pandemic Influenza A(H1N1) Virus

abstract:
  Pregnancy has been associated with severe influenza, an association highlighted during the 2009 pandemic of influenza A(H1N1) virus (A[H1N1]pdm09) infection. To assess the underlying mechanism, we infected pregnant and non-pregnant ferrets with A(H1N1) pdm09 virus. A(H1N1)pdm09-infected pregnant ferrets also had higher levels of inflammatory cytokines in their pulmonary tracts. Systemically, total CD8(+) T cell counts and A(H1N1)pdm09-specific B-cell responses in blood were significantly lower in pregnant ferrets. This model predicts that the poorer outcome for pregnant women during the A(H1N1)pdm09 pandemic was due to an elevated level of viral replication and to a cytokine imbalance that led to a less effective immune response.


id: cord-003115-y40knklf
author: Amlabu, Emmanuel
date: 2018-09-01
txt: ./txt/cord-003115-y40knklf.txt
cache: ./cache/cord-003115-y40knklf.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6057521/
doi: 10.1093/infdis/jiy222
summary:
  The antibodies (α-PfSRA P1, α-PfSRA P2, and α-PfSRA P3) consistently detected multiple processed fragments (17, 32 , and 58 kDa) of the native PfSRA in ring-stage invasion supernatants ( Figure 1B , II-V) or parasite culture supernatants ( Figure 1C , I-IV) and schizont lysates ( Figure 1D , I-IV). falciparum asexual stages by IFAs showed that all α-PfSRA peptide antibodies labeled the surface membranes of merozoites in intact schizonts and released merozoites, respectively (Figure 2A -C). The 3 PfSRA peptide antibodies from rabbits specifically detected breakdown products of native PfSRA in ring-stage invasion supernatant or parasite culture supernatant and schizont lysates. Sequential processing of merozoite surface proteins during and after erythrocyte invasion by Plasmodium falciparum Plasmodium falciparum merozoite surface antigen, PfRH5, elicits detectable levels of invasion-inhibiting antibodies in humans Analysis of antibodies directed against merozoite surface protein 1 of the human malaria parasite Plasmodium falciparum

title:
  Functional Characterization of Plasmodium falciparum Surface-Related Antigen as a Potential Blood-Stage Vaccine Target

abstract:
  Plasmodium falciparum erythrocyte invasion is a multistep process that involves a spectrum of interactions that are not well characterized. We have characterized a 113-kDa immunogenic protein, PF3D7_1431400 (PF14_0293), that possesses coiled-coil structures. The protein is localized on the surfaces of both merozoites and gametocytes, hence the name Plasmodium falciparum surface-related antigen (PfSRA). The processed 32-kDa fragment of PfSRA binds normal human erythrocytes with different sensitivities to enzyme treatments. Temporal imaging from initial attachment to internalization of viable merozoites revealed that a fragment of PfSRA, along with PfMSP1(19,) is internalized after invasion. Moreover, parasite growth inhibition assays showed that PfSRA P1 antibodies potently inhibited erythrocyte invasion of both sialic acid–dependent and –independent parasite strains. Also, immunoepidemiological studies show that malaria-infected populations have naturally acquired antibodies against PfSRA. Overall, the results demonstrate that PfSRA has the structural and functional characteristics of a very promising target for vaccine development.


id: cord-003171-z22ekgtv
author: Babu, Tara M
date: 2018-10-01
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6107991/
doi: 10.1093/infdis/jiy291
title:
  Population Serologic Immunity to Human and Avian H2N2 Viruses in the United States and Hong Kong for Pandemic Risk Assessment

abstract:
  BACKGROUND: Influenza A pandemics cause significant mortality and morbidity. H2N2 viruses have caused a prior pandemic, and are circulating in avian reservoirs. The age-related frequency of current population immunity to H2 viruses was evaluated. METHODS: Hemagglutinin inhibition (HAI) assays against historical human and recent avian influenza A(H2N2) viruses were performed across age groups in Rochester, New York, and Hong Kong, China. The impact of existing cross-reactive HAI immunity on the effective reproduction number was modeled. RESULTS: One hundred fifty individual sera from Rochester and 295 from Hong Kong were included. Eighty-five percent of patients born in Rochester and Hong Kong before 1968 had HAI titers ≥1:40 against A/Singapore/1/57, and >50% had titers ≥1:40 against A/Berkeley/1/68. The frequency of titers ≥1:40 to avian H2N2 A/mallard/England/727/06 and A/mallard/Netherlands/14/07 in subjects born before 1957 was 62% and 24%, respectively. There were no H2 HAI titers >1:40 in individuals born after 1968. These levels of seroprevalence reduce the initial reproduction number of A/Singapore/1/1957 or A/Berkeley/1/68 by 15%–20%. A basic reproduction number (R(0)) of the emerging transmissible virus <1.2 predicts a preventable pandemic. CONCLUSIONS: Population immunity to H2 viruses is insufficient to block epidemic spread of H2 virus. An H2N2 pandemic would have lower impact in those born before 1968.


id: cord-003567-h8uq5z8b
title: Preparing for the Next Influenza Pandemic: The Development of a Universal Influenza Vaccine
author: Crank, Michelle C
date: 2019-04-15
txt: ./txt/cord-003567-h8uq5z8b.txt
cache: ./cache/cord-003567-h8uq5z8b.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6452294/
doi: 10.1093/infdis/jiz043
abstract: nan
summary:
  This issue of The Journal of Infectious Diseases was motivated by the confluence of the 1918 influenza pandemic centenary and the new opportunities afforded by technological advances and breakthroughs along with the improved understanding of influenza biology. 7. Defining the importance of including specific antigenic targets, such as the head or stem domains of hemagglutinin, neuraminidase, or the M2 ectodomain in universal vaccines, and determining whether they are more effective when used in combination or alone could be accomplished through both vaccine protection and natural history studies that provide a better understanding of protective immunity [9] [10] [11] [12] . Improving the characterization of and expanding the reagents for these models would not only benefit influenza vaccine development but would also provide answers to immunological questions relevant to other respiratory virus infections and emerging infectious diseases in general.


id: cord-007009-4wbvdg1r
author: Takahashi, Toru
date: 2014-03-15
txt: ./txt/cord-007009-4wbvdg1r.txt
cache: ./cache/cord-007009-4wbvdg1r.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7107388/
doi: 10.1093/infdis/jit603
summary:
  Severe fever with thrombocytopenia syndrome (SFTS), an infectious disease with a high case-fatality rate, is caused by SFTS virus (SFTSV), a novel bunyavirus reported to be endemic to central and northeastern parts of China [1, 2] . Vero cells were inoculated with RT-PCR-positive patient sera for virus isolation, cultured for 4-7 days, and examined for SFTSV antigen detection by indirect immunofluorescence assay (IFA) with a polyclonal antibody raised against SFTSV recombinant NP (rNP; rabbit anti-SFTSV rNP serum), which was produced as follows. Physicians were asked to volunteer information if they had treated patients who satisfied the following case definition: (1) fever of >38°C; (2) gastrointestinal tract symptoms, such as nausea, vomiting, abdominal pain, diarrhea, and melena; (3) thrombocytopenia, with <100 × 10 9 platelets/L; (4) leukopenia, with <4 × 10 9 white blood cells/L; (5) elevated levels of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase; (6) absence of other causes; and (7) death or admission to an intensive care unit because of the severity symptoms. Detection of severe fever with thrombocytopenia syndrome virus (SFTSV) RNA in the right cervical lymph node by the in situ hybridization ATtailing method.

title:
  The First Identification and Retrospective Study of Severe Fever With Thrombocytopenia Syndrome in Japan

abstract:
  Background. Severe fever with thrombocytopenia syndrome (SFTS) is caused by SFTS virus (SFTSV), a novel bunyavirus reported to be endemic in central and northeastern China. This article describes the first identified patient with SFTS and a retrospective study on SFTS in Japan. Methods. Virologic and pathologic examinations were performed on the patient's samples. Laboratory diagnosis of SFTS was made by isolation/genome amplification and/or the detection of anti-SFTSV immunoglobulin G antibody in sera. Physicians were alerted to the initial diagnosis and asked whether they had previously treated patients with symptoms similar to those of SFTS. Results. A female patient who died in 2012 received a diagnosis of SFTS. Ten additional patients with SFTS were then retrospectively identified. All patients were aged ≥50 years and lived in western Japan. Six cases were fatal. The ratio of males to females was 8:3. SFTSV was isolated from 8 patients. Phylogenetic analyses indicated that all of the Japanese SFTSV isolates formed a genotype independent to those from China. Most patients showed symptoms due to hemorrhage, possibly because of disseminated intravascular coagulation and/or hemophagocytosis. Conclusions. SFTS has been endemic to Japan, and SFTSV has been circulating naturally within the country.


id: cord-007013-tlvgyzft
author: Chan, Kok Fei
date: 2018-08-01
txt: ./txt/cord-007013-tlvgyzft.txt
cache: ./cache/cord-007013-tlvgyzft.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7107400/
doi: 10.1093/infdis/jiy184
summary:
  Previously, we used the ferret model to demonstrate that viral interference can occur following infection with human influenza A and B viruses and will prevent, delay, or limit subsequent infection with an influenza virus of a different type, subtype, or lineage [10, 11] . The peak of hRSV shedding was delayed in ferrets infected with A(H1N1)pdm09 followed by hRSV as compared to control animals infected with hRSV alone (median, 8 vs 6 days; P = .0091 by the Mann-Whitney test; Figure 2Ci ). The median duration of A(H1N1)pdm09 shedding was increased in ferrets infected with hRSV followed by A(H1N1)pdm09 as compared to control animals infected with A(H1N1)pdm09 alone (8 vs 7 days; P = .0196 by the Mann-Whitney test; Figure 2Civ ). Notably, increased expression of inflammatory mediators following infection with influenza virus as compared to hRSV has been observed in studies assessing human clinical samples and in vitro airway epithelial cell cultures [36] [37] [38] [39] .

title:
  Investigating Viral Interference Between Influenza A Virus and Human Respiratory Syncytial Virus in a Ferret Model of Infection

abstract:
  Epidemiological studies have observed that the seasonal peak incidence of influenza virus infection is sometimes separate from the peak incidence of human respiratory syncytial virus (hRSV) infection, with the peak incidence of hRSV infection delayed. This is proposed to be due to viral interference, whereby infection with one virus prevents or delays infection with a different virus. We investigated viral interference between hRSV and 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09) in the ferret model. Infection with A(H1N1)pdm09 prevented subsequent infection with hRSV. Infection with hRSV reduced morbidity attributed to infection with A(H1N1)pdm09 but not infection, even when an increased inoculum dose of hRSV was used. Notably, infection with A(H1N1)pdm09 induced higher levels of proinflammatory cytokines, chemokines, and immune mediators in the ferret than hRSV. Minimal cross-reactive serological responses or interferon γ–expressing cells were induced by either virus ≥14 days after infection. These data indicate that antigen-independent mechanisms may drive viral interference between unrelated respiratory viruses that can limit subsequent infection or disease.


id: cord-007026-ejv0gidp
title: Adenoviral Infections in Singapore: Should New Antiviral Therapies and Vaccines Be Adopted?
author: Coleman, Kristen K
date: 2020-02-15
txt: ./txt/cord-007026-ejv0gidp.txt
cache: ./cache/cord-007026-ejv0gidp.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7107482/
doi: 10.1093/infdis/jiz489
summary:
  METHODS: To understand the epidemiology of HAdV infections in Singapore, we studied 533 HAdV-positive clinical samples collected from 396 pediatric and 137 adult patients in Singapore from 2012 to 2018. CONCLUSIONS: Singapore would benefit from more frequent studies of clinical HAdV genotypes to identify patients at risk for severe disease and help guide the use of new antiviral therapies, such as brincidofovir, and potential administration of HAdV 4 and 7 vaccine. Clinical samples previously collected from HAdV-positive patients admitted to Singapore General Hospital (SGH) and KK Women''s and Children''s Hospital (KKH) between 2012 and 2015 were preserved at −80°C and transferred to Duke-NUS Laboratory of One Health Research for study. Human adenovirus-C datasets consisted of 4 novel genomes from Singapore and 22 representative virus isolates from different genotypes (HAdV-C1, HAdV-C2, HAdV-C5, and HAdV-C6).

abstract:
  BACKGROUND: A number of serious human adenovirus (HAdV) outbreaks have been recently reported: HAdV-B7 (Israel, Singapore, and USA), HAdV-B7d (USA and China), HAdV-D8, -D54, and -C2 (Japan), HAdV-B14p1 (USA, Europe, and China), and HAdV-B55 (China, Singapore, and France). METHODS: To understand the epidemiology of HAdV infections in Singapore, we studied 533 HAdV-positive clinical samples collected from 396 pediatric and 137 adult patients in Singapore from 2012 to 2018. Genome sequencing and phylogenetic analyses were performed to identify HAdV genotypes, clonal clusters, and recombinant or novel HAdVs. RESULTS: The most prevalent genotypes identified were HAdV-B3 (35.6%), HAdV-B7 (15.4%), and HAdV-E4 (15.2%). We detected 4 new HAdV-C strains and detected incursions with HAdV-B7 (odds ratio [OR], 14.6; 95% confidence interval [CI], 4.1–52.0) and HAdV-E4 (OR, 13.6; 95% CI, 3.9–46.7) among pediatric patients over time. In addition, immunocompromised patients (adjusted OR [aOR], 11.4; 95% CI, 3.8–34.8) and patients infected with HAdV-C2 (aOR, 8.5; 95% CI, 1.5–48.0), HAdV-B7 (aOR, 3.7; 95% CI, 1.2–10.9), or HAdV-E4 (aOR, 3.2; 95% CI, 1.1–8.9) were at increased risk for severe disease. CONCLUSIONS: Singapore would benefit from more frequent studies of clinical HAdV genotypes to identify patients at risk for severe disease and help guide the use of new antiviral therapies, such as brincidofovir, and potential administration of HAdV 4 and 7 vaccine.


id: cord-007176-61e9obb3
author: Jackson, George Gee
date: 1973-11-17
txt: ./txt/cord-007176-61e9obb3.txt
cache: ./cache/cord-007176-61e9obb3.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109772/
doi: 10.1093/infdis/128.5.674
abstract: nan
summary:
  RS virus was estimated, from sucrose density gradient centrifugation studies, to be 90-120 nm in diameter [2] ; viral particles in infected cells measured 65 nm by electron microscopy. All adults tested possessed detectable levels of neutralizing antibody to RS virus before challenge, but the titer of naturally acquired antibody had no significant effect on subsequent RS infection of volunteers and was poorly correlated with development of mild clinical illnesses. The neutralization test is more sensitive than CF when serum from infants is used, but rises in neutralizing antibody have been detected in only half of the virus-positive infections in this age group. Virus structures were detected 6-8 hr later [17] .· Infection of WI-38 cells with strain 229E resulted in a reorganization of the cytoplasm, as determined by electron microscopy. Respiratory syncytial virus infection in adult volunteers. Respiratory syncytial virus infection in adult volunteers. Morphology and development of respiratory syncytial virus in cell culture

title:
  Viroses Causing Common Respiratory Infections in Man. III. Respiratory Syncytial Viroses and Coronavimses


id: cord-007180-pho3miid
title: Enteric Lesions and Diarrhea in Gnotobiotic Calves Monoinfected with Cryptosporidium Species
author: Heine, J.
date: 1984-11-17
txt: ./txt/cord-007180-pho3miid.txt
cache: ./cache/cord-007180-pho3miid.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109781/
doi: 10.1093/infdis/150.5.768
summary:
  Clinically affected calves have atrophy of villi and hyperplasia of crypt epithelium (apparently as a result of the destruction of villous epithelium); those areas of the small intestine that are heavily infected with the parasite become inflamed [7, 9, 10] . On the other hand, if confirmed, the reported occurrence of diarrhea and intestinal lesions in gnotobiotic pigs infected with an inoculum treated in a manner that destroys infectious agents other than Cryptosporidium [18] provides strong evidence that the parasite can act as a primary enteropathogen in the absence of other enteric flora. Gnotobiotic calves inoculated with oocysts of Cryptosporidium that had been treated with potassium dichromate and peracetic acid became infected with Cryptosporidium and developed clinical signs and enteric lesions.

abstract:
  The pathogenicity of Cryptosporidium species was studied by inoculation of two gnotobiotic calves with cryptosporidial oocysts that had been decontaminated by treatment with peracetic acid. Two control calves were inoculated with similar material from which the oocysts had been removed by filtration. Oocyst-inoculated animals shed Cryptosporidium in their feces and developed depression, weakness, anorexia, and diarrhea. At necropsy five days after inoculation, endogeneous stages of Cryptosporidium were found in association with epithelial cells throughout the small and large intestines of these animals. The parasites were most numerous in the lower small intestine. Atrophic villi, disordered and degenerate villous epithelium, and hyperplastic crypt epithelium were associated with infection in the small intestine. Control animals remained normal. Extraneous agents were not detected in any of the calves. The results indicate that Cryptosporidium can destroy intestinal epithelial cells and cause diarrhea in monoinfected gnotobiotic calves.


id: cord-007187-gb1txu1o
author: Lindner, Juha
date: 2008-12-01
txt: ./txt/cord-007187-gb1txu1o.txt
cache: ./cache/cord-007187-gb1txu1o.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109795/
doi: 10.1086/592985
summary:
  To date, HBoV genomes have been detected worldwide in respiratory tract samples obtained from children with pulmonary diseases, whereas only limited data on virus-specific immunity are available, mainly because of the lack of recombinant viral antigens. seronegative individuals have been described and were found predominantly among infants and young children (those 2 years of age) [20, 27, 28, 29] , serum samples obtained from 10 healthy infants (mean age, 11.8 months [range, 6 -45 months]) without detectable virus-specific antibodies (median OD 450 value, 0.056 [range, 0.017-0.104]) were selected and representatively included in the study, to ensure the specificity of the serologic analysis performed. By use of viral protein 2 (VP2) viruslike particles (VLPs), all 69 healthy adults who were studied were found to be positive (seropositive) for HBoV-specific IgG antibodies by ELISA. Using HBoV VLPs, we observed frequent VP2-specific humoral immune responses in healthy adults, whereas seronegative status was predominantly detected in young children (age, 2 years) [27, 37] .

title:
  CD4(+) T Helper Cell Responses against Human Bocavirus Viral Protein 2 Viruslike Particles in Healthy Adults

abstract:
  Background. Human bocavirus (HBoV) was recently described as a new member of the Parvoviridae family, and its possible association with respiratory illness in infants has been discussed. To date, HBoV genomes have been detected worldwide in respiratory tract samples obtained from children with pulmonary diseases, whereas only limited data on virus-specific immunity are available, mainly because of the lack of recombinant viral antigens. Methods. HBoV viruslike particles (VLPs) were produced in insect cells and characterized by electron microscopy and cesium chloride gradient centrifugation. HBoV viral protein 2 (VP2)-specific antibodies and CD4(+) T helper cell responses were analyzed by enzyme-linked immunsorbent assay and enzyme-linked immunospot assay. Results. VP2 capsid proteins of HBoV were produced in insect cells infected with a recombinant baculovirus, and the formation of icosahedral VLPs (diameter, 21–25 nm; sedimentation density, 1.33 g/cm(3)) was demonstrated. A significant increase in secretion of VP2-specific interferon-γ was detected in cultures of peripheral blood mononuclear cells obtained from 69 healthy adults found to be positive for HBoV-specific immunoglobulin G antibodies, compared with control stimulations. In parallel, T cell responses against identically expressed parvovirus B19 VP2 VLPs were frequently observed in the individuals studied, without there being obvious cross-reactions between HBoV and parvovirus B19. Conclusions. Data suggest the presence of HBoV-specific immune responses in adults and strongly support a high prevalence of HBoV among humans.


id: cord-007188-tcq8lnwg
author: Cunningham, Anthony L.
date: 1988-08-17
txt: ./txt/cord-007188-tcq8lnwg.txt
cache: ./cache/cord-007188-tcq8lnwg.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109796/
doi: 10.1093/infdis/158.2.386
summary:
  Gastrointestinal viruses, predominantly rotaviruses and adenoviruses, were detected by enzyme-linked immunosorbent assay, electron microscopy, or cell culture in >50% of two groups of homosexual men with symptomatic human immunodeficiency virus (HIV) infection, who did (54%) or did not (50%) have diarrhea. We report here the detection of viruses from the stools of a large proportion of patients with symptomatic HIV infection (AIDS, ARC, and POL) and acute or chronic diarrhea when no other microbial pathogen could be identified. In this study we showed that patients with AIDS or ARC may present with acute diarrhea or exacerbations of chronic diarrhea and that in patients with symptomatic HIV infection and diarrhea, >50% excreted gastrointestinal viruses. These high detection rates for rotavirus and adenovirus in patients with ARC or AIDS-OI are similar to those observed in marrow transplant recipients who also have a T cell immunodeficiency and often have gastrointestinal mucosal damage from graft-versus-host disease [4] .

title:
  Gastrointestinal Viral Infections in Homosexual Men Who were Symptomatic and Seropositive for Human Immunodeficiency Virus

abstract:
  Gastrointestinal viruses, predominantly rotaviruses and adenoviruses, were detected by enzyme-linked immunosorbent assay, electron microscopy, or cell culture in >50% of two groups of homosexual men with symptomatic human immunodeficiency virus (HIV) infection, who did (54%) or did not (50%) have diarrhea. Lower detection rates were observed in HIV-seronegative (15%) and asymptomatic HIV-seropositive (16%) men. In the patients with diarrhea, 95% of the isolates of virus were found in the most immuno suppressed patients, those patients with AIDS-related complex or opportunistic infections associated with AIDS. High excretion rates of these viruses are probably associated with both anal-oral transmission and immunosuppression. These viruses apparently cause acute episodes or relapses of diarrhea in some patients but may be co-pathogens or noncontributory to chronic diarrhea in others.


id: cord-007190-x1v4jpl4
author: Hardison, Jenny L.
date: 2006-06-01
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109801/
doi: 10.1086/503812
title:
  Chemokine CC Receptor 2 Is Important for Acute Control of Cardiac Parasitism but Does Not Contribute to Cardiac Inflammation after Infection with Trypanosoma cruzi

abstract:
  The CC chemokine ligand 2 (CCL2) and CC chemokine receptor 2 (CCR2) are expressed in the heart after infection with Trypanosoma cruzi suggesting that they play an important role in host defense. Infection of CCR2-deficient (CCR2(−/−)) mice with T. cruzi resulted in increased cardiac parasitism, yet the severity of cardiac inflammation was not affected. In addition, expression of interferon-γ and inducible NO synthase in the heart, which are associated with effective killing of trypomastigotes, was not affected in CCR2(−/−) mice. These observations reveal that CCR2 signaling plays a distinct role that is separate from that of influencing either chemotaxis or previously defined anti-trypomastigote mechanisms for the control of T. cruzi’s replication in the heart


id: cord-007201-m87jid5l
title: Diarrhea in Young Red Deer Associated with Infection with Cryptosporidium
author: Tzipori, Saul
date: 1981-08-17
txt: ./txt/cord-007201-m87jid5l.txt
cache: ./cache/cord-007201-m87jid5l.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109846/
doi: 10.1093/infdis/144.2.170
summary:
  In the present communication, an association between severe diarrhea in artificially reared red deer calves and infection with Cryptosporidium is described. Cryostat-cut sections obtained from a specific pathogen-free lamb that was heavily infected with Cryptosporidium derived originally from calves [14] were reacted with 12 convalescent-phase sera from red deer that were recovering from diarrhea. The results of the present communication demonstrate, on the basis of the excretion of typical oocysts in the feces and the attachment of typical stages of the organism to the brush borders of enterocytes, that these artificially reared red deer were infected with Cryptosporidium, There is thus strong circumstantial evidence to incriminate Cryptosporidium as the cause of diarrhea and mortality in the outbreak. The clinical disease was similar to that observed in field outbreaks of diarrhea associated with Cryptosporidium in calves [14] , lambs [9A] , and experimentally infected, specific pathogen-free lambs [13] .

abstract:
  In an outbreak of diarrhea among 82 artificially reared red deer calves, 56 developed the disease and 20 subsequently died. During the outbreak 80% of diarrheal and 50% of apparently healthy calves excreted cryptosporidial oocysts in feces. The coincidence of infection with Cryptosporidium and clinical diarrhea suggested a causal relationship. Histologic examination of intestinal sections from a necropsied deer calf showed lesions consistent with field and experimental cryptosporidiosis in other species. The deer Cryptosporidium subclinically infected newborn mice; in indirect immunofluorescence tests, it could not be distinguished from a calf Cryptosporidium.


id: cord-007220-nlsduenh
author: Black, R. E.
date: 1980-11-17
txt: ./txt/cord-007220-nlsduenh.txt
cache: ./cache/cord-007220-nlsduenh.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109920/
doi: 10.1093/infdis/142.5.660
summary:
  Although classic enteric bacterial pathogens are not isolated from most patients with diarrhea, recent studies indicate that enterotoxigenic Escherichia coli (ETEC) and rotaviruses may frequently cause diarrhea [2] [3] [4] . We therefore studied patients during a two-year period at a treatment center in rural Bangladesh to determine the frequency, severity, and seasonality of diarrhea associated with ETEC, rotavirus, and other enteric agents. V. cholerae group 0: 1 was rarely identified for children less than two years of age but was an important pathogen in older children and adults, while non-group 0: 1 vibrios were found in the stools of 4010-11 010 of the patients of each age group for both years of the study. ETEC organisms were the pathogens most frequently isolated from patients of all ages and were the second most frequently isolated (after rotavirus) from young children coming to the treatment center in rural Bangladesh.

title:
  A Two-Year Study of Bacterial, Viral, and Parasitic Agents Associated with Diarrhea in Rural Bangladesh

abstract:
  Enteric pathogens associated with diarrhea were studied for two years at a diarrhea treatment center in rural Bangladesh. Enterotoxigenic Escherichia coli (ETEC) was the most frequently identified pathogen for patients of all ages. Rotavirus and ETEC were isolated from ∼50% and ∼25%, respectively, of patients less than two years of age. A bacterial or viral pathogen was identified for 70% of these young children and for 56% of all patients with diarrhea. Most ETEC isolates were obtained in the hot dry months of March and April and the hot wet months of August and September. Rotavirus identification peaked in the cool dry months of December and January, but infected patients were found year-round. The low case-fatality rates for patients with watery diarrhea and substantial dehydration further document the usefulness of treating patients with diarrhea with either a glucose- or sucrose-base electrolyte solution such as those used in this treatment center.


id: cord-007234-hcpa8ej5
author: Renwick, Neil
date: 2007-12-15
txt: ./txt/cord-007234-hcpa8ej5.txt
cache: ./cache/cord-007234-hcpa8ej5.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109967/
doi: 10.1086/524312
summary:
  title: A Recently Identified Rhinovirus Genotype Is Associated with Severe Respiratory-Tract Infection in Children in Germany Here we report the investigation, by MassTag PCR, of pediatric respiratory-tract infections in Germany, studying 97 cases for which no pathogen was identified through routine laboratory evaluation. In an attempt to gather additional information on the potential pathogenicity, as well as temporal and geographic distribution, of rhinoviruses, including the recently identified genotype, we evaluated specimens collected, during the 2003-2006 seasons in Bad Kreuznach, Germany, from children hospitalized because of severe LRTI. In this study of samples collected, during a 3-year interval, from hospitalized children with severe undiagnosed respiratory infection, MassTag PCR allowed us to detect viral pathogens in 49 (51%) of 97 cases. Although we did not have samples to test for the presence of HRV in the lower respiratory tract, the high frequency at which HRV was identified as being the sole virus detected suggests a correlation between the agent and the observed LRTI symptoms.

title:
  A Recently Identified Rhinovirus Genotype Is Associated with Severe Respiratory-Tract Infection in Children in Germany

abstract:
  Acute respiratory infection is a significant cause of morbidity and mortality in children worldwide. Accurate identification of causative agents is critical to case management and to prioritization in vaccine development. Sensitive multiplex diagnostics provide us with an opportunity to investigate the relative contributions of individual agents andmayalso facilitate the discovery of new pathogens. Recently, application of MassTag polymerase chain reaction (PCR) to undiagnosed infuenza-like illness in New York State led to the discovery of a novel rhinovirus genotype. Here we report the investigation, by MassTag PCR, of pediatric respiratory-tract infections in Germany, studying 97 cases for which no pathogen was identified through routine laboratory evaluation. Respiratory viruses were identified in 49 cases (51%); of the 55 identified viruses, 41 (75%) were rhinoviruses. The novel genotype represented 73% of rhinoviruses and 55% of all identified viruses. Infections with the novel genotype were associated with upper-respiratory-tract symptoms but, more frequently, with bronchitis, bronchiolitis, and pneumonia.


id: cord-007237-8y7218oj
author: Manning, Ashleigh
date: 2007-05-01
txt: ./txt/cord-007237-8y7218oj.txt
cache: ./cache/cord-007237-8y7218oj.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109978/
doi: 10.1086/513280
summary:
  At autopsy, bone marrow, lymphoid tissue, and brain tissue from human immunodeficiency virus (HIV)—infected individuals with acquired immunodeficiency syndrome (AIDS) and those without AIDS and from HIV-uninfected individuals were screened for parvovirus B19, PARV4, and HBoV DNA by means of quantitative polymerase chain reaction analyses. In the current study, we examined a series of samples of different tissues, collected at autopsy, for the presence of HBoV and PARV4 DNA sequences and compared the frequencies of detection, viral loads, and genetic variability with those for B19. Samples from HIV-infected individuals who did not have AIDS (hereafter referred to as "pre-AIDS study subjects") and those with terminal AIDS at time of death were compared with corresponding samples from HIV-uninfected individuals, to investigate the relationship between viral load and immunosuppression and, thus, the role of the immune system in controlling virus replication. Among the HIV-infected study subjects, a similar difference was found in PARV4 viral loads in bone marrow versus lymphoid tissue (median values of 220 and 46 DNA copies/10 6 cells, respectively; ) (figure 1B).

