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  A Comparative Study of Clinical Presentation and Risk Factors for Adverse Outcome in Patients Hospitalised with Acute Respiratory Disease Due


id: cord-018449-4vdqq961
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  Hints that Cometary Debris Played some Role in Several Tree Ring Dated Environmental Downturns in the Bronze Age


id: cord-018449-4vdqq961
type: WORK_OF_ART
entity:
  the Late Bronze Age and Other Crisis Periods A Volcanic Cause Hints that Cometary Debris Played some Role in Several Tree Ring Dated Environmental Downturns in the Bronze Age Poseidon s Horses Plate Tectonics and Earthquake Storms in the


id: cord-018449-4vdqq961
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  chickenpox oral infection pneumonia hemolytic disease enteropathies cholera typhoid dysentery tetanus hookworm mumps whooping cough


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entity:
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  MERS CoV International Severe Acute Respiratory and Emerging Infection Consortium The Website for the International Severe Acute Respiratory and Emerging Infection Consortium ISARIC Global Research Collaboration for Infectious Disease Preparedness Website Emerging


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  angiotensinconverting enzyme 2 ACE2 aminopeptidase N and carcinoembryonic antigen related cell adhesion molecule 1 CEACAM1


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  Division of Infectious Disease Department of Medicine Samsung Medical Center Sungkyunkwan University School of Medicine


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  Clostridium botulinum mainly type E Tavakoli and Imani Fooladi 2011 The processing is insufficient to kill the


id: cord-017615-zjr6csla
type: LAW
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  the International Treaty on Plant Genetic Resources for Food and Agriculture International Seed Treaty


id: cord-266260-t02jngq0
type: ORG
entity:
  Saudi Arabia Conveyance Contact Investigation for Imported Middle East Respiratory Syndrome Cases Recovery


id: cord-017741-5apdhf2e
type: ORG
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  the Sources of Growth Economic Demographic and Institutional Determinants of Life Insurance Consumption


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  influenza A H7N9 virus Influenza H5 H7 virus vaccination in poultry and reduction of zoonotic infections


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  2016 17 influenza vaccine Cross Sectional survey and surveillance for influenza viruses and MERS CoV


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  lymphocyte count AST aspartate transaminase ALT alanine transaminase BUN blood urea nitrogen CRP C reactive protein LD lactate dehydrogenase Ct threshold cycle rRT


id: cord-274591-p34kk4up
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  National Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and Prevention Influenza


id: cord-275602-cog4nma0
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  interferons IFN ribavirin protease inhibitors mycophenolic acid cyclosporin A chloroquine nitazoxanide antibiotics fusion inhibitors


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  SaudiArabia EPI_ISL_512923 102 Turkey EPI_ISL_495421 103 Turkey EPI_ISL_495445 104 Turkey EPI_ISL_495433 105 Turkey EPI_ISL_429868 106 Turkey EPI_ISL_429867 107 Turkey EPI_ISL_429866 108 Turkey EPI_ISL_428712 109


id: cord-272513-umuiovrd
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  EPI_ISL_435134 122 Wuhan EPI_ISL_402123 123 Wuhan EPI_ISL_454949 124 Wuhan EPI_ISL_454948 125 Wuhan EPI_ISL_406798 126 Wuhan EPI_ISL_454951 127 Wuhan EPI_ISL_403931 Table 3 Catalogue


id: cord-272513-umuiovrd
type: WORK_OF_ART
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  Structural Modeling of SARS CoV 2 Spike Protein Reveals an Evolutionary Distinct and Proteolytically Sensitive Activation Loop


id: cord-280350-ay4cnzn5
type: ORG
entity:
  Chemical Genetics Unit Department of Microbiology Research Center of Infection and Immunology Li Kashing Faculty of Medicine the University of Hong Kong


id: cord-280350-ay4cnzn5
type: CHEMICAL
entity:
  mycophenolic acid flufenamic acid tolfenamic acid meclofenamate sodium mefenamic acid ribavirin mercaptopurine pyrimethamine emetine


id: cord-280350-ay4cnzn5
type: CHEMICAL
entity:
  glycyrrhizin baicalin reserpine aescin valinomycin niclosamide aurintricarboxylic acid mizoribine indomethacin chloroquine


id: cord-297062-dmiplvt2
type: WORK_OF_ART
entity:
  S Hussain A Alwan A Abudayah S Altayyar M Mustafa T Aldaghestani A Alghamedi A Talag or M Malik Clinical


id: cord-293505-1t3hg4wi
type: ORG
entity:
  Hospital Outbreak With Continued Circulation of Recombinant Virus Identified Transmission Dynamics of Middle East Respiratory Syndrome Coronavirus Infection


id: cord-293505-1t3hg4wi
type: LOC
entity:
  Middle East Respiratory Syndrome Infection Control and Prevention Guideline for Healthcare Facilities


id: cord-278238-w1l8h8g8
type: PROTEIN
entity:
  RBD 48 64 65 66 67 68 69 70 Those vaccines have the highest safety profile among vaccine platforms but confer variable degrees of immunogenicity


id: cord-286472-pqtem19t
type: ORG
entity:
  CDC Interim U S Guidance for Monitoring and Movement of Persons with Potential Middle East Respiratory Syndrome MERS CoV Exposure For more


id: cord-284374-sqxlnk9e
type: LOC
entity:
  Middle East Respiratory Syndrome Infection Control and Prevention Guideline for Healthcare Facilities Surveillance


id: cord-288389-z0sz1msj
type: EVENT
entity:
  the Netherlands World Health Organization Seroepidemiological Investigation of Contacts of Middle East Respiratory Syndrome Coronavirus


id: cord-288389-z0sz1msj
type: ORG
entity:
  CoV Patients World Health Organization Case Control Study to Assess Potential Risk Factors Related to Human Illness


id: cord-293403-o1i999hy
type: ORG
entity:
  OECD Forum Taiwan Council of Economic Planning and Development Taiwan Statistical Data Book World Development Indicators


id: cord-299519-hfgmmuy6
type: PROTEIN
entity:
  MERS CoV nucleocapsid protein N spike S ectodomain amino acids 1 1297 and S1 subunit amino acids 1 725 Hashem


id: cord-284581-fl2nt4ak
type: DNA
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  AlexaFlour488 conjugated anti human antibody goat 1 500 ThermoFisher Scientific were used ligand and antibody


id: cord-287886-41isp0wj
type: ORG
entity:
  Microevolution of Outbreak Associated Middle East Respiratory Syndrome Coronavirus Managing MERS CoV


id: cord-299720-f0ny4ur5
type: ORG
entity:
  Korea Ministry of Government Legislation Infectious Disease Control and Prevention Act World Health Organization Laboratory


id: cord-299720-f0ny4ur5
type: ORG
entity:
  Jeong Gu Nam Division of Respiratory Viruses Center of Infectious Disease Korea Centers for Disease Control and Prevention


id: cord-287156-3plpi6i9
type: CELL_LINE
entity:
  Pediatric Hematopoietic Stem Cell Transplant Recipients Acute otitis media and respiratory viruses Etiology of Acute Otitis Media


id: cord-287156-3plpi6i9
type: WORK_OF_ART
entity:
  The Role of Human Coronaviruses in Children Hospitalized for Acute Bronchiolitis Acute Gastroenteritis


id: cord-287156-3plpi6i9
type: ORG
entity:
  SARS CoV 2 Viral Load in Upper Respiratory Specimens of Infected Patients Characteristics of and Important Lessons From the


id: cord-287156-3plpi6i9
type: LOC
entity:
  Prevention Multisystem Inflammatory Syndrome in Children Investigation Team Multisystem Inflammatory Syndrome


id: cord-287156-3plpi6i9
type: WORK_OF_ART
entity:
  Analytical and Clinical Validation of Six Commercial Middle East Respiratory Syndrome Coronavirus RNA Detection Kits


id: cord-287156-3plpi6i9
type: ORG
entity:
  China National Clinical Research Center for Respiratory Diseases Chinese Medical Doctor Association Committee


id: cord-287156-3plpi6i9
type: ORG
entity:
  Pediatrics Chinese Non government Medical Institutions Association Committee on Pediatrics China Association of Traditional Chinese Medicine Committee on Children s Safety Medication Global Pediatric Pulmonology Alliance Diagnosis


id: cord-287156-3plpi6i9
type: DISEASE
entity:
  abnormal chest radiographic findings with bilateral infiltration one 14 3 required ventilatory support and two 28 6 required supplemental oxygen 99


id: cord-305871-w1quh4fx
type: DNA
entity:
  primer 5 0 CAAAACCTTCCCTAAGAAGGAAAAG 3 0 reverse primer 5 0 GCTCCTTTGGAGGTTCAGACAT 3 0 and probe 5 0 FAM ACAAAAGGCACCAAAAGAAGAATCAACAGACC BHQ1 3 0


id: cord-303272-1w8epdht
type: CELL_LINE
entity:
  mammalian cell lines Human betacoronavirus 2c EMC 2012 related viruses in bats Ghana and Europe Genetic characterization of betacoronavirus lineage C viruses


id: cord-303272-1w8epdht
type: DISEASE
entity:
  human coronavirus OC43 antigen One cow and one goat serum reacted with human coronavirus OC43 antigen


id: cord-306004-amv0los1
type: GPE
entity:
  Daejeon the Republic of Korea Risk Factors for Primary Middle East Respiratory Syndrome Coronavirus Illness


id: cord-306004-amv0los1
type: ORG
entity:
  Upregulated in Lungs of Smokers and Chronic Obstructive Pulmonary Disease Patients Identification of


id: cord-309621-6jj19xpr
type: ORG
entity:
  SARS Clinicopathologic Immunohistochemical and Ultrastructural Findings of a Fatal Case of Middle East Respiratory Syndrome Coronavirus Infection


id: cord-314651-e4uaw5fy
type: PROTEIN
entity:
  MERS CoV nucleoprotein NP Sino Biological Inc Beijing China neutrophil marker NIMP 14 Santa Cruz Biotechnology Paso Robles CA USA


id: cord-306923-eujbxdqi
type: GGP
entity:
  Sameera Alghamdi Mohammed G title Factors associated with recovery delay in a sample of patients diagnosed by MERS CoV rRT PCR A Saudi Arabian multicenter retrospective study date 2018 04 25 journal Influenza Other Respir Viruses DOI 10 1111 irv 12560 sha 32ffbe671caf791831bb7516b550b4b27240a5f0 doc_id 306923 cord_uid eujbxdqi BACKGROUND


id: cord-318181-xxc7vdnt
type: GGP
entity:
  Sameera Alghamdi Mohammed G title Early identification of pneumonia patients at increased risk of Middle East respiratory syndrome coronavirus


id: cord-318181-xxc7vdnt
type: GGP
entity:
  sex p 0 079 and age p 0 220 were similar in the two groups The risk of MERS CoV infection was similar in patients with and without fever p 0 267 respiratory symptoms p 0 080 or gastrointestinal symptoms p 0 382 Severe illness p 0 001 contact


id: cord-317403-1wrsuoy7
type: DNA
entity:
  B human adenovirus bocavirus human parainfluenza virus types 1 2 and 3 respiratory syncytial virus A and B human rhinovirus human metapneumovirus


id: cord-312692-jv3425w1
type: PROTEIN
entity:
  macrophage inflammatory protein 1 MIP 1 granulocyte macrophage colony stimulating factor GM CSF interleukin 1 IL 1 IL 12


id: cord-312692-jv3425w1
type: DISEASE
entity:
  respiratory syndrome coronavirus Middle East respiratory syndrome coronavirus causes multiple organ damage


id: cord-320709-2pnqpljt
type: DNA
entity:
  GCTGTCTATCGTCTGAATGGG 3 5 TTCTTGTCCGATGTCCTGAAG 3 and 5 HEX CGATGAGGC Zen ATTTTGTCTGCAAACCC IABkFQ 3 RANTES specific primers 5 AGTTGTCCTAATCACCCGAAAG 3 5 CAGAGTGTTGATGTAGTCCCG 3 and 5 FAM TGTGCCGA C Zen CCGGAGAAGAAAT IABkFQ 3 HPRT specific primers 5 AGATGGTGAAGGTCGCAAG 3 5 CCTGAAGTATTCATTATAGTCAAGGG 3 and 5 FAM ACTTTGTTGGATTTGAAATTCCAG ACAAGTTTG BHQ1


id: cord-319006-6f2sl0bp
type: ORG
entity:
  WHO Collaborating Centre for Research and Training on Viral Zoonoses Faculty of Medicine Chulalongkorn University


id: cord-318585-cp76qr9f
type: WORK_OF_ART
entity:
  Clinical Course and Outcomes of Critically Ill Patients With Middle East Respiratory Syndrome Coronavirus Infection Acute Management and Long Term Survival Among Subjects With


id: cord-318585-cp76qr9f
type: ORG
entity:
  the Japan Agency for Medical Research and Development the Japanese Society for the Promotion of Science JSPS


id: cord-332952-d5l60cgc
type: ORG
entity:
  the Coalition for Epidemic Preparedness Innovations CEPI the Korean Ministry of Food and Drug Safety


id: cord-329190-kv9n2qj3
type: GGP
entity:
  interferons IFN ribavirin lopinavir ritonavir or mycophenolate mofetil 19 22 27 28 29 30 31 However the efficacy and or safety of many of these therapies


id: cord-343302-g9vcchrh
type: WORK_OF_ART
entity:
  Characterization and Demonstration of the Value of a Lethal Mouse Model of Middle East Respiratory Syndrome Coronavirus Infection


id: cord-331228-wbd0s4fo
type: DNA
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  coronavirus human coronavirus EMC human b coronavirus 2c EMC human b coronavirus 2c England Qatar human b coronavirus 2C Jordan N3 and b coronavirus England 1


id: cord-331228-wbd0s4fo
type: PROTEIN
entity:
  transmembrane protease serine protease 2 TMPRSS2 trypsin chymotrypsin elastase thermolysin endoproteinase Lys C


id: cord-331228-wbd0s4fo
type: CHEMICAL
entity:
  amino N terminal receptor binding S1 and carboxyl C terminal membrane fusion S2 subunits The S1 S2 junction


id: cord-331228-wbd0s4fo
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  nasal mucosa oropharyngeal swabs blood conjunctiva lymph nodes gastrointestinal tract kidney heart adrenal gland liver spleen


id: cord-345046-str19r9a
type: PROTEIN
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  lactate dehydrogenase LDH 300 U liter alanine transaminase ALT 50 U Liter and aspartate aminotransferase AST 40 U


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  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-348821-2u6ki9dv
type: LOC
entity:
  Middle East Respiratory Syndrome A Comparative Study of Clinical Presentation and Risk Factors for Adverse Outcome in Patients Hospitalised with Acute Respiratory Disease Due


id: cord-354272-99vw735a
type: ORG
entity:
  Centers for Disease Control and Prevention Military Health Topics Health Readiness Armed Forces Health Surveillance


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type: CELL_LINE
entity:
  nasal turbinates lungs trachea larynx pharynx liver spleen kidney bladder urine duodenum jejunum colon rectum abomasum forestomachs prescapular lymph node retropharyngeal lymph node tracheobronchial lymph node mediastinal lymph node mesenteric lymph node medulla


id: cord-337825-ujq9mxk7
type: CHEMICAL
entity:
  colistin valrubicin icatibant bepotastine epirubicin epoprostenol vapreotide aprepitant caspofungin perphenazine prulifloxacin bictegravir nelfinavir


id: cord-349287-mwj2qby4
type: ORG
entity:
  Interim Guidelines for Collecting Handling and Testing Clinical Specimens from Patients Under Investigation


id: cord-349287-mwj2qby4
type: ORG
entity:
  the Epidemiology of MERS CoV Infection and Guidance for the Public Clinicians and Public Health Authorities Followup of Contacts of Middle East Respiratory Syndrome Coronavirus


id: cord-349287-mwj2qby4
type: DISEASE
entity:
  human herpesvirus HHV rhinoviruses HRV enteroviruses EV respiratory syncytial virus RSV parainfluenzavirus types 1 2 and 3 PIVs influenzaviruses IFVs endemic HCoVs adenoviruses AdVs metapneumovirus MPV


id: cord-331714-2qj2rrgd
type: DNA
entity:
  genome 99 6 99 0 L segment RdRp 99 9 100 0 M segment polyprotein predecessor and 99 7 100 0 S segment


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type: DNA
entity:
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entity:
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type: DISEASE
entity:
  acute diseases of the nervous system serous meningitis encephalomeningitis arachnoiditis acute encephalomyelitis


id: cord-331714-2qj2rrgd
type: CHEMICAL
entity:
  influenza A virus Orthomyxoviridae Influenza A virus Dhori virus Orthomyxoviridae Thogotovirus and Newcastle s disease virus Paromyxoviridae Avulavirus


# bib

id: cord-002070-8y24j34j
title: Infection, Replication, and Transmission of Middle East Respiratory Syndrome Coronavirus in Alpacas
author: Adney, Danielle R.
date: 2016-06-17
txt: ./txt/cord-002070-8y24j34j.txt
cache: ./cache/cord-002070-8y24j34j.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4880070/
doi: 10.3201/eid2206.160192
summary:
  Numerous investigators have reported the presence of MERS-CoV RNA or infectious virus in nasal swab specimens of dromedary camels in Saudi Arabia (3, 4, (8) (9) (10) , Qatar (5, (11) (12) (13) , Oman (14) , the United Arab Emirates (15), Nigeria (16) , and Egypt (17) . We have previously demonstrated that dromedary camels can be experimentally infected with MERS-CoV and found that mild upper respiratory tract disease associated with shedding copious amounts of virus by nasal secretions develops during the first week after infection (21) . We report characterization of an alpaca model of MERS-CoV infection in which we evaluated virus shedding and pathology, transmission by contact, and protective immunity 10 weeks after initial infection. Infectious virus was detected in nasal swab specimens from 2 of 3 alpacas co-housed with experimentally infected animals, and each of the 3 co-housed animals had neutralizing antibodies against MERS-CoV, which indicated virus transmission.

abstract:
  Middle East respiratory syndrome coronavirus is a recently emerged pathogen associated with severe human disease. Zoonotic spillover from camels appears to play a major role in transmission. Because of logistic difficulties in working with dromedaries in containment, a more manageable animal model would be desirable. We report shedding and transmission of this virus in experimentally infected alpacas (n = 3) or those infected by contact (n = 3). Infectious virus was detected in all infected animals and in 2 of 3 in-contact animals. All alpacas seroconverted and were rechallenged 70 days after the original infection. Experimentally infected animals were protected against reinfection, and those infected by contact were partially protected. Necropsy specimens from immunologically naive animals (n = 3) obtained on day 5 postinfection showed virus in the upper respiratory tract. These data demonstrate efficient virus replication and animal-to-animal transmission and indicate that alpacas might be useful surrogates for camels in laboratory studies.


id: cord-007828-c7jxj74b
title: Middle East respiratory syndrome coronavirus infection control: The missing piece?
author: Memish, Ziad A.
date: 2014-11-25
txt: ./txt/cord-007828-c7jxj74b.txt
cache: ./cache/cord-007828-c7jxj74b.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7124258/
doi: 10.1016/j.ajic.2014.08.003
abstract: nan
summary:
  Since the initial occurrence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, 1,2 the disease had caused 837 cases, with a case fatality rate of 34.7%. The World Health Organization (WHO) through its expert technical committees was prompt in developing its first infection control guidelines based on available knowledge on the new emerging virus, but it mostly drew on experience from a similar virus, severe acute respiratory syndrome coronavirus (SARS). Careful review of the recent increase in the number of cases revealed that about 25% were among HCWs. 4 Of the initial 128 recent MERS-CoV infected patients in Jeddah, Kingdom of Saudi Arabia, most (60%) were infected in the health care setting. Screening for Middle East respiratory syndrome coronavirus infection in hospital patients and their healthcare worker and family contacts: a prospective descriptive study Middle East respiratory syndrome coronavirus: a case-control study of hospitalized patients


id: cord-016451-k8m2xz0e
title: Influenza, Measles, SARS, MERS, and Smallpox
author: Chertow, Daniel S.
date: 2020-01-03
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120728/
doi: 10.1007/978-3-030-33803-9_5
abstract:
  Influenza, measles, SARS, MERS, and smallpox illnesses are caused by highly infectious viral pathogens that induce critical illness. These biologically diverse viruses enter and replicate within host cells triggering viral- and host-mediated damage that results in pneumonia and multiorgan failure in severe cases. Early case identification and strict infection control limit healthcare transmission. Vaccination allowed smallpox eradication and limits global measles and seasonal influenza mortality. While SARS-coronavirus (CoV) is no longer circulating, MERS-CoV and zoonotic influenza viruses, with pandemic potential, remain persistent threats. Supportive critical care is the mainstay of treatment for severe disease due to these viral infections.


id: cord-017615-zjr6csla
title: Food Security in an Insecure Future
author: Hillman, John R.
date: 2016-11-25
txt: ./txt/cord-017615-zjr6csla.txt
cache: ./cache/cord-017615-zjr6csla.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122219/
doi: 10.1007/978-3-319-48920-9_12
summary:
  Food security in the Middle East is directly affected by a challenging combination of ongoing destructive conflicts, a global economic downturn, widespread poverty, high population growth, corruption, intolerance, and the potentially damaging consequences of climate change. In a previous article , we considered definitions of food security in the modern era of rising global populations, discussing how food security might be attained in terms of security of water and fossil-fuel-derived energy supplies, climate change, rapid urbanisation, changing dietary trends, and modification of the natural environment leading to depleted natural resources, increasing environmental pollution, and the need to introduce modern technologies. Here, we consider potential adaptations to an insecure global future generally, and to the concerns in the Arab Middle East specifically, in the light of the economic realities of wide disparities in wealth, competition for resources, and widespread poverty in many parts of the globe, coupled to a relatively high population growth, on-going conflicts, attempted cultural genocides, potential conflicts, endemic corruption and nepotism, and epidemics of infectious diseases.

abstract:
  Food security in the Middle East is directly affected by a challenging combination of ongoing destructive conflicts, a global economic downturn, widespread poverty, high population growth, corruption, intolerance, and the potentially damaging consequences of climate change. Many Arab countries demonstrate nearly all the features of those countries classified as poor, less developed, or failing to achieve the eight Millennium Goals. Even the economies of the richer oil-exporting countries in the Region have been seriously damaged by the downturn in oil and gas prices as new sources come on stream elsewhere and demand falls as a result of renewable sources of energy becoming available.


id: cord-017731-xzfo5jjq
title: Foodborne Disease in the Middle East
author: Todd, Ewen C. D.
date: 2016-11-25
txt: ./txt/cord-017731-xzfo5jjq.txt
cache: ./cache/cord-017731-xzfo5jjq.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122377/
doi: 10.1007/978-3-319-48920-9_17
summary:
  Food safety is a concern worldwide and according to the World Health Organization, developing countries are probably more at risk of foodborne illness because many of these, including those in the Middle East, have limited disease surveillance and prevention and control strategies. Like many other parts of the developing world, foodborne disease surveillance is limited and outbreaks are most often reported through the Press but with insufficient detail to determine the etiological agents and the factors contributing to the outbreaks, leading to speculation to the cause by those interested or responsible for food prevention and control. Thus, the main foodborne disease issues are with homemade, restaurant and street food, where isolated claims of illness are followed up by inspections and possible punitive action by public health agencies responsible for food safety.