title:
  Comparison of Tissue Distribution, Persistence, and Molecular Epidemiology of Parvovirus B19 and Novel Human Parvoviruses PARV4 and Human Bocavirus

abstract:
  Background. PARV4 and human bocavirus (HBoV) are newly discovered human parvoviruses with poorly understood epidemiologies and disease associations. We investigated the frequencies of persistence, tissue distribution, and influence of immunosuppression on replication of these viruses. Methods. At autopsy, bone marrow, lymphoid tissue, and brain tissue from human immunodeficiency virus (HIV)—infected individuals with acquired immunodeficiency syndrome (AIDS) and those without AIDS and from HIV-uninfected individuals were screened for parvovirus B19, PARV4, and HBoV DNA by means of quantitative polymerase chain reaction analyses. Results. B19 DNA was detected both in HIV-infected study subjects (13 of 24) and in HIV-uninfected study subjects (8 of 8), whereas PARV4 DNA was detected only in HIV-infected study subjects (17 of 24). HBoV DNA was not detected in any study subjects. The degree of immunosuppression with HIV infection did not influence B19 or PARV4 viral loads. B19 or PARV4 plasma viremia was not detected in any study subjects (n = 76; viral load <25 DNA copies/mL). A significantly older age distribution was found for study subjects infected with B19 genotype 2, compared with those infected with B19 genotype 1. Two genotypes of PARV4 were detected; study subjects carrying prototype PARV4 (genotype 1) were younger (all born after 1958) than those infected with genotype 2 (PARV5; study subjects born between 1949 and 1956). Conclusions. Tight immune control of replication of B19 and PARV4 was retained despite profound immunosuppression. Recent genotype replacement of PARV4, combined with absent sequence diversity among genotype 1 sequences, suggests a recent, epidemic spread in the United Kingdom, potentially through transmission routes shared by HIV.


id: cord-007255-jmjolo9p
title: Ability to replicate in the cytoplasm predicts zoonotic transmission of livestock viruses
author: Pulliam, Juliet R. C.
date: 2009-02-15
txt: ./txt/cord-007255-jmjolo9p.txt
cache: ./cache/cord-007255-jmjolo9p.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110041/
doi: 10.1086/596510
summary:
  The database contains information on the 3 molecular characteristics hypothesized to influence the potential of a virus to cross host species: site of replication (X SR ; whether replication is completed in the cytoplasm or requires nuclear entry), genomic material (X GM ; RNA or DNA), and segmentation of the viral genome (X Seg ; segmented or nonsegmented). Hypothesis testing allowed us to determine how likely it was that the observed patterns were due to chance, whereas model-based prediction allowed us to determine what trait or set of traits was the best predictor of a livestock virus''s ability to infect humans and to estimate the probability that a particular virus species would be able to jump host species, given knowledge of the traits of interest. To examine the magnitude and relative importance of the effects that the 3 molecular characteristics of interest have on the ability of the viral species in the database to infect humans, we developed a set of logistic regression models.

abstract:
  Understanding viral factors that promote cross-species transmission is important for evaluating the risk of zoonotic emergence. Weconstructed a database of viruses of domestic artiodactyls and examined the correlation between traits linked in the literature to cross-species transmission and the ability of viruses to infect humans. Among these traits-genomic material, genome segmentation, and replication without nuclear entry-the last is the strongest predictor of cross-species transmission. This finding highlights nuclear entry as a barrier to transmission and suggests that the ability to complete replication in the cytoplasm may prove to be a useful indicator of the threat of cross-species transmission.


id: cord-007264-r1w9a6gc
author: Turner, Ronald B.
date: 1988-02-17
txt: ./txt/cord-007264-r1w9a6gc.txt
cache: ./cache/cord-007264-r1w9a6gc.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110071/
doi: 10.1093/infdis/157.2.346
summary:
  This study describes a chemoattractant for PMNLs that is elaborated by human embryonic lung fibroblast cells infected with rhinovirus. Chemotaxis assays were done in a 48-well microchemotaxis chamber with normal adult PMNLs. Medium supernatants from rhinovirus-infected cellculture attracted 87 ± 6 (mean ± SE) PMNLs/10 high-power fields (×450) compared with 38 ± 6 PMNLs/10 highpower fields attracted by medium from uninfected cell cultures (P < .0001). Human embryonic lung fibroblast cellsinfected with rhinovirus produced a chemoattractant for PMNLs. Media from R39-infected and uninfected cells attracted 87 ± 6 (mean ± SE) and 38 ± 6 PMNLs/ 10 hpf, respectively (P = .0001). Similarly, medium from uninfected cells disrupted by freezing and thawing attracted a mean of 6 ± 1 PMNLs/lO hpf (P < .0001 compared with Discussion These experiments indicate that attachment of rhinovirus to human embryonic lung fibroblast cells results in the elaboration of a chemoattractant for human PMNLs. This chemoattractant activity is not dependent upon the presence of complement.

title:
  Rhinovirus Infection of Human Embryonic Lung Fibroblasts Induces the Production of a Chemoattractant for Polymorphonuclear Leukocytes

abstract:
  Polymorphonuclear leukocytes (PMNLs) appear in the nasal mucosa during rhinovirus colds before the onset of symptoms. This study describes a chemoattractant for PMNLs that is elaborated by human embryonic lung fibroblast cells infected with rhinovirus. Chemotaxis assays were done in a 48-well microchemotaxis chamber with normal adult PMNLs. Medium supernatants from rhinovirus-infected cellculture attracted 87 ± 6 (mean ± SE) PMNLs/10 high-power fields (×450) compared with 38 ± 6 PMNLs/10 highpower fields attracted by medium from uninfected cell cultures (P < .0001). Elaboration of the chemoattractant was not a result of cell destruction and did not require the presence of infectious virus. This chemoattractant produced by human fibroblast cells may contribute to the influx of PMNLs into the nasal mucosa during rhinovirus infection. The PMNLs may, in turn, have a role in producing symptoms of the common cold.


id: cord-007277-86lynlxn
title: Coronaviruses in the Limelight
author: Kenneth, McIntosh
date: 2005-02-15
txt: ./txt/cord-007277-86lynlxn.txt
cache: ./cache/cord-007277-86lynlxn.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110118/
doi: 10.1086/428510
abstract: nan
summary:
  started their work), but rather that, in some of the earliest work on CoVs during the 1960s, viruses were reported that were then forgotten-viruses that came from adults with respiratory illness, that grew only in human embryonic tracheal organ culture, that caused illness in volunteers, and that were not, or were only distantly, antigenically related to the 2 HCoV species that were subsequently the best studied, HCoV-229E and HCoV-OC43. However, the details from Esper et al.''s study-the seasonal distribution, the percentage of positive samples, the associated respiratory syndromes, and the numbers of infected children at various ages, for example-were heavily influenced by both the particular population that was investigated and the clinical setting, so it is essentially impossible to draw conclusions on the epidemiology, pathogenicity, and relative importance of HCoV-NH in relation to other respiratory viruses. Evidence of a novel human coronavirus that is associated with respiratory tract disease in infants and young children


id: cord-007288-lzxi6q1p
title: Leukocyte Interferon for Treating First Episodes of Genital Herpes in Women
author: Pazin, George J.
date: 1987-12-17
txt: ./txt/cord-007288-lzxi6q1p.txt
cache: ./cache/cord-007288-lzxi6q1p.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110197/
doi: 10.1093/infdis/156.6.891
summary:
  Women experiencing their first episodes of genital herpes were treated, beginning within three days of the onset of lesions, with 5 × 10(4) units of human leukocyte interferon/kg of body weight for 12 doses over 14 days (total, ∼3.6 × 10(7) units) or with placebo in equivalent volumes. We clinically and virologically assessed the effect of early treatmentwith leukocyte interferon (Cantellvariety) [13] on the initial episode of'' genital herpes.Weindirectly evaluated the effect of .interferon on latency by determining the incidence and frequency of both asymptomatic reactivations and symptomatic recurrences during an intensive one-year follow-up period. Overall, interferon treatment at rv3 x 10 6 U/day had an ameliorative effect on both shedding of virus and the time to healing of initial episodes of genital herpes, but had no significant effect on the associated pain.

abstract:
  Women experiencing their first episodes of genital herpes were treated, beginning within three days of the onset of lesions, with 5 × 10(4) units of human leukocyte interferon/kg of body weight for 12 doses over 14 days (total, ∼3.6 × 10(7) units) or with placebo in equivalent volumes. Life-table analysis revealed quicker healing and significant reductions in the duration of shedding of virus in interferon-treated patients. Maximum daily geometric mean titers of virus and total area of unhealed lesions also decreased more quickly. No statistically significant difference in resolution of pain was seen between the two groups. Interferon had no effect on onset or frequency of subsequent recurrences recorded over one year of follow-up. Moderate, transient neutropenia occurred in 13 of 34 interferon-treated patients. A therapeutic effect of human leukocyte interferon on initial genital herpes was documented, but the clinical usefulness of interferon treatment of genital herpes is limited at this time.


id: cord-007295-lq8h1pc6
author: Koudstaal, Wouter
date: 2009-12-15
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110231/
doi: 10.1086/648378
title:
  Pre- and Postexposure Use of Human Monoclonal Antibody against H5N1 and H1N1 Influenza Virus in Mice: Viable Alternative to Oseltamivir

abstract:
  New strategies to prevent and treat influenza virus infections are urgently needed. A recently discovered class of monoclonal antibodies (mAbs) neutralizing an unprecedented spectrum of influenza virus subtypes may have the potential for future use in humans. Here, we assess the efficacies of CR6261, which is representative of this novel class of mAbs, and oseltamivir in mice. We show that a single injection with 15 mg/kg CR6261 outperforms a 5-day course of treatment with oseltamivir (10 mg/kg/day) with respect to both prophylaxis and treatment of lethal H5N1 and H1N1 infections. These results justify further preclinical evaluation of broadly neutralizing mAbs against influenza virus for the prevention and treatment of influenza virus infections


id: cord-007305-pkjfnhro
title: Leukonychia Partialis in Kawasaki Disease
author: Iosub, Silvia
date: 1984-10-17
txt: ./txt/cord-007305-pkjfnhro.txt
cache: ./cache/cord-007305-pkjfnhro.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110293/
doi: 10.1093/infdis/150.4.617-a
abstract: nan
summary:
  COLLEAGUES -Some areas in the northern part of the Israel desert (Negev) are known to be endemic for Borrelia recurrentis infection [1] (tick-borne relapsing fever). None of them developed overt symptoms and signs of tick-borne relapsing fever as observed in the subjects from groups I and II. Our patients had nail abnormalities typical for leukonychia partialis of the acquired type, since color changes had not been noted before the present illness and were transient. We would welcome correspondence from others who have seen nail color abnormalities in Kawasaki disease. COLLEAGUES -We examined paired sera from 62 infants with acute non bacterial gastroenteritis and from 50 age-matched controls (admitted to the hospital for nondiarrheal diseases) for antibody to human coronavirus (HCV) OC43 and neonatal-calf diarrhea coronavirus (NCDCY). Convalescent-phase sera from all the patients positive for excretion of coronavirus-like particles in stools, and seronegative for previous HCV OC43 infections, reacted by IEM with HECY-24 and HECV-35 and, to a lesser extent, with HCY OC43.


id: cord-007375-hqmyund4
title: Host Single-Nucleotide Polymorphisms and Altered Responses to Inactivated Influenza Vaccine
author: Tang, Yi-Wei
date: 2007-10-01
txt: ./txt/cord-007375-hqmyund4.txt
cache: ./cache/cord-007375-hqmyund4.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7111848/
doi: 10.1086/521370
summary:
  We analyzed the relationship between host gene polymorphisms and responses in recipients of inactivated influenza vaccine, who were classified into poor, normal, or adverse response groups. The frequency of the mannose-binding lectin-2 codon 54 allele was significantly different among the 3 types of responders, with a decreased odds ratio for the development of poor or adverse responses (P = .033). The present study explored the possibility that host gene polymorphisms influence inactivated influenza vaccineinduced immune responses by comparing the frequencies of 8 SNPs in the MBL-2 gene and in the TNF-a and IL-10 promoter regions among different groups. We found a significant difference in allele frequency in the MBL-2 codon 54 among the poor, normal, and adverse responders, suggesting that the allele polymorphism is independently associated with poor and adverse responses to influenza vaccination. These findings support the present data by suggesting that the Ϫ1082 allele polymorphism in the IL-10 promoter region may be associated with adverse responses induced by influenza vaccine.

abstract:
  We analyzed the relationship between host gene polymorphisms and responses in recipients of inactivated influenza vaccine, who were classified into poor, normal, or adverse response groups. The frequency of the mannose-binding lectin-2 codon 54 allele was significantly different among the 3 types of responders, with a decreased odds ratio for the development of poor or adverse responses (P = .033). There was no statistical relationship between responses and either tumor necrosis factor-α or interleukin (IL)-10 promoter polymorphisms among the 3 response groups. When poor and normal responses were combined, the -1082 A allele in the IL-10 promoter conferred a significantly decreased risk of the development of adverse responses (P = .041). These data indicate that host polymorphisms play a role in determining responses to influenza vaccine.


id: cord-010638-xjtapifg
title: Nonspecific Proctitis: Association with Human Immunodeficiency Virus Infection in Homosexual Men
author: Law, Carmella L. H.
date: 1992-01-17
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202560/
doi: 10.1093/infdis/165.1.150
abstract:
  In a cross-sectional study of 140 homosexual men attending a sexually transmissible diseases clinic, the association between the presence of antibody to the human immunodeficiency virus (HIV) and the presence of proctitis, as determined by histologic examination, as well as past or present exposure to other pathogens and details of sexual practices was analyzed. Significant associations with HIV seropositivity were found with the number of lifetime partners, positive treponemal serology, and evidence of previous infection with herpes simplex virus. However the major and unique finding was the strong and independent association between proctitis diagnosed by histologic criteria and seropositivity for HIV. Whether this is cause or effect awaits further elucidation.


id: cord-011708-naezfola
author: Frank, Gregory M.
date: 2016-05-01
txt: ./txt/cord-011708-naezfola.txt
cache: ./cache/cord-011708-naezfola.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313907/
doi: 10.1093/infdis/jiv474
abstract: nan
summary:
  To that end, we highlight below 6 key recommendations that the IDSA recently shared with the NSABB as we discuss how best to assess the benefits and risk of GOF research of concern. The IDSA strongly urges the NSABB to narrow its definition of GOF research to be considered for risk-benefit assessment (RBA), to avoid this inadvertent capture of low-risk research, which is not mentioned in the White House Office of Science and Technology Policy''s original description of the types of research that should be included in the deliberative process. The IDSA strongly supports these actions and also urges the NSABB to consider seeking additional perspectives to inform the RBA process, including those of a range of experts in vaccine development, microbial risk assessment, and public health response; physicians whose work is primarily clinical; and the public. Risks and benefits of gain-of-function experiments with pathogens of pandemic potential, such as influenza virus: a call for a science-based discussion

title:
  Infectious Diseases Society of America and Gain-of-Function Experiments With Pathogens Having Pandemic Potential


id: cord-011710-rz23ozxb
author: Aoki, Fred Y.
date: 2013-02-15
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313909/
doi: 10.1093/infdis/jis727
abstract: nan
title:
  The Beneficial Effects of Neuraminidase Inhibitor Drug Therapy on Severe Patient Outcomes During the 2009–2010 Influenza A Virus Subtype H1N1 Pandemic


id: cord-011712-fyrbe8tw
author: Venkatesan, Sudhir
date: 2020-02-01
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313925/
doi: 10.1093/infdis/jiz152
title:
  Neuraminidase Inhibitors and Hospital Length of Stay: A Meta-analysis of Individual Participant Data to Determine Treatment Effectiveness Among Patients Hospitalized With Nonfatal 2009 Pandemic Influenza A(H1N1) Virus Infection

abstract:
  BACKGROUND: The effect of neuraminidase inhibitor (NAI) treatment on length of stay (LoS) in patients hospitalized with influenza is unclear. METHODS: We conducted a one-stage individual participant data (IPD) meta-analysis exploring the association between NAI treatment and LoS in patients hospitalized with 2009 influenza A(H1N1) virus (A[H1N1]pdm09) infection. Using mixed-effects negative binomial regression and adjusting for the propensity to receive NAI, antibiotic, and corticosteroid treatment, we calculated incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Patients with a LoS of <1 day and those who died while hospitalized were excluded. RESULTS: We analyzed data on 18 309 patients from 70 clinical centers. After adjustment, NAI treatment initiated at hospitalization was associated with a 19% reduction in the LoS among patients with clinically suspected or laboratory-confirmed influenza A(H1N1)pdm09 infection (IRR, 0.81; 95% CI, .78–.85), compared with later or no initiation of NAI treatment. Similar statistically significant associations were seen in all clinical subgroups. NAI treatment (at any time), compared with no NAI treatment, and NAI treatment initiated <2 days after symptom onset, compared with later or no initiation of NAI treatment, showed mixed patterns of association with the LoS. CONCLUSIONS: When patients hospitalized with influenza are treated with NAIs, treatment initiated on admission, regardless of time since symptom onset, is associated with a reduced LoS, compared with later or no initiation of treatment.


id: cord-011718-hcyluzkx
author: Gaglani, Manjusha
date: 2014-06-01
txt: ./txt/cord-011718-hcyluzkx.txt
cache: ./cache/cord-011718-hcyluzkx.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313942/
doi: 10.1093/infdis/jit825
summary:
  For the 3 primary analyses, we examined HCP characteristics: demographics, health status, vaccination history, timing of serum sampling, site, proxies for influenza exposure, and HI titer preseason. We thus compared the proportion of HCP with HI ≥ 40 for preseason, post-TIV, and end-of-season serum samples by vaccination history. When compared with HCP included preseason (Table 1) , those post-TIV were more likely to be aged 50-65 years, have high-risk conditions, and receive 2009-2010 seasonal vaccines, and less likely to work in the emergency department. The proportion of HCP who had prior-season MIIV was similar among those providing preseason (42%) and end-of-season (43%) serum samples, but higher among those providing post-TIV sera (57%) ( Table 1 ). Among these 834 vaccinated HCP, history of receipt of MIIV was associated with lower HI GMTs for post-TIV and end-of-season regardless of preseason HI GMTs ( Figure 1 ).

title:
  Antibody Response to Influenza A(H1N1)pdm09 Among Healthcare Personnel Receiving Trivalent Inactivated Vaccine: Effect of Prior Monovalent Inactivated Vaccine

abstract:
  Background. Few data are available on the immunogenicity of repeated annual doses of influenza A(H1N1)pdm09-containing vaccines. Methods. We enrolled healthcare personnel (HCP) in direct patient care during the autumn of 2010 at 2 centers with voluntary immunization. We verified the receipt of A(H1N1)pdm09-containing monovalent inactivated influenza vaccine (MIIV) and 2010–2011 trivalent inactivated vaccine (TIV). We performed hemagglutination inhibition antibody (HI) assays on preseason, post-TIV, and end-of-season serum samples. We compared the proportion of HCPs with HI titer ≥40 against A(H1N1)pdm09 per receipt of prior-season MIIV, current-season TIV, both, or neither. Results. At preseason (n = 1417), HI ≥ 40 was significantly higher among those who received MIIV (34%) vs those who did not (14%) (adjusted relative risk [ARR], 3.26; 95% confidence interval [CI], 2.72–3.81). At post-TIV (n = 865), HI ≥ 40 was lower among HCP who received MIIV and TIV (66%) than among those receiving only TIV (85%) (ARR, 0.93 [95% CI, .84–.997]). At end-of-season (n = 1254), HI ≥ 40 was 40% among those who received both MIIV and TIV and 67% among those receiving only TIV (ARR, 0.76 [95% CI, .65–.88]), 52% among those who received MIIV only, and 12% among those receiving neither. Conclusions. HCP immunization programs should consider effects of host immune response and vaccine antigenic distance on immunogenicity of repeated annual doses of influenza vaccines.


id: cord-012509-887xlllb
author: Roy-Ghanta, Sumita
date: 2014-11-01
txt: ./txt/cord-012509-887xlllb.txt
cache: ./cache/cord-012509-887xlllb.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4195439/
doi: 10.1093/infdis/jiu284
summary:
  We investigated the effect of TIV priming on humoral responses to AS03-adjuvanted and nonadjuvanted A(H1N1)pdm09 vaccines, the role of AS03 on cell-mediated immune (CMI) responses, and vaccine safety. Healthy adults (aged 19–40 years) were randomized 1:1:1:1 to receive TIV or saline followed 4 months later by 2 doses, 3 weeks apart, of adjuvanted or nonadjuvanted A(H1N1)pdm09 vaccine and followed up to study end (day 507). Assessment of HI responses was based on the European Medicines Agency, Committee for Medicinal Products for Human Use (CHMP) guidance targets for pandemic influenza vaccines in adults [32] (point estimates, SCR >40%; SPR >70%; GMFR >2.5) and the Center for Biologics Evaluation and Research (CBER) licensure criteria [33] [lower limits of 95% confidence interval (CI) ≥40% for SCR and ≥70% for SPR]. After TIV or placebo administration (dose 1; days 0-122), GMTs of A(H1N1)pdm09-specific HI responses in both groups remained low (ranges, 12.5-19.9 and 13.3-13.9, respectively), and CHMP or CBER criteria were not met (Supplementary Table 1) .

title:
  Responses to A(H1N1)pdm09 Influenza Vaccines in Participants Previously Vaccinated With Seasonal Influenza Vaccine: A Randomized, Observer-Blind, Controlled Study

abstract:
  Background. Prior receipt of a trivalent seasonal influenza vaccine (TIV) can affect hemagglutination inhibition (HI) antibody responses to pandemic influenza vaccines. We investigated the effect of TIV priming on humoral responses to AS03-adjuvanted and nonadjuvanted A(H1N1)pdm09 vaccines, the role of AS03 on cell-mediated immune (CMI) responses, and vaccine safety. Methods. Healthy adults (aged 19–40 years) were randomized 1:1:1:1 to receive TIV or saline followed 4 months later by 2 doses, 3 weeks apart, of adjuvanted or nonadjuvanted A(H1N1)pdm09 vaccine and followed up to study end (day 507). Pre- and postvaccination responses of HI and neutralizing antibody, CD4(+)/CD8(+) T cells, memory B cells, and plasmablasts were assessed. Results. Ninety-nine of the 133 participants enrolled completed the study. No vaccine-related serious adverse events were recorded. In TIV-primed participants, A(H1N1)pdm09-specific antibody and CD4(+) T-cell and memory B-cell responses to the pandemic vaccine tended to be diminished. Vaccine adjuvantation led to increased responses of vaccine-homologous and -heterologous HI and neutralizing antibodies and CD4(+) T cells, homologous memory B cells, and plasmablasts. Conclusions. In healthy adults, prior TIV administration decreased humoral and CMI responses to A(H1N1)pdm09 vaccine. Adjuvantation of A(H1N1)pdm09 antigen helped to overcome immune interference between the influenza vaccines. No safety concerns were observed. Registration. Clinical Trials.gov identifier NCT00707967.


id: cord-013049-7d436sqg
author: Sobhanie, Mahdee
date: 2016-03-15
txt: ./txt/cord-013049-7d436sqg.txt
cache: ./cache/cord-013049-7d436sqg.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760421/
doi: 10.1093/infdis/jiv526
summary:
  We evaluated a candidate A/Anhui/2013(H7N9) pandemic live attenuated influenza vaccine (pLAIV) in healthy adults, and assessed the ability of 1 or 2 doses to induce immune memory. All subjects received a single 30-µg dose of unadjuvanted, antigenically matched A/Shanghai2/2013(H7N9) pandemic inactivated influenza vaccine (pIIV) 12 weeks after their first dose of pLAIV. Vaccines for control of influenza viruses with pandemic potential are under development, and results of clinical trials have suggested that these vaccines will require the use of adjuvants and multiple doses to induce substantial serum antibody responses [4, 5] . If vaccine virus infection is defined as detection of the virus in culture or by real-time RT-PCR at any time after day 1 or as development of a ≥4-fold increased HAI antibody response, then approximately 20%-30% of subjects were infected after each dose of pLAIV.

title:
  Evaluation of the Safety and Immunogenicity of a Candidate Pandemic Live Attenuated Influenza Vaccine (pLAIV) Against Influenza A(H7N9)

abstract:
  Background. We evaluated a candidate A/Anhui/2013(H7N9) pandemic live attenuated influenza vaccine (pLAIV) in healthy adults, and assessed the ability of 1 or 2 doses to induce immune memory. Methods. Healthy subjects in 2 age groups (18–49 years and 50–70 years) with undetectable hemagglutination-inhibiting (HAI) antibody to H7N9 were enrolled. Younger subjects received either 1 or 2 intranasal doses of 10(7.0) fluorescent focus units of A/Anhui/1/2013 pLAIV, while older subjects received a single dose. All subjects received a single 30-µg dose of unadjuvanted, antigenically matched A/Shanghai2/2013(H7N9) pandemic inactivated influenza vaccine (pIIV) 12 weeks after their first dose of pLAIV. Results. Both vaccines were well tolerated. Serum HAI antibody responses were detected in 0 of 32 younger subjects and 1 of 17 older subjects after 1 dose of pLAIV and in 2 of 16 younger subjects after a second dose. Strong serum antibody responses were detected after a single subsequent dose of pIIV that was broadly reactive against H7 influenza viruses. Conclusions. An A(H7N9) pLAIV candidate was safe in both age groups. Priming with pLAIV resulted in responses to subsequent pIIV that exceeded those seen in naive subjects in previous reports. The A(H7N9) pLAIV induces strong immune memory that can be demonstrated by exposure to subsequent antigenic challenge. Clinical Trials Registration. NCT01995695 and NCT02274545.


id: cord-253768-y35m3vh1
author: Springer, Sandra A
date: 2020-10-01
url: https://doi.org/10.1093/infdis/jiz673
doi: 10.1093/infdis/jiz673
title:
  Federal and State Action Needed to End the Infectious Complications of Illicit Drug Use in the United States: IDSA and HIVMA’s Advocacy Agenda

abstract:
  In response to the opioid crisis, IDSA and HIVMA established a working group to drive an evidence- and human rights-based response to illicit drug use and associated infectious diseases. Infectious diseases and HIV physicians have an opportunity to intervene, addressing both conditions. IDSA and HIVMA have developed a policy agenda highlighting evidence-based practices that need further dissemination. This paper reviews (1) programs most relevant to infectious diseases in the 2018 SUPPORT Act; (2) opportunities offered by the “End the HIV Epidemic” initiative; and (3) policy changes necessary to affect the trajectory of the opioid epidemic and associated infections. Issues addressed include leveraging harm reduction tools and improving integrated prevention and treatment services for the infectious diseases and substance use disorder care continuum. By strengthening collaborations between infectious diseases and addiction specialists, including increasing training in substance use disorder treatment among infectious diseases and addiction specialists, we can decrease morbidity and mortality associated with these overlapping epidemics.


id: cord-255927-0tp4ig4o
title: African Primates: Likely Victims, Not Reservoirs, of Ebolaviruses
author: Hayman, David T S
date: 2019-11-15
txt: ./txt/cord-255927-0tp4ig4o.txt
cache: ./cache/cord-255927-0tp4ig4o.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/infdis/jiz007
doi: 10.1093/infdis/jiz007
abstract: nan
summary:
  This experimental work is supported by field data from related Marburg viruses, first identified after African monkeys infected people in Europe [24] , which apparently persist within large colonies of cave-dwelling Egyptian fruit bats, and RESTV in Asian bats. Thus, together the evidence for bats being the true reservoir host for EVD causing viruses is convincing, but relies on serological evidence of infection rather than virus detection, and the role of nonhuman primates as reservoirs remains uncertain. In other systems, archived sample banks have helped identify Middle East respiratory syndrome coronavirus-seropositive camels in East Africa over 11-year (Kenya) and 30-year (Sudan and Somalia) periods, suggesting extensive virus circulation in camels prior to the first human outbreaks [35] [36] [37] [38] . All of these studies are limited by data, but Ayouba et al''s comprehensive study supports the assumption that bats, not primates, are likely reservoir hosts and that nonhuman primates may be viewed as both sentinels for human infection and victims of EVD [9, 15, 33, 51] .


id: cord-257521-1amcsgmj
author: Hirsilä, Maija
date: 2001-04-15
txt: ./txt/cord-257521-1amcsgmj.txt
cache: ./cache/cord-257521-1amcsgmj.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/11262210/
doi: 10.1086/319675
summary:
  All 7 patients had a significant increase in antibody titers between serum samples collected during the acute and convalescent phases of the illness. Only 1 of the 7 patients from whom these samples were obtained was still positive by PCR at the first control visit 1 week later, but a signal was detected only with the NS-1 primer pair. A у8-fold increase between acute-and convalescent-phase serum samples was found in all 7 individuals with PCR-positive results (table 2). All 7 individuals with PCR-positive results had a у8-fold increase in antibody titers between serum samples collected during the acute and convalescent phases of the illness. In addition, 1 study participant with PCR-negative results also had a significant increase in antibody titer (patient 160; table 2). NPAs obtained from the 7 patients with RT-PCR-positive results at the first control visit 1 week after study entry also were tested.

title:
  Detection by Reverse Transcription–Polymerase Chain Reaction of Influenza C in Nasopharyngeal Secretions of Adults with a Common Cold

abstract:
  The lack of practical methods for a laboratory diagnosis of influenza C virus infections and the seemingly benign nature of the virus contribute to the fact that 50 years after its first isolation, relatively little is known about the epidemiology and the clinical impact of this virus. Reverse transcription–polymerase chain reaction (RT-PCR) was used to amplify influenza C RNA fragments from clinical specimens. Two hundred otherwise healthy adults with recent onset of a common cold were studied. Nasopharyngeal aspirates were collected at entry to the study and 1 week later. Serum samples for antibody determinations were obtained at the first visit and after 3 weeks. Influenza C was detected in 7 of the 200 patients by 2 different RT-PCR formats. All 7 patients had a significant increase in antibody titers between serum samples collected during the acute and convalescent phases of the illness. Influenza C appears to be one of the many viruses that cause acute upper respiratory tract infections in adults


id: cord-258905-0hgdtalg
author: Bond, Katherine
date: 2020-08-06
txt: ./txt/cord-258905-0hgdtalg.txt
cache: ./cache/cord-258905-0hgdtalg.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32761124/
doi: 10.1093/infdis/jiaa467
summary:
  METHODS: Performance characteristics for 5 PoCT lateral flow devices approved for use in Australia were compared to a commercial enzyme immunoassay (ELISA) and a recently described novel surrogate virus neutralization test (sVNT). A testing panel was specifically developed to test PoCT devices for this study (Supplementary Material), consisting of 3 patient populations: (1) sera from 91 patients with SARS-CoV-2 detected by RT-PCR from upper and/or lower respiratory tract specimens; (2) sera from 36 patients with seasonal coronavirus infections or other acute infections (eg, dengue, cytomegalovirus, Epstein-Barr virus); and (3) serum from a random cohort (56 patients) of the Australian population obtained in 2018. In this study, we assessed the performance characteristics of 5 serological PoCT, a commercial ELISA, and a commercial novel sVNT against a large serum panel from a cohort of over 100 patients with RT-PCR-confirmed SARS-CoV-2.

title:
  Evaluation of Serological Tests for SARS-CoV-2: Implications for Serology Testing in a Low-Prevalence Setting

abstract:
  BACKGROUND: Robust serological assays are essential for long-term control of the COVID-19 pandemic. Many recently released point-of-care (PoCT) serological assays have been distributed with little premarket validation. METHODS: Performance characteristics for 5 PoCT lateral flow devices approved for use in Australia were compared to a commercial enzyme immunoassay (ELISA) and a recently described novel surrogate virus neutralization test (sVNT). RESULTS: Sensitivities for PoCT ranged from 51.8% (95% confidence interval [CI], 43.1%–60.4%) to 67.9% (95% CI, 59.4%–75.6%), and specificities from 95.6% (95% CI, 89.2%–98.8%) to 100.0% (95% CI, 96.1%–100.0%). ELISA sensitivity for IgA or IgG detection was 67.9% (95% CI, 59.4%–75.6%), increasing to 93.8% (95% CI, 85.0%–98.3%) for samples >14 days post symptom onset. sVNT sensitivity was 60.9% (95% CI, 53.2%–68.4%), rising to 91.2% (95% CI, 81.8%–96.7%) for samples >14 days post symptom onset, with specificity 94.4% (95% CI, 89.2%–97.5%). CONCLUSIONS: Performance characteristics for COVID-19 serological assays were generally lower than those reported by manufacturers. Timing of specimen collection relative to onset of illness or infection is crucial in reporting of performance characteristics for COVID-19 serological assays. The optimal algorithm for implementing serological testing for COVID-19 remains to be determined, particularly in low-prevalence settings.


id: cord-259004-plst2wno
author: van Elden, Leontine J. R.
date: 2004-02-17
url: https://www.ncbi.nlm.nih.gov/pubmed/14767819/
doi: 10.1086/381207
title:
  Frequent Detection of Human Coronaviruses in Clinical Specimens from Patients with Respiratory Tract Infection by Use of a Novel Real-Time Reverse-Transcriptase Polymerase Chain Reaction

abstract:
  During the past years, human coronaviruses (HCoVs) have been increasingly identified as pathogens associated with more-severe respiratory tract infection (RTI). Diagnostic tests for HCoVs are not frequently used in the routine setting. It is likely that, as a result, the precise role that HCoVs play in RTIs is greatly underestimated. We describe a rapid, sensitive, and highly specific quantitative real-time reverse-transcriptase polymerase chain reaction (RT-PCR) for the detection of HCoV that can easily be implemented in the routine diagnostic setting. HCoV was detected in 28 (11%) of the 261 clinical specimens obtained from patients presenting with symptoms of RTI ranging from common cold to severe pneumonia. Only 1 (0.4%) of the 243 control specimens obtained from patients without symptoms of RTI showed the presence of HCoV. We conclude that HCoVs can be frequently detected in patients presenting with RTI. Real-time RT-PCR provides a tool for large-scale epidemiological studies to further clarify the role that coronavirus infection plays in RTI in humans.


id: cord-261241-eqf6ame6
author: van Beek, Josine
date: 2017-08-15
url: https://doi.org/10.1093/infdis/jix268
doi: 10.1093/infdis/jix268
title:
  Influenza-like Illness Incidence Is Not Reduced by Influenza Vaccination in a Cohort of Older Adults, Despite Effectively Reducing Laboratory-Confirmed Influenza Virus Infections

abstract:
  BACKGROUND: Data on the relative contribution of influenza virus and other respiratory pathogens to respiratory infections in community-dwelling older adults (≥60 years) are needed. METHODS: A prospective observational cohort study was performed in the Netherlands during 2 winters. Nasopharyngeal and oropharyngeal swabs were collected during influenza-like illness (ILI) episodes and from controls. Viruses and bacteria were identified by multiplex ligation–dependent probe amplification assay and conventional bacterial culture. RESULTS: The ILI incidence in the consecutive seasons was 7.2% and 11.6%, and influenza virus caused 18.9% and 34.2% of ILI episodes. Potential pathogen were detected in 80% of the ILI events with influenza virus, coronaviruses, rhinoviruses, human metapneumovirus, respiratory syncytial virus, parainfluenza viruses, and Haemophilus influenzae being the most common. Influenza vaccination reduced influenza virus infection by 73% (95% confidence interval [CI], 26%–90%) and 51% (95% CI, 7%–74%) in ILI patients. However, ILI incidence was similar between vaccinated (7.6% and 10.8%) and nonvaccinated (4.2% and 11.4%) participants in 2011–2012 and 2012–2013, respectively (P > .05). CONCLUSIONS: Influenza virus is a frequent pathogen in older adults with ILI. Vaccination reduces the number of influenza virus infections but not the overall number of ILI episodes: other pathogens fill the gap. We suggest the existence of a pool of individuals with high susceptibility to respiratory infections. CLINICAL TRIALS REGISTRATION: NTR3386.


id: cord-261472-qcu73sdu
title: Cleavage and Serum Reactivity of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein
author: Yao, Yong Xiu
date: 2004-07-01
txt: ./txt/cord-261472-qcu73sdu.txt
cache: ./cache/cord-261472-qcu73sdu.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15195247/
doi: 10.1086/421280
summary:
  Severe acute respiratory syndrome (SARS) coronavirus (SCoV) spike (S) protein is the major surface antigen of the virus and is responsible for receptor binding and the generation of neutralizing antibody. To investigate SCoV S protein, full-length and individual domains of S protein were expressed on the surface of insect cells and were characterized for cleavability and reactivity with serum samples obtained from patients during the convalescent phase of SARS. The possible use of insect cell-displayed S protein for diagnostic application was assessed by examining fragment reactivity with serum samples from patients infected with human CoV 229E and also with serum from a patient with suspected but clinically unconfirmed SARS (serum sample 3118). Of the 2 assay formats we used, nondenatured S protein present on the cell surface provided the most sensitive detection of antibodies, with clear shifts in fluorescence for serum samples from patients with suspected but clinically unconfirmed SARS.

abstract:
  Severe acute respiratory syndrome (SARS) coronavirus (SCoV) spike (S) protein is the major surface antigen of the virus and is responsible for receptor binding and the generation of neutralizing antibody. To investigate SCoV S protein, full-length and individual domains of S protein were expressed on the surface of insect cells and were characterized for cleavability and reactivity with serum samples obtained from patients during the convalescent phase of SARS. S protein could be cleaved by exogenous trypsin but not by coexpressed furin, suggesting that the protein is not normally processed during infection. Reactivity was evident by both flow cytometry and Western blot assays, but the pattern of reactivity varied according to assay and sequence of the antigen. The antibody response to SCoV S protein involves antibodies to both linear and conformational epitopes, with linear epitopes associated with the carboxyl domain and conformational epitopes associated with the amino terminal domain. Recombinant SCoV S protein appears to be a suitable antigen for the development of an efficient and sensitive diagnostic test for SARS, but our data suggest that assay format and choice of S antigen are important considerations.


id: cord-262840-fhfxnr76
author: Gorse, Geoffrey J.
date: 2009-03-15
url: https://doi.org/10.1086/597122
doi: 10.1086/597122
title:
  Human Coronavirus and Acute Respiratory Illness in Older Adults with Chronic Obstructive Pulmonary Disease

abstract:
  BackgroundThe clinical features and incidence of human coronavirus (HCoV) infections in chronically ill older adults need better definition MethodsHCoV infection was determined on the basis of a 4-fold increase in serum antibody and the detection of HCoV by reverse-transcription polymerase chain reaction. Laboratory-documented influenza (LDI) was detected by serologic assay and culture. HCoV illnesses were compared with other acute respiratory illnesses identified by active surveillance, during the 1998–99 winter respiratory-virus season, of 2215 patients with chronic obstructive pulmonary disease who were ⩾50 years old and who received influenza vaccines ResultsHCoV-229E and HCoV-OC43 were associated with 90 (14%) of 665 illnesses (HCoV-229E in 22, HCoV-OC43 in 67, and both in 1), LDI with 107 (16%) of 678 illnesses. In multivariate logistic regression analysis, myalgia was less likely with HCoV infection than with LDI (OR, 0.27 [95% confidence limit, 0.13–0.58]). A majority of these HCoV and LDI illnesses exhibited each of 11 symptoms and signs of acute respiratory illness. Spirometric results worsened most often with LDI, and many acute respiratory illnesses, regardless of etiology, were associated with hospitalization. A total of 8 illnesses were associated with HCoV-NL63, 1 with HCoV-HKU1 ConclusionsThe frequencies of HCoV and LDI illnesses were similar. HCoV illness was less severe than LDI illness, was accompanied by multiple respiratory and systemic symptoms, and was associated with hospitalization


id: cord-266573-vfl08i2p
title: Paying Participants in COVID-19 Trials
author: Largent, Emily A
date: 2020-05-29
txt: ./txt/cord-266573-vfl08i2p.txt
cache: ./cache/cord-266573-vfl08i2p.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/infdis/jiaa284
doi: 10.1093/infdis/jiaa284
summary:
  Given increased risk of undue influence against pandemic background conditions, incentive payment should be avoided unless essential to recruitment and retention in important trials whose social value outweighs this risk. Given the pandemic''s devastating economic effects, as well as the fact that risks may be higher or more uncertain in COVID-19 trials than in nonpandemic research, there is an increased likelihood of undue influence stemming from incentive payments. Rather, in light of pandemic circumstances-similar features of which may be replicated in other contexts, including research conducted in low-and middle-income countries or with participants whose nonresearch options are limited even in the absence of a pandemic-offers of compensation may raise ethical concerns akin to incentives [14] . Acknowledging this challenge, the best IRBs can do is to minimize the possibility of undue influence for trial participants on the whole by making it unlikely for research participation to constitute an objectively unreasonable choice for members of the target study population.

abstract:
  Trials are in development and underway to examine potential interventions for treatment and prophylaxis of coronavirus disease 2019 (COVID-19). How should we think about offering payment to participants in these trials? Payment for research participation is ethically contentious even under ideal circumstances. Here, we review 3 functions of research payment—reimbursement, compensation, and incentive—and identify heightened and novel ethical concerns in the context of a global pandemic. We argue that COVID-19 trial participants should usually be offered reimbursement for research-related expenses, and compensation for their time and effort, as for other types of research under usual circumstances. Given increased risk of undue influence against pandemic background conditions, incentive payment should be avoided unless essential to recruitment and retention in important trials whose social value outweighs this risk. Where essential, however, incentives can be ethically permissible, so long as reasonable efforts are made to minimize the possibility of undue influence.


id: cord-266695-ktbgm0p9
title: SARS-CoV-2 Human Challenge Trials: Too Risky, Too Soon
author: Dawson, Liza
date: 2020-06-04
txt: ./txt/cord-266695-ktbgm0p9.txt
cache: ./cache/cord-266695-ktbgm0p9.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32496536/
doi: 10.1093/infdis/jiaa314
abstract: nan
summary:
  have recently argued that researchers should consider conducting SARS-CoV-2 human challenge studies to hasten vaccine development [1] . However, we disagree that SARS-CoV-2 challenge studies are ethically appropriate at this time, for three reasons: 1) current scientific knowledge of SARS-CoV-2 infection is insufficient to manage risks; 2) autonomous decision-making, while necessary, does not override concerns about risk; and 3) undertaking challenge studies now would imperil confidence in the research enterprise, potentially undermining the global response to the COVID-19 pandemic. Current scientific knowledge is insufficient to manage the risks of severe disease or death of volunteers in SARS-CoV-2 human challenge studies, especially in terms of selecting low risk volunteers [2] . It is not obvious that the possible benefits of developing a successful vaccine in less time justify the risks SARS-CoV-2 challenge studies, as Eyal and colleagues suggest. However, conducting SARS-CoV-2 human challenge trials now unjustifiably threatens both the well-being of volunteers and confidence in the research enterprise.


id: cord-267015-mprsdi2e
author: Zhu, Zhongyu
date: 2008-03-15
txt: ./txt/cord-267015-mprsdi2e.txt
cache: ./cache/cord-267015-mprsdi2e.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/18271743/
doi: 10.1086/528801
summary:
  One of these antibodies, m102, which exhibited the highest level of cross-reactive neutralization of both NiV and HeV G, was affinity maturated by light-chain shuffling combined with random mutagenesis of its heavy-chain variable domain and panning against sG(HeV). We have previously identified neutralizing human monoclonal antibodies against Nipah virus (NiV) and Hendra virus (HeV) by panning a large nonimmune antibody library against a soluble form of the HeV attachment-envelope glycoprotein G (sG HeV ). One of these antibodies, m102, which exhibited the highest level of cross-reactive neutralization of both NiV and HeV G, was affinity maturated by light-chain shuffling combined with random mutagenesis of its heavychain variable domain and panning against sG HeV . To demonstrate that m102.4 measured in plasma was biologically active, serum collected on days 1, 4, and 8 was evaluated using virus neutralization assays, as described above (data not shown). Receptor binding, fusion inhibition, and induction of cross-reactive neutralizing antibodies by a soluble G glycoprotein of Hendra virus

title:
  Exceptionally Potent Cross-Reactive Neutralization of Nipah and Hendra Viruses by a Human Monoclonal Antibody

abstract:
  We have previously identified neutralizing human monoclonal antibodies against Nipah virus (NiV) and Hendra virus (HeV) by panning a large nonimmune antibody library against a soluble form of the HeV attachment-envelope glycoprotein G (sG(HeV)). One of these antibodies, m102, which exhibited the highest level of cross-reactive neutralization of both NiV and HeV G, was affinity maturated by light-chain shuffling combined with random mutagenesis of its heavy-chain variable domain and panning against sG(HeV). One of the selected antibody Fab clones, m102.4, had affinity of binding to sG(HeV) that was equal to or higher than that of the other Fabs; it was converted to IgG1 and tested against infectious NiV and HeV. It exhibited exceptionally potent and cross-reactive inhibitory activity with 50% inhibitory concentrations below 0.04 and 0.6 μg/mL, respectively. The virus-neutralizing activity correlated with the binding affinity of the antibody to sG(HeV) and sG(NiV). m102.4 bound a soluble form of NiV G (sG(NiV)) better than it bound sG(HeV), and it neutralized NiV better than HeV, despite being originally selected against sG(HeV). These results suggest that m102.4 has potential as a therapeutic agent for the treatment of diseases caused by henipaviruses. It could be also used for prophylaxis and diagnosis, and as a research reagent


id: cord-267458-uofy7jyx
author: Jiang, Xiao-Lin
date: 2020-04-22
txt: ./txt/cord-267458-uofy7jyx.txt
cache: ./cache/cord-267458-uofy7jyx.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/infdis/jiaa206
doi: 10.1093/infdis/jiaa206
summary:
  title: Transmission potential of asymptomatic and paucisymptomatic SARS-CoV-2 infections: a three-family cluster study in China We report a three-family cluster of infections involving asymptomatic and paucisymptomatic transmission. Herein, we report a 3-family cluster study of eight patients associated with asymptomatic and pauciasymptomatic (one mild symptom only) SARS-CoV-2 transmission in Shandong Province, China. The first positive SARS-CoV-2 patients in this cluster were identified on January 21, 2020 triggering an epidemiological investigation by the local center for disease control and prevention. Our findings show that the transmission of SARS-CoV-2 by individuals with asymptomatic or paucisymptomatic infections is possible. Patient 5 (asymptomatic) was identified to be infected with SARS-CoV-2 after frequent contact with Patients 3 and 4 during work and home visits. In this study, we detected SARS-CoV-2 in two environmental swabs from the household of Patient 3. A familial cluster of infection associated with the 2019 novel coronavirus indicating potential person-to-person transmission during the incubation period

title:
  Transmission potential of asymptomatic and paucisymptomatic SARS-CoV-2 infections: a three-family cluster study in China

abstract:
  Data concerning the transmission of SARS-CoV-2 in asymptomatic and paucisymptomatic patients are lacking. We report a three-family cluster of infections involving asymptomatic and paucisymptomatic transmission. Eight (53%) of 15 members from three families were confirmed with SARS-CoV-2 infection. Of eight patients, three were asymptomatic and one was paucisymptomatic. An asymptomatic mother transmitted the virus to her son, and a paucisymptomatic father transmitted the virus to his three-month-old daughter. SARS-CoV-2 was detected in the environment of one household. The complete genomes of SARS-CoV-2 from the patients were >99.9% identical and were clustered with other SARS-CoV-2 sequences reported from China and other countries.


id: cord-268490-e8jub01m
title: CSI Microbiology: Emerging Pathogens and a Staged Strategy for Detection and Discovery
author: Moscona, Anne
date: 2007-12-15
txt: ./txt/cord-268490-e8jub01m.txt
cache: ./cache/cord-268490-e8jub01m.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/18190250/
doi: 10.1086/524313
abstract: nan
summary:
  [2] in this issue of the Journal makes 2 unique contributions to this field: it demonstrates the need to consider and identify rhinoviruses as a cause of serious acute respiratory disease in children, and it establishes the MassTag polymerase-chainreaction (PCR) multiplex platform as a practical tool for microbial surveillance. [4] , in the same group, went on to report the use of the method to investigate both undiagnosed influenza-like illness in New York State and the discovery of a novel genetic clade within the picornaviruses; "human rhinovirus New York" was the first new agent to be detected by use of MassTag PCR. [2] report clear evidence that links these viruses to severe respiratory disease: 75% of viruses detected among 97 nasopharyngeal aspirates from children hospitalized with acute respiratory infection-with no pathogen identified by routine methods-were rhinoviruses. MassTag polymerase-chain-reaction detection of respiratory pathogens, including a new rhinovirus genotype, that caused influenza-like illness in New York State during


id: cord-269383-1tyorrb0
author: Lai, Christopher K C
date: 2020-08-01
url: https://doi.org/10.1093/infdis/jiaa487
doi: 10.1093/infdis/jiaa487
title:
  Prospective study comparing deep-throat saliva with other respiratory tract specimens in the diagnosis of novel coronavirus disease (COVID-19)

abstract:
  BACKGROUND: Self-collected specimens has been advocated to avoid infectious exposure to healthcare workers. Self-induced sputum in those with a productive cough, and saliva in those without a productive cough have been proposed, but sensitivity remains uncertain. METHODS: We performed a prospective study in two regional hospitals in Hong Kong RESULTS: We prospectively examined 563 serial samples collected during the virus shedding periods of 50 patients: 150 deep-throat saliva (DTS), 309 pooled-nasopharyngeal (NP) and throat swabs, and 104 sputum. DTS had the lowest overall RT-PCR positive rate (68.7% vs. 89.4% [sputum] and 80.9% [pooled NP and throat swabs]), and the lowest viral RNA concentration (mean log copy/mL 3.54 vs. 5.03 [sputum] and 4.63 [pooled NP and throat swabs]). Analyses with respect to time from symptom onset and severity also revealed similar results. Virus yield of DTS correlated with that of sputum (Pearson correlation index [95% CI]: 0.76 [0.62 – 0.86]). We estimated the overall false-negative rate of DTS could be 31.3%, and increased 2.7 times among patients without sputum. CONCLUSION: DTS produced the lowest viral RNA concentration and RT-PCR positive rate compared to conventional respiratory specimens in all phases of illness. Self-collect sputum should be the choice for patients with sputum.


id: cord-269654-473kac75
title: Ethical Implementation of Immunity Passports During the COVID-19 Pandemic
author: Voo, Teck Chuan
date: 2020-06-24
url: https://www.ncbi.nlm.nih.gov/pubmed/32582943/
doi: 10.1093/infdis/jiaa352
abstract:
  A number of countries are planning the use of “immunity passports” as a way to ease restrictive measures and allow infected and recovered people to return to work during the COVID-19 pandemic. This paper brings together key scientific uncertainties regarding the use of serological tests to assure immune status and a public health ethics perspective to inform key considerations in the ethical implementation of immunity passport policies. Ill-conceived policies have the potential to cause severe unintended harms that could result in greater inequity, the stigmatization of certain sectors of society, and heightened risks and unequal treatment of individuals due to erroneous test results. Immunity passports could, however, be used to achieve collective benefits and benefits for specific populations besides facilitating economic recovery. We conclude that sector-based policies that prioritize access to testing based on societal need are likely to be fairer and logistically more feasible, while minimizing stigma and reducing incentives for fraud. Clear guidelines need to be set out for which sectors of society should be prioritized for testing, and rigorous mechanisms should be in place to validate test results and identify cases of reinfection.


id: cord-270205-fw555w1u
title: Pure Viral Sepsis Secondary to Community-Acquired Pneumonia in Adults: Risk and Prognostic Factors
author: Cillóniz, Catia
date: 2019-10-01
txt: ./txt/cord-270205-fw555w1u.txt
cache: ./cache/cord-270205-fw555w1u.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/31115456/
doi: 10.1093/infdis/jiz257
summary:
  title: Pure Viral Sepsis Secondary to Community-Acquired Pneumonia in Adults: Risk and Prognostic Factors We investigated the risk and prognostic factors of pure viral sepsis in adult patients with community-acquired pneumonia (CAP), using the Sepsis-3 definition. We investigated the risk and prognostic factors of pure viral sepsis in adult patients with community-acquired pneumonia (CAP), using the Sepsis-3 definition. Respiratory viruses are detected as etiological agents in almost one third of cases of community-acquired pneumonia (CAP) [2] [3] [4] [5] and in 7%-36% of patients with severe CAP with a defined microbial etiology [2, 3] . We aimed to investigate the prevalence, risks, and prognostic factors associated with pure viral sepsis in adult patients with CAP, using the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) criteria [6] . We observed that viral sepsis was not a risk factor for in-hospital mortality in patients without septic shock.

abstract:
  We investigated the risk and prognostic factors of pure viral sepsis in adult patients with community-acquired pneumonia (CAP), using the Sepsis-3 definition. Pure viral sepsis was found in 3% of all patients (138 of 4028) admitted to the emergency department with a diagnosis of CAP, 19% of those with CAP (138 of 722) admitted to the intensive care unit, and 61% of those (138 of 225) with a diagnosis of viral CAP. Our data indicate that males and patients aged ≥65 years are at increased risk of viral sepsis.


id: cord-270335-8vqi9c68
title: Rousettus aegyptiacus Bats Do Not Support Productive Nipah Virus Replication
author: Seifert, Stephanie N
date: 2019-11-04
txt: ./txt/cord-270335-8vqi9c68.txt
cache: ./cache/cord-270335-8vqi9c68.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/infdis/jiz429
doi: 10.1093/infdis/jiz429
summary:
  Nipah virus is capable of infecting a broad range of hosts including humans, pigs, ferrets, dogs, cats, hamsters, and at least 2 genera of bats. Studies of wild caught Pteropus spp suggest potential for viral recrudescence [16, 23] ; however, the hypothesis that NiV may persist in an individual bat and re-emerge under times of stress has yet to be confirmed experimentally. In contrast, the Egyptian fruit bat (EFB), Rousettus aegyptiacus, belongs to the same taxonomic family as Pteropus spp, Pteropodidae, and has been successfully used to model Marburg virus transmission [24, 25] and serological cross-reactivity after filovirus challenge [26] . Previous studies have demonstrated that EFB cells are permissive to Ebola virus, but experimentally challenged bats did not shed virus or support productive replication [38, 39] despite compatibility between the Ebola virus glycoprotein and the host receptor, NPC1 [40] .

abstract:
  Nipah virus (NiV) is a bat-borne zoonotic pathogen that can cause severe respiratory distress and encephalitis upon spillover into humans. Nipah virus is capable of infecting a broad range of hosts including humans, pigs, ferrets, dogs, cats, hamsters, and at least 2 genera of bats. Little is known about the biology of NiV in the bat reservoir. In this study, we evaluate the potential for the Egyptian fruit bat (EFB), Rousettus aegyptiacus, to serve as a model organism for studying NiV in bats. Our data suggest that NiV does not efficiently replicate in EFBs in vivo. Furthermore, we show a lack of seroconversion against NiV glycoprotein and a lack of viral replication in primary and immortalized EFB-derived cell lines. Our data show that despite using a conserved target for viral entry, NiV replication is limited in some bat species. We conclude that EFBs are not an appropriate organism to model NiV infection or transmission in bats.


id: cord-270709-jahnjvyk
author: Hasford, Joerg
date: 2020-08-26
url: https://www.ncbi.nlm.nih.gov/pubmed/32845317/
doi: 10.1093/infdis/jiaa456
abstract: nan
title:
  Large Simple Double-Blind Randomized Trials for the Rapid Assessment of the Effectiveness of COVID-19 Vaccines


id: cord-273356-1ius4ksa
author: Sauceda, John A
date: 2020-08-29
url: https://doi.org/10.1093/infdis/jiaa554
doi: 10.1093/infdis/jiaa554
title:
  Findings From a Probability-Based Survey of United States Households About Prevention Measures Based on Race, Ethnicity, and Age in Response to Severe Acute Respiratory Syndrome Coronavirus 2

abstract:
  We investigated individual behaviors taken by white, African American, and Latino United States (US) households in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and likelihood of using digital tools for symptom surveillance/reporting. We analyzed cross-sectional week 1 data (April 2020) of the coronavirus disease 2019 (COVID-19) Impact Survey in a large, nationally representative sample of US adults. In general, all groups engaged in the same prevention behaviors, but whites reported being more likely to use digital tools to report/act on symptoms and seek testing, compared with African Americans and Latinos. Individual behaviors may not explain COVID-19 case disparities, and digital tools for tracking should focus on uptake among race/ethnic minorities.


id: cord-275355-4izc5jxs
title: Transmission of Avian Influenza Viruses to and between Humans
author: Hayden, Frederick
date: 2005-10-15
txt: ./txt/cord-275355-4izc5jxs.txt
cache: ./cache/cord-275355-4izc5jxs.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/16170745/
doi: 10.1086/444399
abstract: nan
summary:
  in this issue of the Journal of Infectious Diseases [1] , and the recent instances of cross-species transmission that caused human disease [2] raise fundamental questions regarding the routes of transmission of avian viruses to and between humans, possible differences in transmission patterns between human and avian influenza viruses, and implications for prevention in those occupationally exposed to infected animals and also in health care, household, and community settings. The findings that seropositivity occurs in small numbers of poultry workers exposed during outbreaks of illness in poultry caused by some avian strains (H7N7, H7N3, and H5N1) but not others (H7N1 and H5N2) argue for actual infection and support the notion that some avian influenza viruses are more likely than others to infect humans [1] . Most cases of human infection due to avian influenza viruses have involved close contact with infected poultry, particularly ill or dying chickens.


id: cord-275863-qos9vu3r
title: Lectin Switching During Dengue Virus Infection
author: Dejnirattisai, Wanwisa
date: 2011-06-15
txt: ./txt/cord-275863-qos9vu3r.txt
cache: ./cache/cord-275863-qos9vu3r.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/21606536/
doi: 10.1093/infdis/jir173
summary:
  In this report we have studied the interaction of dengue viruses produced in insect cells, tumor cell lines, and primary human dendritic cells (DCs) with DC-SIGN and L-SIGN. To formally prove that the loss of infection of DCs was a result of the loss of affinity of DC-produced virus for DC-SIGN, we went on to test infection on 3T3 cells expressing DC-SIGN and included in these assays the related C-type lectin L-SIGN ( Figure 3A ), which has also been reported to be a receptor for dengue virus. C6/36-and DC-derived viruses were incubated with increasing levels of pooled convalescent dengue immune serum and subsequently used to infect U937, a monocyte cell line that expresses the Fc receptor and which shows relatively low infectivity without the presence of enhancing antibodies. Viruses produced in both DCs and insect cells were susceptible to enhancement, over the same range of antibody concentrations, showing that DC-produced virus could exploit ADE to replicate in individuals undergoing a secondary dengue infection ( Figure 6A ).

abstract:
  Dengue virus receptors are relatively poorly characterized, but there has been recent interest in 2 C-type lectin molecules, dendritic cell–specific intercellular adhesion molecule 3 (ICAM-3)–grabbing nonintegrin (DC-SIGN) and its close homologue liver/lymph node–specific ICAM-3–grabbing integrin (L-SIGN), which can both bind dengue and promote infection. In this report we have studied the interaction of dengue viruses produced in insect cells, tumor cell lines, and primary human dendritic cells (DCs) with DC-SIGN and L-SIGN. Virus produced in primary DCs is unable to interact with DC-SIGN but remains infectious for L-SIGN–expressing cells. Skin-resident DCs may thus be a site of initial infection by insect-produced virus, but DCs will likely not participate in large-scale virus replication during dengue infection. These results reveal that differential glycosylation of dengue virus envelope protein is highly dependent on cell state and suggest that studies of virus tropism using virus prepared in insect cells or tumor cell lines should be interpreted with caution.


id: cord-276005-ifn88mjd
title: The Differential Clinical Impact of Human Coronavirus Species in Children With Cystic Fibrosis
author: da Silva Filho, Luiz Vicente Ribeiro Ferreira
date: 2012-08-01
txt: ./txt/cord-276005-ifn88mjd.txt
cache: ./cache/cord-276005-ifn88mjd.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/22459737/
doi: 10.1093/infdis/jis274
summary:
  We investigated the clinical impact of human coronaviruses (HCoV) OC43, 229E, HKU1 and NL63 in pediatric patients with cystic fibrosis (CF) during routine and exacerbation visits. The proportion of cases with acute respiratory exacerbation among patients infected with different HCoV species was compared by χ 2 or Fisher exact tests. The identification of new species of HCoV [7, 8] and the emergence of SARS HCoV [6] highlighted the potential role of these viruses as causative agents of severe lower respiratory tract infections. However, most of the studies on the clinical impact of different HCoV species were only performed among children who were hospitalized for acute respiratory tract infections, with small sample sizes and short periods of sample collection [10] . New human coronavirus, HCoV-NL63, associated with severe lower respiratory tract disease in Australia

abstract:
  We investigated the clinical impact of human coronaviruses (HCoV) OC43, 229E, HKU1 and NL63 in pediatric patients with cystic fibrosis (CF) during routine and exacerbation visits. A total of 408 nasopharyngeal aspirate samples were obtained from 103 patients over a 1-year period. Samples positive for HCoV were submitted for nucleotide sequencing to determine the species. Nineteen samples (4.65%) were positive for HCoV, of which 8 were positive for NL63, 6 for OC43, 4 for HKU1, and 1 for 229E. Identification of HCoV was not associated with an increased rate of respiratory exacerbations, but NL63-positive patients had higher exacerbation rates than patients who were positive for other HCoV species.