abstract:
  Food safety is a concern worldwide and according to the World Health Organization, developing countries are probably more at risk of foodborne illness because many of these, including those in the Middle East, have limited disease surveillance and prevention and control strategies. Specifically, the Middle East and North Africa (MENA) region has the third highest estimated burden of foodborne diseases per population, after the African and South-East Asia regions. However, it is difficult to determine what the burden is since little is published in peer-reviewed journals or government reports for public access. This chapter reviews 16 autonomous nations, namely, Afghanistan, Bahrain, Egypt, Iran, Iraq, Israel, Palestine, Kuwait, Lebanon, Oman, Pakistan, Qatar, Saudi Arabia (KSA), Syrian Arab Republic (Syria), United Arab Emirates (UAE) and Yemen. Countries range in size from Bahrain with 1.8 million inhabitants to Pakistan with a population of 184 million. Agriculture and local food production is much influenced by water availability for irrigation. Water shortages are most severe in the Gulf countries which rely on aquifers, desalination, and recycled waste water for most of their water supplies. This means that most food is imported which is expensive if not subsidized through petrodollars. This impacts food security which is a particular concern in countries under conflict, particularly, Syria, Yemen and Iraq. Gastrointestinal infections are frequent in this region from Salmonella Typhi and other Salmonella spp., Shigella spp., Campylobacter jejuni and C. coli, rotavirus, hepatitis A virus, parasites, and more rarely from Aeromonas, Yersinia enterocolitica, Brucella spp., and Middle East Respiratory Syndrome coronavirus (MERS-CoV). Reports indicate that children are the most susceptible and that many isolates are multidrug resistant. Chemical contamination of water supplies and crops are probably more of a concern than published reports indicate, because of widespread indiscriminate use of fertilizers, antibiotics, and pesticides, coupled with increased industrial pollution affecting the water supplies. Like many other parts of the developing world, foodborne disease surveillance is limited and outbreaks are most often reported through the Press but with insufficient detail to determine the etiological agents and the factors contributing to the outbreaks, leading to speculation to the cause by those interested or responsible for food prevention and control. However, there are some well investigated outbreaks in the region that have those details, and reveal where the shortcomings of both the establishments and the inspection systems have been. Where the causative agents are known, the kinds of pathogens are generally similar to those found in the West, e.g., Salmonella, but many outbreaks seem to have short incubation periods that point to a toxin of some kind of chemical or biological origin, but these are almost never identified. Because of sectarian warfare, residents and refugees have been given food that has made them sick and solders? have been deliberately poisoned. Research has been focused on microbial contamination of locally-sold foodstuffs and manager and employee knowledge of food safety and hygienic conditions in food preparation establishments. An innovative pilot project in Qatar is to use seawater and sunlight for raising crops through the Sahara Forest Project. All countries have some kind of food establishment inspection system, but they tend to be punitive if faults are found in management or employees on the premises rather than being used for their education for improving food safety. Restaurants may be closed down and owners and employees fined for often unspecified infringements. However, some food control agents are moving towards employee training through seminars and courses before problems occur, which is a good disease prevention strategy. Unfortunately, many of the food handlers are from Asian countries with languages other than Arabic and English, which makes effective food safety communication and training difficult. Tourists visiting popular resorts in Turkey and Egypt have suffered from foodborne illnesses, usually of unknown origin but poor hygienic conditions are blamed with law suits following, and the adverse publicity affects the long-term viability of some of these resorts. Food exports, important for local economies, have occasionally been contaminated resulting in recalls and sometimes illnesses and deaths, notably fenugreek seeds from Egypt (E. coli O104:H4), pomegranate arils from Turkey (hepatitis A virus), and tahini from Lebanon (Salmonella). Overall, in recent decades, the Middle East has made strides towards improving food safety for both residents and foreign visitors or ex-pat workers. However, within the countries there are large discrepancies in the extent of effective public health oversight including food safety and food security. Currently, almost all of the countries are involved to a greater or lesser extent in the civil wars in Syria and Yemen, or are affected through political tensions and strife in Egypt, Iraq, Iran, Israel, Palestine, Lebanon and Turkey. In addition, the current overproduction of oil on a world-wide scale has led to a rapid decrease in revenues to most Gulf states. All this points to a severe setback, and an uncertain foreseeable future for improvements in obtaining both sufficient and safe food for residents in this region.


id: cord-017741-5apdhf2e
title: South and East Asian Insurance Market Growth and Development
author: Hussels, Stephanie
date: 2007
txt: ./txt/cord-017741-5apdhf2e.txt
cache: ./cache/cord-017741-5apdhf2e.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122388/
doi: 10.1007/978-0-387-34163-7_17
summary:
  Before delving into the specific demand and supply features of the regional insurance market in South and East Asia, a preliminary statistical review of the countries considered within this chapter is listed in Table 17 .1, including 2003 data on population, gross domestic product (GDP), inflation rates, and net written insurance premiums. In summary, the growth of GDP, changes in socio-economic structures within the region, the increased awareness of the need for insurance, and the need for risk minimization highlighted by recent damaging events have lead to an increased demand for both life and non-life insurance within the South and East Asian region. The motor insurance market is one form of non-life insurance that has not been developed heavily by the South and East Asian bancassurance merchants, as it is less related to the banks'' existing products.

abstract:
  Recent economic research, notably by King and Levine (1993a, 1993b), Levine and Zervos (1998), Levine (1999), Levine, et al. (2000), and Beck, et al. (2000), indicates that financial services and its various components, including insurance and banking, have substantial potential for spreading positive externalities throughout the commercial sector of an economy. Such benefits can stem from improved access to capital by firms, better allocation of capital to investment projects, greater risk management, and enhanced portfolio diversification and liquidity for individual investors. While existing economic research shows the development of financial services is generally important for economic growth, a number of previous studies by Outreville (1990) and Ward and Zurbruegg (2000) provide empirical evidence that insurance market development in its own right can promote economic development. The importance of the insurance industry to the wider economy is seen to stem from the relative size of the insurance industry to GDP in many developed economies, the transfer of risks, and the scale of insurance companies’ financial intermediary functions.


id: cord-018354-o6pmuhd8
title: Human Security in East Asia: Assembling a Puzzle
author: Mine, Yoichi
date: 2018-12-07
txt: ./txt/cord-018354-o6pmuhd8.txt
cache: ./cache/cord-018354-o6pmuhd8.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123208/
doi: 10.1007/978-3-319-97247-3_1
summary:
  The researchers agreed to ask questions about the following three topics in the interviews: first, local perceptions of threats (the ranking of human security issues that are considered important in each country and in the East Asian region); second, the ways of (selective) acceptance of the concept of human security (the understanding of freedoms from fear, from want and to live in dignity, the strategy for combining protection and empowerment, and the understanding of preparedness for calamities, and so on); and third, the question of national sovereignty (whether to allow foreign actors to operate within the country in case of natural disasters and violent conflict, as well as whether to take action in territories of other countries in such a case).

abstract:
  This chapter describes the motivation of the research project, provides the theoretical framework of the entire book, and gives a summary of the findings of the case study chapters. In the process of diffusion of human security norms in East Asia, several features have emerged. First, East Asians have accepted a comprehensive definition of human security regarding the perception of threats. Second, East Asians tend to think that human security and state security are complementary. Third, the constituent elements of the human security norms such as freedom from fear and from want, freedom to live in dignity, protection, and empowerment are already accepted by East Asian nations. We need an extra effort to elevate human security to a full-fledged norm in the region.


id: cord-018449-4vdqq961
title: How Disease Affected the End of the Bronze Age
author: Norrie, Philip
date: 2016-06-26
txt: ./txt/cord-018449-4vdqq961.txt
cache: ./cache/cord-018449-4vdqq961.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123324/
doi: 10.1007/978-3-319-28937-3_5
summary:
  These are the real reason that the end of the Bronze Age in the Near East was called either the "catastrophe" or the "collapse" due to its short time frame of 50 years, the mass migration of the general population and the "Sea Peoples" plus the abandonment of cities such as Hattusa, the capital of the Hittite Empire c.1200 bce. Any historian trying to fi nd the cause of the end of the Bronze Age and the Hittite Empire must explain: the short time frame of approximately 50 years, when it occurred between 1200-1150 BCE ; the mass migrations not only of normal people but also of the "Sea Peoples"; and the fact that so many large cities, such as the Hittite capital Hattusa, were simply abandoned and not destroyed or occupied by raiders or invaders.

abstract:
  Dr. Norrie provides a summary of the fifteen currently accepted causes for the end of the Bronze Age in the Near East and then goes on to discuss the sixteenth reason—infectious disease epidemics. These are the real reason that the end of the Bronze Age in the Near East was called either the “catastrophe” or the “collapse” due to its short time frame of 50 years, the mass migration of the general population and the “Sea Peoples” plus the abandonment of cities such as Hattusa, the capital of the Hittite Empire c.1200 bce. The diseases most likely to cause this collapse are smallpox, bubonic plague and tularemia.


id: cord-018508-pk0ealu5
title: A Farewell to the “Sick Man of East Asia”: The Irony, Deconstruction, and Reshaping of the Metaphor
author: Hu, Yi
date: 2013-08-28
txt: ./txt/cord-018508-pk0ealu5.txt
cache: ./cache/cord-018508-pk0ealu5.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123395/
doi: 10.1007/978-3-642-39982-4_12
summary:
  From the very beginning of the war, the Chinese people and the Chinese government maintained to resort to peaceful methods when solving the Korea problem and that warnings be given to the United States about withdrawing the armed forces from Taiwan, stopping the aggression against North Korea, and solving the problem of Korea and the Far East peacefully. The metaphor of the "Sick Man of East Asia" implied physical and moral denigration to the oppressed state and its people; in addition, the world police system is to prevent, control, and eradicate what was, in their eyes, the physical diseases as well as the social "diseases" -resistance, revolts, rebels, etc. The "sick men" was turned from a metaphor to a self-portrait of and a realistic oppressive discourse to the Chinese people of the time. After the sick men awakened and began an organized resistance, however, the Western powers turned to violence (the War in North Korea) as a new parasitic means.

abstract:
  Susan Sontag revealed how a disease could be turned into a metaphor in social evolution, from merely a disease of the body to moral judgment or even political oppression. In her article “AIDS and its Metaphors” written in 1989, she offers a plan to do away with the metaphor: “With this illness, one that elicits so much guilt and shame, the effort to detach it from these meanings, these metaphors, seems particularly liberating, even consoling. But the metaphors cannot be distanced just by abstaining from them. They have to be exposed, criticized, belabored, used up” (Songtag 2003). In Sontag’s terms, “metaphor” mainly refers to the symbolic social oppression of the diseases. For example, cancer is a metaphor for the defect of the sick person in personality. While diseases were a biological phenomenon, the “metaphor” was a social one. What I would like to demonstrate here was none other than the related “political metaphor” started by the “anti-germ warfare.”


id: cord-022046-q1exf47s
title: An Overview of Middle East Respiratory Syndrome in the Middle East
author: Toosy, Arshad Haroon
date: 2018-09-28
txt: ./txt/cord-022046-q1exf47s.txt
cache: ./cache/cord-022046-q1exf47s.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7152387/
doi: 10.1016/b978-0-323-55228-8.00042-4
abstract: nan
summary:
  Middle East respiratory syndrome (MERS) is an emerging infectious zoonotic disease caused by a novel coronavirus (CoV). 4 Surveillance of DCs in KSA has shown that MERS-CoV clade B has been enzootic in the camel population in Arabia Genetic deep sequencing methods (i.e., high-throughput sequencing) have been readily available to researchers since the disease was first reported. 8 Nevertheless, given the prevalence of MERS-CoV infection in the Middle East''s DC population and due to the potential for spillover to the human population in direct contact with DCs, the development of a vaccine for use in DCs may be feasible. Middle East respiratory syndrome coronavirus (MERS-CoV): animal to human interaction Middle East respiratory syndrome coronavirus infection in dromedary camels in Saudi Arabia Detection of the Middle East respiratory syndrome coronavirus genome in an air sample originating from a camel barn owned by an infected patient


id: cord-030010-wy3kj68l
title: Feeling Asian Together: Coping With #COVIDRacism on Subtle Asian Traits
author: Abidin, Crystal
date: 2020-07-30
txt: ./txt/cord-030010-wy3kj68l.txt
cache: ./cache/cord-030010-wy3kj68l.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399569/
doi: 10.1177/2056305120948223
summary:
  In response, this article investigates how an online Asian community has utilized social media to engage in cathartic expressions, mutual care, and discursive activism amid the rise of anti-Asian racism and xenophobia during COVID-19. In this article, we reflect on our experiences as East Asian diaspora members on SAT and share our observations of meaning-making, identity-making, and community-making as East Asians collectively coping with COVID-19 aggression between January and May 2020. From propagating "quarantine trends" (e.g., homemade dalgona coffees which require the effort of whipped coffee and milk but are Instaworthy to simulate the café experience; and recommendations of Korean dramas in every genre to soothe the soul) to joking about Asian mothers'' pseudo-scientific anti-COVID remedies, SAT''s 1000+ daily posts from its 948223S MSXXX10.1177/2056305120948223Social Media <span class="symbol" cstyle="Mathematical">+</span> SocietyAbidin and Zeng research-article20202020 1 Curtin University, Australia 2 University of Zurich, Switzerland members have swiftly pivoted to reflecting on what it means to be "Asian" during the pandemic.

abstract:
  Since the onset of COVID-19, incidents of racism and xenophobia have been occurring globally, especially toward people of East Asian appearance and descent. In response, this article investigates how an online Asian community has utilized social media to engage in cathartic expressions, mutual care, and discursive activism amid the rise of anti-Asian racism and xenophobia during COVID-19. Specifically, we focus on the 1.7-million-strong Facebook group “Subtle Asian Traits” (SAT). Throughout the COVID-19 pandemic, the 1,200 new posts it publishes daily have swiftly pivoted to the everyday lived experiences of (diaspora) East Asians around the world. In this article, we reflect on our experiences as East Asian diaspora members on SAT and share our observations of meaning-making, identity-making, and community-making as East Asians collectively coping with COVID-19 aggression between January and May 2020.


id: cord-031840-k9l91unc
title: Forum: COVID-19 Dispatches
author: Lu, Li
date: 2020-09-11
txt: ./txt/cord-031840-k9l91unc.txt
cache: ./cache/cord-031840-k9l91unc.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488168/
doi: 10.1177/1532708620953190
summary:
  With death count worldwide reaching 586,000 merely 7 months after its first outbreak in China in late December 2019 and 13.6 million cases reported in 188 countries and territories as of July 2020, this ongoing pandemic has spread far beyond domain of world health problem to become an unprecedented challenge facing humanity at every level. On one hand, the eagerness to build solidarity with East Asian countries represented by Japan and South Korea might be a strategy to react to the racialization of COVID-19 as a "Chinese virus" and the demonization of China as a "public enemy" and "trouble maker" in the Euro-American political and media agenda (Viala-Gaudefroy & Lindaman, 2020). On the other hand, the rise of this East Asian imaginary centering around China''s historical and cultural bonds with Japan and South Korea has far-reaching implications for China''s geopolitical strategies beyond the COVID-19 pandemic and the realm of public health.

abstract:
  COVID-19 pandemic is the first truly global crisis in the digital age. With death count worldwide reaching 586,000 merely 7 months after its first outbreak in China in late December 2019 and 13.6 million cases reported in 188 countries and territories as of July 2020, this ongoing pandemic has spread far beyond domain of world health problem to become an unprecedented challenge facing humanity at every level. In addition to causing social and economic disruptions on a scale unseen before, it has turned the world into a site of biopolitical agon where science and reason are forced to betray their impotence against cultish thinking in the planetary endgame depicted in so many dystopian science fictions. It is in this context that this forum offers a set of modest reflections on the current impacts incurred by the COVID-19 virus. Blending ethnographic observations with theory-driven reflections, the five authors address issues made manifest by the crisis across different regions, while keeping their sight on the sociopolitical problems plaguing our life both individually and collectively. Taken together, they provide a grounded documentary for the archive that the COVID-19 virus is making us to construct.


id: cord-138656-8iyynbup
author: Furuyama, Taima N.
date: 2020-06-20
txt: ./txt/cord-138656-8iyynbup.txt
cache: ./cache/cord-138656-8iyynbup.txt
extension: .txt
mime: text/plain
url: https://arxiv.org/pdf/2006.11609v1.pdf
doi: nan
summary:
  title: Temporal data series of COVID-19 epidemics in the USA, Asia and Europe suggests a selective sweep of SARS-CoV-2 Spike D614G variant From November 2002 to May 2004, SARS-CoV-1 (Severe Acute Respiratory Syndrome caused by Coronavirus type 1) affected 26 countries worldwide, accounted 8,096 confirmed cases and 774 deaths (9.6% fatality ratio) (Drosten et al., 2003; Ksiazek et al., 2003; Lee et al., 2003; Peiris et al., 2003; Zhong et al., 2003 ; Centers for Disease Control and Prevention -Department of Health and Human Services, 2004; World Health Organization, 2004; Centers for Disease Control and Prevention, 2017) . MERS-CoV (Middle East Respiratory Syndrome caused by Coronavirus) spread to 27 countries around the globe, totalizing 2,519 confirmed cases and 866 deaths (34.4% fatality ratio) continuously since April 2012 (Zaki et al., 2012; Hijawi et al., 2013; Centers for Disease Control and Prevention, 2019; World Health Organization, 2019 , 2020b . If there is a correlation between the D614G variant prevalence and higher SARS-CoV-2 transmission, then the epidemiological data might reveal a significant correlation between D614G prevalence and the growth rate coefficients of epidemic curves globally.

title:
  Temporal data series of COVID-19 epidemics in the USA, Asia and Europe suggests a selective sweep of SARS-CoV-2 Spike D614G variant

abstract:
  The COVID-19 pandemic started in Wuhan, China, and caused the worldwide spread of the RNA virus SARS-CoV-2, the causative agent of COVID-19. Because of its mutational rate, wide geographical distribution, and host response variance this coronavirus is currently evolving into an array of strains with increasing genetic diversity. Most variants apparently have neutral effects for disease spread and symptoms severity. However, in the viral Spike protein, which is responsible for host cell attachment and invasion, an emergent variant, containing the amino acid substitution D to G in position 614 (D614G), was suggested to increase viral infection capability. To test whether this variant has epidemiological impact, the temporal distributions of the SARS-CoV-2 samples bearing D or G at position 614 were compared in the USA, Asia and Europe. The epidemiological curves were compared at early and late epidemic stages. At early stages, where containment measures were still not fully implemented, the viral variants are supposed to be unconstrained and its growth curves might approximate the free viral dynamics. Our analysis shows that the D614G prevalence and the growth rates of COVID-19 epidemic curves are correlated in the USA, Asia and Europe. Our results suggest a selective sweep that can be explained, at least in part, by a propagation advantage of this variant, in other words, that the molecular level effects of D614G have sufficient impact on population transmission dynamics as to be detected by differences in rate coefficients of epidemic growth curves.


id: cord-252222-wyamc46k
title: Middle East respiratory syndrome
author: Leung, Chi Hung Czarina
date: 2014-05-13
txt: ./txt/cord-252222-wyamc46k.txt
cache: ./cache/cord-252222-wyamc46k.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/24818865/
doi: 10.1007/s00134-014-3303-y
abstract: nan
summary:
  Middle East respiratory syndrome (MERS) is due to RNA betacoronavirus (MERS-CoV) infection. The apparent epidemiology may be biased by selective reporting of more severe cases and the small total number of patients makes it susceptible to distortion by individual outbreaks. Clinical suspicion, therefore, depends on vigilance and, for the present time, on a history of travel to the Middle East or contact with a patient with respiratory disease and an appropriate travel history [11] . Middle East respiratory syndrome coronavirus: quantification of the extent of the epidemic, surveillance biases, and transmissibility Interhuman transmissibility of Middle East respiratory syndrome coronavirus: estimation of pandemic risk Emerging human Middle East respiratory syndrome coronavirus causes widespread infection and alveolar damage in human lungs Clinical features and virological analysis of a case of Middle East respiratory syndrome coronavirus infection Ribavirin and interferon therapy in patients infected with the Middle East respiratory syndrome coronavirus: an observational study


id: cord-252332-1aqi47jg
title: HIS Middle East Infection Prevention Summit 2015
author: Gray, J. W.
date: 2015-11-30
txt: ./txt/cord-252332-1aqi47jg.txt
cache: ./cache/cord-252332-1aqi47jg.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0195670115003047
doi: 10.1016/j.jhin.2015.08.001
abstract: nan
summary:
  key: cord-252332-1aqi47jg title: HIS Middle East Infection Prevention Summit 2015 cord_uid: 1aqi47jg In June 2015 the Healthcare Infection Society held a twoday Middle East Infection Prevention Summit with the aim of uniting colleagues across the globe in driving down infection rates and improving infection prevention and control practice. In many ways the Middle East is a microcosm for the challenges in infection prevention and control across the world. Two of the themes of the conference that have particular international relevance are the huge challenges presented by multidrug-resistant Gram-negative bacteria in Middle Eastern hospitals, and local experience with Middle East respiratory syndrome coronavirus (MERS-CoV). Middle East respiratory syndrome coronavirus (MERS-CoV); what lessons can we learn? The inaugural Healthcare Infection Society Middle East Summit: a local perspective The inaugural Healthcare Infection Society Middle East Summit: ''No action today.


id: cord-252883-1ub01j2x
title: Focus on Middle East respiratory syndrome coronavirus (MERS-CoV)
author: Bleibtreu, A.
date: 2019-11-11
txt: ./txt/cord-252883-1ub01j2x.txt
cache: ./cache/cord-252883-1ub01j2x.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0399077X19310546
doi: 10.1016/j.medmal.2019.10.004
summary:
  Since the first case of human infection by the Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia in June 2012, more than 2260 cases of confirmed MERS-CoV infection and 803 related deaths have been reported since the 16th of October 2018. The first case of infection attributed to Middle East respiratory syndrome coronavirus (MERS-CoV) was detected in Saudi Arabia in June 2012 [1] . Despite these viruses being identified in several reports as causing lower respiratory tract infections, it was generally accepted that coronaviruses were of low pathogenicity until the emergence of SARS-CoV (Severe Acute Respiratory Syndrome Coronavirus) in 2002, a virus with a fatality rate estimated at 10%. Very shortly afterwards, in September 2012, a second patient was admitted to hospital in the United Kingdom for severe respiratory infection related to a novel coronavirus following travel to the Middle East. Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission

abstract:
  Since the first case of human infection by the Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia in June 2012, more than 2260 cases of confirmed MERS-CoV infection and 803 related deaths have been reported since the 16th of October 2018. The vast majority of these cases (71%) were reported in Saudi Arabia but the epidemic has now spread to 27 countries and has not ceased 6 years later, unlike SARS-CoV that disappeared a little less than 2 years after emerging. Due to the high fatality rate observed in MERS-CoV infected patients (36%), much effort has been put into understanding the origin and pathophysiology of this novel coronavirus to prevent it from becoming endemic in humans. This review focuses in particular on the origin, epidemiology and clinical manifestations of MERS-CoV, as well as the diagnosis and treatment of infected patients. The experience gained over recent years on how to manage the different risks related to this kind of epidemic will be key to being prepared for future outbreaks of communicable disease.