id: cord-277673-kvh60zd5
title: Will Coronavirus Disease 2019 Become Seasonal?
author: Kanzawa, Mia
date: 2020-06-21
txt: ./txt/cord-277673-kvh60zd5.txt
cache: ./cache/cord-277673-kvh60zd5.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32609334/
doi: 10.1093/infdis/jiaa345
summary:
  This manuscript explores the question of the seasonality of severe acute respiratory syndrome coronavirus 2 by reviewing 4 lines of evidence related to viral viability, transmission, ecological patterns, and observed epidemiology of coronavirus disease 2019 in the Southern Hemispheres'' summer and early fall. Although the object of much speculation, few data exist that bear on the question of the seasonality of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1] or, more succinctly, the question of whether the virus will "disappear magically by summer. " There are 4 lines of evidence that bear on this question: (1) seasonality of other human coronaviruses and influenza A, (2) in vivo experiments with influenza transmission, (3) ecological data, and (4) the observed epidemiology of coronavirus disease 2019 in the Southern Hemispheres'' summer and early fall. Rapid expert consultation on SARS-CoV-2 survival in relation to temperature and humidity and potential for seasonality for the COVID-19 pandemic

abstract:
  This manuscript explores the question of the seasonality of severe acute respiratory syndrome coronavirus 2 by reviewing 4 lines of evidence related to viral viability, transmission, ecological patterns, and observed epidemiology of coronavirus disease 2019 in the Southern Hemispheres’ summer and early fall.


id: cord-277735-a9gkath5
author: Leung, Danny Tze Ming
date: 2004-07-15
url: https://www.ncbi.nlm.nih.gov/pubmed/15216476/
doi: 10.1086/422040
title:
  Antibody Response of Patients with Severe Acute Respiratory Syndrome (SARS) Targets the Viral Nucleocapsid

abstract:
  The recent outbreak of severe acute respiratory syndrome (SARS) provided an opportunity to study the antibody response of infected individuals to the causative virus, SARS coronavirus. We examined serum samples obtained from 46 patients with SARS, 40 patients with non-SARS pneumonia, and 38 healthy individuals, by use of Western blotting (WB), enzyme-linked immunoassay (ELISA), and immunofluorescence assay, using both native and bacterially produced antigens of the virus. We found a highly restricted, immunoglobulin G-dominated antibody response in patients with SARS, directed most frequently (89% by ELISA) and predominantly at the nucleocapsid. Almost all of the subjects without SARS had no antinucleocapsid antibodies. The spike protein was the next most frequently targeted, but only 63% of the patients (by ELISA) responded. Other targets of the response identified by use of WB included antigens of 80 and 60 kDa. Several nonstructural proteins cloned were not antigenic, and the culture-derived nucleocapsid appeared to be specifically degraded.


id: cord-278260-3o91v72a
title: COVID 19 Vaccines: Should we fear ADE?
author: Halstead, Scott B
date: 2020-08-12
txt: ./txt/cord-278260-3o91v72a.txt
cache: ./cache/cord-278260-3o91v72a.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32785649/
doi: 10.1093/infdis/jiaa518
summary:
  Within months large numbers of vaccinated children developed a severe breakthrough disease, called "atypical measles." [6] A similar outcome, "vaccine associated enhanced respiratory disease (VAERD)," was observed in infants, 4 -12 months of age, who were given formalininactivated respiratory syncytial virus (RSV) and a few months later infected by RSV. The biological behavior of some coronaviruses in non-human species together with evidence that human coronavirus antibodies enhanced infection of SARS or MERS CoVs in Fc receptor-bearing cells, in vitro, have led to speculations that ADE contributes to disease severity in humans. [11] It has been reported that high levels of SARS CoV-1 IgG antibodies circulated in severe SARS cases and that anti-S IgG neutralizing antibody (NAb) responses developed significantly faster after the onset of clinical symptoms in fatal compared with recovered cases leading some to attribute enhanced tissue damage to ADE. With others, we conclude that the differences in clinical, epidemiological and pathological features of SARS and DENV diseases suggest that iADE does not contribute to the severity of natural human coronavirus infections.

abstract:
  Might COVID 19 vaccines sensitize humans to antibody dependent enhanced (ADE) breakthrough infections? This outcome is unlikely because coronavirus diseases in humans lack the clinical, epidemiological, biological or pathological attributes of ADE disease exemplified by the dengue viruses (DENV). In contrast to DENV, SARS and MERS CoVs predominantly infect respiratory epithelium, not macrophages. Severe disease centers on older persons with pre-existing conditions and not young infants or individuals with previous coronavirus infections. Live virus challenge of animals given SARS or MERS vaccines has resulted in vaccine hypersensitivity reactions (VAH), similar to those in humans given inactivated measles or respiratory syncytial virus vaccines. Safe and effective COVID 19 vaccines must avoid VAH.


id: cord-279311-msh9wvsh
title: Characteristics of Peripheral Lymphocyte Subset Alteration in COVID-19 Pneumonia
author: Wang, Fan
date: 2020-03-30
txt: ./txt/cord-279311-msh9wvsh.txt
cache: ./cache/cord-279311-msh9wvsh.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32227123/
doi: 10.1093/infdis/jiaa150
summary:
  METHODS: The levels of peripheral lymphocyte subsets were measured by flow cytometry in 60 hospitalized COVID-19 patients before and after treatment, and their association with clinical characteristics and treatment efficacy was analyzed. In this study, we aimed to clarify the characteristics and clinical significance of peripheral lymphocyte subset alteration in COVID-19, which might help elucidate the pathogenesis and develop novel biomarkers and therapeutic strategies for COVID-19. In multivariate analysis, posttreatment decrease in CD8 + T cells (P = .011) and B cells (P = .010) and increase in CD4 + / CD8 + ratio (P = .032) indicated a poor efficacy when considering the factors of age, sex, disease severity on admission, oxygen inhalation, antiviral treatment, and use of corticosteroid and immune enhancer ( Table 2) . Effects of severe acute respiratory syndrome (SARS) coronavirus infection on peripheral blood lymphocytes and their subsets

abstract:
  BACKGROUND: In December 2019, novel coronavirus (SARS-CoV-2) pneumonia (COVID-19) was reported in Wuhan and has since rapidly spread throughout China. We aimed to clarify the characteristics and clinical significance of peripheral lymphocyte subset alteration in COVID-19. METHODS: The levels of peripheral lymphocyte subsets were measured by flow cytometry in 60 hospitalized COVID-19 patients before and after treatment, and their association with clinical characteristics and treatment efficacy was analyzed. RESULTS: Total lymphocytes, CD4(+) T cells, CD8(+) T cells, B cells, and natural killer (NK) cells decreased in COVID-19 patients, and severe cases had a lower level than mild cases. The subsets showed a significant association with inflammatory status in COVID-19, especially CD8(+) T cells and CD4(+)/CD8(+) ratio. After treatment, 37 patients (67%) showed clinical response, with an increase in CD8(+) T cells and B cells. No significant change in any subset was detected in nonresponsive cases. In multivariate analysis, posttreatment decrease in CD8(+) T cells and B cells and increase in CD4(+)/CD8(+) ratio were indicated as independent predictors of poor efficacy. CONCLUSIONS: Peripheral lymphocyte subset alteration was associated with clinical characteristics and treatment efficacy of COVID-19. CD8(+) T cells tended to be an independent predictor for COVID-19 severity and treatment efficacy.


id: cord-279725-d82sj80v
title: Severe Acute Respiratory Syndrome-Related Coronavirus Is Inhibited by Interferon-α
author: Ströher, Ute
date: 2004-04-01
txt: ./txt/cord-279725-d82sj80v.txt
cache: ./cache/cord-279725-d82sj80v.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15031783/
doi: 10.1086/382597
summary:
  We evaluated the susceptibility of the SARS-related coronavirus (SARS CoV) to ribavirin and interferon (IFN)-α in vitro by use of cytopathic effect, plaque assay, and immunoblot analysis. To support the search for effective antiviral treatments, we evaluated the susceptibility of SARS CoV isolates (detailed studies were performed with the Tor2 isolate [Toronto, Canada]) to ribavirin and interferon (IFN)-a-2b in vitro. Our data indicate that ribavirin does not inhibit the virus at concentrations attainable in human serum but that IFN-a-2b may be useful and deserves further evaluation as a therapeutic agent. To quantify the effect of IFN-a-2b on the replication of the SARS CoV, Vero E6 cells were infected at an MOI of 0.001 and were incubated in the presence IFN-a-2b (0-5000 IU/mL), as described above. Whether combined therapy with IFN-a-2b and ribavirin would inhibit the replication of the SARS CoV in vitro has not yet been evaluated; the combination is more effective than either agent used alone for the treatment of HCV infection in humans.

abstract:
  Current treatment schemes for severe acute respiratory syndrome (SARS) include broad-spectrum antibiotics, glucocorticoids, and ribavirin. We evaluated the susceptibility of the SARS-related coronavirus (SARS CoV) to ribavirin and interferon (IFN)-α in vitro by use of cytopathic effect, plaque assay, and immunoblot analysis. Ribavirin did not inhibit viral growth at concentrations attainable in human serum. In contrast, IFN-α showed an in vitro inhibitory effect starting at concentrations of 1000 IU/mL. In conclusion, ribavirin alone is unlikely to be beneficial in the prophylaxis or treatment of SARS CoV infections. Clinical trials with IFN-α might be justified to determine a beneficial effect on the outcome of SARS.


id: cord-281158-vjh9z7l4
title: Respiratory Viruses in Babies: Important Insights From Down Under
author: Storch, Gregory A
date: 2018-02-01
txt: ./txt/cord-281158-vjh9z7l4.txt
cache: ./cache/cord-281158-vjh9z7l4.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/infdis/jix600
doi: 10.1093/infdis/jix600
abstract: nan
summary:
  Impressive study attributes include large size, community base, enrollment from birth, scheduled frequent longitudinal sampling with or without illness, high percentage of specimen acquisition rate, even enrollment of subjects throughout the year to account for virus seasonality, and testing of samples with an extensive panel of real-time polymerase chain reaction (PCR) assays. This intensive prospective study of respiratory viruses in infants finds that human rhinovirus (HRV) is by far the most frequent virus detected in the infant respiratory tract. Of the 152 infants followed, 81% experienced a first infection with HRV by 6 months of age, compared to 8.5% for RSV, and 0.7%-9.4% for the other respiratory viruses. Timing of first respiratory virus detection in infants: a community-based birth cohort study Viral etiology of acute respiratory infections with cough in infancy: a community-based birth cohort study Etiology of acute respiratory infections in infants: a prospective birth cohort study


id: cord-285087-i3nz5bvs
author: Heimdal, Inger
date: 2019-04-15
url: https://doi.org/10.1093/infdis/jiy646
doi: 10.1093/infdis/jiy646
title:
  Human Coronavirus in Hospitalized Children With Respiratory Tract Infections: A 9-Year Population-Based Study From Norway

abstract:
  BACKGROUND: The burden of human coronavirus (HCoV)-associated respiratory tract infections (RTIs) in hospitalized children is poorly defined. We studied the occurrence and hospitalization rates of HCoV over 9 years. METHODS: Children from Sør-Trøndelag County, Norway, hospitalized with RTIs and asymptomatic controls, were prospectively enrolled from 2006 to 2015. Nasopharyngeal aspirates were analyzed with semiquantitative polymerase chain reaction (PCR) tests for HCoV subtypes OC43, 229E, NL63, and HKU1, and 13 other respiratory pathogens. RESULTS: HCoV was present in 9.1% (313/3458) of all RTI episodes: 46.6% OC43, 32.3% NL63, 16.0% HKU1, and 5.8% 229E. Hospitalization rates for HCoV-positive children with lower RTIs were 1.5 and 2.8 per 1000 <5 and <1 years of age, respectively. The detection rate among controls was 10.2% (38/373). Codetections occurred in 68.1% of the patients and 68.4% of the controls. In a logistic regression analysis, high HCoV genomic loads (cycle threshold <28 in PCR analysis) were associated with RTIs (odds ratio = 3.12, P = .016) adjusted for relevant factors. CONCLUSIONS: HCoVs occurred in 1 of 10 hospitalized children with RTIs and asymptomatic controls. A high HCoV genomic load was associated with RTI. HCoVs are associated with a substantial burden of RTIs in need of hospitalization.


id: cord-285527-1mceq6v0
author: Kinloch, Natalie N
date: 2020-06-28
url: https://doi.org/10.1093/infdis/jiaa370
doi: 10.1093/infdis/jiaa370
title:
  Suboptimal biological sampling as a probable cause of false-negative COVID-19 diagnostic test results

abstract:
  False-negative SARS-CoV-2 test results can negatively impact the clinical and public health response to COVID-19. We used droplet digital PCR (ddPCR) to demonstrate that human DNA levels, a stable molecular marker of sampling quality, were significantly lower in samples from 40 confirmed or suspected COVID-19 cases that yielded negative diagnostic test results (i.e. suspected false-negative test results) compared to a representative pool of 87 specimens submitted for COVID-19 testing. Our results support suboptimal biological sampling as a contributor to false-negative COVID-19 test results and underscore the importance of proper training and technique in the collection of nasopharyngeal specimens.


id: cord-286596-p10t0dta
author: Erard, Veronique
date: 2006-06-15
txt: ./txt/cord-286596-p10t0dta.txt
cache: ./cache/cord-286596-p10t0dta.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/16703503/
doi: 10.1086/504268
summary:
  We conducted a 12-year retrospective study to determine the effects that the community respiratory-virus species and the localization of respiratory-tract virus infection have on severe airflow decline, a serious and fatal complication occurring after hematopoietic cell transplantation (HCT). Lower-respiratory-tract infection with parainfluenza (odds ratio [OR], 17.9 [95% confidence interval {CI}, 2.0–160]; P=.01) and respiratory syncytial virus (OR, 3.6 [95% CI, 1.0–13]; P=.05) independently increased the risk of development of airflow decline ⩽1 year after HCT. This analysis also identified community respiratory-virus infections during the initial 100 days after HCT as being a significant risk factor for development of severe airflow decline but did not differentiate between specific viral infections or between infection localization in the upper respiratory tract (URT) or lower respiratory tract (LRT) [1] . Respiratory syncitial virus (RSV) infection in hematopoietic stem cell transplant (HCT) recipients: risks factor for acquisition and lower respiratory tract disease, and impact on mortality

title:
  Airflow Decline after Myeloablative Allogeneic Hematopoietic Cell Transplantation: The Role of Community Respiratory Viruses

abstract:
  We conducted a 12-year retrospective study to determine the effects that the community respiratory-virus species and the localization of respiratory-tract virus infection have on severe airflow decline, a serious and fatal complication occurring after hematopoietic cell transplantation (HCT). Of 132 HCT recipients with respiratory-tract virus infection during the initial 100 days after HCT, 50 (38%) developed airflow decline ⩽1 year after HCT. Lower-respiratory-tract infection with parainfluenza (odds ratio [OR], 17.9 [95% confidence interval {CI}, 2.0–160]; P=.01) and respiratory syncytial virus (OR, 3.6 [95% CI, 1.0–13]; P=.05) independently increased the risk of development of airflow decline ⩽1 year after HCT. The airflow decline was immediately detectable after infection and was strongest for lower-respiratory-tract infection with parainfluenza virus; it stabilized during the months after the respiratory-tract virus infection, but, at ⩽1 year after HCT, the initial lung function was not restored. Thus, community respiratory virus–associated airflow decline seems to be specific to viral species and infection localization


id: cord-287210-sars5dmi
author: Woo, Patrick C. Y.
date: 2005-12-01
txt: ./txt/cord-287210-sars5dmi.txt
cache: ./cache/cord-287210-sars5dmi.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/16267760/
doi: 10.1086/497151
summary:
  However, the clinical and molecular epidemiological features of CoV-HKU1–associated pneumonia are unknown MethodsProspectively collected (during a 12-month period) nasopharyngeal aspirates (NPAs) from patients with community-acquired pneumonia from 4 hospitals were subjected to reverse-transcription polymerase chain reaction, for detection of CoV-HKU1. All prospectively collected NPAs from patients with community-acquired pneumonia that were sent to the clinical microbiology laboratories of 4 hospitals in Hong Kong during a 12-month period (22 March 2003 [the beginning of the SARS epidemic in Hong Kong] to 21 March 2004) for detection of SARS-CoV and were found to be negative for SARS-CoV RNA, by reverse-transcription polymerase chain reaction (RT-PCR) [20] , were included in the study. Sequence analysis revealed 0%-2% nucleotide differences between the sequences of the fragments and the sequence of the pol gene from The epidemiological, clinical, and radiological characteristics of the 10 patients with CoV-HKU1-associated community-acquired pneumonia are summarized in table 2.

title:
  Clinical and Molecular Epidemiological Features of Coronavirus HKU1–Associated Community-Acquired Pneumonia

abstract:
  BackgroundRecently, we described the discovery of a novel group 2 coronavirus, coronavirus HKU1 (CoV-HKU1), from a patient with pneumonia. However, the clinical and molecular epidemiological features of CoV-HKU1–associated pneumonia are unknown MethodsProspectively collected (during a 12-month period) nasopharyngeal aspirates (NPAs) from patients with community-acquired pneumonia from 4 hospitals were subjected to reverse-transcription polymerase chain reaction, for detection of CoV-HKU1. The epidemiological, clinical, and laboratory characteristics of patients with CoV-HKU1–associated pneumonia were analyzed. The pol spike (S), and nucleocapsid (N) genes were also sequenced ResultsNPAs from 10 (2.4%) of 418 patients with community-acquired pneumonia were found to be positive for CoV-HKU1. All 10 cases occurred in spring and winter. Nine of these patients were adults, and 4 had underlying diseases of the respiratory tract. In the 6 patients from whom serum samples were available, all had a 4-fold change in immunoglobulin (Ig) G titer and/or presence of IgM against CoV-HKU1. The 2 patients who died had significantly lower hemoglobin levels, monocyte counts, albumin levels, and oxygen saturation levels on admission and had more-extensive involvement visible on chest radiographs. Sequence analysis of the pol S, and N genes revealed 2 genotypes of CoV-HKU1 ConclusionsCoV-HKU1 accounts for 2.4% of community-acquired pneumonia, with 2 genotypes in the study population. Without performance of diagnostic tests, the illness was clinically indistinguishable from other community-acquired pneumonia illnesses


id: cord-288072-42sx52tn
author: Monto, Arnold S.
date: 1974-03-17
txt: ./txt/cord-288072-42sx52tn.txt
cache: ./cache/cord-288072-42sx52tn.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/4816305/
doi: 10.1093/infdis/129.3.271
summary:
  Specimens of blood collected in Tecumseh, Michigan over a four-year period were studied for rise in antibody titer against coronavirus OC43. As part of the study of respiratory infections in Tecumseh, Michigan, specimens of blood were collected on a regular basis from families under surveillance [10] . By testing of specimens collected in early 1967, a large-scale outbreak of infection with coronavirus 229E was detected [11] . All specimens of serum collected from members of 269 families were studied by CF and HAl for rise in titer of antibody to coronavirus OC43. The specimens with rises in CF or HAl titer both showed 66.7% agreement with the neutralization test. Neutralization tests confirmed the difference, and indicated that in the individual case during a period of prevalence of agents related to OC43, even if CF and HAl do not agree, it is likely that an infection with the agent actually did occur.

title:
  The Tecumseh Study of Respiratory Illness. VI. Frequency of and Relationship between Outbreaks of Coronavims Infection

abstract:
  Specimens of blood collected in Tecumseh, Michigan over a four-year period were studied for rise in antibody titer against coronavirus OC43. Peaks of infection were found in the winter and spring of 1966, 1968, and 1969; at other times, infections occurred sporadically. All age groups were involved, especially the very young. Rises in titer by CF and by HAI tests frequently did not occur together in the same individual. Agreement between the two tests was better in 1966 and 1969 than in the other years. A portion of the paired specimens showing rises in CF and/ or HAI titer was tested by neutralization. Rises in neutralizing antibody were usually found in pairs collected in 1966 and 1969 but not in those collected in 1967 and 1968. The infecting viruses in 1966 and 1969 thus appeared more closely related to OC43 than did those in 1967 and 1968.


id: cord-288485-m3g88fl2
author: Lam, Katherine W
date: 2020-07-23
txt: ./txt/cord-288485-m3g88fl2.txt
cache: ./cache/cord-288485-m3g88fl2.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/infdis/jiaa447
doi: 10.1093/infdis/jiaa447
summary:
  title: Continued In-Hospital Angiotensin-Converting Enzyme Inhibitor and Angiotensin II Receptor Blocker Use in Hypertensive COVID-19 Patients Is Associated With Positive Clinical Outcome BACKGROUND: This study investigated continued and discontinued use of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB) during hospitalization of 614 hypertensive laboratory-confirmed COVID-19 patients. Because the widely used antihypertensive medications angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) may upregulate ACE2 receptors [7] [8] [9] , through which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the host cells [10] , concerns have been raised as to whether their use may result in increased morbidity and mortality [4, [11] [12] [13] . The goal of this study was to investigate the effects of in-hospital continuation and discontinuation of ACEi/ARBs on the clinical outcomes of hypertensive COVID-19 patients, controlling for newly developed hypotension or AKI during hospitalization.

title:
  Continued In-Hospital Angiotensin-Converting Enzyme Inhibitor and Angiotensin II Receptor Blocker Use in Hypertensive COVID-19 Patients Is Associated With Positive Clinical Outcome

abstract:
  BACKGROUND: This study investigated continued and discontinued use of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB) during hospitalization of 614 hypertensive laboratory-confirmed COVID-19 patients. METHODS: Demographics, comorbidities, vital signs, laboratory data, and ACEi/ARB usage were analyzed. To account for confounders, patients were substratified by whether they developed hypotension and acute kidney injury (AKI) during the index hospitalization. RESULTS: Mortality (22% vs 17%, P > .05) and intensive care unit (ICU) admission (26% vs 12%, P > .05) rates were not significantly different between non-ACEi/ARB and ACEi/ARB groups. However, patients who continued ACEi/ARBs in the hospital had a markedly lower ICU admission rate (12% vs 26%; P = .001; odds ratio [OR] = 0.347; 95% confidence interval [CI], .187–.643) and mortality rate (6% vs 28%; P = .001; OR = 0.215; 95% CI, .101–.455) compared to patients who discontinued ACEi/ARB. The odds ratio for mortality remained significantly lower after accounting for development of hypotension or AKI. CONCLUSIONS: These findings suggest that continued ACEi/ARB use in hypertensive COVID-19 patients yields better clinical outcomes.


id: cord-288756-r96izsyq
author: Wu, Zhiqiang
date: 2016-02-15
url: https://www.ncbi.nlm.nih.gov/pubmed/26433221/
doi: 10.1093/infdis/jiv476
title:
  ORF8-Related Genetic Evidence for Chinese Horseshoe Bats as the Source of Human Severe Acute Respiratory Syndrome Coronavirus

abstract:
  Several lineage B betacoronaviruses termed severe acute respiratory syndrome (SARS)–like CoVs (SL-CoVs) were identified from Rhinolophus bats in China. These viruses are characterized by a set of unique accessory open reading frames (ORFs) that are located between the M and N genes. Among unique accessory ORFs, ORF8 is most hypervariable. In this study, the ORF8s of all SL-CoVs were classified into 3 types, and, for the first time, it was found that very few SL-CoVs from Rhinolophus sinicus have ORF8s that are identical to that of human SARS-CoV. This finding provides new genetic evidence for Chinese horseshoe bats as the source of human SARS-CoV.


id: cord-288821-nalulzfo
title: Human Coronavirus NL63 Infection in Canada
author: Bastien, Nathalie
date: 2005-02-15
url: https://www.ncbi.nlm.nih.gov/pubmed/15655772/
doi: 10.1086/426869
abstract:
  The isolation of human coronavirus NL63 (HCoV-NL63) in The Netherlands raised questions about its contribution to respiratory illness. In this study, a total of 525 respiratory specimens, collected in Canada primarily during the winter months of 2001–2002, were tested for HCoV-NL63; 19 tested positive for HCoV-NL63, demonstrating virus activity during January–March 2002. Patients with HCoV-NL63 were 1 month-100 years old (median age, 37 years). The main clinical presentations were fever (15/19), sore throat (5/19), and cough (9/19), and 4 patients were hospitalized. These results provide evidence for the worldwide distribution of HCoV-NL63.


id: cord-289255-qwzg7prx
author: Seligman, Stephen J.
date: 2007-02-15
txt: ./txt/cord-289255-qwzg7prx.txt
cache: ./cache/cord-289255-qwzg7prx.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/17230423/
doi: 10.1086/510917
abstract: nan
summary:
  title: Evidence for Quasi Species in Severe Acute Respiratory Syndrome-associated Coronavirus Deletion Mutants have reported data on a 386-nt deletion in severe acute respiratory syndrome-associated coronavirus (SARS-CoV) [1] . Because 1 patient had both the L386del variant and the wild-type variant in the same specimen, they raised the possibility that SARS-CoV exists as a quasi species, at least in some patients. Previous authors studying single-nucleotide variants from Beijing-area isolates in 2003 [2] and from the Singapore 2004 outbreak [3] have also found multiple viral sequences in the same sample that they attributed to quasi species. Although these 3 studies clearly establish the presence of a diversity of SARS-CoV genomes in individual patients, the issue of whether SARS-CoV quasi species exists remains open, particularly with respect to the 386-nt deletion. The large 386-nt deletion in SARS-associated coronavirus: evidence for quasispecies? SARS-associated coronavirus quasispecies in individual patients

title:
  Evidence for Quasi Species in Severe Acute Respiratory Syndrome-associated Coronavirus Deletion Mutants


id: cord-289406-54vyzxjf
author: Edwards, Suzanne
date: 1992-01-17
txt: ./txt/cord-289406-54vyzxjf.txt
cache: ./cache/cord-289406-54vyzxjf.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/1309370/
doi: 10.1093/infdis/165.1.134
summary:
  In a model for virus-induced myocarditis and congestive heart failure, rabbit coronavirus infection was divided into acute (days 2–5) and subacute (days 6–12) phases on the basis of day of death and pathologic findings. Both Coxsackie Band encephalomyocarditis virus infections in mice may progress to myocarditis and congestive heart failure, and some survi-vors may progress to a dilated cardiomyopathy later in life [5, [14] [15] [16] . Rabbits that died on days 10-12 had pleural effusion, pulmonary edema, ascites, enlarged hearts, dilated right and left ventricular cavities, and congestion in the lungs and liver. It seems likely that pleural effusion disease virus infection also results in a significant percentage of animals dying from heart failure, since degeneration and necrosis of myocytes, pulmonary edema, pleural effusion, dilated ventricles, and congestion of the lungs, liver, and spleen are common [18, 26] .

title:
  An Experimental Model for Myocarditis and Congestive Heart Failure after Rabbit Coronavirus Infection

abstract:
  In a model for virus-induced myocarditis and congestive heart failure, rabbit coronavirus infection was divided into acute (days 2–5) and subacute (days 6–12) phases on the basis of day of death and pathologic findings. During the acute phase, the principal histologic lesions were degeneration and necrosis of myocytes, myocytolysis, interstitial edema, and hemorrhage. The severity of these changes increased in the subacute phase. Pleural effusion and congestion of the lungs and liver were also present at this time. Myocarditis was detected by day 9 and peaked by day 12. Heart weights and heart weight-to-body weight ratios were increased, and dilation of the right ventricular cavity became prominent early in infection and persisted. In contrast, dilation of the left ventricle occurred late in the subacute stage. Virus was isolated from infected hearts between days 2 and 12. These data suggest that rabbit coronavirus infection progresses to myocarditis and congestive heart failure.


id: cord-289745-qtorq2qq
author: Esper, Frank
date: 2005-02-15
url: https://www.ncbi.nlm.nih.gov/pubmed/15655770/
doi: 10.1086/428138
title:
  Evidence of a Novel Human Coronavirus That Is Associated with Respiratory Tract Disease in Infants and Young Children

abstract:
  Background. The etiological agents responsible for a substantial proportion of respiratory tract diseases have not been identified. We sought to determine whether novel human coronaviruses (HCoVs) are circulating in New Haven, Connecticut, and, if so, whether they are associated with respiratory tract disease in infants and young children. Methods. We developed a polymerase chain reaction (PCR)-based approach for screening specimens from the respiratory tracts of symptomatic children. PCR probes that target regions of the replicase 1a gene that are conserved among genetically diverse animal CoVs and HCoVs were designed. Using these probes, we identified genomic sequences of a novel HCoV, designated “New Haven coronavirus” (HCoV-NH). Thereafter, we designed specific probes to screen respiratory specimens from children <5 years old for this novel HCoV. Clinical features associated with HCoV-NH infection were identified. Results. Seventy-nine (8.8%) of 895 children tested positive for HCoV-NH. Cough, rhinorrhea, tachypnea, fever, abnormal breath sounds, and hypoxia were the most common findings associated with HCoV-NH infection. Sequence analysis revealed that HCoV-NH is closely related to a novel HCoV recently reported in The Netherlands. Conclusions. The novel HCoVs identified in New Haven and The Netherlands are similar and likely represent the same species. This newly discovered virus may have worldwide distribution and may account for a significant proportion of respiratory tract disease in infants and young children.


id: cord-290277-ndfoppoq
title: Airborne or droplet precautions for health workers treating COVID-19?
author: Bahl, Prateek
date: 2020-04-16
url: https://doi.org/10.1093/infdis/jiaa189
doi: 10.1093/infdis/jiaa189
abstract:
  Cases of COVID-19 have been reported in over 200 countries. Thousands of health workers have been infected and outbreaks have occurred in hospitals, aged care facilities and prisons. World Health Organization (WHO) has issued guidelines for contact and droplet precautions for Healthcare Workers (HCWs) caring for suspected COVID-19 patients, whilst the US Centre for Disease Control (CDC) has recommended airborne precautions. The 1 – 2 m (≈3 – 6 ft) rule of spatial separation is central to droplet precautions and assumes large droplets do not travel further than 2 m (≈6 ft). We aimed to review the evidence for horizontal distance travelled by droplets and the guidelines issued by the World Health Organization (WHO), US Center for Diseases Control (CDC) and European Centre for Disease Prevention and Control (ECDC) on respiratory protection for COVID-19. We found that the evidence base for current guidelines is sparse, and the available data do not support the 1 – 2 m (≈3 – 6 ft) rule of spatial separation. Of ten studies on horizontal droplet distance, eight showed droplets travel more than 2 m (≈6 ft), in some cases more than 8 meters (≈26 ft). Several studies of SARS-CoV-2 support aerosol transmission and one study documented virus at a distance of 4 meters (≈13 ft) from the patient. Moreover, evidence suggests infections cannot neatly be separated into the dichotomy of droplet versus airborne transmission routes. Available studies also show that SARS-CoV-2 can be detected in the air, 3 hours after aeroslisation. The weight of combined evidence supports airborne precautions for the occupational health and safety of health workers treating patients with COVID-19.


id: cord-291486-5h96msv1
author: Kistler, Amy
date: 2007-09-15
txt: ./txt/cord-291486-5h96msv1.txt
cache: ./cache/cord-291486-5h96msv1.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/17703411/
doi: 10.1086/520816
summary:
  The Virochip can detect both known and novel variants of viral pathogens present in RTIs. Given the diversity detected here, larger-scale studies will be necessary to determine whether particular substrains of viruses confer an elevated risk of asthma exacerbation. Each NatURI specimen was analyzed independently in a blinded manner by 3 distinct viral detection methods: Virochip analysis and culture isolation for 9 common respiratory pathogens (HRV; RSV; influenza viruses A and B; human parainfluenza viruses 1, 2, and 3; adenovirus; and human enterovirus) and PCR for HRV. This diversity indicates that future studies that seek to link a particular virus or set of viruses to a discrete clinical outcome, such as exacerbation of asthma symptoms, will need to include large numbers of subjects and use pan-viral detection methods (such as the Virochip) that can differentiate among such isolates.

title:
  Pan-Viral Screening of Respiratory Tract Infections in Adults With and Without Asthma Reveals Unexpected Human Coronavirus and Human Rhinovirus Diversity

abstract:
  Background. Between 50% and 80% of asthma exacerbations are associated with viral respiratory tract infections (RTIs), yet the influence of viral pathogen diversity on asthma outcomes is poorly understood because of the limited scope and throughput of conventional viral detection methods. Methods. We investigated the capability of the Virochip, a DNA microarray—based viral detection platform, to characterize viral diversity in RTIs in adults with and without asthma. Results. The Virochip detected viruses in a higher proportion of samples (65%) than did culture isolation (17%) while exhibiting high concordance (98%) with and comparable sensitivity (97%) and specificity (98%) to pathogen-specific polymerase chain reaction. A similar spectrum of viruses was identified in the RTIs of each patient subgroup; however, unexpected diversity among human coronaviruses (HCoVs) and human rhinoviruses (HRVs) was revealed. All but one of the HCoVs corresponded to the newly recognized HCoV-NL63 and HCoV-HKU1 viruses, and >20 different serotypes of HRVs were detected, including a set of 5 divergent isolates that formed a distinct genetic subgroup. Conclusions. The Virochip can detect both known and novel variants of viral pathogens present in RTIs. Given the diversity detected here, larger-scale studies will be necessary to determine whether particular substrains of viruses confer an elevated risk of asthma exacerbation.


id: cord-293299-gdew0ueo
title: Influenza Research in the Soviet Union—1974
author: Jordan, William S.
date: 1974-12-17
txt: ./txt/cord-293299-gdew0ueo.txt
cache: ./cache/cord-293299-gdew0ueo.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/4372278/
doi: 10.1093/infdis/130.6.686
abstract: nan
summary:
  A long historical tradition for the use of livevirus vaccines in the Soviet Union dates from Smorodintsev''s experimental infection of volunteers with influenza virus in 1937 [2] . Since registered morbidity rather than a more direct measure of real influenza-ARD morbidity is used, the model probably has more applicability for health planners, who need to anticipate increased requirements for delivery of health care associated with epidemics, and for industrial organizations that face future production losses, than for those concerned with anticipating changes in the health status of the population per se. Although data from the morbidity registration system in the Soviet Union provide the basic information for this model, data from the 52 All-Union reporting centers appear to be used as well, particularly for obtaining early warning of the location of the initial epidemic outbreak in the country.


id: cord-293579-w5sub348
author: Che, Xiao-yan
date: 2005-06-15
txt: ./txt/cord-293579-w5sub348.txt
cache: ./cache/cord-293579-w5sub348.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15897988/
doi: 10.1086/430355
summary:
  By use of Western blot analysis, indirect immunofluorescence assay (IFA), and enzyme-linked immunosorbent assay (ELISA), antigenic cross-reactivity between severe acute respiratory syndrome (SARS)—associated coronavirus (SARS-CoV) and 2 HCoVs (229E and OC43) was demonstrated in immunized animals and human serum. In the present study, we cloned the nucleocapsid genes of SARS-CoV, HCoV-229E, and HCoV-OC43 and produced specific animal antisera to determine if the nucleocapsid protein is responsible for the observed antigenic cross-reactivity. The serum samples from patients with SARS had antibody responses to SARS-CoV as well as to HCoV-229E and HCoV-OC43 when nucleocapsid proteins were used in the Western blot analysis and when CoV-infected cells were used in the IFA. Furthermore, antibodies to SARS-CoV could be detected in only 1 serum sample from a healthy donor by either IFA or nucleocapsid protein-based Western blot analysis, even though patients with SARS had antibodies to HCoV-229E and HCoV-OC43.

title:
  Antigenic Cross-Reactivity between Severe Acute Respiratory Syndrome—Associated Coronavirus and Human Coronaviruses 229E and OC43

abstract:
  Cross-reactivity between antibodies to different human coronaviruses (HCoVs) has not been systematically studied. By use of Western blot analysis, indirect immunofluorescence assay (IFA), and enzyme-linked immunosorbent assay (ELISA), antigenic cross-reactivity between severe acute respiratory syndrome (SARS)—associated coronavirus (SARS-CoV) and 2 HCoVs (229E and OC43) was demonstrated in immunized animals and human serum. In 5 of 11 and 10 of 11 patients with SARS, paired serum samples showed a ⩾4-fold increase in antibody titers against HCoV-229E and HCoV-OC43, respectively, by IFA. Overall, serum samples from convalescent patients who had SARS had a 1-way cross-reactivity with the 2 known HCoVs. Antigens of SARS-CoV and HCoV-OC43 were more cross-reactive than were those of SARS-CoV and HCoV-229E.


id: cord-296197-ohfhnpma
title: A Simplified and Standardized Polymerase Chain Reaction Format for the Diagnosis of Leishmaniasis
author: Deborggraeve, Stijn
date: 2008-11-15
url: https://www.ncbi.nlm.nih.gov/pubmed/18816188/
doi: 10.1086/592509
abstract:
  Background. Definite diagnosis of Leishmania infections is based on demonstration of the parasite by microscopic analysis of tissue biopsy specimens or aspirate samples. However, microscopy generally shows low sensitivity and requires invasive sampling. Methods. We describe here the development of a simple and rapid test for the detection of polymerase chain reaction-amplified Leishmania DNA. A phase 1 evaluation of the text was conducted in clinical samples from 60 nonendemic and 45 endemic control subjects and from 44 patients with confirmed cutaneous leishmaniasis (CL), 12 with mucocutaneous leishmaniasis (MCL), and 43 with visceral leishmaniasis (VL) from Peru, Kenya, and Sudan. Results. The lower detection limits of the assay are 10 fg of Leishmania DNA and 1 parasite in 180 µL of blood. The specificity was 98.3% (95% confidence interval [CI], 91.1%–99.7%) and 95.6% (95% CI, 85.2%–98.8%) for nonendemic and endemic control samples, respectively, and the sensitivity was 93.2% (95% CI, 81.8%–97.7%), 91.7% (95% CI, 64.6%–98.5%), and 86% (95% CI, 72.7%–93.4%) for lesions from patients with CL or MCL and blood from patients with VL, respectively. Conclusions. The Leishmania OligoC-TesT showed high specificity and sensitivity in clinical samples and was able to detect the parasite in samples obtained by less invasive means, such as blood, lymph, and lesion scrapings. The assay is a promising new tool for simplified and standardized molecular detection of Leishmania parasites.


id: cord-297432-2edncbgn
author: Helleberg, Marie
date: 2020-07-23
txt: ./txt/cord-297432-2edncbgn.txt
cache: ./cache/cord-297432-2edncbgn.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32702095/
doi: 10.1093/infdis/jiaa446
summary:
  A man in his fifties treated with chemoimmunotherapy for chronic lymphocytic leukemia experienced a 9-week course of COVID-19 with high fever and severe viral pneumonia. Recently, preliminary results of the Adaptive COVID-19 Treatment Trial (ACTT), a multicenter randomized controlled trial of remdesivir versus placebo for treatment of coronavirus disease 2019 (COVID-19) in hospitalized patients, demonstrated that remdesivir reduced time to recovery, in particular for those not yet having experienced respiratory failure with need for assisted ventilation [1] . We here report the clinical course and findings in an immunocompromised patient with remission of COVID-19 during treatment with remdesivir but relapse soon after discontinuation. We present a case of severe COVID-19 in a patient with B-and T-lymphocyte impairment secondary to CLL treated with chemoimmunotherapy 3 months prior to the SARS-CoV-2 infection. The course and findings in this clinical case suggest that remdesivir has a rapid onset of action and can suppress, but may not eradicate, SARS-CoV-2 in immunocompromised patients.

title:
  Persistent COVID-19 in an Immunocompromised Patient Temporarily Responsive to Two Courses of Remdesivir Therapy

abstract:
  The antiviral drug remdesivir has been shown clinically effective for treatment of COVID-19. We here demonstrate suppressive but not curative effect of remdesivir in an immunocompromised patient. A man in his fifties treated with chemoimmunotherapy for chronic lymphocytic leukemia experienced a 9-week course of COVID-19 with high fever and severe viral pneumonia. During two 10-day courses of remdesivir starting 24 and 45 days after fever onset, pneumonia and spiking fevers remitted, but relapsed after discontinuation. Kinetics of temperature, C-reactive protein, and lymphocyte counts mirrored the remitting/relapsing SARS-CoV-2 infection. Combination therapy or longer treatment duration may be needed in immunocompromised patients.


id: cord-299149-lc2dxvxz
author: Chen, I-Cheng Mark
date: 2019-06-15
txt: ./txt/cord-299149-lc2dxvxz.txt
cache: ./cache/cord-299149-lc2dxvxz.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/infdis/jiz046
doi: 10.1093/infdis/jiz046
summary:
  ResPlex II assays and real-time polymerase chain reaction assays were used to detect viral pathogens in nasal wash samples, and survival analyses were performed to determine whether infection with particular viruses conferred short-lived relative cross-protection against FRI. We reanalyzed the Singapore Armed Forces FRI surveillance program data by using survival analyses to assess whether there was any evidence, at the individual level, that infection with particular viruses was conferring short-lived relative cross-protection against subsequent FRI episodes, including those caused by other virus groups. AdV-positive episodes tended to protect against subsequent infection with AdV (P = .090) and also 3 other virus groups All models were adjusted for study year, type of BMT intake, age, ethnicity, smoking history, history of asthma, and influenza vaccination. Infections from the adenovirus and influenza virus families conferred significant cross-protective effects against subsequent FRI episodes relative to other circulating viruses.

title:
  Evidence for Cross-Protection Against Subsequent Febrile Respiratory Illness Episodes From Prior Infections by Different Viruses Among Singapore Military Recruits 2009–2014

abstract:
  BACKGROUND: Few studies have evaluated the relative cross-protection conferred by infection with different groups of viruses through studies of sequential infections in humans. We investigated the presence of short-lived relative cross-protection conferred by specific prior viral infections against subsequent febrile respiratory illness (FRI). METHODS: Men enlisted in basic military training between December 2009 and December 2014 were recruited, with the first FRI as the study entry point. ResPlex II assays and real-time polymerase chain reaction assays were used to detect viral pathogens in nasal wash samples, and survival analyses were performed to determine whether infection with particular viruses conferred short-lived relative cross-protection against FRI. RESULTS: Prior infection with adenovirus (hazard ratio [HR], 0.24; 95% confidence interval [CI], .14–.44) or influenza virus (HR, 0.52; 95% CI, .38–.73) conferred relative protection against subsequent FRI episode. Results were statistically significant even after adjustment for the interval between enlistment and FRI (P < .001). Adenovirus-positive participants with FRI episodes tended to be protected against subsequent infection with adenovirus, coronavirus, enterovirus/rhinovirus, and influenza virus (P = .062–.093), while men with influenza virus–positive FRI episodes tended be protected against subsequent infection with adenovirus (P = .044) and influenza virus (P = .081). CONCLUSION: Prior adenovirus or influenza virus infection conferred cross-protection against subsequent FRI episodes relative to prior infection due to other circulating viruses.


id: cord-299835-92karhpl
author: Ho, Khek Y.
date: 2004-02-17
url: https://www.ncbi.nlm.nih.gov/pubmed/14767817/
doi: 10.1086/381558
title:
  Mild Illness Associated with Severe Acute Respiratory Syndrome Coronavirus Infection: Lessons from a Prospective Seroepidemiologic Study of Health-Care Workers in a Teaching Hospital in Singapore

abstract:
  Background. Severe acute respiratory syndrome (SARS) is a newly recognized infectious disease that has recently emerged in East Asia and North America. Although the clinical features of acute infection have been well described, mildly symptomatic or asymptomatic infections have not been well characterized. Objective. To assess the spectrum of illness in health-care workers (HCWs). Methods. A prospective seroepidemiologic cohort study was conducted on 372 HCWs in a large teaching hospital in Singapore who were both exposed and not exposed to patients with SARS. Participating HCWs completed a questionnaire and provided paired serum samples, which were analyzed by 2 different laboratories blinded to clinical data, by use of an enzyme-linked immunosorbent assay based on a protocol developed by the Centers for Disease Control and Prevention and a dot-blot immunoassay, with confirmation by a viral neutralization assay. Results. A total of 21 patients with SARS were treated at our hospital. They were associated with transmission to 14 staff members, patients, and visitors in our hospital. Of the 372 HCWs participating in the present study, 8 were found to have positive antibodies to the SARS coronavirus in both samples by use of both test methods, and 6 had pneumonia and had been hospitalized for either probable or suspected SARS infection, whereas 2 had fever but did not have changes on chest radiographs. All seropositive HCWs had been exposed either directly or indirectly to patients with SARS. No asymptomatic, nonexposed staff members were found to be seropositive. There was a trend towards protection for HCWs who, while fully protected, had had contact with patients with SARS. Conclusions. Although the majority of cases of SARS are associated with pneumonia, a small number of mildly symptomatic individuals do seroconvert. HCWs who are exposed to patients with SARS can be infected with SARS, regardless of the intensity of exposure. This has implications for surveillance and infection control planning, in the event that SARS returns next winter.


id: cord-300019-8vxqr3mc
author: Shi, Ting
date: 2019-03-08
url: https://www.ncbi.nlm.nih.gov/pubmed/30849176/
doi: 10.1093/infdis/jiy662
title:
  The Etiological Role of Common Respiratory Viruses in Acute Respiratory Infections in Older Adults: A Systematic Review and Meta-analysis

abstract:
  Acute respiratory tract infections (ARI) constitute a substantial disease burden in adults and elderly individuals. We aimed to identify all case-control studies investigating the potential role of respiratory viruses in the etiology of ARI in older adults aged ≥65 years. We conducted a systematic literature review (across 7 databases) of case-control studies published from 1996 to 2017 that investigated the viral profile of older adults with and those without ARI. We then computed a pooled odds ratio (OR) with a 95% confidence interval and virus-specific attributable fraction among the exposed (AFE) for 8 common viruses: respiratory syncytial virus (RSV), influenza virus (Flu), parainfluenza virus (PIV), human metapneumovirus (HMPV), adenovirus (AdV), rhinovirus (RV), bocavirus (BoV), and coronavirus (CoV). From the 16 studies included, there was strong evidence of possible causal attribution for RSV (OR, 8.5 [95% CI, 3.9–18.5]; AFE, 88%), Flu (OR, 8.3 [95% CI, 4.4–15.9]; AFE, 88%), PIV (OR, not available; AFE, approximately 100%), HMPV (OR, 9.8 [95% CI, 2.3–41.0]; AFE, 90%), AdV (OR, not available; AFE, approximately 100%), RV (OR, 7.1 [95% CI, 3.7–13.6]; AFE, 86%) and CoV (OR, 2.8 [95% CI, 2.0–4.1]; AFE, 65%) in older adults presenting with ARI, compared with those without respiratory symptoms (ie, asymptomatic individuals) or healthy older adults. However, there was no significant difference in the detection of BoV in cases and controls. This review supports RSV, Flu, PIV, HMPV, AdV, RV, and CoV as important causes of ARI in older adults and provides quantitative estimates of the absolute proportion of virus-associated ARI cases to which a viral cause can be attributed. Disease burden estimates should take into account the appropriate AFE estimates (for older adults) that we report.


id: cord-301340-lhh04pum
title: Human Torovirus: A New Nosocomial Gastrointestinal Pathogen
author: Jamieson, Frances B.
date: 1998-11-17
txt: ./txt/cord-301340-lhh04pum.txt
cache: ./cache/cord-301340-lhh04pum.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/9780245/
doi: 10.1086/314434
summary:
  Torovirus-like particles purified from stool specimens were further shown to be toroviruses on the basis of their morphology, immunospecific interactions with Breda virus antiserum, ability to elicit an immune response following infection, and the high degree of homology of the 3 end of their genome with that of the Berne and Breda viruses [19] . At a different time from that of study 1, patients whose stool specimens were positive for torovirus, rotavirus, or astrovirus by electron microscopy were enrolled in study 2. In torovirus-positive patients, stool specimens were examined daily by electron microscopy during the hospitalization and at follow-up. Nine additional torovirus-positive patients developed bloody diarrhea within 2-15 days after study enrollment and had no other pathogen in the stool sample. Stool specimens collected on a follow-up visit 2-6 months after study enrollment from 168 patients infected with torovirus showed that 14 were shedding the virus.

abstract:
  Studies were undertaken to determine if human torovirus is associated with gastroenteritis and to examine the clinical features of torovirus illness in children. The fecal excretion of torovirus in patients with gastroenteritis was compared with that in matched asymptomatic controls in a case-control study. Toroviruses were identified in 72 (35.0%) of 206 gastroenteritis cases compared with 30 (14.5%) of 206 controls (P < .001). Clinical features of torovirus gastroenteritis in 172 patients positive for torovirus were compared with those of 115 patients infected with rotavirus or astrovirus. Persons infected with torovirus were more frequently immunocompromised (43.0% vs. 15.7%) and nosocomially infected (57.6% vs. 31.3%). They also experienced less vomiting (46.4% vs. 66.7%) but had more bloody diarrhea (11.2% vs. 1.8%). An antibody response to torovirus developed mainly in older, nonimmunocompromised children (P < .01). These studies demonstrate an association between torovirus excretion and gastroenteritis in the pediatric population among immunocompromised hospitalized patients and in previously healthy patients.


id: cord-304766-h9kuytuf
author: Lei, Hao
date: 2020-09-08
txt: ./txt/cord-304766-h9kuytuf.txt
cache: ./cache/cord-304766-h9kuytuf.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/infdis/jiaa570
doi: 10.1093/infdis/jiaa570
summary:
  To suppress the COVID-19 pandemic, from January 23-25, 2020, 30 provinces began a 1-level response and implemented a set of non-pharmaceutical interventions (NPIs), including not only the classical isolation of the confirmed/suspected cases and quarantine of their close contacts in special facilities, but also unprecedented measures like strict community containments with social distancing, such as the Wuhan city travel ban to prevent the exportation of cases from Wuhan and other priority areas of Hubei Province, extension of the Spring Festival holiday, suspension of traffic and transportation, closure of school and entertainment venues, banning of mass gathering activities, compulsory community use of facemasks in public areas, and information about the epidemic and prevention measures widely disseminated, public risk communications and health education strengthened, new hospital built to ensure that all cases could be treated [2] .

title:
  Non-pharmaceutical interventions used to control COVID-19 reduced seasonal influenza transmission in China

abstract:
  To suppress the ongoing COVID-19 pandemic, the Chinese government has implemented a set of non-pharmaceutical interventions (NPIs). Because COVID-19 and influenza have similar means of transmission, it is hypothesized that NPIs targeting COVID-19 may also affect influenza transmission. In this study, the extent to which NPIs targeting COVID-19 have affected seasonal influenza transmission was explored. Indicators of seasonal influenza activity in the epidemiological year 2019/20 were compared with those in 2017/18 and 2018/19. Results show that the incidence rate of seasonal influenza reduced by 64% in 2019/20 (p&0.001). These findings suggest that NPIs aimed at controlling COVID-19 significantly reduced the seasonal influenza transmission in China. (105 words)


id: cord-306983-6w2fvtfy
author: Wang, Siye
date: 2010-10-01
txt: ./txt/cord-306983-6w2fvtfy.txt
cache: ./cache/cord-306983-6w2fvtfy.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/20731583/
doi: 10.1086/656044
summary:
  Influenza A virus infection resulted in significant increases in TNF-α, IL-6, IL-1β, viral hemagglutininprocessing protease trypsin levels, and viral replication with vascular hyperpermeability in lung and brain in the first 6 days of infection. The present study reports several new observations: (1) proinflammatory cytokines, TNF-a, IL-1b, and IL-6, when upregulated by influenza A virus infection, induce trypsin expression in various organs and human endothelial cells; (2) the upregulated trypsin induces [Ca 2+ ] i mobilization via activation of the PAR-2, followed by loss of zonula occludens-1 and vascular hyperpermeability; (3) inhibitors of NF-kB and activator protein 1 effectively suppress the upregulation of proinflammatory cytokines and trypsin and improve the survival rates of infected mice. The present results allow us to propose a new mechanism of junctional permeability regulation: upregulated trypsin by influenza A virus and/or proinflammatory cytokines induces increase in [Ca 2+ ] i and loss of zonula occludens-1 in endothelial cells via PAR-2 signaling.

title:
  Influenza Virus—Cytokine-Protease Cycle in the Pathogenesis of Vascular Hyperpermeability in Severe Influenza

abstract:
  Background. Severe influenza is characterized by cytokine storm and multiorgan failure with edema. The aim of this study was to define the impact of the cytokine storm on the pathogenesis of vascular hyperpermeability in severe influenza. Methods. Weanling mice were infected with influenza A WSN/33(H1N1) virus. The levels of proinflammatory cytokines, tumor necrosis factor (TNF) α, interleukin (IL) 6, IL-1β, and trypsin were analyzed in the lung, brain, heart, and cultured human umbilical vein endothelial cells. The effects of transcriptional inhibitors on cytokine and trypsin expressions and viral replication were determined. Results. Influenza A virus infection resulted in significant increases in TNF-α, IL-6, IL-1β, viral hemagglutininprocessing protease trypsin levels, and viral replication with vascular hyperpermeability in lung and brain in the first 6 days of infection. Trypsin upregulation was suppressed by transcriptional inhibition of cytokines in vivo and by anti-cytokine antibodies in endothelial cells. Calcium mobilization and loss of tight junction constituent, zonula occludens-1, associated with cytokine- and trypsin-induced endothelial hyperpermeability were inhibited by a protease-activated receptor-2 antagonist and a trypsin inhibitor. Conclusions. The influenza virus-cytokine-protease cycle is one of the key mechanisms of vascular hyperpermeability in severe influenza.


id: cord-307918-8y89p11a
author: Onyango, Clayton O.
date: 2012-12-15
txt: ./txt/cord-307918-8y89p11a.txt
cache: ./cache/cord-307918-8y89p11a.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/infdis/jis536
doi: 10.1093/infdis/jis536
summary:
  Nasopharyngeal samples from children aged <12 years who were admitted to Kilifi District Hospital during 2007–2010 with severe or very severe pneumonia and resided in the local demographic surveillance system were screened for influenza A, B, and C viruses by molecular methods. The following clinical and laboratory features obtained on admission or that relate to discharge outcome were compared between influenza-positive and influenza-negative children: duration of hospitalization >14 days, very severe pneumonia, wheezing, hypoxia (oxygen saturation level <90%, by fingertip pulse oximetry), circulatory shock (capillary refill time ≥3 seconds), severe anemia (hemoglobin level <5 g/dL), prematurity, congenital heart disease, positivity for HIV antibody (by 2 rapid tests), severe underweight (weight for age Z score ≤3), slide positivity for Plasmodium species, bacteremia, concurrent viral infection diagnosis, and death before discharge [2] . Our study identified all 3 influenza viruses in circulation in this rural coastal Kenya location among patients hospitalized with severe or very severe pneumonia and among outpatients with URTI.

title:
  Influenza Surveillance Among Children With Pneumonia Admitted to a District Hospital in Coastal Kenya, 2007–2010

abstract:
  Background. Influenza data gaps in sub-Saharan Africa include incidence, case fatality, seasonal patterns, and associations with prevalent disorders. Methods. Nasopharyngeal samples from children aged <12 years who were admitted to Kilifi District Hospital during 2007–2010 with severe or very severe pneumonia and resided in the local demographic surveillance system were screened for influenza A, B, and C viruses by molecular methods. Outpatient children provided comparative data. Results. Of 2002 admissions, influenza A virus infection was diagnosed in 3.5% (71), influenza B virus infection, in 0.9% (19); and influenza C virus infection, in 0.8% (11 of 1404 tested). Four patients with influenza died. Among outpatients, 13 of 331 (3.9%) with acute respiratory infection and 1 of 196 without acute respiratory infection were influenza positive. The annual incidence of severe or very severe pneumonia, of influenza (any type), and of influenza A, was 1321, 60, and 43 cases per 100 000 <5 years of age, respectively. Peak occurrence was in quarters 3–4 each year, and approximately 50% of cases involved infants: temporal association with bacteremia was absent. Hypoxia was more frequent among pneumonia cases involving influenza (odds ratio, 1.78; 95% confidence interval, 1.04–1.96). Influenza A virus subtypes were seasonal H3N2 (57%), seasonal H1N1 (12%), and 2009 pandemic H1N1 (7%). Conclusions. The burden of influenza was small during 2007–2010 in this pediatric hospital in Kenya. Influenza A virus subtype H3N2 predominated, and 2009 pandemic influenza A virus subtype H1N1 had little impact.


id: cord-308979-qhlvd2mt
author: Sumino, Kaharu C.
date: 2005-09-15
url: https://www.ncbi.nlm.nih.gov/pubmed/16107959/
doi: 10.1086/432728
title:
  Detection of Severe Human Metapneumovirus Infection by Real-Time Polymerase Chain Reaction and Histopathological Assessment

abstract:
  BackgroundInfections with common respiratory tract viruses can cause high mortality, especially in immunocompromised hosts, but the impact of human metapneumovirus (hMPV) in this setting was previously unknown MethodsWe evaluated consecutive bronchoalveolar lavage and bronchial wash fluid samples from 688 patients—72% were immunocompromised and were predominantly lung transplant recipients—for hMPV by use of quantitative real-time polymerase chain reaction (PCR), and positive results were correlated with clinical outcome and results of viral cultures, in situ hybridization, and lung histopathological assessment ResultsSix cases of hMPV infection were identified, and they had a similar frequency and occurred in a similar age range as other paramyxoviral infections. Four of 6 infections occurred in immunocompromised patients. Infection was confirmed by in situ hybridization for the viral nucleocapsid gene. Histopathological assessment of lung tissue samples showed acute and organizing injury, and smudge cell formation was distinct from findings in infections with other paramyxoviruses. Each patient with high titers of hMPV exhibited a complicated clinical course requiring prolonged hospitalization ConclusionsOur results provide in situ evidence of hMPV infection in humans and suggest that hMPV is a cause of clinically severe lower respiratory tract infection that can be detected during bronchoscopy by use of real-time PCR and routine histopathological assessment


id: cord-309786-8zyf9e3k
author: Karron, Ruth A
date: 2019-10-12
txt: ./txt/cord-309786-8zyf9e3k.txt
cache: ./cache/cord-309786-8zyf9e3k.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/infdis/jiz408
doi: 10.1093/infdis/jiz408
summary:
  RESULTS: In RSV-seronegative children, the 10(5) PFU dose was overattenuated, but the 10(6) PFU dose was well tolerated, infectious (RSV/ΔNS2/Δ1313/I1314L replication detected in 90% of vaccinees), and immunogenic (geometric mean serum RSV plaque-reduction neutralizing antibody titer, 1:64). b A >4 fold-rise in serum RSV neutralizing antibody was detected in a placebo recipient in the 10 5 PFU dose cohort, probably indicating infection with wild-type RSV between study days 28 and 56. b A >4 fold-rise in serum RSV neutralizing antibody was detected in a placebo recipient in the 10 5 PFU dose cohort, probably indicating infection with wild-type RSV between study days 28 and 56. Live respiratory syncytial virus (RSV) vaccine candidate containing stabilized temperature-sensitivity mutations is highly attenuated in RSV-seronegative infants and children

title:
  Safety and Immunogenicity of the Respiratory Syncytial Virus Vaccine RSV/ΔNS2/Δ1313/I1314L in RSV-Seronegative Children

abstract:
  BACKGROUND: Respiratory syncytial virus (RSV) is the leading global cause of severe pediatric acute respiratory tract illness, and a vaccine is needed. RSV/ΔNS2/Δ1313/I1314L contains 2 attenuating elements: (1) deletion of the interferon antagonist NS2 gene and (2) deletion of codon 1313 of the RSV polymerase gene and the stabilizing missense mutation I1314L. This live vaccine candidate was temperature-sensitive, genetically stable, replication restricted, and immunogenic in nonhuman primates. METHODS: A single intranasal dose of RSV/ΔNS2/Δ1313/I1314L was evaluated in a double-blind, placebo-controlled trial (vaccine-placebo ratio, 2:1) at 10(6) plaque-forming units (PFU) in 15 RSV-seropositive children and at 10(5) and 10(6) PFU in 21 and 30 RSV-seronegative children, respectively. RESULTS: In RSV-seronegative children, the 10(5) PFU dose was overattenuated, but the 10(6) PFU dose was well tolerated, infectious (RSV/ΔNS2/Δ1313/I1314L replication detected in 90% of vaccinees), and immunogenic (geometric mean serum RSV plaque-reduction neutralizing antibody titer, 1:64). After the RSV season, 9 of 20 vaccinees had increases in the RSV titer that were significantly greater than those in 8 of 10 placebo recipients (1:955 vs 1:69, respectively), indicating that the vaccine primed for anamnestic responses after natural RSV exposure. CONCLUSION: Rational design yielded a genetically stable candidate RSV vaccine that is attenuated yet immunogenic in RSV-seronegative children, warranting further evaluation. CLINICAL TRIALS REGISTRATION: NCT01893554.