id: cord-255488-nvgz53su
title: Development of a Mouse-Adapted MERS Coronavirus
author: Li, Kun
date: 2019-09-14
txt: ./txt/cord-255488-nvgz53su.txt
cache: ./cache/cord-255488-nvgz53su.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/978-1-0716-0211-9_13
doi: 10.1007/978-1-0716-0211-9_13
summary:
  An animal model that supports MERS-CoV infection and causes severe lung disease is useful to study pathogenesis and evaluate therapies and vaccines. To generate a mouse model with associated morbidity and mortality from respiratory disease, we serially passaged HCoV-EMC/2012 strain in the lungs of young hDPP4 KI mice. Alternative strategies for the creation of mouse models of MERS-CoV infection are generation of DPP4 humanized mice and adaptation of the virus to the animals. Similarly, our human DPP4 knock-in mouse model supported MERS-CoV replication but did not lead to a severe lung disease phenotype [33] . Generation of a transgenic mouse model of Middle East respiratory syndrome coronavirus infection and disease Middle East respiratory syndrome coronavirus causes multiple organ damage and lethal disease in mice transgenic for human dipeptidyl peptidase 4 Mouse-adapted MERS coronavirus causes lethal lung disease in human DPP4 knockin mice

abstract:
  First identified in 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel virus that can cause acute respiratory distress syndrome (ARDS), multiorgan failure, and death, with a case fatality rate of ~35%. An animal model that supports MERS-CoV infection and causes severe lung disease is useful to study pathogenesis and evaluate therapies and vaccines. The murine dipeptidyl peptidase 4 (Dpp4) protein is not a functional receptor for MERS-CoV; thus, mice are resistant to MERS-CoV infection. We generated human DPP4 knock-in (hDPP4 KI) mice by replacing exons 10–12 at the mouse Dpp4 locus with exons 10–12 from the human DPP4 gene. The resultant human DPP4 KI mice are permissive to MERS-CoV (HCoV-EMC/2012 strain) infection but develop no disease. To generate a mouse model with associated morbidity and mortality from respiratory disease, we serially passaged HCoV-EMC/2012 strain in the lungs of young hDPP4 KI mice. After 30 in vivo passages, an adapted virus clone was isolated and designated MERS(MA)6.1.2. This virus clone produced significantly higher titers than the parental clone in the lungs of hDPP4 KI mice and caused diffuse lung injury and a fatal respiratory infection. In this chapter, we will describe in detail the procedures used to mouse adapt MERS-CoV by serial passage of the virus in lungs. We also describe the methods used to isolate virus clones and characterize virus infection.


id: cord-256784-wfaqim7d
title: MERS-CoV vaccine candidates in development: The current landscape
author: Modjarrad, Kayvon
date: 2016-06-03
txt: ./txt/cord-256784-wfaqim7d.txt
cache: ./cache/cord-256784-wfaqim7d.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/27083424/
doi: 10.1016/j.vaccine.2016.03.104
summary:
  Middle East Respiratory Syndrome (MERS-CoV) was first isolated in September 2012 from a patient in Saudi Arabia who presented two months earlier with severe acute respiratory infection and acute renal failure [1] . Middle East respiratory syndrome coronavirus infection in dromedary camels in Saudi Arabia A truncated receptor-binding domain of MERS-CoV spike protein potently inhibits MERS-CoV infection and induces strong neutralizing antibody responses: implication for developing therapeutics and vaccines Effects of human anti-spike protein receptor binding domain antibodies on severe acute respiratory syndrome coronavirus neutralization escape and fitness Middle East respiratory syndrome coronavirus spike protein delivered by modified vaccinia virus Ankara efficiently induces virus-neutralizing antibodies Systemic and mucosal immunity in mice elicited by a single immunization with human adenovirus type 5 or 41 vector-based vaccines carrying the spike protein of Middle East respiratory syndrome coronavirus Exceptionally potent neutralization of Middle East respiratory syndrome coronavirus by human monoclonal antibodies

abstract:
  Middle East respiratory syndrome coronavirus (MERS-CoV), an emerging infectious disease of growing global importance, has caused severe acute respiratory disease in more than 1600 people, resulting in more than 600 deaths. The high case fatality rate, growing geographic distribution and vaguely defined epidemiology of MERS-CoV have created an urgent need for effective public health countermeasures, paramount of which is an effective means of prevention through a vaccine or antibody prophylaxis. Despite the relatively few number of cases to-date, research and development of MERS-CoV vaccine candidates is advancing quickly. This review surveys the landscape of these efforts across multiple groups in academia, government and industry.


id: cord-256806-g42n51n9
author: Khudhair, Ahmed
date: 2019-05-17
txt: ./txt/cord-256806-g42n51n9.txt
cache: ./cache/cord-256806-g42n51n9.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/31002068/
doi: 10.3201/eid2505.181728
summary:
  title: Risk Factors for MERS-CoV Seropositivity among Animal Market and Slaughterhouse Workers, Abu Dhabi, United Arab Emirates, 2014–2017 Camel contact is a recognized risk factor for Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Our study aimed to identify risk factors for MERS-CoV seropositivity among live-animal market and slaughterhouse workers. The survey consisted of questions covering worker demographics; occupational history; contact with various animal species; travel history; medical history; consumption of raw camel milk, raw camel meat, and camel urine; specific tasks performed with camels; types of personal protective equipment (PPE) worn; and handwashing practices (Appendix 1, https://wwwnc.cdc.gov/EID/article/25/5/18-1728-App1.pdf). Our study investigated risk factors for MERS-CoV seropositivity in animal market and slaughterhouse workers at a site previously associated with zoonotic transmission of MERS-CoV. Among market workers, handling live camels and either administering medications to camels or cleaning equipment were practices associated with significantly increased risk for MERS-CoV seropositivity.

title:
  Risk Factors for MERS-CoV Seropositivity among Animal Market and Slaughterhouse Workers, Abu Dhabi, United Arab Emirates, 2014–2017

abstract:
  Camel contact is a recognized risk factor for Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Because specific camel exposures associated with MERS-CoV seropositivity are not fully understood, we investigated worker–camel interactions and MERS-CoV seroprevalence. We assessed worker seroprevalence in 2 slaughterhouses and 1 live-animal market in Abu Dhabi, United Arab Emirates, during 2014–2017 and administered an epidemiologic survey in 2016 and 2017. Across 3 sampling rounds during 2014–2017, we sampled 100–235 workers, and 6%–19% were seropositive for MERS-CoV at each sampling round. One (1.4%) of 70 seronegative workers tested at multiple rounds seroconverted. On multivariable analyses, working as a camel salesman, handling live camels or their waste, and having diabetes were associated with seropositivity among all workers, whereas handling live camels and either administering medications or cleaning equipment was associated with seropositivity among market workers. Characterization of high-risk exposures is critical for implementation of preventive measures.


id: cord-259051-6kuh4njb
author: Elkholy, Amgad A.
date: 2019-05-02
txt: ./txt/cord-259051-6kuh4njb.txt
cache: ./cache/cord-259051-6kuh4njb.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.jiph.2019.04.011
doi: 10.1016/j.jiph.2019.04.011
summary:
  title: MERS-CoV infection among healthcare workers and risk factors for death: Retrospective analysis of all laboratory-confirmed cases reported to WHO from 2012 to 2 June 2018 BACKGROUND: Approximately half of the reported laboratory-confirmed infections of Middle East respiratory syndrome coronavirus (MERS-CoV) have occurred in healthcare settings, and healthcare workers constitute over one third of all secondary infections. This study aimed to describe secondary cases of MERS-CoV infection among healthcare workers and to identify risk factors for death. METHODS: A retrospective analysis was conducted on epidemiological data of laboratory-confirmed MERS-CoV cases reported to the World Health Organization from September 2012 to 2 June 2018. In this study, we use the epidemiological data of all MERS cases reported to date to WHO to describe secondary cases of MERS-CoV infection among healthcare workers and to identify the risk factors for death among healthcare workers with secondary infection.

title:
  MERS-CoV infection among healthcare workers and risk factors for death: Retrospective analysis of all laboratory-confirmed cases reported to WHO from 2012 to 2 June 2018

abstract:
  BACKGROUND: Approximately half of the reported laboratory-confirmed infections of Middle East respiratory syndrome coronavirus (MERS-CoV) have occurred in healthcare settings, and healthcare workers constitute over one third of all secondary infections. This study aimed to describe secondary cases of MERS-CoV infection among healthcare workers and to identify risk factors for death. METHODS: A retrospective analysis was conducted on epidemiological data of laboratory-confirmed MERS-CoV cases reported to the World Health Organization from September 2012 to 2 June 2018. We compared all secondary cases among healthcare workers with secondary cases among non-healthcare workers. Multivariable logistic regression identified risk factors for death. RESULTS: Of the 2223 laboratory-confirmed MERS-CoV cases reported to WHO, 415 were healthcare workers and 1783 were non-healthcare workers. Compared with non-healthcare workers cases, healthcare workers cases were younger (P < 0.001), more likely to be female (P < 0.001), non-nationals (P < 0.001) and asymptomatic (P < 0.001), and have fewer comorbidities (P < 0.001) and higher rates of survival (P < 0.001). Year of infection (2013–2018) and having no comorbidities were independent protective factors against death among secondary healthcare workers cases. CONCLUSION: Being able to protect healthcare workers from high threat respiratory pathogens, such as MERS-CoV is important for being able to reduce secondary transmission of MERS-CoV in healthcare-associated outbreaks. By extension, reducing infection in healthcare workers improves continuity of care for all patients within healthcare facilities.


id: cord-259703-9ef3u2mz
title: Infection with Middle East respiratory syndrome coronavirus.
author: Alsolamy, Sami
date: 2015
txt: ./txt/cord-259703-9ef3u2mz.txt
cache: ./cache/cord-259703-9ef3u2mz.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/26566382/
doi: nan
abstract: nan
summary:
  T he Middle East respiratory syndrome coronavirus (MERS-CoV) was first recognized as a new febrile respiratory illness in Saudi Arabia in June 2012. Middle East respiratory syndrome coronavirus (MERS-CoV) -Saudi Arabia: Disease outbreak news Family cluster of Middle East respiratory syndrome coronavirus infections Presence of Middle East respiratory syndrome coronavirus antibodies in Saudi Arabia: A nationwide, cross-sectional, serological study Clinical features and viral diagnosis of two cases of infection with Middle East respiratory syndrome coronavirus: A report of nosocomial transmission Association of higher MERS-CoV virus load with severe disease and death, Saudi Arabia Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection Clinical management of severe acute respiratory infection when Middle East respiratory syndrome coronavirus (MERS-CoV) infection is suspected -Interim guidance Repurposing of clinically developed drugs for treatment of middle East respiratory syndrome coronavirus infection Infection Prevention and Control Recommendations for Hospitalized Patients with Middle East Respiratory Syndrome Coronavirus (MERS-CoV).


id: cord-260518-mswb3q67
author: Zumla, Alimuddin
date: 2016-06-15
txt: ./txt/cord-260518-mswb3q67.txt
cache: ./cache/cord-260518-mswb3q67.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S1201971216310967
doi: 10.1016/j.ijid.2016.06.012
summary:
  Since the Kingdom of Saudi Arabia is host to millions of pilgrims each year travelling from all continents, 29 tackling the threat of MERS and other infectious diseases with epidemic potential will require enhanced closer cooperation between those who provide human health, animal health, and environmental health services, locally, nationally, regionally, and internationally: the Middle Eastern, European, African, Asian, and American governments, veterinary groups, the WHO, the Food and Agriculture Organization (FAO), the African Union, the United Nations International Children''s Emergency Fund (UNICEF), The World Bank, Office International des Epizooties (OIE), CDC, Public Health England, the newly formed Africa CDC, and funding agencies among others. The persistence of MERS-CoV 4 years since its first discovery has created major opportunities for each of the Middle Eastern and African countries to take leadership of the ''One Health'' approach with a view to bringing this under regional and global umbrellas, to tackle new emerging and re-emerging infectious diseases with epidemic potential.

title:
  Taking forward a ‘One Health’ approach for turning the tide against the Middle East respiratory syndrome coronavirus and other zoonotic pathogens with epidemic potential

abstract:
  The appearance of novel pathogens of humans with epidemic potential and high mortality rates have threatened global health security for centuries. Over the past few decades new zoonotic infectious diseases of humans caused by pathogens arising from animal reservoirs have included West Nile virus, Yellow fever virus, Ebola virus, Nipah virus, Lassa Fever virus, Hanta virus, Dengue fever virus, Rift Valley fever virus, Crimean-Congo haemorrhagic fever virus, severe acute respiratory syndrome coronavirus, highly pathogenic avian influenza viruses, Middle East Respiratory Syndrome Coronavirus, and Zika virus. The recent Ebola Virus Disease epidemic in West Africa and the ongoing Zika Virus outbreak in South America highlight the urgent need for local, regional and international public health systems to be be more coordinated and better prepared. The One Health concept focuses on the relationship and interconnectedness between Humans, Animals and the Environment, and recognizes that the health and wellbeing of humans is intimately connected to the health of animals and their environment (and vice versa). Critical to the establishment of a One Health platform is the creation of a multidisciplinary team with a range of expertise including public health officers, physicians, veterinarians, animal husbandry specialists, agriculturalists, ecologists, vector biologists, viral phylogeneticists, and researchers to co-operate, collaborate to learn more about zoonotic spread between animals, humans and the environment and to monitor, respond to and prevent major outbreaks. We discuss the unique opportunities for Middle Eastern and African stakeholders to take leadership in building equitable and effective partnerships with all stakeholders involved in human and health systems to take forward a ‘One Health’ approach to control such zoonotic pathogens with epidemic potential.


id: cord-262542-vevsgkp6
author: Alharbi, Naif Khalaf
date: 2017-06-27
txt: ./txt/cord-262542-vevsgkp6.txt
cache: ./cache/cord-262542-vevsgkp6.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0264410X17306564
doi: 10.1016/j.vaccine.2017.05.032
summary:
  title: ChAdOx1 and MVA based vaccine candidates against MERS-CoV elicit neutralising antibodies and cellular immune responses in mice A single dose of ChAdOx1 MERS with tPA elicited cellular immune responses as well as neutralising antibodies that were boosted to a significantly higher level by MVA MERS. Here, we report development of MERS-CoV vaccine candidates that are based on two different viral vectors: Chimpanzee Adenovirus, Oxford University #1 (ChAdOx1) [26] and Modified Vaccinia virus Ankara (MVA) [27, 28] . Previously, we reported the ability of the strong early F11 promoter to enhance cellular immunogenicity of vaccine antigen candidates for malaria and influenza, as compared to utilising p7.5 or mH5 early/late promoters which resulted in a lower level of gene expression immediately after virus infection of target cells, but higher levels at a later stage [31] .

title:
  ChAdOx1 and MVA based vaccine candidates against MERS-CoV elicit neutralising antibodies and cellular immune responses in mice

abstract:
  Abstract The Middle East respiratory syndrome coronavirus (MERS-CoV) has infected more than 1900 humans, since 2012. The syndrome ranges from asymptomatic and mild cases to severe pneumonia and death. The virus is believed to be circulating in dromedary camels without notable symptoms since the 1980s. Therefore, dromedary camels are considered the only animal source of infection. Neither antiviral drugs nor vaccines are approved for veterinary or medical use despite active research on this area. Here, we developed four vaccine candidates against MERS-CoV based on ChAdOx1 and MVA viral vectors, two candidates per vector. All vaccines contained the full-length spike gene of MERS-CoV; ChAdOx1 MERS vaccines were produced with or without the leader sequence of the human tissue plasminogen activator gene (tPA) where MVA MERS vaccines were produced with tPA, but either the mH5 or F11 promoter driving expression of the spike gene. All vaccine candidates were evaluated in a mouse model in prime only or prime-boost regimens. ChAdOx1 MERS with tPA induced higher neutralising antibodies than ChAdOx1 MERS without tPA. A single dose of ChAdOx1 MERS with tPA elicited cellular immune responses as well as neutralising antibodies that were boosted to a significantly higher level by MVA MERS. The humoral immunogenicity of a single dose of ChAdOx1 MERS with tPA was equivalent to two doses of MVA MERS (also with tPA). MVA MERS with mH5 or F11 promoter induced similar antibody levels; however, F11 promoter enhanced the cellular immunogenicity of MVA MERS to significantly higher magnitudes. In conclusion, our study showed that MERS-CoV vaccine candidates could be optimized by utilising different viral vectors, various genetic designs of the vectors, or different regimens to increase immunogenicity. ChAdOx1 and MVA vectored vaccines have been safely evaluated in camels and humans and these MERS vaccine candidates should now be tested in camels and in clinical trials.


id: cord-263016-28znb322
title: Middle East respiratory syndrome coronavirus (MERS-CoV): what lessons can we learn?
author: Omrani, A.S.
date: 2015-08-22
txt: ./txt/cord-263016-28znb322.txt
cache: ./cache/cord-263016-28znb322.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/26452615/
doi: 10.1016/j.jhin.2015.08.002
summary:
  Infection prevention/control and management guidelines for patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection Infection prevention and control guidelines for patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection Revised interim case definition for reporting to WHO e Middle East respiratory syndrome coronavirus (MERS-CoV) Revised interim case definition for reporting to WHO e Middle East respiratory syndrome coronavirus (MERS-CoV) Investigation of cases of human infection with Middle East respiratory syndrome coronavirus (MERS-CoV); interim guidance updated 3 Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels Middle East respiratory syndrome coronavirus infection in dromedary camels in Saudi Arabia Investigation of an imported case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in

abstract:
  The Middle East Respiratory Coronavirus (MERS-CoV) was first isolated from a patient who died with severe pneumonia in June 2012. As of 19 June 2015, a total of 1,338 MERS-CoV infections have been notified to the World Health Organization (WHO). Clinical illness associated with MERS-CoV ranges from mild upper respiratory symptoms to rapidly progressive pneumonia and multi-organ failure. A significant proportion of patients present with non-respiratory symptoms such as headache, myalgia, vomiting and diarrhoea. A few potential therapeutic agents have been identified but none have been conclusively shown to be clinically effective. Human to human transmission is well documented, but the epidemic potential of MERS-CoV remains limited at present. Healthcare-associated clusters of MERS-CoV have been responsible for the majority of reported cases. The largest outbreaks have been driven by delayed diagnosis, overcrowding and poor infection control practices. However, chains of MERS-CoV transmission can be readily interrupted with implementation of appropriate control measures. As with any emerging infectious disease, guidelines for MERS-CoV case identification and surveillance evolved as new data became available. Sound clinical judgment is required to identify unusual presentations and trigger appropriate control precautions. Evidence from multiple sources implicates dromedary camels as natural hosts of MERS-CoV. Camel to human transmission has been demonstrated, but the exact mechanism of infection remains uncertain. The ubiquitously available social media have facilitated communication and networking amongst healthcare professionals and eventually proved to be important channels for presenting the public with factual material, timely updates and relevant advice.


id: cord-263042-qdmunb9l
author: Zhao, Yongkun
date: 2016-11-24
txt: ./txt/cord-263042-qdmunb9l.txt
cache: ./cache/cord-263042-qdmunb9l.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0166354216303928
doi: 10.1016/j.antiviral.2016.11.016
summary:
  Passive transfer of equine immune antibodies significantly reduced virus titers and accelerated virus clearance from the lungs of MERS-CoV infected mice. Our data show that horses immunized with MERS-CoV VLPs can serve as a primary source of protective F(ab'')(2) for potential use in the prophylactic or therapeutic treatment of exposed or infected patients. Several research groups have developed and produced anti-MERS patientderived or humanized monoclonal neutralizing antibodies in vitro that were able to protect MERS-CoV infected mice (Corti et al., 2015; Li et al., 2015; Zhao et al., 2014) . Prophylactic or therapeutic treatment of MERS-CoV infected mice with either IgG or F(ab'') 2 significantly decreased the virus load in their lungs. In both prophylactic and therapeutic settings, passive transfer of equine immune antibodies resulted in a 2e4 log reduction of virus titers in the lungs of MERS-CoV infected mice, and accelerated virus clearance in the serum treated group (Fig. 5A, B) .

title:
  Passive immunotherapy for Middle East Respiratory Syndrome coronavirus infection with equine immunoglobulin or immunoglobulin fragments in a mouse model

abstract:
  Middle East Respiratory Syndrome (MERS) is a highly lethal pulmonary infection caused by a coronavirus (CoV), MERS-CoV. With the continuing spread of MERS-CoV, prophylactic and therapeutic treatments are urgently needed. In this study, we prepared purified equine F(ab’)(2) from horses immunized with MERS-CoV virus-like particles (VLPs) expressing MERS-CoV S, M and E proteins. Both IgG and F(ab’)(2) efficiently neutralized MERS-CoV replication in tissue culture. Passive transfer of equine immune antibodies significantly reduced virus titers and accelerated virus clearance from the lungs of MERS-CoV infected mice. Our data show that horses immunized with MERS-CoV VLPs can serve as a primary source of protective F(ab’)(2) for potential use in the prophylactic or therapeutic treatment of exposed or infected patients.


id: cord-263508-row2mn17
title: The emerging novel Middle East respiratory syndrome coronavirus: The “knowns” and “unknowns”
author: Chan, Jasper Fuk-Woo
date: 2013-07-21
txt: ./txt/cord-263508-row2mn17.txt
cache: ./cache/cord-263508-row2mn17.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0929664613001770
doi: 10.1016/j.jfma.2013.05.010
summary:
  Ten years after the devastating epidemic of severe acute respiratory syndrome (SARS) caused by SARS coronavirus (SARS-CoV), which resulted in a total of 774 deaths among more than 8000 confirmed cases in over 30 countries, the world is facing a new challenge posted by a "SARS-like" infection caused by another novel coronavirus emerging from the Middle East, which was originally named human coronavirus EMC/2012 (HCoV-EMC) and recently renamed by the Coronavirus Study Group of the International Committee for Taxonomy of Viruses as Middle East respiratory syndrome coronavirus (MERS-CoV). 6,7,10e14 Although the number of laboratory-confirmed cases remains limited, the severe clinical manifestations with an unusually high mortality rate of over 50%, the spread of the infection beyond the geographical confinement in the Middle East, and the epidemiological evidence of human-to-human transmission arising from the recent clusters of cases in a family in the United Kingdom (Cases 10 to 12), and in hospitals in KSA (Cases 18 to 30, 32 and 33) and France (Cases 31 and 34), have raised significant concerns on the possible emergence of another SARS-like epidemic in the near future.

abstract:
  A novel lineage C betacoronavirus, originally named human coronavirus EMC/2012 (HCoV-EMC) and recently renamed Middle East respiratory syndrome coronavirus (MERS-CoV), that is phylogenetically closely related to Tylonycteris bat coronavirus HKU4 and Pipistrellus bat coronavirus HKU5, which we discovered in 2007 from bats in Hong Kong, has recently emerged in the Middle East to cause a severe acute respiratory syndrome (SARS)-like infection in humans. The first laboratory-confirmed case, which involved a 60-year-old man from Bisha, the Kingdom of Saudi Arabia (KSA), who died of rapidly progressive community-acquired pneumonia and acute renal failure, was announced by the World Health Organization (WHO) on September 23, 2012. Since then, a total of 70 cases, including 39 fatalities, have been reported in the Middle East and Europe. Recent clusters involving epidemiologically-linked household contacts and hospital contacts in the Middle East, Europe, and Africa strongly suggested possible human-to-human transmission. Clinical and laboratory research data generated in the past few months have provided new insights into the possible animal reservoirs, transmissibility, and virulence of MERS-CoV, and the optimal laboratory diagnostic options and potential antiviral targets for MERS-CoV-associated infection.