id: cord-312552-udky2ko7
author: Fouque, Florence
date: 2020-10-29
url: https://doi.org/10.1093/infdis/jiaa489
doi: 10.1093/infdis/jiaa489
title:
  Introduction to a Landscape Analysis of Multisectoral Approaches for Prevention and Control of Infectious and Vector-Borne Diseases

abstract:
  The Swiss Development Cooperation, Canada’s International Development Research Centre, the Swiss Tropical Public Health Institute, and the UNICEF/United Nations Development Programme (UNDP)/World Bank/World Health Organization (WHO) Special Programme for Research and Training in Tropical Diseases (TDR) collaborated on a project to review, understand and promote the use of multisectoral approaches (MSAs) in the prevention and control of vector-borne diseases (VBDs). The objectives of the project were to support a landscape analysis of how MSAs have been used in the prevention and control of VBDs; to develop a theoretical framework for guiding the implementation of interventions; and to test the recommendations in real-life conditions. To realize these objectives, the project supported several activities, including commissioning a series of scientific reviews on MSAs in 5 thematic areas, sharing the key findings of these reviews in workshops and events, and developing a guidance framework for the implementation of MSAs. These activities have produced the theoretical framework that will be tested in real-life conditions through the support of case studies. The collaboration on implementing multisectoral activities against VBDs will continue among TDR, the Swiss Tropical Public Health Institute, and new partners such as the WHO Water Sanitation and Hygiene Group, UNDP, and UN-Habitat, in order to face the challenges identified and propose solutions tailored to specific contexts. The prevention and control of VBDs require strong and adapted MSAs with the full participation of all relevant sectors.


id: cord-313000-as507p4t
author: Dare, Ryan K.
date: 2007-11-01
url: https://www.ncbi.nlm.nih.gov/pubmed/17922396/
doi: 10.1086/521308
title:
  Human Coronavirus Infections in Rural Thailand: A Comprehensive Study Using Real-Time Reverse-Transcription Polymerase Chain Reaction Assays

abstract:
  Background. We sought to determine whether infections with human coronaviruses (HCoVs) 229E, OC43, HKU1, and NL63 are associated with pneumonia and to define the epidemiology of HCoV infection in rural Thailand. Methods. We developed a real-time reverse-transcription polymerase chain reaction (RT-PCR) assay panel for the recognized HCoV types and compared HCoV infections in patients hospitalized with pneumonia, outpatients with influenza-like illness, and asymptomatic control patients between September 2003 and August 2005. Results. During study year 1, 43 (5.9%) of 734 patients with pneumonia had HCoV infections; 72.1% of the infections were with OC43. During study year 2, when control patients were available, 21 (1.8%) of 1156 patients with pneumonia, 12 (2.3%) of 513 outpatients, and 6 (2.1%) of 281 control patients had HCoV infections. Compared with infection in control patients, infection with any HCoV type or with all types combined was not associated with pneumonia (adjusted odds ratio for all HCoV types, 0.67 [95% confidence interval, 0.26–1.75]; P= .40 ). HCoV infections were detected throughout both study years; 93.6% of OC43 infections in the first year occurred from January through March. Conclusions. HCoV infections were infrequently detected in rural Thailand by use of sensitive real-time RTPCR assays. We found no association between HCoV infection and illness. However, we noted year-to-year variation in the prevalence of HCoV strains, which likely influenced our results.


id: cord-313344-rqvi2ksc
title: Fatal Severe Acute Respiratory Syndrome Is Associated with Multiorgan Involvement by Coronavirus
author: Farcas, Gabriella A.
date: 2005-01-15
url: https://www.ncbi.nlm.nih.gov/pubmed/15609228/
doi: 10.1086/426870
abstract:
  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). We report on the distribution and viral load of SARS-CoV in multiple organ samples from patients who died of SARS during the Toronto outbreak. SARS-CoV was detected in lung (100%), bowel (73%), liver (41%), and kidney (38%) in 19 patients who died of SARS, with the highest viral loads observed in lung (1.0 × 10(10) copies/g) and bowel (2.7 × 10(9) copies/g). Fatal SARS was associated with multiorgan viral dissemination in a distribution that has implications for disease manifestation, viral shedding, and transmission.


id: cord-315328-8g40ukml
author: Clementi, Nicola
date: 2020-06-19
txt: ./txt/cord-315328-8g40ukml.txt
cache: ./cache/cord-315328-8g40ukml.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32559285/
doi: 10.1093/infdis/jiaa350
summary:
  In this report, we demonstrate that IFN-β-1a was highly effective in inhibiting in vitro SARS-CoV-2 replication at clinically achievable concentration when administered after virus infection. In this report, we demonstrate that IFN-β-1a was highly effective in inhibiting in vitro SARS-CoV-2 replication at clinically achievable concentration when administered after virus infection. In the current study, we assessed its anti-SARS-CoV-2 activity in vitro to give a preclinical background to clinical trials evaluating the possible therapeutic role of IFN-β-1a in patients with coronavirus disease 2019 (COVID-19). Vero E6 cells were treated with concentrations ranging from 5000 to 0.01 IU/mL of IFN-β-1a 1 hour after inoculation with SARS-CoV-2 and monitored for cytopathic effect and real-time-PCR quantitative evaluation at 48, 72, and 96 hours after infection. Our in vitro observations shed light for the first time on that antiviral activity of IFN-β-1a against SARS-CoV-2 when administered after the infection of cells, highlighting its possible efficacy in an early therapeutic setting.

title:
  Interferon-β-1a Inhibition of Severe Acute Respiratory Syndrome–Coronavirus 2 In Vitro When Administered After Virus Infection

abstract:
  The ongoing coronavirus disease 2019 pandemic has forced the clinical and scientific community to try drug repurposing of existing antiviral agents as a quick option against severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2). Under this scenario, interferon (IFN) β-1a, whose antiviral potential is already known, and which is a drug currently used in the clinical management of multiple sclerosis, may represent as a potential candidate. In this report, we demonstrate that IFN-β-1a was highly effective in inhibiting in vitro SARS-CoV-2 replication at clinically achievable concentration when administered after virus infection.


id: cord-315448-bosazmlm
title: Dynamics of neutralizing antibody titers in the months after SARS-CoV-2 infection
author: Crawford, Katharine H D
date: 2020-09-30
txt: ./txt/cord-315448-bosazmlm.txt
cache: ./cache/cord-315448-bosazmlm.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/33000143/
doi: 10.1093/infdis/jiaa618
summary:
  Here we quantify how levels of these antibodies change in the months following SARS-CoV-2 infection by examining longitudinal samples collected between ~30 and 152 days post symptom onset from a prospective cohort of 32 recovered individuals with asymptomatic, mild, or moderate-severe disease. Most of these studies have reported that over the first three months, antibodies targeting spike decline several fold from a peak reached a few weeks post symptom onset [5, 7, 19] , suggesting that the early dynamics of the antibody response to SARS-CoV-2 are similar to those for other acute viral infections. A c c e p t e d M a n u s c r i p t 5 Here we build on these studies by measuring both the neutralizing and binding antibody levels in serial plasma samples from 32 SARS-CoV-2-infected individuals across a range of disease severity with follow-up as long as 152 days post symptom onset.

abstract:
  Most individuals infected with SARS-CoV-2 develop neutralizing antibodies that target the viral spike protein. Here we quantify how levels of these antibodies change in the months following SARS-CoV-2 infection by examining longitudinal samples collected between ~30 and 152 days post symptom onset from a prospective cohort of 32 recovered individuals with asymptomatic, mild, or moderate-severe disease. Neutralizing antibody titers declined an average of about four-fold from one to four months post symptom onset. This decline in neutralizing antibody titers was accompanied by a decline in total antibodies capable of binding the viral spike or its receptor-binding domain. Importantly, our data are consistent with the expected early immune response to viral infection, where an initial peak in antibody levels is followed by a decline to a lower plateau. Additional studies of long-lived B-cells and antibody titers over longer time frames are necessary to determine the durability of immunity to SARS-CoV-2.


id: cord-315457-w1nx9g91
title: Desperate times call for temperate measures: practicing infectious diseases during a novel pandemic
author: Siedner, Mark J
date: 2020-04-21
txt: ./txt/cord-315457-w1nx9g91.txt
cache: ./cache/cord-315457-w1nx9g91.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32315424/
doi: 10.1093/infdis/jiaa209
abstract: nan
summary:
  authors: Siedner, Mark J; Gandhi, Rajesh T; Kim, Arthur Y Of the thousands of peer-reviewed articles indexed in Pubmed, exactly one has reported the results of a randomized controlled trial; a single-centered study with approximately 200 COVID-19 infected individuals, investigating a drug developed for another virus, and resulting in a null finding. And although we agree with ethical obligations that compel medical researchers to make their data publicly available so it can inform the epidemic response, we also remain acutely aware that there has been a corresponding pandemic of COVID-19 misinformation. In the coming months, there will be results from well-designed and peer-reviewed trials that we hope will reveal therapeutic options for the treatment and prevention of COVID-19. In the meantime, we will be asked countless times to help decide which ones are which, often by trusted colleagues in search of a miracle for patients in extremis.


id: cord-315476-7rdiesav
title: Characterization of Human Metapneumoviruses Isolated from Patients in North America
author: Peret, Teresa C. T.
date: 2002-06-01
txt: ./txt/cord-315476-7rdiesav.txt
cache: ./cache/cord-315476-7rdiesav.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/12023774/
doi: 10.1086/340518
summary:
  In this study, 11 isolates from 10 patients with respiratory disease from Quebec, Canada, were tested by a reverse-transcriptase polymerase chain reaction based on the fusion protein gene. In this study, 11 isolates from 10 patients with respiratory disease from Quebec, Canada, were tested by a reverse-transcriptase polymerase chain reaction based on the fusion protein gene. In the present article, we describe polymerase chain reaction (PCR) and sequencing studies done on 11 isolates from respiratory specimens from 10 Canadian patients with acute respiratory tract illness. Published nucleocapsid (N) and fusion (F) gene sequences of HMPV and avian pneumovirus were used to develop primers for detection and sequencing of HMPV at the Respiratory Virus Section (Centers for Disease Control and Prevention, Atlanta). We detected virus in isolates from children with acute respiratory tract infection, as described in the first report of HMPV [1] .

abstract:
  Human metapneumovirus (HMPV) was recently identified in The Netherlands and was linked to acute respiratory tract illness. In this study, 11 isolates from 10 patients with respiratory disease from Quebec, Canada, were tested by a reverse-transcriptase polymerase chain reaction based on the fusion protein gene. Identified sequences were consistent with HMPV. The patients were 2 months to 87 years of age (median age, 58 years) and presented with acute respiratory tract illness during the winter season. Sequence studies of the nucleocapsid, fusion, and polymerase genes identified 2 main lineages of HMPV and cocirculation of both lineages during the same year. These findings support a previous finding that HMPV is a human respiratory pathogen that merits further study.


id: cord-317232-qk72i0gv
author: Gierer, Stefanie
date: 2015-03-15
txt: ./txt/cord-317232-qk72i0gv.txt
cache: ./cache/cord-317232-qk72i0gv.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/25057042/
doi: 10.1093/infdis/jiu407
summary:
  title: Inhibition of Proprotein Convertases Abrogates Processing of the Middle Eastern Respiratory Syndrome Coronavirus Spike Protein in Infected Cells but Does Not Reduce Viral Infectivity However, activation of viral glycoproteins, including activation of the S protein of certain strains of the coronavirus infectious bronchitis virus (IBV) [18] , may also proceed in the constitutive secretory pathway of infected cells and is often accomplished by furin and other proprotein convertases [19] [20] [21] [22] . Treatment of MERS-CoV-infected cells with a proprotein convertase inhibitor (PCI) abrogated S protein cleavage but did not alter viral infectivity, indicating that S protein processing in infected cells is dispensable for MERS-S activation. In sum, our results identify MERS-S as a substrate of proprotein convertases but indicate that the activity of these enzymes is dispensable for MERS-CoV spread in target cell lines and potentially also in the infected human host.

title:
  Inhibition of Proprotein Convertases Abrogates Processing of the Middle Eastern Respiratory Syndrome Coronavirus Spike Protein in Infected Cells but Does Not Reduce Viral Infectivity

abstract:
  Middle East respiratory syndrome coronavirus (MERS-CoV) infection is associated with a high case-fatality rate, and the potential pandemic spread of the virus is a public health concern. The spike protein of MERS-CoV (MERS-S) facilitates viral entry into host cells, which depends on activation of MERS-S by cellular proteases. Proteolytic activation of MERS-S during viral uptake into target cells has been demonstrated. However, it is unclear whether MERS-S is also cleaved during S protein synthesis in infected cells and whether cleavage is required for MERS-CoV infectivity. Here, we show that MERS-S is processed by proprotein convertases in MERS-S–transfected and MERS-CoV–infected cells and that several RXXR motifs located at the border between the surface and transmembrane subunit of MERS-S are required for efficient proteolysis. However, blockade of proprotein convertases did not impact MERS-S–dependent transduction of target cells expressing high amounts of the viral receptor, DPP4, and did not modulate MERS-CoV infectivity. These results show that MERS-S is a substrate for proprotein convertases and demonstrate that processing by these enzymes is dispensable for S protein activation. Efforts to inhibit MERS-CoV infection by targeting host cell proteases should therefore focus on enzymes that process MERS-S during viral uptake into target cells.


id: cord-317421-xzf723w2
title: Infectious Disease Outbreaks: The Need For an All-in Approach
author: Schieffelin, John S
date: 2020-04-08
txt: ./txt/cord-317421-xzf723w2.txt
cache: ./cache/cord-317421-xzf723w2.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/infdis/jiaa167
doi: 10.1093/infdis/jiaa167
abstract: nan
summary:
  As of March 29, 2020, the 2018 to 2020 outbreak of Ebola virus disease (EVD) in the Democratic Republic of Congo (DRC) has led to 3453 cases and 2264 deaths [1] . In their article entitled "Identifying mechanisms of violence that impact Ebola virus disease transmission during the 2018-2019 outbreak in the Democratic Republic of the Congo, " Kelly et al [7] test the hypothesis that violent events directly targeting the Ebola response result in greater transmission than violence that does not directly target the Ebola response. These goals can only be accomplished through social mobilization and risk communication, highly specialized medical care and infection control practices, support for safe burial practices, and vaccination of those most at risk [10, 11] . Identifying mechanisms of violence that impact Ebola virus disease transmission during the 2018-2019 outbreak in the Democratic Republic of the Congo


id: cord-320445-pdvkyzci
author: Fry, Alicia M.
date: 2007-04-01
url: https://www.ncbi.nlm.nih.gov/pubmed/17330795/
doi: 10.1086/512163
title:
  Human Bocavirus: A Novel Parvovirus Epidemiologically Associated with Pneumonia Requiring Hospitalization in Thailand

abstract:
  Background. We detected human bocavirus (HBoV) infection in 4.5% of hospitalized patients with pneumonia in rural Thailand. However, the role of HBoV as a pathogen is unclear. Methods. We compared HBoV infection in patients with pneumonia with that in asymptomatic control patients enrolled between 1 September 2004 and 31 August 2005 in the same hospitals in Thailand.We examined outpatients with influenza-like illness for HBoV infection and tested for 13 additional respiratory viruses. Epidemiologic and clinical characteristics of HBoV infection are described. Results. HBoV infection was detected in 20 (3.9%) of 512 outpatients and 3 (1%) of 280 control patients. Coinfection with other viruses was detected in 83% of patients with pneumonia and in 90% of outpatients. Compared with control patients, HBoV infection was significantly associated with pneumonia requiring hospitalization (adjusted odds ratio, 3.56 [95% confidence interval, 1.06–11.91]; P = .04). Eighty-three percent of HBoV infections were detected in patients with pneumonia who were <5 years old. More patients with pneumonia associated with HBoV—respiratory syncytial virus (RSV) or human parainfluenza virus (HPIV) coinfections had wheezing than patients with RSV and HPIV infections alone (9 [53%] of 17 vs. 32 [23%] of 138]; P = .01). Conclusions. HBoV infection was epidemiologically associated with pneumonia among young children in rural Thailand, but infection and illness may be dependent on coinfection with other viruses.


id: cord-320764-p4ydngag
author: Breiman, Robert F.
date: 2013-12-15
url: https://doi.org/10.1093/infdis/jit462
doi: 10.1093/infdis/jit462
abstract: nan
title:
  Surveillance for Respiratory Infections in Low- and Middle-Income Countries: Experience From the Centers for Disease Control and Prevention's Global Disease Detection International Emerging Infections Program


id: cord-321006-rxuq3ux8
author: Chang, Luan-Yin
date: 2006-01-15
txt: ./txt/cord-321006-rxuq3ux8.txt
cache: ./cache/cord-321006-rxuq3ux8.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/16362893/
doi: 10.1086/498875
summary:
  title: Lack of Association between Infection with a Novel Human Coronavirus (HCoV), HCoV-NH, and Kawasaki Disease in Taiwan We investigated whether infection with a novel human coronavirus (HCoV), called "New Haven coronavirus" (HCoV-NH)—which is similar to and likely represents the same species as another novel HCoV, HCoV-NL63—is associated with Kawasaki disease (KD) in Taiwan. The evidence that suggests that the etiology of KD can be traced to an infectious agent includes temporal clustering and marked seasonality, geographic clustering, a strong association between the frequency of KD and infectious-disease surveillance [2, 9] , and age distribution (with the highest incidence among children 6 months to 2 years old, who have little maternal antibody and are, in general, the most susceptible to infection) [2] . An aliquot (2.6 mL) of RNA isolated from the clinical specimens, the positive template (10, 100, 1000, and 10,000 copies of the in vitro-transcribed RNA), and the negative control (distilled water) were subjected to real-time RT-PCR.

title:
  Lack of Association between Infection with a Novel Human Coronavirus (HCoV), HCoV-NH, and Kawasaki Disease in Taiwan

abstract:
  We investigated whether infection with a novel human coronavirus (HCoV), called “New Haven coronavirus” (HCoV-NH)—which is similar to and likely represents the same species as another novel HCoV, HCoV-NL63—is associated with Kawasaki disease (KD) in Taiwan. Fifty-three patients with KD were enrolled in our study. Serum, peripheral-blood mononuclear cells, nasopharyngeal aspirates, throat swabs, and rectal swabs from these patients were assayed for HCoV-NL63 by real-time reverse-transcriptase (RT) polymerase chain reaction (PCR), and the throat swabs, nasopharyngeal aspirates, and rectal swabs were also assayed for HCoV-NH by RT-PCR. All PCR results were negative for both HCoV-NL63 and HCoV-NH; therefore, we did not find any association between HCoV-NH infection and KD in Taiwan


id: cord-321132-xdpb3ukt
author: Lhomme, Sebastien
date: 2014-01-15
txt: ./txt/cord-321132-xdpb3ukt.txt
cache: ./cache/cord-321132-xdpb3ukt.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/infdis/jit438
doi: 10.1093/infdis/jit438
summary:
  We investigated the association between the genetic heterogeneity of HEV quasispecies in ORF1 and the outcome of infection in solid-organ transplant patients. Both sequence entropy and genetic distances during the hepatitis E acute phase were higher in patients whose infection became chronic than in those who cleared the virus. Both sequence entropy and genetic distances during the hepatitis E acute phase were higher in patients whose infection became chronic than in those who cleared the virus. We therefore analysed the characteristics of HEV quasispecies at the acute phase of hepatitis E in 2 groups of SOT patients, one whose infection became chronic and the other who cleared the virus. Both the complexity and diversity of the PPR and the macro domain were higher in viral population of the patients whose infection became chronic than in those who cleared the virus.

title:
  Influence of Polyproline Region and Macro Domain Genetic Heterogeneity on HEV Persistence in Immunocompromised Patients

abstract:
  Hepatitis E virus (HEV) can chronically infect immunocompromised patients. The polyproline region (PPR) and the macro domain of ORF1 protein may modulate virus production and/or the host immune response. We investigated the association between the genetic heterogeneity of HEV quasispecies in ORF1 and the outcome of infection in solid-organ transplant patients. Both sequence entropy and genetic distances during the hepatitis E acute phase were higher in patients whose infection became chronic than in those who cleared the virus. Hence, great quasispecies heterogeneity in the regions encoding the PPR and the macro domain may facilitate HEV persistence.


id: cord-321580-3ru92tra
author: Hadler, James L
date: 2020-09-07
txt: ./txt/cord-321580-3ru92tra.txt
cache: ./cache/cord-321580-3ru92tra.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/infdis/jiaa571
doi: 10.1093/infdis/jiaa571
abstract: nan
summary:
  The initial country-level responses to SARS-CoV-2 have provided substantial evidence of their collective impact on the COVID-19 pandemic and, incidentally, on seasonal influenza epidemics. As a country, it has perhaps the largest influenza sentinel surveillance system in the world, including active testing for influenza, and it was the first country to implement highly successful NPIs against SARS-CoV-2, giving it the best opportunity to see a possible change in influenza before the expected seasonal decline. To know what might happen with influenza this coming fall and winter, we need to know what has happened prospectively in southern hemisphere countries, especially those that like the US have used fewer NPI''s and used them with less rigor and, correspondingly, been less successful in controlling SARS-CoV-2 transmission. Nonpharmaceutical interventions used to control COVID-19 reduced seasonal influenza transmission in China

title:
  Will SARS-CoV-2 prevention efforts affect the coming influenza season in the United States and northern hemisphere?


id: cord-324001-m7ys95z7
author: Kobinger, Gary P.
date: 2010-04-01
txt: ./txt/cord-324001-m7ys95z7.txt
cache: ./cache/cord-324001-m7ys95z7.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/20170374/
doi: 10.1086/651171
summary:
  Groups of five 16-to 20-weekold ferrets without antibodies against circulating influenza strains were immunized with one of the 2008 seasonal inactivated split vaccines (Fluviral; GlaxoSmithKline) or the cold-adapted live attenuated vaccine (FluMist; MedImmune), a swine influenza vaccine (FluSure; Pfizer), or a matched laboratory-produced inactivated vaccine (pH1N1inact). HAI antibody titers against the pandemic H1N1 2009 MX10 isolate were detected at day 7 in ferrets receiving the laboratory-produced matched vaccine pH1N1inact or the swine influenza vaccine FluSure, reaching titers 140 on day 7 or 10, respectively. Toward this end, we compared the antibody and cellular responses elicited by 2 seasonal vaccines (Fluviral and FluMist), the commercial swine vaccine FluSure, and a laboratory-produced matched inactivated whole-virus preparation. A curious observation is the more severe cases of disease and the higher mortality rate noted for animals vaccinated with FluMist, which correlated with slightly more infectious virus in the nasal washes of this group at day 3.

title:
  Assessment of the Efficacy of Commercially Available and Candidate Vaccines against a Pandemic H1N1 2009 Virus

abstract:
  Background. The emergence and global spread of the pandemic H1N1 2009 influenza virus have raised questions regarding the protective effect of available seasonal vaccines and the efficacy of a newly produced matched vaccine. Methods. Ferrets were immunized with the 2008–2009 formulations of commercially available live attenuated (FluMist; MedImmune) or split-inactivated (Fluviral; GlaxoSmithKline) vaccines, a commercial swine vaccine (FluSure; Pfizer), or a laboratory-produced matched inactivated whole-virus vaccine (A/Mexico/InDRE4487/2009). Adaptive immune responses were monitored, and the animals were challenged with A/Mexico/InDRE4487/2009 after 5 weeks. Results. Only animals that received the swine or matched vaccines developed detectable hemagglutination- inhibiting antibodies against the challenge virus, whereas a T cell response was exclusively detected in animals vaccinated with FluMist. After challenge, all animals had high levels of virus replication in the upper respiratory tract. However, preexisting anti—pandemic H1N1 2009 antibodies resulted in reduced clinical signs and improved survival. Surprisingly, FluMist was associated with a slight increase in mortality and greater lung damage, which correlated with early up-regulation of interleukin-10. Conclusions. The present study demonstrates that a single dose of matched inactivated vaccine confers partial protection against a pandemic H1N1 2009 virus, and it suggests that a higher dose or prime-boost regimen may be required. The consequences of mismatched immunity to influenza merit further investigation.


id: cord-324280-e8mj6ecl
title: Asymptomatic Summertime Shedding of Respiratory Viruses
author: Shaman, Jeffrey
date: 2018-04-01
txt: ./txt/cord-324280-e8mj6ecl.txt
cache: ./cache/cord-324280-e8mj6ecl.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/infdis/jix685
doi: 10.1093/infdis/jix685
summary:
  Here, we explore respiratory virus infection rates in a segment of this population through a convenience survey and sampling study of adult visitors to a New York City tourist attraction during spring and summer 2016. Among all participants there was a statistically significant positive association between reporting a greater tendency to get sick and total self-reported symptom score (P < .0001 by the Tukey test); however, there was no significant association between reporting a greater tendency to get sick and actual detection of respiratory virus shedding (P = .10 by χ 2 analysis). The best-fit logistic regression model supported an association between an increased likelihood of testing positive for respiratory virus infection and a higher total symptom score (P < .0001) and being Hispanic (P < .005).

abstract:
  To determine rates of both symptomatic and asymptomatic infection among ambulatory adults, we collected nasopharyngeal swab specimens, demographic characteristics, and survey information from 1477 adult visitors to a New York City tourist attraction during April–July 2016. Multiplex polymerase chain reaction analysis was used to identify specimens positive for common respiratory viruses. A total of 7.2% of samples tested positive for respiratory viruses; among positive samples, 71.0% contained rhinovirus, and 21.5% contained coronavirus. Influenza virus, respiratory syncytial virus, and parainfluenza virus were also detected. Depending on symptomatologic definition, 57.7%–93.3% of positive samples were asymptomatic. These findings indicate that significant levels of asymptomatic respiratory viral shedding exist during summer among the ambulatory adult population.


id: cord-324701-7vjdlt1v
title: Analysis of Ebola Virus Entry Into Macrophages
author: Dahlmann, Franziska
date: 2015-10-01
txt: ./txt/cord-324701-7vjdlt1v.txt
cache: ./cache/cord-324701-7vjdlt1v.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/infdis/jiv140
doi: 10.1093/infdis/jiv140
summary:
  Lectins, TAM receptor tyrosine kinases (Tyro3, Axl, Mer), T cell immunoglobulin and mucin domain (TIM) proteins, integrins, and Niemann-Pick C1 (NPC1) have been reported to promote entry of ebolaviruses into certain cellular systems. Here, we show that mannose-specific lectins, TIM-1 and Axl augment entry into certain cell lines but do not contribute to Ebola virus (EBOV)-glycoprotein (GP)–driven transduction of macrophages. To confirm and extend these observations, we compared the ability of lectins, TIM proteins, and the TAM family member Axl to augment EBOV-GP-driven entry into 293T cells, which can be efficiently transfected and are highly susceptible to transduction mediated by ebolavirus GPs [11] . Quantitative RT-PCR revealed that less Axl and TIM-1 mRNA is produced in MDMs compared with susceptible cell lines, and siRNA-knock-down showed that expression of these factors is dispensable for GP-driven entry into MDMs. In contrast, Mer but not Axl expression was required for efficient GPdriven transduction and EBOV infection of MDMs. Similarly, Mer but not Axl or Tyro3 was found to be essential for efficient phagocytosis of apoptotic cells by macrophages [46] , indicating that Mer is the TAM receptor kinase active in macrophages.

abstract:
  Ebolaviruses constitute a public health threat, particularly in Central and Western Africa. Host cell factors required for spread of ebolaviruses may serve as targets for antiviral intervention. Lectins, TAM receptor tyrosine kinases (Tyro3, Axl, Mer), T cell immunoglobulin and mucin domain (TIM) proteins, integrins, and Niemann-Pick C1 (NPC1) have been reported to promote entry of ebolaviruses into certain cellular systems. However, the factors used by ebolaviruses to invade macrophages, major viral targets, are poorly defined. Here, we show that mannose-specific lectins, TIM-1 and Axl augment entry into certain cell lines but do not contribute to Ebola virus (EBOV)-glycoprotein (GP)–driven transduction of macrophages. In contrast, expression of Mer, integrin αV, and NPC1 was required for efficient GP-mediated transduction and EBOV infection of macrophages. These results define cellular factors hijacked by EBOV for entry into macrophages and, considering that Mer and integrin αV promote phagocytosis of apoptotic cells, support the concept that EBOV relies on apoptotic mimicry to invade target cells.


id: cord-327501-8s6dvanf
author: Schwaiger, Julia
date: 2020-09-17
txt: ./txt/cord-327501-8s6dvanf.txt
cache: ./cache/cord-327501-8s6dvanf.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32941626/
doi: 10.1093/infdis/jiaa593
summary:
  Testing 54 intravenous immunoglobulin preparations, produced from plasma collected in Europe and the United States, confirmed highly potent neutralization of a seasonal coronavirus; however, no cross-neutralization of the new SARS-CoV-2 was seen. The question is of significant clinical relevance, as SARS-CoV-2 cross-neutralizing antibodies in IVIGs, if they were present, might afford some protection to people with immune deficiencies and may even represent a treatment option for coronavirus disease 2019 (COVID-19) patients. The current study tested a representative number of IVIG lots for nAbs against SARS-CoV-2 and the longer-circulating HCoV-229E, to establish clarity about cross-neutralization of the pandemic virus by antibodies induced by earlier circulating seasonal coronaviruses. SARS-CoV-2 nAb titers were below the limit of detection for all 54 IVIG lots tested, irrespective of geographic origin of the plasma (Europe vs United States) and plasma collection modality (recovered vs source) ( Figure 1A) .

title:
  No SARS-CoV-2 Neutralization by Intravenous Immunoglobulins Produced From Plasma Collected Before the 2020 Pandemic

abstract:
  The 2020 SARS-CoV-2 pandemic is caused by a zoonotic coronavirus transmitted to humans, similar to earlier events. Whether the other, seasonally circulating coronaviruses induce cross-reactive, potentially even cross-neutralizing, antibodies to the new species in humans is unclear. The question is particularly relevant for people with immune deficiencies, as their health depends on treatment with immunoglobulin preparations that need to contain neutralizing antibodies against the pathogens in their environment. Testing 54 intravenous immunoglobulin preparations, produced from plasma collected in Europe and the United States, confirmed highly potent neutralization of a seasonal coronavirus; however, no cross-neutralization of the new SARS-CoV-2 was seen.


id: cord-327673-3uem0e22
author: Qin, Gang
date: 2009-09-01
url: https://doi.org/10.1086/605413
doi: 10.1086/605413
title:
  Phosphoantigen-Expanded Human γδ T Cells Display Potent Cytotoxicity against Monocyte-Derived Macrophages Infected with Human and Avian Influenza Viruses

abstract:
  BackgroundInfluenza virus is a cause of substantial annual morbidity and mortality worldwide. The potential emergence of a new pandemic strain (eg, avian influenza virus) is a major concern. Currently available vaccines and anti-influenza drugs have limited effectiveness for influenza virus infections, especially for new pandemic strains. Therefore, there is an acute need to develop alternative strategies for influenza therapy. γδ T cells have potent antiviral activities against different viruses, but no data are available concerning their antiviral activity against influenza viruses MethodsIn this study, we used virus-infected primary human monocyte-derived macrophages (MDMs) to examine the antiviral activity of phosphoantigen isopentenyl pyrophosphate (IPP)–expanded human Vγ9Vδ2 T cells against influenza viruses ResultsVγ9Vδ2 T cells were selectively activated and expanded by IPP from peripheral blood mononuclear cells. IPP-expanded Vγ9Vδ2 T cells efficiently killed MDMs infected with human (H1N1) or avian (H9N2 or H5N1) influenza virus and significantly inhibited viral replication. The cytotoxicity of Vγ9Vδ2 T cells against influenza virus–infected MDMs was dependent on NKG2D activation and was mediated by Fas–Fas ligand and perforin–granzyme B pathways ConclusionOur findings suggest a potentially novel therapeutic approach to seasonal, zoonotic avian, and pandemic influenza—the use of phosphoantigens to activate γδ T cells against influenza virus infections


id: cord-329061-1xut73dq
title: Characterization of the Virus of Sialodacryoadenitis of Rats: A Member of the Coronavirus Group
author: Bhatt, Pravin N.
date: 1972-08-17
txt: ./txt/cord-329061-1xut73dq.txt
cache: ./cache/cord-329061-1xut73dq.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/4559849/
doi: 10.1093/infdis/126.2.123
summary:
  The virus that causes sialodacryoadenitis in rats has been isolated in mice and in primary cultures of rat-kidney cells and has been characterized as a heat-labile RNA virus that is sensitive to lipid solvents and is relatively stable at pH 3.0. Rats were inoculated intranasally with 0.1 ml of virus-infected salivary-gland suspension, observed daily for evidence of overt illness, and sacrificed at various intervals. Monolayers obtained from explant cultures of submaxillary, parotid, Harderian, and exorbital glands of germfree rats, monolayers of trypsin-dispersed brain cells of infant mice, and a line of polyoma-transformed mouse cells (Py-AL/N) [6J were also tested. The neutralization (N) test with sera immune to murine viruses was performed in infant mice, and these animals were observed for 14 days after inoculation. Infectious virus or viral antigen was not detected when tissue-culture fluids from infected-mouse-brain and Py-AL/N cultures were inoculated ic into infant mice or when monolayers were examined by indirect immunofluorescence. E. Shope tested 118 viral antigens prepared from infected mouse brains with antiserum to SDA virus.

abstract:
  The virus that causes sialodacryoadenitis in rats has been isolated in mice and in primary cultures of rat-kidney cells and has been characterized as a heat-labile RNA virus that is sensitive to lipid solvents and is relatively stable at pH 3.0. This virus is antigenically related to the virus of hepatitis in mice and to coronavirus of rats. The range of hosts of this agent appears to be narrow. On the basis of available biologic characteristics, it has been placed in the coronavirus group.


id: cord-329392-fufattj8
author: den Hartog, Gerco
date: 2020-08-08
url: https://www.ncbi.nlm.nih.gov/pubmed/32766833/
doi: 10.1093/infdis/jiaa479
title:
  SARS-CoV-2–Specific Antibody Detection for Seroepidemiology: A Multiplex Analysis Approach Accounting for Accurate Seroprevalence

abstract:
  BACKGROUND: The COVID-19 pandemic necessitates better understanding of the kinetics of antibody production induced by infection with SARS-CoV-2. We aimed to develop a high-throughput multiplex assay to detect antibodies to SARS-CoV-2 to assess immunity to the virus in the general population. METHODS: Spike protein subunits S1 and receptor binding domain, and nucleoprotein were coupled to microspheres. Sera collected before emergence of SARS-CoV-2 (n = 224) and of non-SARS-CoV-2 influenza-like illness (n = 184), and laboratory-confirmed cases of SARS-CoV-2 infection (n = 115) with various severities of COVID-19 were tested for SARS-CoV-2–specific IgG concentrations. RESULTS: Our assay discriminated SARS-CoV-2–induced antibodies and those induced by other viruses. The assay specificity was 95.1%–99.0% with sensitivity 83.6%–95.7%. By merging the test results for all 3 antigens a specificity of 100% was achieved with a sensitivity of at least 90%. Hospitalized COVID-19 patients developed higher IgG concentrations and the rate of IgG production increased faster compared to nonhospitalized cases. CONCLUSIONS: The bead-based serological assay for quantitation of SARS-CoV-2–specific antibodies proved to be robust and can be conducted in many laboratories. We demonstrated that testing of antibodies against multiple antigens increases sensitivity and specificity compared to single-antigen–specific IgG determination.


id: cord-330645-46qaljq1
author: Waghmare, Alpana
date: 2020-07-25
txt: ./txt/cord-330645-46qaljq1.txt
cache: ./cache/cord-330645-46qaljq1.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/infdis/jiaa451
doi: 10.1093/infdis/jiaa451
summary:
  Using longitudinal home-based self-sampling, we demonstrate nasal cytokine levels correlate and cluster according to immune cell of origin. Nasal foam swab self-sampling at home provides a precise, mechanistic readout of respiratory virus shedding and local immune responses. Here we demonstrate that home self-sampling with nasal foam swabs is well-tolerated and provides reliable results for monitoring viral load and molecular immune responses to respiratory virus infection. We have previously demonstrated increased sensitivity of self-collected foam nasal swabs compared to nasal washes in immunocompetent adults with respiratory viral infections [21] , and in longitudinal studies in solid organ transplant recipients [22] , with good compliance and participants reporting no issues with swab discomfort. M a n u s c r i p t In summary, we establish a foam swab-based sampling method that is optimal for patient selftesting, both at home and in the clinical setting, permits serial therapeutic monitoring, and is suitable for tracking the natural virologic and immunologic course of respiratory virus infections.

title:
  Reliability of self-sampling for accurate assessment of respiratory virus viral and immunologic kinetics

abstract:
  The SARS-CoV-2 pandemic demonstrates the need for accurate and convenient approaches to diagnose and therapeutically monitor respiratory viral infections. We demonstrated that self-sampling with foam swabs is well-tolerated and provides quantitative viral output concordant with flocked swabs. Using longitudinal home-based self-sampling, we demonstrate nasal cytokine levels correlate and cluster according to immune cell of origin. Periods of stable viral loads are followed by rapid elimination, which could be coupled with cytokine expansion and contraction. Nasal foam swab self-sampling at home provides a precise, mechanistic readout of respiratory virus shedding and local immune responses.


id: cord-332175-d5suvj8g
author: Allen, Jawara
date: 2020-04-11
txt: ./txt/cord-332175-d5suvj8g.txt
cache: ./cache/cord-332175-d5suvj8g.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32277235/
doi: 10.1093/infdis/jiaa178
abstract: nan
summary:
  Three weeks later-on the day I was scheduled to start the clinical portion of my medical training-there were 418 700 confirmed cases of COVID-19 globally [1] . By that time, many courses had started remote instruction, most research laboratories had been closed to all nonessential personnel, and medical school core clerkships had been temporarily canceled, all in an effort to decrease student exposure to COVID-19 and help "flatten the curve. But as a medical student eager to reenter the world of clinical care, the personal stories from the communities that would be most impacted by this relentless pathogen soon consumed my thoughts. Few other events before have so poignantly highlighted the global nature of health, the vulnerability of certain populations around the world, and the need for more infectious disease specialists. But the importance of infectious disease specialists will not end once the number of newly diagnosed COVID-19 cases starts to decrease. To protect those communities, we need more infectious disease specialists.

title:
  My Future in Medicine: How COVID-19 Is Inspiring the Next Generation of Infectious Disease Specialists


id: cord-332303-0bbw64p5
title: Airborne SARS-CoV-2 is Rapidly Inactivated by Simulated Sunlight
author: Schuit, Michael
date: 2020-06-11
txt: ./txt/cord-332303-0bbw64p5.txt
cache: ./cache/cord-332303-0bbw64p5.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/infdis/jiaa334
doi: 10.1093/infdis/jiaa334
summary:
  This study examined the effect of simulated sunlight, relative humidity, and suspension matrix on the stability of SARS-CoV-2 in aerosols. Therefore, the present study examined the influence of both simulated sunlight and relative humidity on the stability of SARS-CoV-2 in aerosols generated from virus suspended in different liquid matrices. Two different environmentally controlled rotating drum aerosol chambers, with volumes of 16-L and 208-L, were used in the present study to expose aerosols containing SARS-CoV-2 to controlled levels of temperature, relative humidity, and simulated sunlight. The present study examined the influence of simulated sunlight and relative humidity on the stability of SARS-CoV-2 in aerosols generated from virus suspended in either simulated saliva or culture medium at 20°C. The half-lives estimated from the mean decay constants across all relative humidity levels without simulated sunlight present were 55 and 86 minutes for aerosols generated from virus suspended in culture medium and simulated saliva, respectively.

abstract:
  Aerosols represent a potential route of transmission of COVID-19. This study examined the effect of simulated sunlight, relative humidity, and suspension matrix on the stability of SARS-CoV-2 in aerosols. Both simulated sunlight and matrix significantly affected the decay rate of the virus. Relative humidity alone did not affect the decay rate; however, minor interactions between relative humidity and the other factors were observed. Decay rates in simulated saliva, under simulated sunlight levels representative of late winter/early fall and summer were 0.121±0.017 min(-1) (90% loss: 19 minutes) and 0.379±0.072 min(-1) (90% loss: 6 minutes), respectively. The mean decay rate without simulated sunlight across all relative humidity levels was 0.008±0.011 min(-1) (90% loss: 125 minutes). These results suggest that the potential for aerosol transmission of SARS-CoV-2 may be dependent on environmental conditions, particularly sunlight. These data may be useful to inform mitigation strategies to minimize the potential for aerosol transmission.


id: cord-332537-rtdu4jae
title: Airborne Severe Acute Respiratory Syndrome Coronavirus and Its Implications
author: Tong, Tommy R.
date: 2005-05-01
txt: ./txt/cord-332537-rtdu4jae.txt
cache: ./cache/cord-332537-rtdu4jae.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15809896/
doi: 10.1086/429637
abstract: nan
summary:
  Airborne transmission of the severe acute respiratory syndrome (SARS) coronavirus (CoV) has been the favored explanation for its transmission on an aircraft [1] and appeared to explain a large community outbreak of SARS in the Amoy Gardens in Hong Kong [2] . in this issue of the Journal of Infectious Diseases [3] suggests that airborne dissemination of SARS-CoV may also occur in the health-care setting. However, if SARS-CoV is naturally airborne (produced by breathing and coughing), as was shown by Booth et al., then there is sufficient concern that it can be transmitted successfully by air. Acknowledgment of the fact that SARS-CoV can be aerosolized justifies the actions of those who have already committed resources for providing a safer environment in terms of preventing airborne transmission of infectious diseases and might provide the needed pressure for others to follow suit. Evidence of airborne transmission of the severe acute respiratory syndrome virus


id: cord-333411-hqtb4a2c
title: Location Matters: Geographic Disparities and Impact of Coronavirus Disease 2019 (COVID-19)
author: Tan, Tina Q
date: 2020-09-17
url: https://www.ncbi.nlm.nih.gov/pubmed/32942299/
doi: 10.1093/infdis/jiaa583
abstract:
  The COVID-19 pandemic in the United States has revealed major disparities in the access to testing and messaging about the pandemic based on the geographic location of individuals, particularly in communities of color, rural areas, and areas of low income. This geographic disparity, in addition to deeply rooted structural inequities, have posed additional challenges to adequately diagnose and provide care for individuals of all ages living in these settings. We describe the impact that COVID-19 has had on geographic disparate populations in the United States and share our recommendations to what might be done to ameliorate the current situation.


id: cord-333429-bq7kfpby
author: Shi, Ding
date: 2020-07-02
txt: ./txt/cord-333429-bq7kfpby.txt
cache: ./cache/cord-333429-bq7kfpby.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/infdis/jiaa388
doi: 10.1093/infdis/jiaa388
summary:
  title: Clinical characteristics and factors associated with long-term viral excretion in patients with SARS-CoV-2 infection: a single center 28-day study Male sex (HR, 0.58 [95% CI, 0.35-0.98]), immunoglobulin use (HR, 0.42 [95% CI, 0.24-0.76]), APACHE II score (HR, 0.89 [95% CI, 0.84-0.96]), and lymphocyte count (HR, 1.81 [95% CI, 1.05-3.1]) were independent factors associated with a prolonged duration of SARS-CoV-2 shedding. We identified that male sex, immunoglobulin use, APACHE II score, and lymphopenia were independent risk factors associated with the duration of SARS-CoV-2 RNA shedding, whereas ARV A c c e p t e d M a n u s c r i p t combination therapy and corticosteroid treatment were not independent factors. In conclusion, we found that male sex, immunoglobulin use, APACHE II score, and lymphopenia were independent risk factors associated with the duration of SARS-CoV-2 RNA shedding, whereas ARV combination therapy and corticosteroid treatment were not.

title:
  Clinical characteristics and factors associated with long-term viral excretion in patients with SARS-CoV-2 infection: a single center 28-day study

abstract:
  BACKGROUND: Despite the ongoing spread of COVID-19, knowledge about factors affecting prolonged viral excretion is limited. METHODS: In this study, we retrospectively collected data from 99 hospitalized patients with COVID-19 between January 19 and February 17 in Zhejiang Province, China. We classified them into two groups based on whether the virus test results eventually became negative. Cox proportional hazards regression was used to evaluate factors associated with SARS-CoV-2 shedding. RESULTS: Among 99 patients, 61 patients had SARS-CoV-2 clearance (virus-negative group), but 38 patients had sustained positive results (virus-positive group). The median duration of SARS-CoV-2 excretion was 15 days (IQR 12-19) among the virus-negative patients. The shedding time was significantly increased if fecal SARS-CoV-2 RNA test results was positive. Male sex (HR, 0.58 [95% CI, 0.35-0.98]), immunoglobulin use (HR, 0.42 [95% CI, 0.24-0.76]), APACHE II score (HR, 0.89 [95% CI, 0.84-0.96]), and lymphocyte count (HR, 1.81 [95% CI, 1.05-3.1]) were independent factors associated with a prolonged duration of SARS-CoV-2 shedding. Antiviral therapy and corticosteroid treatment were not independent factors. CONCLUSIONS: SARS-CoV-2 RNA clearance time was associated with sex, disease severity and lymphocyte function. The current antiviral protocol and low-to-moderate dosage of corticosteroid had little effect on the duration of viral excretion.


id: cord-334242-m5dr19v4
author: Teran, Luis M.
date: 1999-03-01
url: https://www.ncbi.nlm.nih.gov/pubmed/9952375/
doi: 10.1086/314618
title:
  RANTES, Macrophage-Inhibitory Protein 1α, and the Eosinophil Product Major Basic Protein Are Released into Upper Respiratory Secretions during Virus-Induced Asthma Exacerbations in Children

abstract:
  The presence of cytokines and the toxic eosinophil granule product major basic protein (MBP) was investigated in nasal aspirates from children with naturally occurring virus-induced asthma exacerbations and compared with levels in nasal aspirates taken from the same children when asymptomatic. Increased levels of MBP accompanied by increased levels of the chemokines RANTES and macrophage-inhibitory protein 1α were observed in nasal aspirates from children during the virus-induced exacerbations. Granulocyte-macrophage colony-stimulating factor was mostly undetectable in samples obtained during both symptomatic and asymptomatic periods. Interleukin-5 levels were low, but tended to increase in samples from symptomatic children. These data confirm that the eosinophil product MBP and the eosinophil chemoattractant chemokines RANTES and macrophage-inhibitory protein 1α are increased in upper respiratory viral infections associated with asthma exacerbations and suggest an important role for these chemokines in regulating eosinophil influx and activation. These chemokines may represent targets for therapeutic intervention in virus-induced asthma exacerbations.


id: cord-334988-brumg6jh
author: Traugott, Marianna
date: 2020-05-30
txt: ./txt/cord-334988-brumg6jh.txt
cache: ./cache/cord-334988-brumg6jh.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/infdis/jiaa305
doi: 10.1093/infdis/jiaa305
summary:
  We comparatively assessed sensitivities and specificities of 4 commercial enzyme-linked immunosorbent assays (ELISAs) and 2 rapid tests in 77 patients with polymerase chain reaction–confirmed severe acute respiratory syndrome coronavirus 2 infection, grouped by interval since symptom onset. We comparatively assessed sensitivities and specificities of 4 commercial enzyme-linked immunosorbent assays (ELISAs) and 2 rapid tests in 77 patients with polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 infection, grouped by interval since symptom onset. In the current study, we compared the diagnostic ability of 4 enzyme-linked immunosorbent assays (ELISAs), which assess SARS-CoV-2-specific antibodies of different immunoglobulin (Ig) classes (Euroimmun SARS-CoV-2 IgA and IgG and Wantai SARS-CoV-2 IgM and total antibody), and 2 rapid tests (Wantai SARS-CoV-2 Ab Rapid Test and Hangzhou AllTest Biotech 2019-nCoV IgG/IgM Rapid Test) in 77 patients with symptomatic SARS-CoV-2 infection. Of the 77 patients with PCR-confirmed SARS-CoV-2 infection, 30 individuals (12 female, 18 male; median age, 58 years; age range, 15-83 years) provided serum/plasma samples that were obtained at symptom onset or 1-5 days after the onset of disease (group 1).

title:
  Performance of Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Assays in Different Stages of Infection: Comparison of Commercial Enzyme-Linked Immunosorbent Assays and Rapid Tests

abstract:
  We comparatively assessed sensitivities and specificities of 4 commercial enzyme-linked immunosorbent assays (ELISAs) and 2 rapid tests in 77 patients with polymerase chain reaction–confirmed severe acute respiratory syndrome coronavirus 2 infection, grouped by interval since symptom onset. Although test sensitivities were low (<40%) within the first 5 days after disease onset, immunoglobulin (Ig) M, IgA, and total antibody ELISAs increased in sensitivity to >80% between days 6 and 10 after symptom onset. The evaluated tests (including IgG and rapid tests) provided positive results in all patients at or after the 11th day after onset of disease. The specificities of the ELISAs were 83% (IgA), 98% (IgG), and 97% (IgM and total antibody).


id: cord-335375-n6q70o35
author: Chan, Paul K. S.
date: 2005-07-01
txt: ./txt/cord-335375-n6q70o35.txt
cache: ./cache/cord-335375-n6q70o35.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15942907/
doi: 10.1086/430615
summary:
  Samples collected р50 days after fever onset were also tested for anti-SARS-CoV IgM antibody, so that IgM antibody detection and IgG antibody avidity measurement could be compared with respect to demonstrating a recent infection. Changes in severe acute respiratory syndrome-associated coronavirus-specific IgG antibody avidity in paired serum samples ples were measured by an in-house indirect immunofluorescence assay that has been described elsewhere [12] . Of the 45 samples collected р50 days after fever onset, only 18 (40.0%) were positive for anti-SARS-CoV IgM antibody, as determined by the ELISARS assay. Of the 26 paired samples, only 6 (23.1%) showed a significant (у4-fold) increase in anti-SARS-CoV IgG antibody titer (as determined by an in-house indirect immunofluorescence assay) from the first to the second sample, a result that could be regarded as evidence of recent infection. Our data show that anti-SARS-CoV IgG antibody avidity is low during primary infection and increases with time in a unidirectional manner.

title:
  Antibody Avidity Maturation during Severe Acute Respiratory Syndrome–Associated Coronavirus Infection

abstract:
  The maturation of virus-specific immunoglobulin G avidity during severe acute respiratory syndrome–associated coronavirus infection was examined. The avidity indices were low (mean ± SD, 30.8% ± 11.6%) among serum samples collected ⩽50 days after fever onset, intermediate (mean ± SD, 52.1% ± 14.1%) among samples collected between days 51 and 90, and high (mean ± SD, 78.1% ± 8.0%) among samples collected after day 90. Avidity indices of 40% and 55% could be considered as cutoff values for determination of recent (⩽50 days) and past (>65 days) infection, respectively. Measurement of antibody avidity can be used to differentiate primary infection from reexposure and to assess humoral responses to candidate vaccines


id: cord-338776-2wa30218
author: Zhao, Xiaoyu
date: 2020-02-15
txt: ./txt/cord-338776-2wa30218.txt
cache: ./cache/cord-338776-2wa30218.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/infdis/jiz483
doi: 10.1093/infdis/jiz483
summary:
  The cytokine and/or chemokine induction was significantly attenuated by siRNA depletion of retinoic acid-inducible-I-like receptors (RLR) or adaptor, indicating that RLR signaling also contributed to MERS-CoV-induced proinflammatory response. We first used the inhibitors of RLR and CLR signaling pathway to evaluate their potential contribution for mediating the proinflammatory response in MERS-CoV-infected macrophages. To assess the contribution of RLR or CLR pathway to induce proinflammatory response, we measured the expression levels of a series of key proinflammatory cytokines and/or chemokines in MERS-CoV-infected MDMs in the presence of these inhibitors ( Figure 1B ). Overall, the above results suggested that RLR and CLR signaling might be involved in viral recognition and trigger the proinflammatory response upon MERS-CoV infection in macrophages. Our results indicate that CLR and RLR signaling may be involved in mediating the immune activation in MERS-CoV-infected human macrophages.

title:
  Activation of C-Type Lectin Receptor and (RIG)-I-Like Receptors Contributes to Proinflammatory Response in Middle East Respiratory Syndrome Coronavirus-Infected Macrophages

abstract:
  BACKGROUND: Human infection with Middle East respiratory syndrome coronavirus (MERS-CoV) poses an ongoing threat to public health worldwide. The studies of MERS patients with severe disease and experimentally infected animals showed that robust viral replication and intensive proinflammatory response in lung tissues contribute to high pathogenicity of MERS-CoV. We sought to identify pattern recognition receptor (PRR) signaling pathway(s) that mediates the inflammatory cascade in human macrophages upon MERS-CoV infection. METHODS: The potential signaling pathways were manipulated individually by pharmacological inhibition, small interfering ribonucleic acid (siRNA) depletion, and antibody blocking. The MERS-CoV-induced proinflammatory response was evaluated by measuring the expression levels of key cytokines and/or chemokines. Reverse transcription-quantitative polymerase chain reaction assay, flow cytometry analysis, and Western blotting were applied to evaluate the activation of related PRRs and engagement of adaptors. RESULTS: MERS-CoV replication significantly upregulated C-type lectin receptor (CLR) macrophage-inducible Ca(2+)-dependent lectin receptor (Mincle). The role of Mincle for MERS-CoV-triggered cytokine/chemokine induction was established based on the results of antibody blockage, siRNA depletion of Mincle and its adaptor spleen tyrosine kinase (Syk), and Syk pharmacological inhibition. The cytokine and/or chemokine induction was significantly attenuated by siRNA depletion of retinoic acid-inducible-I-like receptors (RLR) or adaptor, indicating that RLR signaling also contributed to MERS-CoV-induced proinflammatory response. CONCLUSIONS: The CLR and RLR pathways are activated and contribute to the proinflammatory response in MERS-CoV-infected macrophages.


id: cord-339271-t7cxqkp1
title: Epidemiological and clinical characteristics of 26 asymptomatic SARS-CoV-2 carriers
author: Pan, Yanfeng
date: 2020-04-22
txt: ./txt/cord-339271-t7cxqkp1.txt
cache: ./cache/cord-339271-t7cxqkp1.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/infdis/jiaa205
doi: 10.1093/infdis/jiaa205
summary:
  The median period from diagnosis to negative nucleic acid test was significantly different between patients with normal or atypical chest computed tomography (CT) findings (n=16, 61.5%; 7.5 days [2–20 days]) and patients with typical ground-glass or patchy opacities on CT(n=10, 38.5%; 12.5 days[8–22 days]; P<0.01). Here, we identified a total of 26 persistently asymptomatic patients with positive test results for SARS-CoV-2 nucleic acid to determine the clinical characteristics and asymptomatic carrier transmission of COVID-19 infection. A total of 26 hospitalized patients with a SARS-CoV-2 epidemiological history and positive SARS-CoV-2 nucleic acid test results were identified to analyze the epidemiological and clinical characteristics of COVID-19infected asymptomatic carriers. Discharge criteria for COVID-19 were as follows: 1) normal body temperature for more than 3 days; 2) significantly improved respiratory symptoms; 3) significantly improved chest radiography; and 4) two consecutive negative SARS-CoV-2 nucleic acid test results (sampling interval at least 1 day).

abstract:
  BACKGROUND: We retrospectively analysed 26 persistently asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) carriers. METHODS: Epidemiological and clinical characteristics from the 26 asymptomatic patients with positive results for SARS-CoV-2 RNA testing were obtained. RESULTS: Twenty-two patients (84.6%) correlated with clustering occurrence. The median period from contact to diagnosis and the last positive nucleic acid test was 19 (8–24 days) and 21.5 days (10–36 days), respectively. The median period from diagnosis to negative nucleic acid test was significantly different between patients with normal or atypical chest computed tomography (CT) findings (n=16, 61.5%; 7.5 days [2–20 days]) and patients with typical ground-glass or patchy opacities on CT(n=10, 38.5%; 12.5 days[8–22 days]; P<0.01). Seven patients (70.0%) with initial positive nucleic acid test results had a negative result simultaneously with improved CT findings. Obvious improvement in CT findings was observed in three patients (30.0%) despite positive nucleic acid test results. CONCLUSION: In asymptomatic patients, changes in biochemical and inflammatory variables are small and changes on chest CT can occur. It is worth noting the long existence of SARS-CoV-2 in some asymptomatic patients and false-negative results need to be considered in SARS-CoV-2nucleic acid test.


id: cord-341548-gazsszs6
title: Infections with Viruses and Mycoplasma pneumoniae during Exacerbations of Chronic Bronchitis
author: Buscho, R. O.
date: 1978-04-17
txt: ./txt/cord-341548-gazsszs6.txt
cache: ./cache/cord-341548-gazsszs6.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/206630/
doi: 10.1093/infdis/137.4.377
summary:
  The association of viral and Mycoplasma pneumoniae infections with acute exacerbations of chronic bronchitis was studied by serologic or isolation techniques in 46 adult men during the five years from 1964 through 1968. Because of the high prevalence and morbidity of chronic bronchitis among patients of Veterans Administration Hospitals, we have conducted surveillance of one of these groups to assess the impact of respiratory tract infections on the natural course of this disease and to investigate further the occurrence and relative importance of viruses and mycoplasmas in exacerbations [3] . Evidence of viral and Mycoplasma pneumoniae infections (obtained mainly by serologic testing and to a lesser extent by isolation of organisms) was correlated with the pattern of clinical disease in patients with chronic bronchitis. pneumoniae were detected in 50 (30.1%) of 166 exacerbations of chronic bronchitis in the 46 adult patients studied (table 2) .

abstract:
  The association of viral and Mycoplasma pneumoniae infections with acute exacerbations of chronic bronchitis was studied by serologic or isolation techniques in 46 adult men during the five years from 1964 through 1968. Serologic evidence of viral or M. pneumoniae infection was detected in 25% of 166 episodes of exacerbation and 14% of 138 remission periods (P = 0.02). Influenza A virus, parainfluenza virus type 3, and coronavirus OC43 predominated; infections with other viruses were infrequent. Infection with M. pneumoniae was detected serologically in four patients, but this organism was never isolated from sputum specimens. Rhinoviruses were isolated from frozen-stored sputum specimens in 2.7% of the episodes of exacerbation and from 0.55% of the remission intervals (P not significant). These data suggest that although exacerbations of chronic bronchitis may be accompanied by viral and M. pneumoniae infections, patients with chronic bronchitis also acquire such infections without a worsening of their respiratory status.


id: cord-341667-ayl71jpc
author: Van Reeth, Kristien
date: 1998-04-17
url: https://www.ncbi.nlm.nih.gov/pubmed/9534986/
doi: 10.1086/517398
title:
  Bronchoalveolar Interferon-α, Tumor Necrosis Factor-α, Interleukin-1, and Inflammation during Acute Influenza in Pigs: A Possible Model for Humans?

abstract:
  Biologically active interferon-α, tumor necrosis factor-α (TNF-α), and interleukin-1 (IL-1) were detected in bronchoalveolar lavage (BAL) fluids of 3-week-old cesarian-derived colostrum-deprived pigs inoculated with H1N1 influenza virus. Cytokine titers and lung virus titers were significantly higher 18–24 h after inoculation than at 48–72 h after inoculation in all 4 litters of pigs examined. All three cytokines were positively correlated with a 3- to 4-fold increase in BAL cell numbers (P < .036) and with a drastic neutrophil infiltration (24%–77% of BAL cells vs. 0–1.5% in controls) (P < .001). In addition, cytokine production coincided with the onset of general and respiratory symptoms of influenza and with the development of a necrotizing bronchopneumonia. This study is the first demonstration of TNF-α and IL-1 in BAL fluids of a natural influenza virus host. It documents that pigs may be a highly valuable experimental model in human influenza virus pneumonia.


id: cord-342996-honeavwj
author: Mair-Jenkins, John
date: 2015-01-01
txt: ./txt/cord-342996-honeavwj.txt
cache: ./cache/cord-342996-honeavwj.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/25030060/
doi: 10.1093/infdis/jiu396
summary:
  title: The Effectiveness of Convalescent Plasma and Hyperimmune Immunoglobulin for the Treatment of Severe Acute Respiratory Infections of Viral Etiology: A Systematic Review and Exploratory Meta-analysis We conducted a systematic review and exploratory meta-analysis to evaluate the clinical effectiveness of convalescent plasma, serum, or hyperimmune immunoglobulin for the treatment of severe acute respiratory infections (SARIs) of viral etiology, to help inform clinical management of MERS-CoV infection. Four observational studies [24, 30, 37, 48] and 1 systematic review [22] reported data on severe cases of influenza A(H1N1)pdm09 infection treated with convalescent plasma (Table 3 and Supplementary Table 3 ). A case-comparison study at moderate risk of bias [30] reported no significant difference in length of hospital stay between treatment and control patients with severe pandemic influenza A (H1N1) infection who required ECMO ( Table 3) .