id: cord-264901-w285on4x
title: The risk factors associated with MERS-CoV patient fatality: A global survey
author: Ahmadzadeh, Jamal
date: 2019-07-31
txt: ./txt/cord-264901-w285on4x.txt
cache: ./cache/cord-264901-w285on4x.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0732889318307387
doi: 10.1016/j.diagmicrobio.2019.114876
summary:
  Risk factors associated with Middle East respiratory syndrome coronavirus (MERS-CoV) infection outcome were established by analyses of WHO data from September 23, 2012 to 18 June 2018. For this study, we used the publicly available World Health Organization (WHO) MERS global epidemiologic data (World Health Organization 2019) to assess characteristics, clinical information, global distribution status, and probable risk factors associated with MERS-CoV patient mortality. In this worldwide comprehensive survey, were analyzed publicly available data from the WHO website:(http://www.who.int/csr/don/ archive/disease/coronavirus_infections/en/) related to laboratory-confirmed MERS-CoV cases from September 23, 2012 until June 18, 2018. The current study focuses on the epidemiological trend of MERS-CoV infection and mortality rate analysis of its worldwide cases in the aforementioned dates. Therefore, it might be more appropriate to conduct further large-scale epidemiological studies with complete data related to all morbid cases of MERS to obtain a better understanding of MERS-CoV emergence in humans and also associated risk factors related of this infection.

abstract:
  Risk factors associated with Middle East respiratory syndrome coronavirus (MERS-CoV) infection outcome were established by analyses of WHO data from September 23, 2012 to 18 June 2018. Of the 2220 reported cases, 1408 cases, including 451 MERS-CoV deaths, were analyzed. The case fatality rate was 32% (95% CI: 29.4–34.5). Compared to MERS patients ≤30 years old, those with >30 years had the adjusted odds ratio estimate for death of 2.38 [95% CI: 1.75–3.22]. This index was 1.43 [95% CI: 1.06–1.92] for Saudi patients in comparison to non-Saudi; 1.76 [95% CI: 1.39–2.22] for patient with comorbidity in comparison to those without comorbidity; 0.58 [95% CI: 0.44–0.75] for those who had close contact to a camel in the past 14 days and 0.42 [95% CI: 0.31–0.57] for patients with >14 days with onset of signs and hospital admission compared to patients with ≤14 days.


id: cord-264956-wbi0ird5
author: Ahmed, Anwar E.
date: 2018-04-14
txt: ./txt/cord-264956-wbi0ird5.txt
cache: ./cache/cord-264956-wbi0ird5.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1111/hdi.12661
doi: 10.1111/hdi.12661
summary:
  An important lesson was learned from the world''s largest Middle East respiratory syndrome coronavirus (MERS-CoV) outbreaks that occurred in Saudi Arabia and South Korea: that health care-associated infection is a major cause of rapid pathogen spread in health care settings with a high risk of cluster infections. 12, 13 A valid risk-predictive model for MERS-CoV infection in dialysis patients may increase the likelihood of early virus detection. The authors attempt to develop an algorithm that combines demographic, clinical, radiological, and laboratory data to assess the early risk of MERS-CoV infection in dialysis patients who are suspected of having MERS-CoV infection and were diagnosed by real-time reverse transcription-PCR (rRT-PCR) between September 2012 and June 2016. This is the first study to develop a risk-prediction model in dialysis patients who screened for MERS-CoV infection by rRT-PCR. The model accurately predicts high-risk of MERS-CoV infection in dialysis patients.

title:
  Development of a risk‐prediction model for Middle East respiratory syndrome coronavirus infection in dialysis patients

abstract:
  Introduction The Middle East respiratory syndrome coronavirus (MERS‐CoV) infection can cause transmission clusters and high mortality in hemodialysis facilities. We attempted to develop a risk‐prediction model to assess the early risk of MERS‐CoV infection in dialysis patients. Methods This two‐center retrospective cohort study included 104 dialysis patients who were suspected of MERS‐CoV infection and diagnosed with rRT‐PCR between September 2012 and June 2016 at King Fahd General Hospital in Jeddah and King Abdulaziz Medical City in Riyadh. We retrieved data on demographic, clinical, and radiological findings, and laboratory indices of each patient. Findings A risk‐prediction model to assess early risk for MERS‐CoV in dialysis patients has been developed. Independent predictors of MERS‐CoV infection were identified, including chest pain (OR = 24.194; P = 0.011), leukopenia (OR = 6.080; P = 0.049), and elevated aspartate aminotransferase (AST) (OR = 11.179; P = 0.013). The adequacy of this prediction model was good (P = 0.728), with a high predictive utility (area under curve [AUC] = 76.99%; 95% CI: 67.05% to 86.38%). The prediction of the model had optimism‐corrected bootstrap resampling AUC of 71.79%. The Youden index yielded a value of 0.439 or greater as the best cut‐off for high risk of MERS infection. Discussion This risk‐prediction model in dialysis patients appears to depend markedly on chest pain, leukopenia, and elevated AST. The model accurately predicts the high risk of MERS‐CoV infection in dialysis patients. This could be clinically useful in applying timely intervention and control measures to prevent clusters of infections in dialysis facilities or other health care settings. The predictive utility of the model warrants further validation in external samples and prospective studies.


id: cord-265279-0zjpqnqp
title: Use of the Human Coronavirus 2012 (MERS) GeneSig kit for MERS-CoV detection
author: Hoteit, Rouba
date: 2016-04-16
txt: ./txt/cord-265279-0zjpqnqp.txt
cache: ./cache/cord-265279-0zjpqnqp.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S2452014416300218
doi: 10.1016/j.genrep.2016.04.004
summary:
  CONCLUSION: The GeneSig Human Coronavirus 2012 (MERS) kit is very useful for the screening of suspected respiratory cases in the Middle East area as well as other regions. The aim of this study was to assess the use of a MERS-CoV specific assay for screening of respiratory samples referred to a major tertiary care center in anticipation of the possible spread of the virus in the region. The GeneSig Human Coronavirus 2012 (MERS) kit is a rapid and useful kit for the screening of suspected respiratory cases in the Middle East area as well as other regions. Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study Clinical aspects and outcomes of 70 patients with Middle East respiratory syndrome coronavirus infection: a single-center experience in Saudi Arabia Middle East respiratory syndrome coronavirus (MERS-CoV) c WHO

abstract:
  INTRODUCTION: Mortality due to MERS-CoV infection is common especially among immunocompromised patients. The pathogenesis and the transmission mode of this virus are still not well understood. The name of the virus is derived from the area of its appearance and the genomic sequence that was used in the development of qRT-PCR assays for MERS-CoV detection was retrieved from the first detected case isolate. The employed assays target various regions including the area upstream of the envelope gene (upE) that is used for screening and the open reading frames (ORF) 1a and 1b used for confirmation. AIM: This study assesses the use of a MERS-CoV specific assay for screening of respiratory samples in anticipation of the possible spread of the virus in the region. METHODS: 46 respiratory specimens were tested using the qualitative one-step qRT-PCR GeneSig Human Coronavirus 2012 (MERS) kit (PrimerDesign™). RESULTS: Out of the 46 tested samples, 45 were negative for MERS-CoV and one sample was found MERS-CoV positive. CONCLUSION: The GeneSig Human Coronavirus 2012 (MERS) kit is very useful for the screening of suspected respiratory cases in the Middle East area as well as other regions.


id: cord-265380-2gs34xcw
author: Leist, Sarah R.
date: 2019-09-14
txt: ./txt/cord-265380-2gs34xcw.txt
cache: ./cache/cord-265380-2gs34xcw.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/31883094/
doi: 10.1007/978-1-0716-0211-9_12
summary:
  Precise molecular engineering of mouse DPP4 (mDPP4) with clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology maintained inherent expression profiles, and limited MERS-CoV susceptibility to tissues that naturally express mDPP4, notably the lower respiratory tract wherein MERS-CoV elicits severe pulmonary pathology. utilized a unique approach for producing susceptible mice that could replicate human isolates of MERS-CoV in the lungs by infecting mouse lungs with an adenovirus that constitutively expresses the full-length hDPP4 gene ( Fig. 1) [37] . Attempts to restrict hDPP4 expression to epithelial cells of the lungs using constitutive tissue specific promoters (e.g., cytokeratin K18) yielded outcomes similar to those observed with SARS-CoV mouse models, wherein high levels of MERS-CoV infection/replication were detected in the brains (Fig. 1 ) [39] . Elevated human dipeptidyl peptidase 4 expression reduces the susceptibility of hDPP4 transgenic mice to Middle East respiratory syndrome coronavirus infection and disease

title:
  Genetically Engineering a Susceptible Mouse Model for MERS-CoV-Induced Acute Respiratory Distress Syndrome

abstract:
  Since 2012, monthly cases of Middle East respiratory syndrome coronavirus (MERS-CoV) continue to cause severe respiratory disease that is fatal in ~35% of diagnosed individuals. The ongoing threat to global public health and the need for novel therapeutic countermeasures have driven the development of animal models that can reproducibly replicate the pathology associated with MERS-CoV in human infections. The inability of MERS-CoV to replicate in the respiratory tracts of mice, hamsters, and ferrets stymied initial attempts to generate small animal models. Identification of human dipeptidyl peptidase IV (hDPP4) as the receptor for MERS-CoV infection opened the door for genetic engineering of mice. Precise molecular engineering of mouse DPP4 (mDPP4) with clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology maintained inherent expression profiles, and limited MERS-CoV susceptibility to tissues that naturally express mDPP4, notably the lower respiratory tract wherein MERS-CoV elicits severe pulmonary pathology. Here, we describe the generation of the 288–330(+/+) MERS-CoV mouse model in which mice were made susceptible to MERS-CoV by modifying two amino acids on mDPP4 (A288 and T330), and the use of adaptive evolution to generate novel MERS-CoV isolates that cause fatal respiratory disease. The 288–330(+/+) mice are currently being used to evaluate novel drug, antibody, and vaccine therapeutic countermeasures for MERS-CoV. The chapter starts with a historical perspective on the emergence of MERS-CoV and animal models evaluated for MERS-CoV pathogenesis, and then outlines the development of the 288–330(+/+) mouse model, assays for assessing a MERS-CoV pulmonary infection in a mouse model, and describes some of the challenges associated with using genetically engineered mice.


id: cord-265666-27ckjl7w
title: Working experiences of nurses during the Middle East respiratory syndrome outbreak
author: Kang, Hee Sun
date: 2018-05-30
txt: ./txt/cord-265666-27ckjl7w.txt
cache: ./cache/cord-265666-27ckjl7w.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1111/ijn.12664
doi: 10.1111/ijn.12664
summary:
  RESULTS: The following 4 major themes emerged: "experiencing burnout owing to the heavy workload," "relying on personal protective equipment for safety," "being busy with catching up with the new guidelines related to Middle East respiratory syndrome," and "caring for suspected or infected patients with caution." Participants experienced burnout because of the high volume of work and expressed safety concerns about being infected. CONCLUSION: This study showed that creating a supportive and safe work environment is essential by ensuring adequate nurse staffing, supplying best‐quality personal protective equipment, and improving communication to provide the quality of care during infection outbreak. The critical care response to a hospital outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection: An observational study

abstract:
  AIMS: To explore working experiences of nurses during Middle East respiratory syndrome outbreak. BACKGROUND: Since the first case of Middle East respiratory syndrome was reported on May 20, 2015 in South Korea, 186 people, including health care workers, were infected, and 36 died. DESIGN: A qualitative descriptive study. METHODS: Seven focus groups and 3 individual in‐depth interviews were conducted from August to December 2015. Content analysis was used. RESULTS: The following 4 major themes emerged: “experiencing burnout owing to the heavy workload,” “relying on personal protective equipment for safety,” “being busy with catching up with the new guidelines related to Middle East respiratory syndrome,” and “caring for suspected or infected patients with caution.” Participants experienced burnout because of the high volume of work and expressed safety concerns about being infected. Unclear and frequently changing guidelines were 1 of the common causes of confusion. Participants expressed that they need to be supported while caring for suspected or infected patients. CONCLUSION: This study showed that creating a supportive and safe work environment is essential by ensuring adequate nurse staffing, supplying best‐quality personal protective equipment, and improving communication to provide the quality of care during infection outbreak.


id: cord-266260-t02jngq0
title: A database of geopositioned Middle East Respiratory Syndrome Coronavirus occurrences
author: Ramshaw, Rebecca E.
date: 2019-12-13
txt: ./txt/cord-266260-t02jngq0.txt
cache: ./cache/cord-266260-t02jngq0.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1038/s41597-019-0330-0
doi: 10.1038/s41597-019-0330-0
summary:
  As a World Health Organization Research and Development Blueprint priority pathogen, there is a need to better understand the geographic distribution of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and its potential to infect mammals and humans. Middle East Respiratory Syndrome Coronavirus (MERS-CoV) emerged as a global health concern in 2012 when the first human case was documented in Saudi Arabia 1 . Previous literature reviews have looked at healthcare-associated outbreaks 9 , importation events resulting in secondary cases 10, 11 , occurrences among dromedary camels 12, 13 , or to summarize current knowledge and knowledge gaps of MERS-CoV 14, 15 . This database seeks fill gaps in literature and build upon existing notification data by enhancing the geographic resolution of MERS-CoV data and providing occurrences of both mammal and environmental detections in addition to human cases. First cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infections in France, investigations and implications for the prevention of human-to-human transmission

abstract:
  As a World Health Organization Research and Development Blueprint priority pathogen, there is a need to better understand the geographic distribution of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and its potential to infect mammals and humans. This database documents cases of MERS-CoV globally, with specific attention paid to zoonotic transmission. An initial literature search was conducted in PubMed, Web of Science, and Scopus; after screening articles according to the inclusion/exclusion criteria, a total of 208 sources were selected for extraction and geo-positioning. Each MERS-CoV occurrence was assigned one of the following classifications based upon published contextual information: index, unspecified, secondary, mammal, environmental, or imported. In total, this database is comprised of 861 unique geo-positioned MERS-CoV occurrences. The purpose of this article is to share a collated MERS-CoV database and extraction protocol that can be utilized in future mapping efforts for both MERS-CoV and other infectious diseases. More broadly, it may also provide useful data for the development of targeted MERS-CoV surveillance, which would prove invaluable in preventing future zoonotic spillover.


id: cord-267333-8b7hvorz
title: Unraveling the Mysteries of Middle East Respiratory Syndrome Coronavirus
author: Watson, John T.
date: 2014-06-17
txt: ./txt/cord-267333-8b7hvorz.txt
cache: ./cache/cord-267333-8b7hvorz.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/24983095/
doi: 10.3201/eid2006.140322
abstract: nan
summary:
  As of February 23, 2014, the World Health Organization has reported 182 laboratory-confirmed cases of MERS-CoV infection, including 79 deaths, indicating an ongoing risk for transmission to humans in the Arabian Peninsula (2). Understanding the role of dromedary camels and possibly other animals in transmission of MERS-CoV to humans remains a priority for future investigation to enable development of targeted control measures and prevent future cases and deaths from this emerging pathogen. State of knowledge and data gaps of Middle East respiratory syndrome coronavirus (MERS-CoV) in humans Interim infection prevention and control recommendations for hospitalized patients with Middle East respiratory syndrome coronavirus (MERS-CoV) Middle East respiratory syndrome coronavirus in dromedary camels: an outbreak investigation Middle East respiratory syndrome coronavirus infection in dromedary camels in Saudi Arabia Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study


id: cord-268879-ajd7ofc8
title: Contemporary Concise Review 2018: Respiratory infections and tuberculosis
author: Hui, David S.
date: 2019-03-30
txt: ./txt/cord-268879-ajd7ofc8.txt
cache: ./cache/cord-268879-ajd7ofc8.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1111/resp.13542
doi: 10.1111/resp.13542
abstract: nan
summary:
  The huge clinical burden of common respiratory viruses, such as respiratory syncytial virus (RSV) and seasonal influenza, on healthcare resources and utilization highlights the importance for developing more effective treatment modalities in order to reduce morbidity and mortality. 20 The therapeutic role of baloxavir in older or immunocompromised patients with severe seasonal or avian A(H7N9) influenza especially with some time delay in administration of the drug later in the clinical course of the infection or in combination with an NAI requires investigation. While the sizeable protective effects of metformin in the abovementioned studies suggest a potential role of the drug as host-directed therapy in the treatment of latent TB infection and active TB, randomized trials are need to delineate its exact role(s) before introduction into clinical practices. Mortality in patients with community-onset pneumonia at low risk of drug-resistant pathogens: impact of β-lactam plus macrolide combination therapy


id: cord-268943-arjtjy53
title: Contact Investigation for Imported Case of Middle East Respiratory Syndrome, Germany
author: Reuss, Annicka
date: 2014-04-17
txt: ./txt/cord-268943-arjtjy53.txt
cache: ./cache/cord-268943-arjtjy53.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/24655721/
doi: 10.3201/eid2004.131375
summary:
  Infection with Middle East respiratory syndrome coronavirus (MERS-CoV) was suspected on March 21 and confirmed on March 23; the patient, who had contact with an ill camel shortly before symptom onset, died on March 26. After MERS-CoV infection was diagnosed, the City Health Department, in cooperation with the state health department, the Institute for Virology in Bonn, and the Robert Koch Institute, initiated an investigation to 1) monitor all contacts of the patient to identify possible person-to-person transmission, 2) assess infection control measures, and 3) explore possible sources for the patient''s infection to prevent further cases. Because the MERS-CoV patient was on mechanical ventilation and could not be interviewed, family contacts who had accompanied him to Germany were interviewed about the onset of his symptoms and possible exposures in the 10 days before disease onset.

abstract:
  On March 19, 2013, a patient from United Arab Emirates who had severe respiratory infection was transferred to a hospital in Germany, 11 days after symptom onset. Infection with Middle East respiratory syndrome coronavirus (MERS-CoV) was suspected on March 21 and confirmed on March 23; the patient, who had contact with an ill camel shortly before symptom onset, died on March 26. A contact investigation was initiated to identify possible person-to-person transmission and assess infection control measures. Of 83 identified contacts, 81 were available for follow-up. Ten contacts experienced mild symptoms, but test results for respiratory and serum samples were negative for MERS-CoV. Serologic testing was done for 53 (75%) of 71 nonsymptomatic contacts; all results were negative. Among contacts, the use of FFP2/FFP3 face masks during aerosol exposure was more frequent after MERS-CoV infection was suspected than before. Infection control measures may have prevented nosocomial transmission of the virus.


id: cord-269232-rhhmvnlp
title: First isolation of West Nile virus from a dromedary camel
author: Joseph, Sunitha
date: 2016-06-08
txt: ./txt/cord-269232-rhhmvnlp.txt
cache: ./cache/cord-269232-rhhmvnlp.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/27273223/
doi: 10.1038/emi.2016.53
summary:
  Although antibodies against West Nile virus (WNV) have been detected in the sera of dromedaries in the Middle East, North Africa and Spain, no WNV has been isolated or amplified from dromedary or Bactrian camels. Notably, the amino-acid residues at 14 positions in the present dromedary WNV genome differed from those in most of the closely related WNV strains in cluster 2 of lineage 1a, with the majority of these differences observed in the putative E and NS5 proteins. [6] [7] [8] [9] [10] [11] [12] [13] In this article, we report the first isolation of WNV from a dromedary calf in the United Arab Emirates during the process of MERS-CoV screening and the results of the comparative genome and phylogenetic analysis. 20 Notably, 14 amino-acid residues in the present dromedary WNV genome differed from those in most of the closely related WNV strains in cluster 2 of lineage 1a (Figure 3) , with the majority of these differences observed in the putative E and NS5 proteins.

abstract:
  Although antibodies against West Nile virus (WNV) have been detected in the sera of dromedaries in the Middle East, North Africa and Spain, no WNV has been isolated or amplified from dromedary or Bactrian camels. In this study, WNV was isolated from Vero cells inoculated with both nasal swab and pooled trachea/lung samples from a dromedary calf in Dubai. Complete-genome sequencing and phylogenetic analysis using the near-whole-genome polyprotein revealed that the virus belonged to lineage 1a. There was no clustering of the present WNV with other WNVs isolated in other parts of the Middle East. Within lineage 1a, the dromedary WNV occupied a unique position, although it was most closely related to other WNVs of cluster 2. Comparative analysis revealed that the putative E protein encoded by the genome possessed the original WNV E protein glycosylation motif NYS at E154–156, which contained the N-linked glycosylation site at N-154 associated with increased WNV pathogenicity and neuroinvasiveness. In the putative NS1 protein, the A70S substitution observed in other cluster 2 WNVs and P250, which has been implicated in neuroinvasiveness, were present. In addition, the foo motif in the putative NS2A protein, which has been implicated in neuroinvasiveness, was detected. Notably, the amino-acid residues at 14 positions in the present dromedary WNV genome differed from those in most of the closely related WNV strains in cluster 2 of lineage 1a, with the majority of these differences observed in the putative E and NS5 proteins. The present study is the first to demonstrate the isolation of WNV from dromedaries. This finding expands the possible reservoirs of WNV and sources of WNV infection.


id: cord-269885-r8molh8c
title: MERS-CoV Infection in a Pregnant Woman in Korea
author: Jeong, Soo Young
date: 2017-08-08
txt: ./txt/cord-269885-r8molh8c.txt
cache: ./cache/cord-269885-r8molh8c.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/28875620/
doi: 10.3346/jkms.2017.32.10.1717
summary:
  We report the first case of MERS-CoV infection during pregnancy occurred outside of the Middle East. We experienced a case of a Korean pregnant woman who was confirmed for a MERS-CoV infection via a polymerase chain reaction (PCR) test. Unlike other cases, this case is not only the first MERS-CoV infection during pregnancy occurred outside of the Middle East, but also the first case of MERS confirmed on 3rd trimester of pregnancy showing good outcome of both mother and baby. Middle East Respiratory Syndrome Coronavirus (MERS-CoV) nosocomial outbreak in South Korea: insights from modeling Interim infection prevention and control recommendations for hospitalized patients with Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Impact of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) on pregnancy and perinatal outcome Middle East Respiratory Syndrome Coronavirus infection during pregnancy: a report of 5 cases from Saudi Arabia

abstract:
  Middle East respiratory syndrome (MERS) is a lethal respiratory disease — caused by MERS-coronavirus (MERS-CoV) which was first identified in 2012. Especially, pregnant women can be expected as highly vulnerable candidates for this viral infection. In May 2015, this virus was spread in Korea and a pregnant woman was confirmed with positive result of MERS-CoV polymerase chain reaction (PCR). Her condition was improved only with conservative treatment. After a full recovery of MERS, the patient manifested abrupt vaginal bleeding with rupture of membrane. Under an impression of placenta abruption, an emergent cesarean section was performed. Our team performed many laboratory tests related to MERS-CoV and all results were negative. We report the first case of MERS-CoV infection during pregnancy occurred outside of the Middle East. Also, this case showed relatively benign maternal course which resulted in full recovery with subsequent healthy full-term delivery without MERS-CoV transmission.