title:
  The Effectiveness of Convalescent Plasma and Hyperimmune Immunoglobulin for the Treatment of Severe Acute Respiratory Infections of Viral Etiology: A Systematic Review and Exploratory Meta-analysis

abstract:
  Background. Administration of convalescent plasma, serum, or hyperimmune immunoglobulin may be of clinical benefit for treatment of severe acute respiratory infections (SARIs) of viral etiology. We conducted a systematic review and exploratory meta-analysis to assess the overall evidence. Methods. Healthcare databases and sources of grey literature were searched in July 2013. All records were screened against the protocol eligibility criteria, using a 3-stage process. Data extraction and risk of bias assessments were undertaken. Results. We identified 32 studies of SARS coronavirus infection and severe influenza. Narrative analyses revealed consistent evidence for a reduction in mortality, especially when convalescent plasma is administered early after symptom onset. Exploratory post hoc meta-analysis showed a statistically significant reduction in the pooled odds of mortality following treatment, compared with placebo or no therapy (odds ratio, 0.25; 95% confidence interval, .14–.45; I(2) = 0%). Studies were commonly of low or very low quality, lacked control groups, and at moderate or high risk of bias. Sources of clinical and methodological heterogeneity were identified. Conclusions. Convalescent plasma may reduce mortality and appears safe. This therapy should be studied within the context of a well-designed clinical trial or other formal evaluation, including for treatment of Middle East respiratory syndrome coronavirus CoV infection.


id: cord-344271-5aynmdsk
author: de Souza Luna, Luciano Kleber
date: 2007-03-01
txt: ./txt/cord-344271-5aynmdsk.txt
cache: ./cache/cord-344271-5aynmdsk.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/17262708/
doi: 10.1086/511432
summary:
  title: Spectrum of Viruses and Atypical Bacteria in Intercontinental Air Travelers with Symptoms of Acute Respiratory Infection Using sensitive polymerase chain reactions, we studied the spectrum of atypical bacteria and respiratory viruses in travelers fulfilling the case definition of severe acute respiratory syndrome. These assays were used to determine a point prevalence of the full spectrum of respiratory viruses and atypical bacteria in SARS-compatible patients. Inf and PIV were clearly the most prevalent agents in flight patients, at 14.2% and 15.5%, respectively, without significant differences between age groups (1-way analysis of variance [ANOVA], 95% significance level). Baseline data on the prevalence of respiratory viruses and atypical bacteria after air travel are not currently available. It cannot be told whether the high prevalence and diversity of respiratory viruses seen in our study is specific to patients with recent intercontinental air travel.

title:
  Spectrum of Viruses and Atypical Bacteria in Intercontinental Air Travelers with Symptoms of Acute Respiratory Infection

abstract:
  Respiratory infections after air travel are frequent, but epidemiological data are incomplete. Using sensitive polymerase chain reactions, we studied the spectrum of atypical bacteria and respiratory viruses in travelers fulfilling the case definition of severe acute respiratory syndrome. A pathogen was identified in 67 travelers (43.2%). Influenza and parainfluenza viruses were most prevalent, at 14.2% and 15.5%, respectively. Prevalences of adenoviruses, human metapneumovirus, coronaviruses, and rhinoviruses ranged between 2.6% and 4.8%. Human bocavirus, respiratory syncytial virus, and Legionella, Mycoplasma, and Chlamydophila species were absent or appeared at frequencies of <1%. To our knowledge, these are the first specific baseline data for the mentioned agents in the context of air travel.


id: cord-344954-gpb25fga
author: Hashem, Anwar M
date: 2019-11-15
txt: ./txt/cord-344954-gpb25fga.txt
cache: ./cache/cord-344954-gpb25fga.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/infdis/jiz137
doi: 10.1093/infdis/jiz137
summary:
  title: A Highly Immunogenic, Protective, and Safe Adenovirus-Based Vaccine Expressing Middle East Respiratory Syndrome Coronavirus S1-CD40L Fusion Protein in a Transgenic Human Dipeptidyl Peptidase 4 Mouse Model Given its critical role in viral replication, the S protein has been the focus for MERS-CoV vaccine development similar to severe acute respiratory syndrome coronavirus (SARS-CoV), where it has been the main target for vaccines that led to robust induction of neutralizing antibody (nAb)-mediated protection in immunized animals [6] [7] [8] . We showed in this study that although rAd5 expressing S1 or CD40-targeted S1 were both capable of inducing significant levels of IgG and nAbs specific to MERS-CoV in immunized mice, incorporation of CD40L substantially enhances the immunogenicity of S1, as demonstrated by the effectiveness of a single immunization dose, which was sufficient to elicit stronger and robust immune responses compared to control groups, consistent with our previous reports [37, 38] .

title:
  A Highly Immunogenic, Protective, and Safe Adenovirus-Based Vaccine Expressing Middle East Respiratory Syndrome Coronavirus S1-CD40L Fusion Protein in a Transgenic Human Dipeptidyl Peptidase 4 Mouse Model

abstract:
  BACKGROUND: Infection control measures have played a major role in limiting human/camel-to-human transmission of Middle East respiratory syndrome coronavirus (MERS-CoV); however, development of effective and safe human or camel vaccines is warranted. METHODS: We extended and optimized our previous recombinant adenovirus 5 (rAd5)–based vaccine platform characterized by in vivo amplified and CD40-mediated specific responses to generate MERS-CoV S1 subunit-based vaccine. We generated rAd5 constructs expressing CD40-targeted S1 fusion protein (rAd5-S1/F/CD40L), untargeted S1 (rAd5-S1), and Green Fluorescent Protein (rAd5-GFP), and evaluated their efficacy and safety in human dipeptidyl peptidase 4 transgenic (hDPP4 Tg(+)) mice. RESULTS: Immunization of hDPP4 Tg(+) mice with a single dose of rAd5-S1/F/CD40L elicited as robust and significant specific immunoglobulin G and neutralizing antibodies as those induced with 2 doses of rAd5-S1. After MERS-CoV challenge, both vaccines conferred complete protection against morbidity and mortality, as evidenced by significantly undetectable/reduced pulmonary viral loads compared to the control group. However, rAd5-S1– but not rAd5-S1/F/CD40L–immunized mice exhibited marked pulmonary perivascular hemorrhage post–MERS-CoV challenge despite the observed protection. CONCLUSIONS: Incorporation of CD40L into rAd5-based MERS-CoV S1 vaccine targeting molecule and molecular adjuvants not only enhances immunogenicity and efficacy but also prevents inadvertent pulmonary pathology after viral challenge, thereby offering a promising strategy to enhance safety and potency of vaccines.


id: cord-345101-h0i5o0do
title: Transient lymphopenia and interstitial pneumonia with endotheliitis in SARS-CoV-2-infected macaques
author: Koo, Bon-Sang
date: 2020-08-03
txt: ./txt/cord-345101-h0i5o0do.txt
cache: ./cache/cord-345101-h0i5o0do.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32745172/
doi: 10.1093/infdis/jiaa486
summary:
  Using a reliable primate model is critical for developing therapeutic advances to treat humans infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The absence of a reliable preclinical animal model that recapitulates patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection poses a major limitation to the development of improved diagnostics and therapeutics. Studies reported that SARS-CoV-2 developed no severe clinical signs, but pulmonary pneumonia in 50% of cynomolgus macaques, recapitulating mild symptoms in humans [6] . The viral RNA was highest in the upper respiratory swab samples and lung tissues at the earliest phase of infection, and the viral antigen was present in the lungs ( Figure 1C and D) , suggesting the predominant site of the virus. Using a high viral titre administered through combined routes, virus assays, and histopathological changes suggests that both cynomolgus and rhesus macaques are permissive to infection of SARS-CoV-2 and recapitulate COVID-19-like disease in human.

abstract:
  Using a reliable primate model is critical for developing therapeutic advances to treat humans infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Here, we exposed macaques to high titres of SARS-CoV-2 via combined transmission routes. We observed acute interstitial pneumonia with endotheliitis in the lungs of all infected macaques. All macaques had a significant loss of total lymphocytes during infection, which were restored over time. These data show that SARS-CoV-2 causes a coronavirus disease 2019 (COVID-19)-like disease in macaques. This new model could investigate the interaction between SARS-CoV-2 and the immune system to test therapeutic strategies.


id: cord-345727-bcxkycjh
author: Karimata, Yosuke
date: 2018-09-15
txt: ./txt/cord-345727-bcxkycjh.txt
cache: ./cache/cord-345727-bcxkycjh.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/29733351/
doi: 10.1093/infdis/jiy261
summary:
  title: Clinical Features of Human Metapneumovirus Pneumonia in Non-Immunocompromised Patients: An Investigation of Three Long-Term Care Facility Outbreaks BACKGROUND: Several studies have reported outbreaks due to human metapneumovirus (hMPV) in long-term care facilities (LTCF) for the elderly. Even though it is usually a mild and self-limiting disease, hMPV can potentially cause severe lower respiratory infections, especially in young children, the elderly, and immunocompromised patients [3] [4] [5] [12] [13] [14] . Several studies have reported outbreaks due to hMPV in long-term care facilities (LTCF) for the elderly and described the high incidence of pneumonia [3] [4] [5] [14] [15] [16] [17] . In conclusion, we report the clinical and radiological features of hMPV pneumonia in non-immunocompromised patients collected from 3 outbreaks in LTCF in Okinawa, Japan. An outbreak of severe respiratory tract infection due to human metapneumovirus in a long-term care facility for the elderly in Oregon

title:
  Clinical Features of Human Metapneumovirus Pneumonia in Non-Immunocompromised Patients: An Investigation of Three Long-Term Care Facility Outbreaks

abstract:
  BACKGROUND: Several studies have reported outbreaks due to human metapneumovirus (hMPV) in long-term care facilities (LTCF) for the elderly. However, most of these reports are epidemiological studies and do not investigate the clinical features of hMPV pneumonia. METHODS: Three independent outbreaks of hMPV occurred at separate LTCF for intellectually challenged and elderly residents. A retrospective evaluation of hMPV pneumonia and its clinical and radiological features was conducted using available medical records and data. RESULTS: In 105 hMPV infections, 49% of patients developed pneumonia. The median age of pneumonia cases was significantly higher than non-pneumonia cases (P < .001). Clinical manifestations of hMPV pneumonia included high fever, wheezing in 43%, and respiratory failure in 31% of patients. An elevated number of white blood cells as well as increased levels of C-reactive protein, creatine phosphokinase, and both aspartate and alanine transaminases was also observed among pneumonia cases. Evaluation of chest imaging revealed proximal bronchial wall thickenings radiating outward from the hilum in most patients. CONCLUSIONS: The aforementioned characteristics should be considered as representative of hMPV pneumonia. Patients presenting with these features should have laboratory testing performed for prompt diagnosis.


id: cord-346411-d2re00r9
author: Boonyaratanakornkit, Jim
date: 2020-02-01
txt: ./txt/cord-346411-d2re00r9.txt
cache: ./cache/cord-346411-d2re00r9.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/infdis/jiz470
doi: 10.1093/infdis/jiz470
summary:
  In a small study of adults, the majority of which were HCT recipients or had a hematologic malignancy, with matched NP and BAL specimens, PCR-based NP testing for respiratory viruses in patients with clinical evidence of LRT disease had a high negative predictive value (NPV) and a lower positive predictive value (PPV) [5] . A larger study that included mostly immunocompromised patients concluded that if a pathogen (a respiratory virus or 1 of 3 bacterial pathogens detected by a multiplex PCR panel) was already identified from an NP sample, BAL testing is unlikely to provide additional information; however, a significant number (20%) of subjects had a pathogen detected in the BAL without a positive NP sample [6] . In the present study, we characterized the rates of discordance in respiratory viral detection between matched URT and LRT samples in a large cohort of HCT candidates/recipients who underwent BAL for suspected LRTI and had concomitant URT testing.

title:
  Predictive Value of Respiratory Viral Detection in the Upper Respiratory Tract for Infection of the Lower Respiratory Tract With Hematopoietic Stem Cell Transplantation

abstract:
  BACKGROUND: Hematopoietic cell transplant (HCT) recipients are frequently infected with respiratory viruses (RVs) in the upper respiratory tract (URT), but the concordance between URT and lower respiratory tract (LRT) RV detection is not well characterized. METHODS: Hematopoietic cell transplant candidates and recipients with respiratory symptoms and LRT and URT RV testing via multiplex PCR from 2009 to 2016 were included. Logistic regression models were used to analyze risk factors for LRT RV detection. RESULTS: Two-hundred thirty-five HCT candidates or recipients had URT and LRT RV testing within 3 days. Among 115 subjects (49%) positive for a RV, 37% (42 of 115) had discordant sample pairs. Forty percent (17 of 42) of discordant pairs were positive in the LRT but negative in the URT. Discordance was common for adenovirus (100%), metapneumovirus (44%), rhinovirus (34%), and parainfluenza virus type 3 (28%); respiratory syncytial virus was highly concordant (92%). Likelihood of LRT detection was increased with URT detection (oods ratio [OR] = 73.7; 95% confidence interval [CI], 26.7–204) and in cytomegalovirus-positive recipients (OR = 3.70; 95% CI, 1.30–10.0). CONCLUSIONS: High rates of discordance were observed for certain RVs. Bronchoalveolar lavage sampling may provide useful diagnostic information to guide management in symptomatic HCT candidates and recipients.


id: cord-350201-tluc2ck7
title: Zoonotic Infection With Pigeon Paramyxovirus Type 1 Linked to Fatal Pneumonia
author: Kuiken, Thijs
date: 2018-10-01
txt: ./txt/cord-350201-tluc2ck7.txt
cache: ./cache/cord-350201-tluc2ck7.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/infdis/jiy036
doi: 10.1093/infdis/jiy036
summary:
  The impetus for the current study was the identification of a virus related to avian paramyxovirus type 1 (APMV-1) from a fatal human case of unknown cause in the Netherlands by viral metagenomics analysis [8] . In this study, we fully characterized the Dutch clinical isolate of APMV-1-like virus, determined its phylogenetic relationship to other APMV-1 strains, and correlated presence of this virus with lesions in tissues obtained from the patient at autopsy. Domestic pigeons were inoculated intratracheally with the Dutch clinical virus isolate to determine infectivity and transmissibility, clinical signs, and pathological changes (Supplementary Methods). This is consistent with the New York case, where evidence of PPMV-1 infection in feces and urine also suggested extrarespiratory Pigeon Paramyxovirus-Linked Pneumonia • JID 2018:218 (1 October) • 1041 Table 1 spread [11] . It is relevant for these PPMV-1 cases that the risk of 2 pigeon-associated diseases-chlamydiosis and cryptococcosis-was largely a function of the immune status of patients, rather than contact with infected birds [32, 33] .

abstract:
  The characteristics and risk factors of pigeon paramyxovirus type 1 (PPMV-1) infection in humans are poorly known. We performed virological, pathological, and epidemiological analyses of a Dutch case, and compared the results with those of a US case. Both infections occurred in transplant patients under immunosuppressive therapy and caused fatal respiratory failure. Both virus isolates clustered with PPMV-1, which has pigeons and doves as reservoir. Experimentally inoculated pigeons became infected and transmitted the virus to naive pigeons. Both patients were likely infected by contact with infected pigeons or doves. Given the large populations of feral pigeons with PPMV-1 infection in cities, increasing urbanization, and a higher proportion of immunocompromised individuals, the risk of severe human PPMV-1 infections may increase. We recommend testing for avian paramyxovirus type 1, including PPMV-1, in respiratory disease cases where common respiratory pathogens cannot be identified.


id: cord-350302-xmyqqgn5
author: Li, Pengfei
date: 2020-08-15
txt: ./txt/cord-350302-xmyqqgn5.txt
cache: ./cache/cord-350302-xmyqqgn5.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/infdis/jiaa321
doi: 10.1093/infdis/jiaa321
abstract: nan
summary:
  title: Estimating Global Epidemiology of Low-Pathogenic Human Coronaviruses in Relation to the COVID-19 Context Studies were included and data extracted only if they reported participants with symptoms of acute respiratory tract infections or influenza like illness. Australia 74 125 30 30 149 1876 9 35 251 68 47 81 7 26 198 175 40 580 21 35 28 30 116 26 230 303 25 367 11 3 5 23 81 6 60 66 1652 48 71 20 131 80 29 18 1231 12 523 514 2277 526 561 6221 70 988 277 739 6064 1041 665 593 244 300 1910 4259 1059 7158 450 417 309 311 2060 1404 2693 3899 407 3910 172 411 114 369 2370 67 972 1528 40 150 686 1166 112 8462 372 2428 369 24 [2, 3] , our included studies only detected LPH-CoV in individuals with respiratory illness or symptoms.

title:
  Estimating Global Epidemiology of Low-Pathogenic Human Coronaviruses in Relation to the COVID-19 Context


id: cord-350737-nrtrhq1f
title: Serology of Severe Acute Respiratory Syndrome: Implications for Surveillance and Outcome
author: Chen, Xinchun
date: 2004-04-01
txt: ./txt/cord-350737-nrtrhq1f.txt
cache: ./cache/cord-350737-nrtrhq1f.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15031782/
doi: 10.1086/380397
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] .

abstract:
  Background. Severe acute respiratory syndrome (SARS) is a novel infectious disease. No information is currently available on host-specific immunity against the SARS coronavirus (CoV), and detailed characteristics of the epidemiology of SARS CoV infection have not been identified. Methods. ELISA was used to detect antibody to SARS CoV. Reverse-transcriptase polymerase chain reaction was used to detect SARS CoV RNA. T cells in peripheral blood of patients were quantified by flow cytometry. Results. Of 36 patients with probable SARS CoV infection, 30 (83.3%) were positive for IgG antibody to SARS CoV; in contrast, only 3 of 48 patients with suspected SARS CoV infection, 0 of 112 patients with fever but without SARS, and 0 of 96 healthy control individuals were positive for it. IgG antibody to SARS CoV was first detected between day 5 and day 47 after onset of illness (mean ± SD, 18.7±10.4). Conclusion. Detection of antibody to SARS CoV is useful in the diagnosis of SARS; however, at the incubation and initial phases of the illness, serological assay is of little value, because of late seroconversion in most patients.


id: cord-350749-ihkxouz8
author: Panda, Aditya K
date: 2020-07-29
txt: ./txt/cord-350749-ihkxouz8.txt
cache: ./cache/cord-350749-ihkxouz8.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32726446/
doi: 10.1093/infdis/jiaa455
abstract: nan
summary:
  title: Plasmodium falciparum Infection May Protect a Population from Severe Acute Respiratory Syndrome Coronavirus 2 Infection The authors have suggested that prior exposure of children to coronavirus OC43 offers protection against severe COVID-19 phenotype by possible crossimmunity. These observations encouraged us to investigate the possible role of Plasmodium infection on coronavirus disease 2019 (COVID-19) infection or severity. Based on these observations on Plasmodium infection and positive-strand RNA viruses, we hypothesized that there could be a possible association between malaria and SARS-CoV-2 infection. To validate our observation, we investigated the prevalence of COVID-19 in the Plasmodium falciparum-endemic area of Odisha, India, Odisha is highly endemic for P. falciparum for the last 10 years (2010-2019) from the National Vector Borne Disease Control Program and COVID-19 infection status in Odisha from the government of Odisha website (see https://health. Naturally-occurring anti-alphagalactosyl antibodies in human Plasmodium falciparum infections-a possible role for autoantibodies in malaria

title:
  Plasmodium falciparum Infection May Protect a Population from Severe Acute Respiratory Syndrome Coronavirus 2 Infection


id: cord-351571-gwtkrt5u
author: Mackay, Ian M.
date: 2013-05-01
txt: ./txt/cord-351571-gwtkrt5u.txt
cache: ./cache/cord-351571-gwtkrt5u.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/infdis/jis476
doi: 10.1093/infdis/jis476
summary:
  Human rhinovirus (HRV) infections trigger exacerbations of asthma and chronic obstructive pulmonary disease and the majority of acute respiratory illnesses (ARIs), some of which meet criteria for influenza-like illness. Nevertheless, each available majority sequence of an HRV-C type has to date represented a genetically unique, phylogenetically distinct, and globally distributed virus detected in patients with ARIs. There are specific seasonal and annual variations in respiratory virus circulation and interactions [11] [12] [13] . We sought to quantify the genetic diversity, epidemiology, and impact of HRV and enterovirus species, conjointly referred to hereafter as picornaviruses, circulating among a community cohort of preschool-aged children who provided respiratory samples over a 1-year period. Clinical features and complete genome characterization of a distinct human rhinovirus genetic cluster, probably representing a previously undetected HRV species, HRV-C, associated with acute respiratory illness in children

title:
  Community-Wide, Contemporaneous Circulation of a Broad Spectrum of Human Rhinoviruses in Healthy Australian Preschool-Aged Children During a 12-Month Period

abstract:
  Human rhinovirus (HRV) replication triggers exacerbation of asthma and causes most acute respiratory illnesses (ARIs), which may manifest as influenza-like illness. The recent assignment of 60 previously unknown HRV types to a third HRV species, Human rhinovirus C, raised questions about the prevalence of these picornavirus types in the community, the extent of HRV diversity at a single site, and whether the HRVs have an equally diverse clinical impact on their hosts. We quantified HRV diversity, and there was no clinical impact attributable to HRV species and genotypes among a community population of preschool-aged children with ARI who provided respiratory samples during 2003. All HRV species were represented among 138 children with ARI, and 74 distinct HRV types were cocirculating. Fever accompanied 32.8% of HRV-positive ARI cases. HRVs were less likely than DNA viruses to be codetected with another virus, suggesting virus interference at the community level, demonstrated by the inverse correlation between influenza virus detection and HRV detection.


id: cord-351776-otx5qwyu
author: Ibáñez-Samaniego, Luis
date: 2020-06-21
txt: ./txt/cord-351776-otx5qwyu.txt
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extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32563190/
doi: 10.1093/infdis/jiaa355
summary:
  In this study, we evaluated the association between FIB-4, a liver fibrosis index, and the risk of progression to critical illness in middle-aged patients with COVID-19. To overcome this problem, we analyzed our data in different ways: (1) we retrieved available information on blood test done within 6 months before COVID-19 diagnosis in a relatively small number of patients (15% of the total series): at the time of COVID-19 diagnosis, AST and ALT increased significantly while platelets remained stable as compared with previous values; however, there were no significant changes in FIB-4 categories; (2) we evaluated specifically the prognostic value of isolated baseline AST: in contrast to previous reports, AST was not an independent predictor either at univariate level or when adjusted by other clinical and laboratory covariates; and (3) finally, we evaluated specifically the association between the elevation of AST (ie, AST above the upper limit of normality) and the need for MV, which identified that AST elevation was an independent risk factor.

title:
  Elevation of Liver Fibrosis Index FIB-4 Is Associated With Poor Clinical Outcomes in Patients With COVID-19

abstract:
  BACKGROUND: COVID-19 is a potentially severe disease caused by the recently described SARS-CoV-2. Whether liver fibrosis might be a relevant player in the natural history of COVID-19 is currently unknown. We aimed to evaluate the association between FIB-4 and the risk of progression to critical illness in middle-aged patients with COVID-19. METHODS: In this multicenter, retrospective study with prospective follow-up of 160 patients aged 35–65 years with COVID-19, FIB-4, clinical, and biochemical variables were collected at baseline. FIB-4 ≥2.67 defined patients with risk for advanced liver fibrosis. RESULTS: Risk for advanced fibrosis was estimated in 28.1% of patients. Patients with FIB-4 ≥2.67 more frequently required mechanical ventilation (37.8% vs 18.3%; P = .009). In multivariate analysis, FIB-4 ≥2.67 (odds ratio [OR], 3.41; 95% confidence interval [CI], 1.30–8.92), cardiovascular risk factors (OR, 5.05; 95% CI, 1.90–13.39), previous respiratory diseases (OR, 4.54; 95% CI, 1.36–15.10), and C-reactive protein (OR, 1.01; 95% CI, 1.01–1.02) increased significantly the risk of ICU admission. Bootstrap confirmed FIB-4 as an independent risk factor. CONCLUSIONS: In middle-aged patients with COVID-19, FIB-4 may have a prognostic role. The link between liver fibrosis and the natural history of COVID-19 should be evaluated in future studies.


id: cord-352433-sts48u9i
title: Direct Observation of Repeated Infections With Endemic Coronaviruses
author: Galanti, Marta
date: 2020-07-07
txt: ./txt/cord-352433-sts48u9i.txt
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url: https://www.ncbi.nlm.nih.gov/pubmed/32692346/
doi: 10.1093/infdis/jiaa392
summary:
  BACKGROUND: Although the mechanisms of adaptive immunity to pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are still unknown, the immune response to the widespread endemic coronaviruses HKU1, 229E, NL63, and OC43 provide a useful reference for understanding repeat infection risk. CONCLUSIONS: This study provides evidence that reinfections with the same endemic coronavirus are not atypical in a time window shorter than 1 year and that the genetic basis of innate immune response may be a greater determinant of infection severity than immune memory acquired after a previous infection. However, in Korea, as reported by the Korean Centers for Disease Control and Prevention, viable SARS-CoV-2 was not isolated in cell culture of respiratory samples from potentially reinfected individuals [5] ; thus, these subsequent positive results may have been due to inactive genetic material detected by molecular testing.

abstract:
  BACKGROUND: Although the mechanisms of adaptive immunity to pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are still unknown, the immune response to the widespread endemic coronaviruses HKU1, 229E, NL63, and OC43 provide a useful reference for understanding repeat infection risk. METHODS: Here we used data from proactive sampling carried out in New York City from fall 2016 to spring 2018. We combined weekly nasal swab collection with self-reports of respiratory symptoms from 191 participants to investigate the profile of recurring infections with endemic coronaviruses. RESULTS: During the study, 12 individuals tested positive multiple times for the same coronavirus. We found no significant difference between the probability of testing positive at least once and the probability of a recurrence for the betacoronaviruses HKU1 and OC43 at 34 weeks after enrollment/first infection. We also found no significant association between repeat infections and symptom severity, but found strong association between symptom severity and belonging to the same family. CONCLUSIONS: This study provides evidence that reinfections with the same endemic coronavirus are not atypical in a time window shorter than 1 year and that the genetic basis of innate immune response may be a greater determinant of infection severity than immune memory acquired after a previous infection.


id: cord-352526-t8odetzw
author: Pinto, Bruna G G
date: 2020-06-11
txt: ./txt/cord-352526-t8odetzw.txt
cache: ./cache/cord-352526-t8odetzw.txt
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mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32526012/
doi: 10.1093/infdis/jiaa332
summary:
  Although angiotensin-converting enzyme 2 (ACE2) is crucial for SARS-CoV2 to bind and enter host cells, no study has systematically assessed the ACE2 expression in the lungs of patients with these diseases. Here, we analyzed over 700 lung transcriptome samples of patients with comorbidities associated with severe COVID-19 and found that ACE2 was highly expressed in these patients, compared to control individuals. Correlation and network analyses revealed many potential regulators of ACE2 in the human lung, including genes related to histone modifications, such as HAT1, HDAC2, and KDM5B. The molecular mechanism responsible for the increased disease severity in patients with these comorbidities is not fully understood, but previous studies suggest a role for angiotensin-converting enzyme 2 (ACE2) (5) . Here, we showed that the expression of the gene encoding the ACE2 receptor in lung tissue is upregulated by diseases representing comorbidities along with COVID-19.

title:
  ACE2 Expression is Increased in the Lungs of Patients with Comorbidities Associated with Severe COVID-19

abstract:
  Patients who died from COVID-19 often had comorbidities, such as hypertension, diabetes, and chronic obstructive lung disease. Although angiotensin-converting enzyme 2 (ACE2) is crucial for SARS-CoV2 to bind and enter host cells, no study has systematically assessed the ACE2 expression in the lungs of patients with these diseases. Here, we analyzed over 700 lung transcriptome samples of patients with comorbidities associated with severe COVID-19 and found that ACE2 was highly expressed in these patients, compared to control individuals. This finding suggests that patients with such comorbidities may have higher chances of developing severe COVID-19. Correlation and network analyses revealed many potential regulators of ACE2 in the human lung, including genes related to histone modifications, such as HAT1, HDAC2, and KDM5B. Our systems biology approach offers a possible explanation for increase of COVID-19 severity in patients with certain comorbidities.


id: cord-353495-c3s5n5vo
title: An Animal Model of MERS Produced by Infection of Rhesus Macaques With MERS Coronavirus
author: Yao, Yanfeng
date: 2014-01-15
txt: ./txt/cord-353495-c3s5n5vo.txt
cache: ./cache/cord-353495-c3s5n5vo.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/24218506/
doi: 10.1093/infdis/jit590
summary:
  In 2012, a novel coronavirus (CoV) associated with severe respiratory disease, Middle East respiratory syndrome (MERS-CoV; previously known as human coronavirus–Erasmus Medical Center or hCoV-EMC), emerged in the Arabian Peninsula. The infected monkeys showed clinical signs of disease, virus replication, histological lesions, and neutralizing antibody production, indicating that this monkey model is suitable for studies of MERS-CoV infection. The development of animal models for MERS-CoV infection of humans is of utmost importance to study the pathogenesis of this virus and to test the efficacy of potential therapeutic or prophylactic intervention strategies. Therefore, in the present study, we explored the suitability of the rhesus monkey as an animal model for MERS-CoV isolate human coronavirus-Erasmus Medical Center (hCoV-EMC) infection or disease. Rhesus macaques can be infected by MERS-CoV in the laboratory, but we recognize that it is necessary to search for more suitable animal model that will have similar disease presentations as that observed among those laboratoryconfirmed human cases.

abstract:
  In 2012, a novel coronavirus (CoV) associated with severe respiratory disease, Middle East respiratory syndrome (MERS-CoV; previously known as human coronavirus–Erasmus Medical Center or hCoV-EMC), emerged in the Arabian Peninsula. To date, 114 human cases of MERS-CoV have been reported, with 54 fatalities. Animal models for MERS-CoV infection of humans are needed to elucidate MERS pathogenesis and to develop vaccines and antivirals. In this study, we developed rhesus macaques as a model for MERS-CoV using intratracheal inoculation. The infected monkeys showed clinical signs of disease, virus replication, histological lesions, and neutralizing antibody production, indicating that this monkey model is suitable for studies of MERS-CoV infection.