id: cord-270258-9vgpphiu
author: Ko, Jae-Hoon
date: 2016-08-09
url: https://api.elsevier.com/content/article/pii/S0163445316302092
doi: 10.1016/j.jinf.2016.08.005
title:
  Predictive factors for pneumonia development and progression to respiratory failure in MERS-CoV infected patients

abstract:
  BACKGROUND: After the 2015 Middle East respiratory syndrome (MERS) outbreak in Korea, prediction of pneumonia development and progression to respiratory failure was emphasized in control of MERS outbreak. METHODS: MERS-CoV infected patients who were managed in a tertiary care center during the 2015 Korean MERS outbreak were reviewed. To analyze predictive factors for pneumonia development and progression to respiratory failure, we evaluated clinical variables measured within three days from symptom onset. RESULTS: A total of 45 patients were included in the study: 13 patients (28.9%) did not develop pneumonia, 19 developed pneumonia without respiratory failure (42.2%), and 13 progressed to respiratory failures (28.9%). The identified predictive factors for pneumonia development included age ≥45 years, fever ≥37.5 °C, thrombocytopenia, lymphopenia, CRP ≥ 2 mg/dL, and a threshold cycle value of PCR less than 28.5. For respiratory failure, the indicators included male, hypertension, low albumin concentration, thrombocytopenia, lymphopenia, and CRP ≥ 4 mg/dL (all P < 0.05). With ≥ two predictive factors for pneumonia development, 100% of patients developed pneumonia. Patients lacking the predictive factors did not progress to respiratory failure. CONCLUSION: For successful control of MERS outbreak, MERS-CoV infected patients with ≥ two predictive factors should be intensively managed from the initial presentation.


id: cord-271004-gtmo5ixs
author: Al-Tawfiq, Jaffar A.
date: 2017-10-12
url: https://www.ncbi.nlm.nih.gov/pubmed/29031867/
doi: 10.1016/j.tmaid.2017.10.004
title:
  Influenza is more common than Middle East Respiratory Syndrome Coronavirus (MERS-CoV) among hospitalized adult Saudi patients

abstract:
  BACKGROUND: Since the initial description of Middle East Respiratory Syndrome Coronavirus (MERS-CoV), we adopted a systematic process of screening patients admitted with community acquired pneumonia. Here, we report the result of the surveillance activity in a general hospital in Saudi Arabia over a four year period. MATERIALS AND METHODS: All admitted patients with community acquired pneumonia from 2012 to 2016 were tested for MERS-CoV. In addition, testing for influenza viruses was carried out starting April 2015. RESULTS: During the study period, a total of 2657 patients were screened for MERS-CoV and only 20 (0.74%) tested positive. From January 2015 to December 2016, a total of 1644 patients were tested for both MERS-CoV and influenza. None of the patients tested positive for MERS-CoV and 271 (16.4%) were positive for influenza. The detected influenza viruses were Influenza A (107, 6.5%), pandemic 2009 H1N1 (n = 120, 7.3%), and Influenza B (n = 44, 2.7%). Pandemic H1N1 was the most common influenza in 2015 with a peak in peaked October to December and influenza A other than H1N1 was more common in 2016 with a peak in August and then October to December. CONCLUSIONS: MERS-CoV was a rare cause of community acquired pneumonia and other viral causes including influenza were much more common. Thus, admitted patients are potentially manageable with Oseltamivir or Zanamivir therapy.


id: cord-271681-jmoyy8rb
author: Assiri, Abdullah M.
date: 2016-06-14
url: https://doi.org/10.1093/infdis/jiw236
doi: 10.1093/infdis/jiw236
title:
  Epidemiology of a Novel Recombinant Middle East Respiratory Syndrome Coronavirus in Humans in Saudi Arabia

abstract:
  BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory illness in humans. Fundamental questions about circulating viruses and transmission routes remain. METHODS: We assessed routinely collected epidemiologic data for MERS-CoV cases reported in Saudi Arabia during 1 January– 30 June 2015 and conducted a more detailed investigation of cases reported during February 2015. Available respiratory specimens were obtained for sequencing. RESULTS: During the study period, 216 MERS-CoV cases were reported. Full genome (n = 17) or spike gene sequences (n = 82) were obtained from 99 individuals. Most sequences (72 of 99 [73%]) formed a discrete, novel recombinant subclade (NRC-2015), which was detected in 6 regions and became predominant by June 2015. No clinical differences were noted between clades. Among 87 cases reported during February 2015, 13 had no recognized risks for secondary acquisition; 12 of these 13 also denied camel contact. Most viruses (8 of 9) from these 13 individuals belonged to NRC-2015. DISCUSSIONS: Our findings document the spread and eventual predominance of NRC-2015 in humans in Saudi Arabia during the first half of 2015. Our identification of cases without recognized risk factors but with similar virus sequences indicates the need for better understanding of risk factors for MERS-CoV transmission.


id: cord-272306-92rz2byz
author: Morra, Mostafa Ebraheem
date: 2018-04-17
url: https://www.ncbi.nlm.nih.gov/pubmed/29664167/
doi: 10.1002/rmv.1977
title:
  Clinical outcomes of current medical approaches for Middle East respiratory syndrome: A systematic review and meta‐analysis

abstract:
  Middle East respiratory syndrome (MERS) is a respiratory disease caused by MERS coronavirus. Because of lack of vaccination, various studies investigated the therapeutic efficacy of antiviral drugs and supportive remedies. A systematic literature search from 10 databases was conducted and screened for relevant articles. Studies reporting information about the treatment of MERS coronavirus infection were extracted and analyzed. Despite receiving treatment with ribavirin plus IFN, the case fatality rate was as high as 71% in the IFN‐treatment group and exactly the same in patients who received supportive treatment only. Having chronic renal disease, diabetes mellitus and hypertension increased the risk of mortality (P < .05), and chronic renal disease is the best parameter to predict the mortality. The mean of survival days from onset of illness to death was 46.6 (95% CI, 30.5‐62.6) for the IFN group compared with 18.8 (95% CI, 10.3‐27.4) for the supportive‐only group (P = .001). Delay in starting treatment, older age group, and preexisting comorbidities are associated with worse outcomes. In conclusion, there is no difference between IFN treatment and supportive treatment for MERS patients in terms of mortality. However, ribavirin and IFN combination might have efficacious effects with timely administration and monitoring of adverse events. Large‐scale prospective randomized studies are required to assess the role of antiviral drugs for the treatment of this high mortality infection.


id: cord-272513-umuiovrd
title: Variant analysis of SARS-CoV-2 genomes in the Middle East
author: Bindayna, Khalid Mubarak
date: 2020-10-09
url: https://doi.org/10.1101/2020.10.09.332692
doi: 10.1101/2020.10.09.332692
abstract:
  Background Coronavirus (COVID-19) was introduced into society in late 2019 and has now reached over 26 million cases and 850,000 deaths. The Middle East has a death toll of ∼50,000 and over 20,000 of these are in Iran, which has over 350,000 confirmed cases. We expect that Iranian cases caused outbreaks in the neighbouring countries and that variant mapping and phylogenetic analysis can be used to prove this. We also aim to analyse the variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to characterise the common genome variants and provide useful data in the global effort to prevent further spread of COVID-19. Methods The approach uses bioinformatics approaches including multiple sequence alignment, variant calling and annotation and phylogenetic analysis to identify the genomic variants found in the region. The approach uses 122 samples from the 13 countries of the Middle East sourced from the Global Initiative on Sharing All Influenza Data (GISAID). Findings We identified 2200 distinct genome variants including 129 downstream gene variants, 298 frame shift variants, 789 missense variants, 1 start lost, 13 start gained, 1 stop lost, 249 synonymous variants and 720 upstream gene variants. The most common, high impact variants were 10818delTinsG, 2772delCinsC, 14159delCinsC and 2789delAinsA. Variant alignment and phylogenetic tree generation indicates that samples from Iran likely introduced COVID-19 to the rest of the Middle East. Interpretation The phylogenetic and variant analysis provides unique insight into mutation types in genomes. Initial introduction of COVID-19 was most likely due to Iranian transmission. Some countries show evidence of novel mutations and unique strains. Increased time in small populations is likely to contribute to more unique genomes. This study provides more in depth analysis of the variants affecting in the region than any other study. Funding None


id: cord-273626-zy8qjaai
title: The battle against SARS and MERS coronaviruses: Reservoirs and Animal Models
author: Gong, Shu‐ran
date: 2018-07-28
url: https://doi.org/10.1002/ame2.12017
doi: 10.1002/ame2.12017
abstract:
  In humans, infection with the coronavirus, especially the severe acute respiratory syndrome coronavirus (SARS‐CoV) and the emerging Middle East respiratory syndrome coronavirus (MERS‐CoV), induces acute respiratory failure, resulting in high mortality. Irregular coronavirus related epidemics indicate that the evolutionary origins of these two pathogens need to be identified urgently and there are still questions related to suitable laboratory animal models. Thus, in this review we aim to highlight key discoveries concerning the animal origin of the virus and summarize and compare current animal models.


id: cord-274591-p34kk4up
author: Horby, Peter W,
date: 2013-06-17
txt: ./txt/cord-274591-p34kk4up.txt
cache: ./cache/cord-274591-p34kk4up.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3201/eid1906.121783
doi: 10.3201/eid1906.121783
summary:
  The region is certainly a hot spot of socioeconomic and environmental change, and although some changes (e.g., urbanization and agricultural intensification) may reduce the probability of emerging infectious diseases, the effect of any individual emergence event may be increased by the greater concentration and connectivity of livestock, persons, and products. The SARS epidemic provided a dramatic demonstration of the weaknesses in national and global capacities to detect and respond to emerging infectious diseases, and it was in many ways a watershed event that had a transformative effect on many of the clinical, public health, and other professionals involved. Surveillance and response capacities have improved in the last decade, and East and Southeast Asia are far better prepared to detect and respond to emerging infectious diseases.

title:
  Prospects for Emerging Infections in East and Southeast Asia 10 Years after Severe Acute Respiratory Syndrome

abstract:
  It is 10 years since severe acute respiratory syndrome (SARS) emerged, and East and Southeast Asia retain a reputation as a hot spot of emerging infectious diseases. The region is certainly a hot spot of socioeconomic and environmental change, and although some changes (e.g., urbanization and agricultural intensification) may reduce the probability of emerging infectious diseases, the effect of any individual emergence event may be increased by the greater concentration and connectivity of livestock, persons, and products. The region is now better able to detect and respond to emerging infectious diseases than it was a decade ago, but the tools and methods to produce sufficiently refined assessments of the risks of disease emergence are still lacking. Given the continued scale and pace of change in East and Southeast Asia, it is vital that capabilities for predicting, identifying, and controlling biologic threats do not stagnate as the memory of SARS fades.


id: cord-275313-mfyff9ne
title: Treatment strategies for Middle East respiratory syndrome coronavirus
author: Modjarrad, Kayvon
date: 2016-01-01
txt: ./txt/cord-275313-mfyff9ne.txt
cache: ./cache/cord-275313-mfyff9ne.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/26866060/
doi: nan
summary:
  Most recently, Middle East respiratory syndrome coronavirus (MERS-CoV) has emerged as a novel cause of severe acute respiratory illness after first being identified in a Saudi Arabian patient in 2012 [2] . Much of the work to develop safe and effective MERS-CoV countermeasures has centred on vaccines, but the relatively low prevalence of the disease, the sporadic nature of the case clusters and the dearth of detailed knowledge on chains of transmission highlight the need for greater investments into the discovery of effective therapeutic and secondary prophylactic regimens for infected and exposed individuals. Feasibility, safety, clinical, and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol Towards the prophylactic and therapeutic use of human neutralizing monoclonal antibodies for Middle East respiratory syndrome coronavirus (MERS-CoV) Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection

abstract:
  Middle East respiratory syndrome coronavirus (MERS-CoV), an emerging infectious disease of growing global importance, has caused severe acute respiratory disease in more than 1600 people, resulting in almost 600 deaths. The high case fatality rate, growing geographic distribution and vaguely defined epidemiology of this novel pathogen have created an urgent need for effective public health countermeasures, including safe and effective treatment strategies. Despite the relatively few numbers of cases to date, research and development of MERS-CoV therapeutic candidates is advancing quickly. This review surveys the landscape of these efforts and assesses their potential for use in affected populations.


id: cord-275602-cog4nma0
title: Emerging Infectious Diseases: a Review
author: Watkins, Kevin
date: 2018-06-22
txt: ./txt/cord-275602-cog4nma0.txt
cache: ./cache/cord-275602-cog4nma0.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/s40138-018-0162-9
doi: 10.1007/s40138-018-0162-9
summary:
  SUMMARY: In addition to the aforementioned pathogens, the Severe Acute Respiratory Syndrome, Middle East Respiratory Syndrome, Nipah virus, New Delhi metallo-ß-lactamase-1 Enterobacteriaceae, Rift Valley Fever virus, and Crimean-Congo Hemorrhagic Fever virus are reviewed. In 1992, an expert committee that produced the Institute of Medicine report on emerging infections defined them as "new, reemerging, or drug-resistant infections whose incidence in humans has increased within the past two decades or whose incidence threatens to increase in the near future." Additionally, six major contributors to these diseases were presented and included changes in human demographics and behavior, advances in technology and changes in industry practices, economic development and changes in land-use patterns, dramatic increases in volume and speed of international travel and commerce, microbial adaptation and change, and breakdown of public health capacity [1] . The World Health Organization has prioritized a number of infectious diseases as requiring urgent need for research and development given the concern for potential of severe outbreaks.

abstract:
  PURPOSE OF REVIEW: This review highlights some of the recent concerning emerging infectious diseases, a number of them specifically that the World Health Organization has categorized as priorities for research. RECENT FINDINGS: Emerging and reemerging infectious diseases account for significant losses in not only human life, but also financially. There are a number of contributing factors, most commonly surrounding human behavior, that lead to disease emergence. Zoonoses are the most common type of infection, specifically from viral pathogens. The most recent emerging diseases in the USA are Emergomyces canadensis, the Heartland virus, and the Bourbon virus. SUMMARY: In addition to the aforementioned pathogens, the Severe Acute Respiratory Syndrome, Middle East Respiratory Syndrome, Nipah virus, New Delhi metallo-ß-lactamase-1 Enterobacteriaceae, Rift Valley Fever virus, and Crimean-Congo Hemorrhagic Fever virus are reviewed. These pathogens are very concerning with a high risk for potential epidemic, ultimately causing both significant mortality and financial costs. Research should be focused on monitoring, prevention, and treatment of these diseases.


id: cord-277781-v9hw1cdi
author: Ejima, Keisuke
date: 2014-04-07
url: https://api.elsevier.com/content/article/pii/S0022519313005894
doi: 10.1016/j.jtbi.2013.12.024
title:
  Probabilistic differential diagnosis of Middle East respiratory syndrome (MERS) using the time from immigration to illness onset among imported cases

abstract:
  Abstract Middle East respiratory syndrome (MERS) has spread worldwide since 2012. As the clinical symptoms of MERS tend to be non-specific, the incubation period has been shown to complement differential diagnosis, especially to rule out influenza. However, because an infection event is seldom directly observable, the present study aims to construct a diagnostic model that predicts the probability of MERS diagnosis given the time from immigration to illness onset among imported cases which are suspected of MERS. Addressing censoring by considering the transmission dynamics in an exporting country, we demonstrate that the illness onset within 2 days from immigration is suggestive of influenza. Two exceptions to suspect MERS even for those with illness onset within 2 days since immigration are (i) when we observe substantial community transmissions of MERS and (ii) when the cases are at high risk of MERS (e.g. cases with close contact in hospital or household). It is vital to collect the information of the incubation period upon emergence of a novel infectious disease, and moreover, in our model, the fundamental transmission dynamics including the initial growth rate has to be explored to differentiate the disease diagnoses with non-specific symptoms.


id: cord-278238-w1l8h8g8
title: Middle East respiratory syndrome coronavirus vaccines: current status and novel approaches
author: Okba, Nisreen MA
date: 2017-04-13
url: https://www.ncbi.nlm.nih.gov/pubmed/28412285/
doi: 10.1016/j.coviro.2017.03.007
abstract:
  Middle East respiratory syndrome coronavirus (MERS-CoV) is a cause of severe respiratory infection in humans, specifically the elderly and people with comorbidities. The re-emergence of lethal coronaviruses calls for international collaboration to produce coronavirus vaccines, which are still lacking to date. Ongoing efforts to develop MERS-CoV vaccines should consider the different target populations (dromedary camels and humans) and the correlates of protection. Extending on our current knowledge of MERS, vaccination of dromedary camels to induce mucosal immunity could be a promising approach to diminish MERS-CoV transmission to humans. In addition, it is equally important to develop vaccines for humans that induce broader reactivity against various coronaviruses to be prepared for a potential next CoV outbreak.


id: cord-280350-ay4cnzn5
title: Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus
author: Chan, Jasper F.W.
date: 2013-10-03
txt: ./txt/cord-280350-ay4cnzn5.txt
cache: ./cache/cord-280350-ay4cnzn5.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/24096239/
doi: 10.1016/j.jinf.2013.09.029
summary:
  We then assessed the anti-MERS-CoV activities of the identified compounds and of interferons, nelfinavir, and lopinavir because of their reported anti-coronavirus activities in terms of cytopathic effect inhibition, viral yield reduction, and plaque reduction assays in Biosafety Level-3 laboratory. Given the limited time available to develop novel anti-MERS-CoV agents in this evolving epidemic, we attempted to provide an alternative solution by identifying potential broad-spectrum antiviral agents against MERS-CoV and influenza A viruses by a small compound-based forward chemical genetics approach using chemical libraries consisting of 1280 drug compounds already marketed or having reached clinical trials in the United States, Europe, or Asia (Microsource Discovery Systems, USA). 25 We then assessed the anti-MERS-CoV activities of the identified drug compounds in cell culture by cytopathic effect (CPE) inhibition, viral yield reduction, and plaque reduction assay (PRA) assays, as well as drug cytotoxicity.

abstract:
  OBJECTIVES: Middle East respiratory syndrome coronavirus (MERS-CoV) has emerged to cause fatal infections in patients in the Middle East and traveler-associated secondary cases in Europe and Africa. Person-to-person transmission is evident in outbreaks involving household and hospital contacts. Effective antivirals are urgently needed. METHODS: We used small compound-based forward chemical genetics to screen a chemical library of 1280 known drugs against influenza A virus in Biosafety Level-2 laboratory. We then assessed the anti-MERS-CoV activities of the identified compounds and of interferons, nelfinavir, and lopinavir because of their reported anti-coronavirus activities in terms of cytopathic effect inhibition, viral yield reduction, and plaque reduction assays in Biosafety Level-3 laboratory. RESULTS: Ten compounds were identified as primary hits in high-throughput screening. Only mycophenolic acid exhibited low EC(50) and high selectivity index. Additionally, ribavirin and interferons also exhibited in-vitro anti-MERS-CoV activity. The serum concentrations achievable at therapeutic doses of mycophenolic acid and interferon-β1b were 60–300 and 3–4 times higher than the concentrations at which in-vitro anti-MERS-CoV activities were demonstrated, whereas that of ribavirin was ∼2 times lower. Combination of mycophenolic acid and interferon-β1b lowered the EC(50) of each drug by 1–3 times. CONCLUSIONS: Interferon-β1b with mycophenolic acid should be considered in treatment trials of MERS.


id: cord-281529-2rec51xg
title: Middle East respiratory syndrome coronavirus in dromedary camels: an outbreak investigation
author: Haagmans, Bart L
date: 2013-12-17
txt: ./txt/cord-281529-2rec51xg.txt
cache: ./cache/cord-281529-2rec51xg.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/24355866/
doi: 10.1016/s1473-3099(13)70690-x
summary:
  We tested for the presence of MERS-CoV in dromedary camels from a farm in Qatar linked to two human cases of the infection in October, 2013. 13 Both MERS-CoV spike protein binding antibodies and virus neutralising antibodies were reported in dromedary camels from diff erent regions, including Oman and Egypt, but no virus shedding could be detected and, therefore, the signifi cance of these observations remained an issue of debate. The camel MERS-CoV clustered with viral sequences obtained from the two human cases related to the farm and with a sequence from Hafr-Al-Batin as the next closest relative (fi gure 1). However, virological testing was unable to detect MERS-CoV viral sequences in camels, probably because only faecal and serum samples were analysed. Our report describes the fi rst detection of MERS-CoV in dromedary camels on a farm in Qatar that had been linked to human cases of the disease.

abstract:
  BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe lower respiratory tract infection in people. Previous studies suggested dromedary camels were a reservoir for this virus. We tested for the presence of MERS-CoV in dromedary camels from a farm in Qatar linked to two human cases of the infection in October, 2013. METHODS: We took nose swabs, rectal swabs, and blood samples from all camels on the Qatari farm. We tested swabs with RT-PCR, with amplification targeting the E gene (upE), nucleocapsid (N) gene, and open reading frame (ORF) 1a. PCR positive samples were tested by different MERS-CoV specific PCRs and obtained sequences were used for phylogentic analysis together with sequences from the linked human cases and other human cases. We tested serum samples from the camels for IgG immunofluorescence assay, protein microarray, and virus neutralisation assay. FINDINGS: We obtained samples from 14 camels on Oct 17, 2013. We detected MERS-CoV in nose swabs from three camels by three independent RT-PCRs and sequencing. The nucleotide sequence of an ORF1a fragment (940 nucleotides) and a 4·2 kb concatenated fragment were very similar to the MERS-CoV from two human cases on the same farm and a MERS-CoV isolate from Hafr-Al-Batin. Eight additional camel nose swabs were positive on one or more RT-PCRs, but could not be confirmed by sequencing. All camels had MERS-CoV spike-binding antibodies that correlated well with the presence of neutralising antibodies to MERS-CoV. INTERPRETATION: Our study provides virological confirmation of MERS-CoV in camels and suggests a recent outbreak affecting both human beings and camels. We cannot conclude whether the people on the farm were infected by the camels or vice versa, or if a third source was responsible. FUNDING: European Union projects EMPERIE (contract number 223498), ANTIGONE (contract number 278976), and the VIRGO consortium.


id: cord-282293-pdhjl508
author: Park, Wan Beom
date: 2016-01-14
url: https://doi.org/10.3346/jkms.2016.31.2.315
doi: 10.3346/jkms.2016.31.2.315
title:
  Isolation of Middle East Respiratory Syndrome Coronavirus from a Patient of the 2015 Korean Outbreak

abstract:
  During the 2015 outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) in Korea, 186 persons were infected, resulting in 38 fatalities. We isolated MERS-CoV from the oropharyngeal sample obtained from a patient of the outbreak. Cytopathic effects showing detachment and rounding of cells were observed in Vero cell cultures 3 days after inoculation of the sample. Spherical virus particles were observed by transmission electron microscopy. Full-length genome sequence of the virus isolate was obtained and phylogenetic analyses showed that it clustered with clade B of MERS-CoV.


id: cord-283586-o8m6xdra
author: Spanakis, Nikolaos
date: 2014-12-31
txt: ./txt/cord-283586-o8m6xdra.txt
cache: ./cache/cord-283586-o8m6xdra.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.ijantimicag.2014.07.026
doi: 10.1016/j.ijantimicag.2014.07.026
summary:
  Abstract Serological, molecular and phylogenetic analyses of a recently imported case of Middle East respiratory syndrome coronavirus (MERS-CoV) in Greece are reported. Although MERS-CoV remained detectable in the respiratory tract secretions of the patient until the fourth week of illness, viraemia was last detected 2 days after initiation of triple combination therapy with pegylated interferon, ribavirin and lopinavir/ritonavir, administered from Day 13 of illness. An upsurge of Middle East respiratory syndrome coronavirus (MERS-CoV) infection has been recently described in countries of the Arabian Peninsula resulting in exported cases from these countries to the European Union [1] . Published reports propose the use of known antivirals based on extrapolation of data from: (i) the severe acute respiratory syndrome (SARS) epidemic that was also associated with the circulation of a novel coronavirus; (ii) in vitro data; (iii) animal experimental infections and therapy data; and (iv) limited clinical data for actual MERS-CoV infections [2] [3] [4] .

title:
  Virological and serological analysis of a recent Middle East respiratory syndrome coronavirus infection case on a triple combination antiviral regimen

abstract:
  Abstract Serological, molecular and phylogenetic analyses of a recently imported case of Middle East respiratory syndrome coronavirus (MERS-CoV) in Greece are reported. Although MERS-CoV remained detectable in the respiratory tract secretions of the patient until the fourth week of illness, viraemia was last detected 2 days after initiation of triple combination therapy with pegylated interferon, ribavirin and lopinavir/ritonavir, administered from Day 13 of illness. Phylogenetic analysis of the virus showed close similarity with other human MERS-CoVs from the recent Jeddah outbreak in Saudi Arabia. Immunoglobulin G (IgG) titres peaked 3 weeks after the onset of illness, whilst IgM levels remained constantly elevated during the follow-up period (second to fifth week of illness). Serological testing confirmed by virus neutralisation assay detected an additional case that was a close contact of the patient.


id: cord-284374-sqxlnk9e
author: Park, Jiyeon
date: 2020-01-15
url: https://doi.org/10.1038/s41598-019-57216-x
doi: 10.1038/s41598-019-57216-x
title:
  Infection Prevention Measures for Surgical Procedures during a Middle East Respiratory Syndrome Outbreak in a Tertiary Care Hospital in South Korea

abstract:
  In 2015, we experienced the largest in-hospital Middle East respiratory syndrome (MERS) outbreak outside the Arabian Peninsula. We share the infection prevention measures for surgical procedures during the unexpected outbreak at our hospital. We reviewed all forms of related documents and collected information through interviews with healthcare workers of our hospital. After the onset of outbreak, a multidisciplinary team devised institutional MERS-control guidelines. Two standard operating rooms were converted to temporary negative-pressure rooms by physically decreasing the inflow air volume (−4.7 Pa in the main room and −1.2 Pa in the anteroom). Healthcare workers were equipped with standard or enhanced personal protective equipment according to the MERS-related patient’s profile and symptoms. Six MERS-related patients underwent emergency surgery, including four MERS-exposed and two MERS-confirmed patients. Negative conversion of MERS-CoV polymerase chain reaction tests was noticed for MERS-confirmed patients before surgery. MERS-exposed patients were also tested twice preoperatively, all of which were negative. All operative procedures in MERS-related patients were performed without specific adverse events or perioperative MERS transmission. Our experience with setting up a temporary negative-pressure operation room and our conservative approach for managing MERS-related patients can be referred in cases of future unexpected MERS outbreaks in non-endemic countries.


id: cord-284581-fl2nt4ak
author: Kleine-Weber, Hannah
date: 2019-07-19
txt: ./txt/cord-284581-fl2nt4ak.txt
cache: ./cache/cord-284581-fl2nt4ak.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0042682219301916
doi: 10.1016/j.virol.2019.07.016
summary:
  title: Spike proteins of novel MERS-coronavirus isolates from Northand West-African dromedary camels mediate robust viral entry into human target cells A recent study showed that MERS-CoV found in North/West(Morocco) and West-African (Burkina Faso and Nigeria) dromedary camels are genetically distinct from Arabian viruses and have reduced replicative capacity in human cells, potentially due to amino acid changes in one or more viral proteins. Here, we show that the spike (S) proteins of the prototypic Arabian MERS-CoV strain, human betacoronavirus 2c EMC/2012, and the above stated African MERS-CoV variants do not appreciably differ in expression, DPP4 binding and ability to drive entry into target cells. We employed a previously described vesicular stomatitis virus (VSV)-based pseudotyping system to study MERS-S-driven host cell entry (Kleine-Weber et al., 2018 known to adequately model key aspects of the coronavirus entry process. Host cell entry driven by the S proteins of North/West-and West-African MERS-CoV isolates from dromedary camels is robust.

title:
  Spike proteins of novel MERS-coronavirus isolates from North- and West-African dromedary camels mediate robust viral entry into human target cells

abstract:
  The highly pathogenic Middle East respiratory syndrome (MERS)-related coronavirus (CoV) is transmitted from dromedary camels, the natural reservoir, to humans. For at present unclear reasons, MERS cases have so far only been observed in the Arabian Peninsula, although MERS-CoV also circulates in African dromedary camels. A recent study showed that MERS-CoV found in North/West- (Morocco) and West-African (Burkina Faso and Nigeria) dromedary camels are genetically distinct from Arabian viruses and have reduced replicative capacity in human cells, potentially due to amino acid changes in one or more viral proteins. Here, we show that the spike (S) proteins of the prototypic Arabian MERS-CoV strain, human betacoronavirus 2c EMC/2012, and the above stated African MERS-CoV variants do not appreciably differ in expression, DPP4 binding and ability to drive entry into target cells. Thus, virus-host-interactions at the entry stage may not limit spread of North- and West-African MERS-CoV in human cells.


id: cord-286472-pqtem19t
title: MIDDLE EAST RESPIRATORY SYNDROME (MERS) CORONAVIRUS
author: McFee, R.B.
date: 2020-07-28
txt: ./txt/cord-286472-pqtem19t.txt
cache: ./cache/cord-286472-pqtem19t.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0011502920301152
doi: 10.1016/j.disamonth.2020.101053
abstract: nan
summary:
  This newly identified respiratory viral illness was caused by a novel coronavirus, which was initially designated as human betacoronavirus (2) (3) (4) (5) , but was eventually named Middle East Respiratory Syndrome Coronavirus (MERS CoV). It is important to consider multisystem function as well as pulmonary status in patients with severe respiratory illness, including suspected MERS CoV, especially those returning from regions where aggressive pathogens are noted. Patients recently returning from the Middle East, presenting with significant respiratory illness, with CT findings of peribronchial region abnormalities, organizing pneumonia, should be considered for MERS CoV infection, and if possible, queried about international travel and occupational exposures. Middle East Respiratory Syndrome Coronavirus (MERS CoV) Infection Feasibility, safety, clinical and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol


id: cord-286631-3fmg3scx
author: Pormohammad, Ali
date: 2020-06-05
txt: ./txt/cord-286631-3fmg3scx.txt
cache: ./cache/cord-286631-3fmg3scx.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32502331/
doi: 10.1002/rmv.2112
summary:
  title: Comparison of confirmed COVID‐19 with SARS and MERS cases ‐ Clinical characteristics, laboratory findings, radiographic signs and outcomes: A systematic review and meta‐analysis The trigger for rapid screening and treatment of COVID-19 patients is based on clinical symptoms, laboratory, and radiographic findings that are similar to SARS and MERS infections. In this study, we attempted to distinguish the clinical symptoms, laboratory findings, radiographic signs, and outcomes of confirmed COVID-19, SARS, and MERS patients. Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study Clinical aspects and outcomes of 70 patients with Middle East respiratory syndrome coronavirus infection: a single-center experience in Saudi Arabia Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection Middle East respiratory syndrome coronavirus: a case-control study of hospitalized patients

title:
  Comparison of confirmed COVID‐19 with SARS and MERS cases ‐ Clinical characteristics, laboratory findings, radiographic signs and outcomes: A systematic review and meta‐analysis

abstract:
  INTRODUCTION: Within this large‐scale study, we compared clinical symptoms, laboratory findings, radiographic signs, and outcomes of COVID‐19, SARS, and MERS to find unique features. METHOD: We searched all relevant literature published up to February 28, 2020. Depending on the heterogeneity test, we used either random or fixed‐effect models to analyze the appropriateness of the pooled results. Study has been registered in the PROSPERO database (ID 176106). RESULT: Overall 114 articles included in this study; 52 251 COVID‐19 confirmed patients (20 studies), 10 037 SARS (51 studies), and 8139 MERS patients (43 studies) were included. The most common symptom was fever; COVID‐19 (85.6%, P < .001), SARS (96%, P < .001), and MERS (74%, P < .001), respectively. Analysis showed that 84% of Covid‐19 patients, 86% of SARS patients, and 74.7% of MERS patients had an abnormal chest X‐ray. The mortality rate in COVID‐19 (5.6%, P < .001) was lower than SARS (13%, P < .001) and MERS (35%, P < .001) between all confirmed patients. CONCLUSIONS: At the time of submission, the mortality rate in COVID‐19 confirmed cases is lower than in SARS‐ and MERS‐infected patients. Clinical outcomes and findings would be biased by reporting only confirmed cases, and this should be considered when interpreting the data.


id: cord-287156-3plpi6i9
title: Children in Coronaviruses’ Wonderland: What Clinicians Need to Know
author: Lassandro, Giuseppe
date: 2020-07-01
txt: ./txt/cord-287156-3plpi6i9.txt
cache: ./cache/cord-287156-3plpi6i9.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32670520/
doi: 10.4084/mjhid.2020.042
summary:
  Among the seven coronaviruses that affect humans (SARS)-CoV, the Middle East respiratory syndrome (MERS)-CoV, and the most recent coronavirus disease 2019 (COVID-19) represent potential life-threatening diseases worldwide. Children appear to be less susceptible to develop severe clinical disease and present usually with mild and aspecific symptoms similar to other respiratory infections typical of childhood. 8, 9 Additionally, three HCoVs responsible for outbreaks involving high case fatality rates have been detected in humans in the last two decades: the severe acute respiratory syndrome (SARS)-CoV, the Middle East respiratory syndrome (MERS)-CoV and the new coronavirus disease 2019 (COVID-19) ( Table 1) . Principal features of severe acute respiratory syndrome (SARS)-CoV, the Middle East respiratory syndrome (MERS)-CoV and the most recent coronavirus disease 2019 (COVID19) . Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission

abstract:
  Human coronaviruses (HCoVs) commonly cause mild upper-respiratory tract illnesses but can lead to more severe and diffusive diseases. A variety of signs and symptoms may be present, and infections can range in severity from the common cold and sore throat to more serious laryngeal or tracheal infections, bronchitis, and pneumonia. Among the seven coronaviruses that affect humans (SARS)-CoV, the Middle East respiratory syndrome (MERS)-CoV, and the most recent coronavirus disease 2019 (COVID-19) represent potential life-threatening diseases worldwide. In adults, they may cause severe pneumonia that evolves in respiratory distress syndrome and multiorgan failure with a high mortality rate. Children appear to be less susceptible to develop severe clinical disease and present usually with mild and aspecific symptoms similar to other respiratory infections typical of childhood. However, some children, such as infants, adolescents, or those with underlying diseases may be more at-risk categories and require greater caution from clinicians. Available data on pediatric coronavirus infections are rare and scattered in the literature. The purpose of this review is to provide to clinicians a complete and updated panel useful to recognize and characterize the broad spectrum of clinical manifestations of coronavirus infections in the pediatric age.


id: cord-287761-73qgx58i
author: Aly, Mahmoud
date: 2017-10-13
txt: ./txt/cord-287761-73qgx58i.txt
cache: ./cache/cord-287761-73qgx58i.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1371/journal.pone.0183850
doi: 10.1371/journal.pone.0183850
summary:
  Within a time span of 4 years from June 2012 to July 2016, we collect samples form MERS-CoV infected individuals from National Guard Hospital, Riyadh, and Ministry of health Saudi Arabia and other GCC countries. GCC countries including Saudi Arabia now have the infrastructure in place that allows physicians and scientific community to identify and immediately respond to the potential risks posed by new outbreaks of MERS-CoV infections in the region. The emergence of MERS-CoV dates back to July 2012 when an elderly patient of age 60 years died from an acute pneumonia in Saudi Arabia, and a new coronavirus strain was isolated from his lung tissue [1] . With regard to viral origin and transmission, the first case of MERS-CoV infection did not relate it to any particular contact with animals before the disease onset; however, other studies did link it to Dromedary camels [5] [6] [7] [8] .

title:
  Occurrence of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) across the Gulf Corporation Council countries: Four years update

abstract:
  The emergence of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infections has become a global issue of dire concerns. MERS-CoV infections have been identified in many countries all over the world whereas high level occurrences have been documented in the Middle East and Korea. MERS-CoV is mainly spreading across the geographical region of the Middle East, especially in the Arabian Peninsula, while some imported sporadic cases were reported from the Europe, North America, Africa, and lately Asia. The prevalence of MERS-CoV infections across the Gulf Corporation Council (GCC) countries still remains unclear. Therefore, the objective of the current study was to report the prevalence of MERS-CoV in the GCC countries and to also elucidate on its demographics in the Arabian Peninsula. To date, the World Health Organization (WHO) has reported 1,797 laboratory-confirmed cases of MERS-CoV infection since June 2012, involving 687 deaths in 27 different countries worldwide. Within a time span of 4 years from June 2012 to July 2016, we collect samples form MERS-CoV infected individuals from National Guard Hospital, Riyadh, and Ministry of health Saudi Arabia and other GCC countries. Our data comprise a total of 1550 cases (67.1% male and 32.9% female). The age-specific prevalence and distribution of MERS-CoV was as follow: <20 yrs (36 cases: 3.28%), 20–39 yrs (331 cases: 30.15%), 40–59 yrs (314 cases: 28.60%), and the highest-risk elderly group aged ≥60 yrs (417 cases: 37.98%). The case distribution among GCC countries was as follows: Saudi Arabia (1441 cases: 93%), Kuwait (4 cases: 0.3%), Bahrain (1 case: 0.1%), Oman (8 cases: 0.5%), Qatar (16 cases: 1.0%), and United Arab Emirates (80 cases: 5.2%). Thus, MERS-CoV was found to be more prevalent in Saudi Arabia especially in Riyadh, where 756 cases (52.4%) were the worst hit area of the country identified, followed by the western region Makkah where 298 cases (20.6%) were recorded. This prevalence update indicates that the Arabian Peninsula, particularly Saudi Arabia, is the hardest hit region regarding the emerging MERS-CoV infections worldwide. GCC countries including Saudi Arabia now have the infrastructure in place that allows physicians and scientific community to identify and immediately respond to the potential risks posed by new outbreaks of MERS-CoV infections in the region. Given the continuum of emergence and the large magnitude of the disease in our region, more studies will be required to bolster capabilities for timely detection and effective control and prevention of MERS-CoV in our region.


id: cord-287886-41isp0wj
author: Al-Tawfiq, Jaffar A
date: 2016-11-08
txt: ./txt/cord-287886-41isp0wj.txt
cache: ./cache/cord-287886-41isp0wj.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/27872828/
doi: 10.5409/wjcp.v5.i4.391
summary:
  AIM: To summarize the reported Middle East respiratory syndrome-coronavirus (MERS-CoV) cases, the associated clinical presentations and the outcomes. We also searched MEDLINE and PubMed for the keywords: Middle East respiratory syndrome-coronavirus, MERS-CoV in combination with pediatric, children, childhood, infancy and pregnancy from the initial discovery of the virus in 2012 to 2016. We searched MEDLINE and PubMed for the keywords Middle East respiratory syndrome-coronavirus, MERS-CoV, in combination with pediatric, children, childhood, infancy and pregnancy from the initial discovery of the virus in June 2012 until April 19, 2016. Middle East respiratory syndrome-coronavirus (MERS-CoV) was first isolated in 2012 from a patient in the Kingdom of Saudi Arabia (KSA). Middle East respiratory syndrome-coronavirus (MERS-CoV) was first isolated in 2012 from a patient in the Kingdom of Saudi Arabia (KSA). Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study

title:
  Middle East respiratory syndrome coronavirus disease is rare in children: An update from Saudi Arabia

abstract:
  AIM: To summarize the reported Middle East respiratory syndrome-coronavirus (MERS-CoV) cases, the associated clinical presentations and the outcomes. METHODS: We searched the Saudi Ministry of Health website, the World Health Organization website, and the Flutracker website. We also searched MEDLINE and PubMed for the keywords: Middle East respiratory syndrome-coronavirus, MERS-CoV in combination with pediatric, children, childhood, infancy and pregnancy from the initial discovery of the virus in 2012 to 2016. The retrieved articles were also read to further find other articles. Relevant data were placed into an excel sheet and analyzed accordingly. Descriptive analytic statistics were used in the final analysis as deemed necessary. RESULTS: From June 2012 to April 19, 2016, there were a total of 31 pediatric MERS-CoV cases. Of these cases 13 (42%) were asymptomatic and the male to female ratio was 1.7:1. The mean age of patients was 9.8 ± 5.4 years. Twenty-five (80.6%) of the cases were reported from the Kingdom of Saudi Arabia. The most common source of infection was household contact (10 of 15 with reported source) and 5 patients acquired infection within a health care facility. Using real time reverse transcriptase polymerase chain reaction of pediatric patients revealed that 9 out of 552 (1.6%) was positive in the Kingdom of Saudi Arabia. CONCLUSION: Utilizing serology for MERS-CoV infection in Jordan and Saudi Arabia did not reveal any positive patients. Thus, the number of the pediatric MERS-CoV is low; the exact reason for the low prevalence of the disease in children is not known.


id: cord-288389-z0sz1msj
author: Fanoy, Ewout B
date: 2014-10-17
txt: ./txt/cord-288389-z0sz1msj.txt
cache: ./cache/cord-288389-z0sz1msj.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/25328533/
doi: 10.1186/1742-7622-11-16
summary:
  title: Travel-related MERS-CoV cases: an assessment of exposures and risk factors in a group of Dutch travellers returning from the Kingdom of Saudi Arabia, May 2014 BACKGROUND: In May 2014, Middle East respiratory syndrome coronavirus (MERS-CoV) infection, with closely related viral genomes, was diagnosed in two Dutch residents, returning from a pilgrimage to Medina and Mecca, Kingdom of Saudi Arabia (KSA). METHODS: All travellers, including the two cases, completed a questionnaire focussing on potential human, animal and food exposures to MERS-CoV. Exposure to MERS-CoV during a hospital visit is considered a likely source of infection for Case 1 but not for Case 2. Investigation of an imported case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in Middle East respiratory syndrome coronavirus (MERS-CoV) infections in two returning travellers in the Netherlands World Health Organization: Case-Control Study to Assess Potential Risk Factors Related to Human Illness Caused by Middle East Respiratory Syndrome Coronavirus (MERS-CoV)

title:
  Travel-related MERS-CoV cases: an assessment of exposures and risk factors in a group of Dutch travellers returning from the Kingdom of Saudi Arabia, May 2014

abstract:
  BACKGROUND: In May 2014, Middle East respiratory syndrome coronavirus (MERS-CoV) infection, with closely related viral genomes, was diagnosed in two Dutch residents, returning from a pilgrimage to Medina and Mecca, Kingdom of Saudi Arabia (KSA). These patients travelled with a group of 29 other Dutch travellers. We conducted an epidemiological assessment of the travel group to identify likely source(s) of infection and presence of potential risk factors. METHODS: All travellers, including the two cases, completed a questionnaire focussing on potential human, animal and food exposures to MERS-CoV. The questionnaire was modified from the WHO MERS-CoV questionnaire, taking into account the specific route and activities of the travel group. RESULTS: Twelve non-cases drank unpasteurized camel milk and had contact with camels. Most travellers, including one of the two patients (Case 1), visited local markets, where six of them consumed fruits. Two travellers, including Case 1, were exposed to coughing patients when visiting a hospital in Medina. Four travellers, including Case 1, visited two hospitals in Mecca. All travellers had been in contact with Case 1 while he was sick, with initially non-respiratory complaints. The cases were found to be older than the other travellers and both had co-morbidities. CONCLUSIONS: This epidemiological study revealed the complexity of MERS-CoV outbreak investigations with multiple potential exposures to MERS-CoV reported such as healthcare visits, camel exposure, and exposure to untreated food products. Exposure to MERS-CoV during a hospital visit is considered a likely source of infection for Case 1 but not for Case 2. For Case 2, the most likely source could not be determined. Exposure to MERS-CoV via direct contact with animals or dairy products seems unlikely for the two Dutch cases. Furthermore, exposure to a common but still unidentified source cannot be ruled out. More comprehensive research into sources of infection in the Arabian Peninsula is needed to strengthen and specify the prevention of MERS-CoV infections.


id: cord-290319-decr6wrd
title: A more detailed picture of the epidemiology of Middle East respiratory syndrome coronavirus
author: Kayali, Ghazi
date: 2015-05-31
txt: ./txt/cord-290319-decr6wrd.txt
cache: ./cache/cord-290319-decr6wrd.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/25863563/
doi: 10.1016/s1473-3099(15)70128-3
abstract: nan
summary:
  7 The virus isolated from dromedaries has spike proteins with conserved receptor-binding domains for the human dipeptidyl peptidase-4 receptor, 8, 9 and MERS-CoV has been detected in camels that were in close contact with people with Middle East respiratory syndrome. The fi ndings from this study suggest that young men in Saudi Arabia who have contact with camels in cultural or occupational settings are becoming infected with MERS-CoV, often without being diagnosed, and might proceed to introduce the virus to the general population in which more severe illness triggers testing for the virus and disease recognition. 6 In The Lancet Infectious Diseases, Mélanie Drolet and colleagues present the fi ndings of a timely systematic review and metaanalysis assessing the population-level and herd eff ects of HPV vaccination programmes so far.


id: cord-291367-rtmsrh16
author: Zumla, Alimuddin
date: 2015-07-02
txt: ./txt/cord-291367-rtmsrh16.txt
cache: ./cache/cord-291367-rtmsrh16.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.ijid.2015.06.020
doi: 10.1016/j.ijid.2015.06.020
abstract: nan
summary:
  4, 5 The recent unprecedented outbreak of the MERS 6, 7 in South Korea which arose consequential to the importation of MERS-CoV by a South Korean traveler to the Middle East, alarmed global public health authorities and highlights the potential of MERS-CoV to spread across the globe and cause local outbreaks. National surveillance systems should be on alert for the low but long-lasting risk of MERS-CoV infected pilgrims returning from the Umrah throughout the year, and also for the large numbers of refugees at several conflict zones in the Middle East (those migrating from Syria to Turkey and from the Yemen border into Saudi Arabia and beyond). The Hajj pilgrimage and surveillance for Middle East Respiratory syndrome coronavirus in pilgrims from African countries Infection prevention and control during health care for probable or confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection.

title:
  Middle East Respiratory Syndrome - need for increased vigilance and watchful surveillance for MERS-CoV in sub-Saharan Africa


id: cord-293403-o1i999hy
title: E-health in the East Asian tigers
author: Holliday, Ian
date: 2004-09-11
txt: ./txt/cord-293403-o1i999hy.txt
cache: ./cache/cord-293403-o1i999hy.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S1386505604001807
doi: 10.1016/j.ijmedinf.2004.08.001
summary:
  OBJECTIVE: The article analyzes e-health progress in East Asia''s leading tiger economies: Japan, Hong Kong, Singapore, South Korea and Taiwan. In this article, we examine the progress of e-health in the five leading economies of East Asia: Japan, Hong Kong, Singapore, South Korea and Taiwan. Against the dual backdrop of sophisticated IT societies that make extensive use of the Internet and cost-effective healthcare systems driven in variable ways by actors from the public and private sectors, we now turn to a survey of e-health in the East Asian tigers. Throughout the region, the major quasi-autonomous state agencies, such as the national health insurance agencies in Japan, South Korea and Taiwan, the HKHA in Hong Kong and the two big healthcare clusters in Singapore, also have sites. Over the next 5 years, the HKHA is planning to create a Hong Kong Health Information Infrastructure, with the aim of networking all healthcare providers in the public, private and social welfare sectors.

abstract:
  OBJECTIVE: The article analyzes e-health progress in East Asia's leading tiger economies: Japan, Hong Kong, Singapore, South Korea and Taiwan. It describes five main dimensions of e-health provision in the tigers: policymaking, regulation, provision, funding and physician-patient relations. METHODS: We conducted a series of fieldwork interviews and analyzed key healthcare websites. RESULTS AND CONCLUSION: Our main finding is that the development of e-health in the region is less advanced than might be expected. Our explanation focuses on institutional, cultural and financial factors.


id: cord-293505-1t3hg4wi
author: Bernard-Stoecklin, Sibylle
date: 2019-05-14
txt: ./txt/cord-293505-1t3hg4wi.txt
cache: ./cache/cord-293505-1t3hg4wi.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/31089148/
doi: 10.1038/s41598-019-43586-9
summary:
  Such large healthcare-associated (HCA) outbreaks have mainly been limited to the Kingdom of Saudi Arabia (KSA) and the United Arabian Emirates (UAE) until the spring 2015, when a single imported case of MERS returning from the Middle East initiated a cluster of 186 cases in the Republic of Korea (ROK) across at least 17 hospitals and much of the country 18 . We analyzed epidemiological datasets of laboratory-confirmed MERS patients and focused our study on eleven healthcare-associated outbreaks that were reported in KSA and ROK since 2015, when policies and procedures for case identification and comprehensive contact identification and follow up became systematic and were implemented by affected countries. We defined a HCA-outbreak as the occurrence of 5 or more laboratory-confirmed MERS-CoV infections with reported epidemiologic links between cases and during which the human-to-human transmission events were documented within a single healthcare facility, with no more than 14 days apart between cases symptom onset.

title:
  Comparative Analysis of Eleven Healthcare-Associated Outbreaks of Middle East Respiratory Syndrome Coronavirus (Mers-Cov) from 2015 to 2017

abstract:
  Since its emergence in 2012, 2,260 cases and 803 deaths due to Middle East respiratory syndrome coronavirus (MERS-CoV) have been reported to the World Health Organization. Most cases were due to transmission in healthcare settings, sometimes causing large outbreaks. We analyzed epidemiologic and clinical data of laboratory-confirmed MERS-CoV cases from eleven healthcare-associated outbreaks in the Kingdom of Saudi Arabia and the Republic of Korea between 2015–2017. We quantified key epidemiological differences between outbreaks. Twenty-five percent (n = 105/422) of MERS cases who acquired infection in a hospital setting were healthcare personnel. In multivariate analyses, age ≥65 (OR 4.8, 95%CI: 2.6–8.7) and the presence of underlying comorbidities (OR: 2.7, 95% CI: 1.3–5.7) were associated with increased mortality whereas working as healthcare personnel was protective (OR 0.07, 95% CI: 0.01–0.34). At the start of these outbreaks, the reproduction number ranged from 1.0 to 5.7; it dropped below 1 within 2 to 6 weeks. This study provides a comprehensive characterization of MERS HCA-outbreaks. Our results highlight heterogeneities in the epidemiological profile of healthcare-associated outbreaks. The limitations of our study stress the urgent need for standardized data collection for high-threat respiratory pathogens, such as MERS-CoV.


id: cord-293691-ewerquin
author: Sauerhering, Lucie
date: 2020-07-02
txt: ./txt/cord-293691-ewerquin.txt
cache: ./cache/cord-293691-ewerquin.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32616594/
doi: 10.1183/13993003.01826-2019
summary:
  RATIONALE: While severe coronavirus infections, including Middle East respiratory syndrome coronavirus (MERS-CoV) cause lung injury with high mortality rates, protective treatment strategies are not approved for clinical use. METHODS: Calu-3 cells and primary human alveolar epithelial cells (hAEC) were infected with MERS-CoV and treated with CsA or ALV or inhibitors targeting cyclophilin inhibitor-regulated molecules including Calcineurin, NFAT, or MAP kinases. To address the previously proposed antiviral activity of CsA in clinically relevant cells, we infected the human bronchial epithelial cell line Calu-3 and primary human alveolar epithelial cells (hAEC) with MERS-CoV and analyzed intracellular viral RNA and infectious particle release in presence of DMSO or CsA ( Figure 1 ). Our data demonstrated that silencing of IRF1 but not treatment by control siRNA lead to a significant increase in MERS-CoV released viral particles in CsA-treated cells ( Figure 6A , B).

title:
  Cyclophilin Inhibitors Restrict Middle East Respiratory Syndrome Coronavirus Via Interferon λ In Vitro And In Mice

abstract:
  RATIONALE: While severe coronavirus infections, including Middle East respiratory syndrome coronavirus (MERS-CoV) cause lung injury with high mortality rates, protective treatment strategies are not approved for clinical use. OBJECTIVES: We elucidated the molecular mechanisms by which the cyclophilin inhibitors Cyclosporin A (CsA) and Alisporivir (ALV) restrict MERS-CoV to validate their suitability as readily-available therapy in MERS-CoV infection. METHODS: Calu-3 cells and primary human alveolar epithelial cells (hAEC) were infected with MERS-CoV and treated with CsA or ALV or inhibitors targeting cyclophilin inhibitor-regulated molecules including Calcineurin, NFAT, or MAP kinases. Novel CsA-induced pathways were identified by RNA sequencing and manipulated by gene knockdown or neutralising antibodies. Viral replication was quantified by qRT-PCR and TCID(50). Data were validated in a murine MERS-CoV infection model. RESULTS: CsA and ALV both reduced MERS-CoV titers and viral RNA replication in Calu-3 and hAEC improving epithelial integrity. While neither Calcineurin nor NFAT inhibition reduced MERS-CoV propagation, blockade of c-Jun N-terminal kinase diminished infectious viral particle release but not RNA accumulation. Importantly, CsA induced interferon regulatory factor 1 (IRF1), a pronounced type-III-interferon (IFNλ) response and expression of antiviral genes. Down-regulation of IRF1 or IFNλ increased MERS-CoV propagation in presence of CsA. Importantly, oral application of CsA reduced MERS-CoV replication in vivo, correlating with elevated lung IFNλ levels and improved outcome. CONCLUSIONS: We provide evidence that cyclophilin inhibitors efficiently decrease MERS-CoV replication in vitro and in vivo via upregulation of inflammatory, antiviral cell responses, in particular IFNλ. CsA might therefore represent a promising candidate to treat MERS-CoV infection.


id: cord-293938-40zyv1h8
title: Coronaviruses and the human airway: a universal system for virus-host interaction studies
author: Jonsdottir, Hulda R.
date: 2016-02-06
txt: ./txt/cord-293938-40zyv1h8.txt
cache: ./cache/cord-293938-40zyv1h8.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1186/s12985-016-0479-5
doi: 10.1186/s12985-016-0479-5
summary:
  The emergence of both Severe Acute Respiratory Syndrome and Middle East Respiratory syndrome CoVs as well as the yearly circulation of four common CoVs highlights the importance of elucidating the different mechanisms employed by these viruses to evade the host immune response, determine their tropism and identify antiviral compounds. Tracheobronchial HAE cultures recapitulate the primary entry point of human respiratory viruses while the alveolar model allows for elucidation of mechanisms involved in viral infection and pathogenesis in the alveoli. Given the documented history of coronaviruses overcoming the species barrier and causing severe disease in humans, it is important to investigate the zoonotic potential of close evolutionary relatives of common HCoVs in a culture model that recapitulates the aspects of the human airway, e.g. morphology and receptor distribution. The establishment of transgenic animal models for human disease is attainable when either the virus receptor has been identified, which is not the case for all HCoVs, or when viruses can be adapted to a different host.

abstract:
  Human coronaviruses (HCoVs) are large RNA viruses that infect the human respiratory tract. The emergence of both Severe Acute Respiratory Syndrome and Middle East Respiratory syndrome CoVs as well as the yearly circulation of four common CoVs highlights the importance of elucidating the different mechanisms employed by these viruses to evade the host immune response, determine their tropism and identify antiviral compounds. Various animal models have been established to investigate HCoV infection, including mice and non-human primates. To establish a link between the research conducted in animal models and humans, an organotypic human airway culture system, that recapitulates the human airway epithelium, has been developed. Currently, different cell culture systems are available to recapitulate the human airways, including the Air-Liquid Interface (ALI) human airway epithelium (HAE) model. Tracheobronchial HAE cultures recapitulate the primary entry point of human respiratory viruses while the alveolar model allows for elucidation of mechanisms involved in viral infection and pathogenesis in the alveoli. These organotypic human airway cultures represent a universal platform to study respiratory virus-host interaction by offering more detailed insights compared to cell lines. Additionally, the epidemic potential of this virus family highlights the need for both vaccines and antivirals. No commercial vaccine is available but various effective antivirals have been identified, some with potential for human treatment. These morphological airway cultures are also well suited for the identification of antivirals, evaluation of compound toxicity and viral inhibition.


id: cord-295633-vkjcheaz
author: Hao, Xin‐yan
date: 2019-10-30
txt: ./txt/cord-295633-vkjcheaz.txt
cache: ./cache/cord-295633-vkjcheaz.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1002/ame2.12088
doi: 10.1002/ame2.12088
summary:
  After infection, we analyzed the mouse characteristics of weight loss, survival, viral replication, tissue pathology, viral antigen distribution, and cytokine and chemokine profiles, which provide additional data to investigate the pathogenesis of MERS-CoV-induced disease and evaluate relevant therapeutics and vaccines. Instillation control DMEM suspension To analyze clinical signs, weight loss, and survival On days 3, 5, 7, and 9 postinfection, three animals randomly selected from each group underwent necropsy to obtain tissue specimens for assessing viral distribution, associated histopathology, and cytokine levels using quantitative reverse transcription-PCR (qRT-PCR), hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC), and enzyme-linked immunosorbent assay (ELISA). *P < .05, **P < .01, ***P < .001, and ****P < .0001 Mice in the instillation group died acutely or were euthanized when they researched 25% weight loss; these mice had a 0% survival rate by day 5, so no tissue lesion results were available on days 7 and 9 mice infected with MERS-CoV via the aerosol inhalation or intranasal instillation route, but no obvious lesions were found in other tissues.

title:
  The characteristics of hDPP4 transgenic mice subjected to aerosol MERS coronavirus infection via an animal nose‐only exposure device

abstract:
  BACKGROUND: Middle East respiratory syndrome coronavirus (MERS‐CoV), which is not fully understood in regard to certain transmission routes and pathogenesis and lacks specific therapeutics and vaccines, poses a global threat to public health. METHODS: To simulate the clinical aerosol transmission route, hDPP4 transgenic mice were infected with MERS‐CoV by an animal nose‐only exposure device and compared with instillation‐inoculated mice. The challenged mice were observed for 14 consecutive days and necropsied on days 3, 5, 7, and 9 to analyze viral load, histopathology, viral antigen distribution, and cytokines in tissues. RESULTS: MERS‐CoV aerosol‐infected mice with an incubation period of 5‐7 days showed weight loss on days 7‐11, obvious lung lesions on day 7, high viral loads in the lungs on days 3‐9 and in the brain on days 7‐9, and 60% survival. MERS‐CoV instillation‐inoculated mice exhibited clinical signs on day 1, obvious lung lesions on days 3‐5, continuous weight loss, 0% survival by day 5, and high viral loads in the lungs and brain on days 3‐5. Viral antigen and high levels of proinflammatory cytokines and chemokines were detected in the aerosol and instillation groups. Disease, lung lesion, and viral replication progressions were slower in the MERS‐CoV aerosol‐infected mice than in the MERS‐CoV instillation‐inoculated mice. CONCLUSION: hDPP4 transgenic mice were successfully infected with MERS‐CoV aerosols via an animal nose‐only exposure device, and aerosol‐ and instillation‐infected mice simulated the clinical symptoms of moderate diffuse interstitial pneumonia. However, the transgenic mice exposed to aerosol MERS‐CoV developed disease and lung pathology progressions that more closely resembled those observed in humans.


id: cord-295971-jtv1jj2z
author: Cho, Sun Young
date: 2016-07-09
txt: ./txt/cord-295971-jtv1jj2z.txt
cache: ./cache/cord-295971-jtv1jj2z.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0140673616306237
doi: 10.1016/s0140-6736(16)30623-7
summary:
  BACKGROUND: In 2015, a large outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection occurred following a single patient exposure in an emergency room at the Samsung Medical Center, a tertiary-care hospital in Seoul, South Korea. INTERPRETATION: Our results showed increased transmission potential of MERS-CoV from a single patient in an overcrowded emergency room and provide compelling evidence that health-care facilities worldwide need to be prepared for emerging infectious diseases. Excluding three patients with confi rmed MERS-CoV infection who were not identifi ed in the initial patient contact investigation (appendix p 5), the overall attack rate for patients in the emergency room was 4% (30 of 675). No MERS-CoV infection was reported in patients and visitors who had been in the emergency room on May 29 during the time period when they were exposed only to zones II (n=81) or III (n=15), while Patient 14 was confi ned to zone IV.

title:
  MERS-CoV outbreak following a single patient exposure in an emergency room in South Korea: an epidemiological outbreak study

abstract:
  BACKGROUND: In 2015, a large outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection occurred following a single patient exposure in an emergency room at the Samsung Medical Center, a tertiary-care hospital in Seoul, South Korea. We aimed to investigate the epidemiology of MERS-CoV outbreak in our hospital. METHODS: We identified all patients and health-care workers who had been in the emergency room with the index case between May 27 and May 29, 2015. Patients were categorised on the basis of their exposure in the emergency room: in the same zone as the index case (group A), in different zones except for overlap at the registration area or the radiology suite (group B), and in different zones (group C). We documented cases of MERS-CoV infection, confirmed by real-time PCR testing of sputum samples. We analysed attack rates, incubation periods of the virus, and risk factors for transmission. FINDINGS: 675 patients and 218 health-care workers were identified as contacts. MERS-CoV infection was confirmed in 82 individuals (33 patients, eight health-care workers, and 41 visitors). The attack rate was highest in group A (20% [23/117] vs 5% [3/58] in group B vs 1% [4/500] in group C; p<0·0001), and was 2% (5/218) in health-care workers. After excluding nine cases (because of inability to determine the date of symptom onset in six cases and lack of data from three visitors), the median incubation period was 7 days (range 2–17, IQR 5–10). The median incubation period was significantly shorter in group A than in group C (5 days [IQR 4–8] vs 11 days [6–12]; p<0·0001). There were no confirmed cases in patients and visitors who visited the emergency room on May 29 and who were exposed only to potentially contaminated environment without direct contact with the index case. The main risk factor for transmission of MERS-CoV was the location of exposure. INTERPRETATION: Our results showed increased transmission potential of MERS-CoV from a single patient in an overcrowded emergency room and provide compelling evidence that health-care facilities worldwide need to be prepared for emerging infectious diseases. FUNDING: None.


id: cord-297062-dmiplvt2
title: Presentation and outcome of Middle East respiratory syndrome in Saudi intensive care unit patients
author: Almekhlafi, Ghaleb A.
date: 2016-05-07
txt: ./txt/cord-297062-dmiplvt2.txt
cache: ./cache/cord-297062-dmiplvt2.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1186/s13054-016-1303-8
doi: 10.1186/s13054-016-1303-8
summary:
  authors: Almekhlafi, Ghaleb A.; Albarrak, Mohammed M.; Mandourah, Yasser; Hassan, Sahar; Alwan, Abid; Abudayah, Abdullah; Altayyar, Sultan; Mustafa, Mohamed; Aldaghestani, Tareef; Alghamedi, Adnan; Talag, Ali; Malik, Muhammad K.; Omrani, Ali S.; Sakr, Yasser BACKGROUND: Middle East respiratory syndrome coronavirus infection is associated with high mortality rates but limited clinical data have been reported. We describe the clinical features and outcomes of patients admitted to an intensive care unit (ICU) with Middle East respiratory syndrome coronavirus (MERS-CoV) infection. METHODS: Retrospective analysis of data from all adult (>18 years old) patients admitted to our 20-bed mixed ICU with Middle East respiratory syndrome coronavirus infection between October 1, 2012 and May 31, 2014. We performed a retrospective study to describe the clinical features and outcomes of patients admitted to our ICU with laboratory-confirmed MERS-CoV infection. This report describes the clinical features and outcomes of 31critically ill patients with confirmed Middle East respiratory syndrome coronavirus (MERS-CoV) infection.

abstract:
  BACKGROUND: Middle East respiratory syndrome coronavirus infection is associated with high mortality rates but limited clinical data have been reported. We describe the clinical features and outcomes of patients admitted to an intensive care unit (ICU) with Middle East respiratory syndrome coronavirus (MERS-CoV) infection. METHODS: Retrospective analysis of data from all adult (>18 years old) patients admitted to our 20-bed mixed ICU with Middle East respiratory syndrome coronavirus infection between October 1, 2012 and May 31, 2014. Diagnosis was confirmed in all patients using real-time reverse transcription polymerase chain reaction on respiratory samples. RESULTS: During the observation period, 31 patients were admitted with MERS-CoV infection (mean age 59 ± 20 years, 22 [71 %] males). Cough and tachypnea were reported in all patients; 22 (77.4 %) patients had bilateral pulmonary infiltrates. Invasive mechanical ventilation was applied in 27 (87.1 %) and vasopressor therapy in 25 (80.6 %) patients during the intensive care unit stay. Twenty-three (74.2 %) patients died in the ICU. Nonsurvivors were older, had greater APACHE II and SOFA scores on admission, and were more likely to have received invasive mechanical ventilation and vasopressor therapy. After adjustment for the severity of illness and the degree of organ dysfunction, the need for vasopressors was an independent risk factor for death in the ICU (odds ratio = 18.33, 95 % confidence interval: 1.11–302.1, P = 0.04). CONCLUSIONS: MERS-CoV infection requiring admission to the ICU is associated with high morbidity and mortality. The need for vasopressor therapy is the main risk factor for death in these patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-016-1303-8) contains supplementary material, which is available to authorized users.


id: cord-297853-peqkcix2
author: Khan, Raymond M.
date: 2016-11-01
txt: ./txt/cord-297853-peqkcix2.txt
cache: ./cache/cord-297853-peqkcix2.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0196655316304345
doi: 10.1016/j.ajic.2016.05.006
summary:
  title: Middle East respiratory syndrome coronavirus on inanimate surfaces: A risk for health care transmission The Middle East Respiratory syndrome coronavirus (MERS-CoV) has been responsible for multiple health care–associated outbreaks. The Middle East Respiratory syndrome coronavirus (MERS-CoV) has been responsible for multiple health care-associated outbreaks. In September 2012, the Middle East respiratory syndrome coronavirus (MERS-CoV) was identified from a patient in Saudi Arabia. 3 Further, data from the South Korean outbreak (May 2015) demonstrated that several environmental surfaces frequently touched by laboratory-confirmed MERS patients and health care workers were contaminated by MERS-CoV. Our finding of MERS-CoV RNA on environmental samples within our ICU shows that the viral material may contaminate fomites and can be a theoretical cause of nosocomial infections. CDC''s early response to a novel viral disease, middle east respiratory syndrome coronavirus (MERS-CoV) Stability of Middle East respiratory syndrome coronavirus (MERS-CoV) under different environmental conditions

title:
  Middle East respiratory syndrome coronavirus on inanimate surfaces: A risk for health care transmission

abstract:
  The Middle East Respiratory syndrome coronavirus (MERS-CoV) has been responsible for multiple health care–associated outbreaks. We investigated whether high-touch surfaces in 3 rooms of laboratory-confirmed MERS-CoV patients were contaminated with MERS-CoV RNA. We found 2 out of 51 surfaces were contaminated with MERS-CoV viral genetic material. Hence, environmental contamination may be a potential source of health care transmission and outbreaks. Meticulous environmental cleaning may be important in preventing transmission within the health care setting.


id: cord-297954-87w2itin
author: Memish, Ziad A.
date: 2015-07-15
txt: ./txt/cord-297954-87w2itin.txt
cache: ./cache/cord-297954-87w2itin.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S1477893915001131
doi: 10.1016/j.tmaid.2015.06.012
summary:
  title: Middle East respiratory syndrome coronavirus (MERS-CoV): A cluster analysis with implications for global management of suspected cases Since the initial description of the Middle East respiratory syndrome (MERS) in September 2012, a total of 1038 cases of MERS-CoV including 460 deaths have been reported from Saudi Arabia. Contact screening showed positive test in 1 of 56 (1.8%) household contacts, and 3 of 250 (1.2%) HCWs. Summary Since the initial description of the Middle East respiratory syndrome (MERS) in September 2012, a total of 1038 cases of MERS-CoV including 460 deaths have been reported from Saudi Arabia. Since Middle East respiratory syndrome (MERS) was described in September 2012, a total of 1038 cases of MERS-CoV including 460 deaths have been reported from Saudi Arabia [1] . Screening for Middle East respiratory syndrome coronavirus infection in hospital patients and their healthcare worker and family contacts: a prospective descriptive study

title:
  Middle East respiratory syndrome coronavirus (MERS-CoV): A cluster analysis with implications for global management of suspected cases

abstract:
  Since the initial description of the Middle East respiratory syndrome (MERS) in September 2012, a total of 1038 cases of MERS-CoV including 460 deaths have been reported from Saudi Arabia. From August 24, 2013 to September 3, 2013, a total of 397 patients and contacts were tested for MERS-CoV. Of those tested, there were 18 (4.5%) MERS-CoV cases reported in Al-Madinah al-Munawwarah with one large cluster. In this report, we describe the outcome, epidemiology and clinical characteristics of this cluster of which 4 cases involved healthcare workers. Fourteen cases appeared to be linked to one cluster involving healthcare workers (HCWs), family and patient contacts. Of the 18 cases, five (including 2 HCWs) were community acquired, two were household contacts, and 11 were healthcare associated (including 4 HCWs). All except 4 cases were symptomatic and the case fatality rate was 39% (7 of 18). The outbreak resulted in human to human transmission of an estimated 6 cases. Contact screening showed positive test in 1 of 56 (1.8%) household contacts, and 3 of 250 (1.2%) HCWs.


id: cord-298941-xf2ukinp
author: Al-Abdallat, Mohammad Mousa
date: 2014-05-14
txt: ./txt/cord-298941-xf2ukinp.txt
cache: ./cache/cord-298941-xf2ukinp.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/24829216/
doi: 10.1093/cid/ciu359
summary:
  BACKGROUND: In April 2012, the Jordan Ministry of Health investigated an outbreak of lower respiratory illnesses at a hospital in Jordan; 2 fatal cases were retrospectively confirmed by real-time reverse transcription polymerase chain reaction (rRT-PCR) to be the first detected cases of Middle East respiratory syndrome (MERS-CoV). Following the discovery of Middle East respiratory syndrome coronavirus (MERS-CoV) in September 2012 [2] , specimens from the 2 fatal cases in Jordan were retrospectively tested and both yielded positive results for MERS-CoV by real-time reverse transcription polymerase chain reaction (rRT-PCR), and were reported to the World Health Organization (WHO). Using newly developed serologic assays to determine MERS-CoV antibody responses among case contacts in this outbreak, epidemiologists from the JMoH, US Centers for Disease Control and Prevention (CDC), and regional partners conducted a retrospective seroepidemiologic investigation to (1) confirm whether surviving outbreak members had presence of antibodies to MERS-CoV, (2) ascertain whether viral transmission occurred among household contacts or to other healthcare personnel, and (3) describe the clinical features of all detected MERS-CoV infections in Jordan.

title:
  Hospital-Associated Outbreak of Middle East Respiratory Syndrome Coronavirus: A Serologic, Epidemiologic, and Clinical Description

abstract:
  BACKGROUND: In April 2012, the Jordan Ministry of Health investigated an outbreak of lower respiratory illnesses at a hospital in Jordan; 2 fatal cases were retrospectively confirmed by real-time reverse transcription polymerase chain reaction (rRT-PCR) to be the first detected cases of Middle East respiratory syndrome (MERS-CoV). METHODS: Epidemiologic and clinical characteristics of selected potential cases were assessed through serum blood specimens, medical record reviews, and interviews with surviving outbreak members, household contacts, and healthcare personnel. Cases of MERS-CoV infection were identified using 3 US Centers for Disease Control and Prevention serologic tests for detection of anti–MERS-CoV antibodies. RESULTS: Specimens and interviews were obtained from 124 subjects. Seven previously unconfirmed individuals tested positive for anti–MERS-CoV antibodies by at least 2 of 3 serologic tests, in addition to 2 fatal cases identified by rRT-PCR. The case-fatality rate among the 9 total cases was 22%. Six subjects were healthcare workers at the outbreak hospital, yielding an attack rate of 10% among potentially exposed outbreak hospital personnel. There was no evidence of MERS-CoV transmission at 2 transfer hospitals having acceptable infection control practices. CONCLUSIONS: Novel serologic tests allowed for the detection of otherwise unrecognized cases of MERS-CoV infection among contacts in a Jordanian hospital-associated respiratory illness outbreak in April 2012, resulting in a total of 9 test-positive cases. Serologic results suggest that further spread of this outbreak to transfer hospitals did not occur. Most subjects had no major, underlying medical conditions; none were on hemodialysis. Our observed case-fatality rate was lower than has been reported from outbreaks elsewhere.


id: cord-299519-hfgmmuy6
title: Severe Middle East Respiratory Syndrome (MERS) Pneumonia
author: Alenazi, Thamer H.
date: 2019-10-26
txt: ./txt/cord-299519-hfgmmuy6.txt
cache: ./cache/cord-299519-hfgmmuy6.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/B9780128012383114886
doi: 10.1016/b978-0-12-801238-3.11488-6
summary:
  A febrile acute respiratory illness with clinical, radiological, or histopathological evidence of pulmonary parenchymal disease (e.g. pneumonia or Acute Respiratory Distress Syndrome) that cannot be explained fully by any other etiology AND The person resides or traveled in the Middle East, or in countries where MERS-CoV is known to be circulating in dromedary camels or where human infections have recently occurred AND Testing for MERS-CoV is inconclusive. Ribavirin and interferon therapy in patients infected with the Middle East respiratory syndrome coronavirus: An observational study Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: A descriptive study Middle East respiratory syndrome coronavirus infection during pregnancy: A report of 5 cases from Saudi Arabia An observational, laboratory-based study of outbreaks of middle East respiratory syndrome coronavirus in Jeddah and Riyadh, kingdom of Saudi Arabia Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: A retrospective cohort study

abstract:
  Middle East Respiratory Syndrome (MERS) is a viral respiratory infection, which ranges from asymptomatic infection to severe pneumonia and multiorgan failure, caused by a novel coronavirus named Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Majority of cases have been reported from Saudi Arabia. MERS cases occur as sporadic cases or as clusters or hospital outbreaks. Dromedary camels are thought to be a host for MERS-CoV. Direct contact with dromedary camels within 14 days prior to infection was identified as an independent risk factor for MERS. Diagnosis of MERS is based on a positive real-time reverse transcriptase polymerase chain reaction (rRT-PCR), obtained from a respiratory specimen. The mainstay of management of MERS-CoV infection is supportive care. There is no specific antiviral therapy for MERS-CoV infection at present, although several modalities of treatment options have been examined or are under investigation.


id: cord-299565-shlhreve
title: Global research trends of World Health Organization’s top eight emerging pathogens
author: Sweileh, Waleed M.
date: 2017-02-08
txt: ./txt/cord-299565-shlhreve.txt
cache: ./cache/cord-299565-shlhreve.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1186/s12992-017-0233-9
doi: 10.1186/s12992-017-0233-9
summary:
  According to WHO, the list of pathogens, which required urgent attention for research and development pertaining to preparedness, included "Crimean Congo haemorrhagic fever, Ebola virus, Marburg, Lassa fever, Middle East respiratory syndrome (MERS) and Severe acute respiratory syndrome (SARS) coronavirus diseases, Nipah, and Rift Valley fever" [1] . ( TITLE ( "Crimean-Congo" OR ebola OR "Middle East Respiratory Syndrome" OR "Severe acute respiratory syndrome" OR lassa OR nipah OR "Rift valley" OR marburg OR mers OR merscov OR sars OR ebolavirus OR crimean ) AND TITLE-ABS ( virus OR viral OR fever OR hemorrhagic OR haemorrhagic OR corona* OR coronavirus OR infection OR infectious ) AND TITLE ( vaccin* ) ) AND PUBYEAR > 1995 AND PUBYEAR < 2016 AND ( LIMIT-TO ( SRCTYPE , "j" ) ) AND ( EXCLUDE ( DOCTYPE , "er" ) ) N = 472

abstract:
  BACKGROUND: On December 8(th), 2015, World Health Organization published a priority list of eight pathogens expected to cause severe outbreaks in the near future. To better understand global research trends and characteristics of publications on these emerging pathogens, we carried out this bibliometric study hoping to contribute to global awareness and preparedness toward this topic. METHOD: Scopus database was searched for the following pathogens/infectious diseases: Ebola, Marburg, Lassa, Rift valley, Crimean-Congo, Nipah, Middle Eastern Respiratory Syndrome (MERS), and Severe Respiratory Acute Syndrome (SARS). Retrieved articles were analyzed to obtain standard bibliometric indicators. RESULTS: A total of 8619 journal articles were retrieved. Authors from 154 different countries contributed to publishing these articles. Two peaks of publications, an early one for SARS and a late one for Ebola, were observed. Retrieved articles received a total of 221,606 citations with a mean ± standard deviation of 25.7 ± 65.4 citations per article and an h-index of 173. International collaboration was as high as 86.9%. The Centers for Disease Control and Prevention had the highest share (344; 5.0%) followed by the University of Hong Kong with 305 (4.5%). The top leading journal was Journal of Virology with 572 (6.6%) articles while Feldmann, Heinz R. was the most productive researcher with 197 (2.3%) articles. China ranked first on SARS, Turkey ranked first on Crimean-Congo fever, while the United States of America ranked first on the remaining six diseases. Of retrieved articles, 472 (5.5%) were on vaccine – related research with Ebola vaccine being most studied. CONCLUSION: Number of publications on studied pathogens showed sudden dramatic rise in the past two decades representing severe global outbreaks. Contribution of a large number of different countries and the relatively high h-index are indicative of how international collaboration can create common health agenda among distant different countries.


id: cord-299720-f0ny4ur5
author: Kim, Seung Woo
date: 2017-03-01
txt: ./txt/cord-299720-f0ny4ur5.txt
cache: ./cache/cord-299720-f0ny4ur5.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/27940937/
doi: 10.1093/cid/ciw768
summary:
  title: Risk Factors for Transmission of Middle East Respiratory Syndrome Coronavirus Infection During the 2015 Outbreak in South Korea Transmission heterogeneity was observed during the 2015 Korean outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Transmission heterogeneity was a significant characteristic of the 2015 South Korean outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection [1] . Epidemiological reports from the outbreak were evaluated to collect data regarding basic demographic characteristics, medical history, MERS-CoV exposure, symptoms and their onset date(s), sampling date(s), contact history, and post-exposure infection control. In the univariate analyses, transmission was associated with underlying respiratory disease, Ct value, interval from symptom onset to diagnosis, number of contacts, and pre-isolation hospitalization or ER visits. It appears that both host infectivity and the number of contacts influenced MERS-CoV transmission, whereas super-spreading events were mostly associated with a greater likelihood of encountering other people under diverse environmental conditions.

title:
  Risk Factors for Transmission of Middle East Respiratory Syndrome Coronavirus Infection During the 2015 Outbreak in South Korea

abstract:
  BACKGROUND. Transmission heterogeneity was observed during the 2015 Korean outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Only 22 of 186 cases transmitted the infection, and 5 super-spreading events caused 150 transmissions. We investigated the risk factors for MERS-CoV transmission. METHODS. Epidemiological reports were used to classify patients as nonspreaders, spreaders, or those associated with a super-spreading event (5 or more transmissions). Logistic regression analyses were used to evaluate the factors for MERS-CoV transmission. RESULTS. Compared to nonspreaders, spreaders exhibited a longer interval from symptom onset to isolation (7 days vs 3 days) and more frequent pre-isolation pneumonia diagnoses (68.2% vs 17.1%). Spreaders also exhibited higher values for pre-isolation contacts (149 vs 17.5), pre-isolation hospitalization (68.2% vs 16.5%), and emergency room (ER) visits (50% vs 7.3%). Spreaders exhibited lower cycle thresholds for the upE and ORF1a genes (22.7 vs 27.2 and 23.7 vs 27.9, respectively). In multivariate analysis, transmission was independently associated with the cycle threshold (odds ratio [OR], 0.84; 95% confidence interval [CI], 0.75–0.96) and pre-isolation hospitalization or ER visits (OR, 6.82; 95% CI, 2.06–22.84). The super-spreading events exhibited higher values for pre-isolation contacts (777 vs 78), pre-isolation ER visits (100% vs 35.3%), and doctor shopping (100% vs 47.1%) compared to non-super-spreading events. CONCLUSIONS. These findings indicate that transmission is determined by host infectivity and the number of contacts, whereas super-spreading events were determined by the number of contacts and hospital visits. These relationships highlight the importance of rapidly enforcing infection control measures to prevent outbreaks.


id: cord-300536-8okuomi6
title: Unique Challenges to Control the Spread of COVID-19 in the Middle East
author: Baloch, Zulqarnain
date: 2020-07-13
txt: ./txt/cord-300536-8okuomi6.txt
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extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32690454/
doi: 10.1016/j.jiph.2020.06.034
summary:
  These challenges include compromised healthcare systems, prolonged regional conflicts and humanitarian crises, suboptimal levels of transparency and cooperation, and frequent religious gatherings. These challenges include compromised healthcare systems, prolonged regional conflicts and humanitarian crises, suboptimal levels of transparency and cooperation, and frequent religious gatherings. Besides weakening healthcare systems, wars and conflicts in the Middle East have also led to large-scale humanitarian crises. In Iran, the early COVID-19 cases were recorded in Qom (Fig. 3B) , a city that attracts millions of pilgrims from countries including Lebanon, As pilgrims concentrating on religious rituals, there are close contacts among worshipers and insufficient self-protective measures, and therefore amplify the risk of transmission and potential super spreading of SARS-CoV-2 [24] . These include compromised healthcare systems, prolonged regional conflicts and humanitarian crises, suboptimal levels of transparency and cooperation, and frequent religious gatherings.

abstract:
  The COVID-19 pandemic is spreading at unprecedented pace among the Middle East and neighboring countries. This region is geographically, economically, politically, culturally and religiously a very sensitive area, which impose unique challenges for effective control of this epidemic. These challenges include compromised healthcare systems, prolonged regional conflicts and humanitarian crises, suboptimal levels of transparency and cooperation, and frequent religious gatherings. These factors are interrelated and collectively determine the response to the pandemic in this region. Here, we in-depth emphasize these challenges and take a glimpse of possible solutions towards mitigating the spread of COVID-19.


id: cord-303272-1w8epdht
author: Reusken, Chantal BEM
date: 2013-08-09
txt: ./txt/cord-303272-1w8epdht.txt
cache: ./cache/cord-303272-1w8epdht.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S1473309913701646
doi: 10.1016/s1473-3099(13)70164-6
summary:
  title: Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study Cattle (n=80), sheep (n=40), goats (n=40), dromedary camels (n=155), and various other camelid species (n=34) were tested for specific serum IgG by protein microarray using the receptor-binding S1 subunits of spike proteins of MERS-CoV, severe acute respiratory syndrome coronavirus, and human coronavirus OC43. We tested the sera for the presence of IgG antibodies reactive with MERS-CoV, SARS-CoV, and human coronavirus OC43 S1 antigens in a protein microarray. plaque reduction neutralisation tests for bovine coronavirus and MERS-CoV (B): two representative sera are shown (numbers 15 and 5, corresponding to camel ID numbers in table 2) in dilutions of 1/40, 1/160, and 1/640 as well as the virus input control. Sera were tested for IgG antibodies reactive with MERS-CoV, SARS-CoV, and human coronavirus OC43 S1 antigens in a protein microarray (fi gure 1).

title:
  Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study

abstract:
  BACKGROUND: A new betacoronavirus—Middle East respiratory syndrome coronavirus (MERS-CoV)—has been identified in patients with severe acute respiratory infection. Although related viruses infect bats, molecular clock analyses have been unable to identify direct ancestors of MERS-CoV. Anecdotal exposure histories suggest that patients had been in contact with dromedary camels or goats. We investigated possible animal reservoirs of MERS-CoV by assessing specific serum antibodies in livestock. METHODS: We took sera from animals in the Middle East (Oman) and from elsewhere (Spain, Netherlands, Chile). Cattle (n=80), sheep (n=40), goats (n=40), dromedary camels (n=155), and various other camelid species (n=34) were tested for specific serum IgG by protein microarray using the receptor-binding S1 subunits of spike proteins of MERS-CoV, severe acute respiratory syndrome coronavirus, and human coronavirus OC43. Results were confirmed by virus neutralisation tests for MERS-CoV and bovine coronavirus. FINDINGS: 50 of 50 (100%) sera from Omani camels and 15 of 105 (14%) from Spanish camels had protein-specific antibodies against MERS-CoV spike. Sera from European sheep, goats, cattle, and other camelids had no such antibodies. MERS-CoV neutralising antibody titres varied between 1/320 and 1/2560 for the Omani camel sera and between 1/20 and 1/320 for the Spanish camel sera. There was no evidence for cross-neutralisation by bovine coronavirus antibodies. INTERPRETATION: MERS-CoV or a related virus has infected camel populations. Both titres and seroprevalences in sera from different locations in Oman suggest widespread infection. FUNDING: European Union, European Centre For Disease Prevention and Control, Deutsche Forschungsgemeinschaft.


id: cord-304054-sn7rswab
title: Chapter 8 The Middle East Respiratory Syndrome Coronavirus: An Emerging Virus of Global Threat
author: Khan, Gulfaraz
date: 2020-12-31
txt: ./txt/cord-304054-sn7rswab.txt
cache: ./cache/cord-304054-sn7rswab.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/B9780128194003000089
doi: 10.1016/b978-0-12-819400-3.00008-9
summary:
  Abstract Middle East respiratory syndrome (MERS) is a viral respiratory illness caused by a coronavirus (CoV), first identified in Saudi Arabia in 2012. Although the natural reservoir of MERS-CoV infection and mode of transmission to humans is not known, one factor appears to be common to all primary cases; they are epidemiologically linked to the Middle East region. Cross-sectional surveillance of Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels and other mammals in Egypt Risk factors for primary Middle East respiratory syndrome coronavirus illness in humans, Saudi Arabia Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study Middle East respiratory syndrome coronavirus infection during pregnancy: a report of 5 cases from Saudi Arabia Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission Transmission of Middle East Respiratory syndrome coronavirus infections in healthcare settings

abstract:
  Abstract Middle East respiratory syndrome (MERS) is a viral respiratory illness caused by a coronavirus (CoV), first identified in Saudi Arabia in 2012. Since then, almost 2000 cases have been reported from 27 countries, with Saudi Arabia being the epicenter. This newly emerging virus is highly pathogenic and has a case mortality rate of 35%. It is similar to the CoV causing severe acute respiratory syndrome CoV (SARS-CoV) in that both belong to the genus beta CoVs that are of zoonotic origin and cause lower respiratory infection. The natural reservoir for MERS-CoV remains unknown. Serological studies indicate that most dromedary camels in the Middle East have been infected with this virus, and they maybe the potential intermediate host. However, the mode of transmission from camels to humans is poorly understood. The majority of confirmed human cases have resulted from human-to-human transmission, most probably via respiratory route. Patients most at risk of developing severe MERS-CoV infection appear to be those with underlying conditions such as diabetes, hypertension, obesity, cardiac diseases, chronic respiratory diseases, and cancer. Unlike SARS-CoV, MERS-CoV is considered an ongoing public health problem, particularly for the Middle East region. In this chapter, we outline the prevailing information regarding the emergence and epidemiology of this virus, its mode of transmission and pathogenicity, its clinical features, and the potential strategies for prevention.


id: cord-304057-d2r92nji
author: Harrath, Rafik
date: 2018-04-26
txt: ./txt/cord-304057-d2r92nji.txt
cache: ./cache/cord-304057-d2r92nji.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1002/jmv.25186
doi: 10.1002/jmv.25186
summary:
  title: Sero‐prevalence of Middle East respiratory syndrome coronavirus (MERS‐CoV) specific antibodies in dromedary camels in Tabuk, Saudi Arabia A primary sero‐prevalence study of MERS‐CoV preexisting neutralizing antibodies in Dromedary camel serum was conducted in Tabuk, western north region of KSA, in order to assess the seopositivity of these animals and to explain their possible role in the transmission of the infection to Human. 11, 16, 17 Results have shown that a high number (85%) of dromedary camels from the different farms of Tabuk Riyadh and screened by ELISA test showed that 74% of the animals were found to have antibodies to MERS-CoV. 7 In the same study, 264 archived serum samples collected from dromedary camels from 1992 to 2010 in Riyadh and Kharj were also analyzed by ELISA and showed a high seroprevalence (92%) of MERS-CoV neutralizing antibodies. Middle East respiratory syndrome coronavirus neutralizing serum antibodies in dromedary camels: a comparative serological study Seroprevalence of Middle East respiratory syndrome coronavirus (MERS-CoV) specific antibodies in dromedary camels in

title:
  Sero‐prevalence of Middle East respiratory syndrome coronavirus (MERS‐CoV) specific antibodies in dromedary camels in Tabuk, Saudi Arabia

abstract:
  The Middle East Respiratory Syndrome Coronavirus (MERS‐CoV) is a novel Coronavirus which was responsible of the first case of human acute respiratory syndrome in the Kingdom of Saudi Arabia (KSA), 2012. Dromedary camels are considered as potential reservoirs for the virus and seem to be the only animal host which may transmit the infection to human. Further studies are required to better understand the animal sources of zoonotic transmission route and the risks of this infection. A primary sero‐prevalence study of MERS‐CoV preexisting neutralizing antibodies in Dromedary camel serum was conducted in Tabuk, western north region of KSA, in order to assess the seopositivity of these animals and to explain their possible role in the transmission of the infection to Human. One hundred seventy one (171) serum samples were collected from healthy dromedary camels with different ages and genders in Tabuk city and tested for specific serum IgG by ELISA using the receptor‐binding S1 subunits of spike proteins of MERS‐CoV. 144 (84,21%) of the total camel sera shown the presence of protein‐specific antibodies against MERS‐CoV. These results may provide evidence that MERS‐CoV has previously infected dromedary camels in Tabuk and may support the possible role of camels in the human infection.


id: cord-305317-08a1oin2
title: Middle East respiratory syndrome coronavirus: Implications for health care facilities
author: Maltezou, Helena C.
date: 2014-12-31
txt: ./txt/cord-305317-08a1oin2.txt
cache: ./cache/cord-305317-08a1oin2.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0196655314009316
doi: 10.1016/j.ajic.2014.06.019
summary:
  Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel betacoronavirus of the Coronaviridae family that causes a severe respiratory disease with a high case fatality rate. 2, 3, 6, 8, 22, 24 During the largest so farepublished outbreak of MERS-CoV that occurred in Al-Hasa, Saudi Arabia, in 2013, 4 health care facilities were affected through transfer of patients but also possibly because of repeated introductions of cases from the community. Studies about the effectiveness of infection control measures will provide answers and eventually promote safety in health care facilities both for patients and HCWs. Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study Investigation of an imported case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in Interim infection prevention and control recommendations for hospitalized patients with Middle East respiratory syndrome coronavirus (MERS-CoV)

abstract:
  Background Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel coronavirus that causes a severe respiratory disease with high case fatality rate. Starting in March 2014, a dramatic increase of cases has occurred in the Arabian Peninsula, many of which were acquired in health care settings. As of May 9, 2014, 536 laboratory-confirmed cases and 145 deaths have been reported globally. Methods Review of publicly available data about MERS-CoV health care–associated transmission. Results We identified 11 events of possible or confirmed health care–associated transmission with high morbidity and mortality, mainly among patients with comorbidities. Health care workers are also frequently affected; however, they tend to have milder symptoms and better prognosis. Gaps in infection control were noted in all events. Currently, health care–associated outbreaks are playing a pivotal role in the evolution of the MERS-CoV epidemic in countries in the Arabian Peninsula. Conclusion There is a need to increase infection control capacity in affected areas and areas at increased risk of being affected to prevent transmission in health care settings. Vaccines and antiviral agents are urgently needed. Overall, our knowledge about the epidemiologic characteristics of MERS-CoV that impact health care transmission is very limited. As the MERS-CoV epidemic continues to evolve, issues concerning best infection control measures will arise, and studies to better define their effectiveness in real life are needed.


id: cord-305773-ikm1famj
title: Clinical imaging research of the first Middle East respiratory syndrome in China
author: Lan, Bowen
date: 2015-11-23
txt: ./txt/cord-305773-ikm1famj.txt
cache: ./cache/cord-305773-ikm1famj.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.jrid.2015.11.004
doi: 10.1016/j.jrid.2015.11.004
summary:
  Based on the first case of Middle East respiratory syndrome found in China, a clinical research in combination with radiological findings was studied. Differential imaging diagnosis on the basis of epidemiological and experimental pathogen detection is helpful for clinical diagnosis of MERS, even in distinguishing from SARS and pneumonia caused by H7N9 avian influenza. Middle East respiratory syndrome (MERS), also known as camel flu, is a viral respiratory illness caused by a novel human beta-coronavirus (CoV) [1e3] . On the sixth day after his hospitalization, MERS-COV was negative via the virological detection of sputum, and his body temperature had decreased to be normal, which indicated that the virus has a direct relationship with the fever. 1) Small pieces of high density shadows in the two lower lungs near the heart edge were observed during the early period via chest X-ray examination, suggesting that it firstly progressed to pneumonia (about one week). Middle East respiratory syndrome coronavirus (MERS-CoV) infection: chest CT findings

abstract:
  Middle East respiratory syndrome is a viral respiratory illness caused by a novel human beta-coronavirus. Based on the first case of Middle East respiratory syndrome found in China, a clinical research in combination with radiological findings was studied. Fever was the main clinical manifestation of this patient, and the primary imaging findings were basically the same as viral pneumonia. Differential imaging diagnosis on the basis of epidemiological and experimental pathogen detection is helpful for clinical diagnosis of MERS, even in distinguishing from SARS and pneumonia caused by H7N9 avian influenza.


id: cord-305871-w1quh4fx
author: Hindawi, Salwa I.
date: 2017-12-14
txt: ./txt/cord-305871-w1quh4fx.txt
cache: ./cache/cord-305871-w1quh4fx.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/29239484/
doi: 10.1111/trf.14422
summary:
  Furthermore, inoculation of inactivated plasma on Vero E6 cells did not result in any cytopathic effect (CPE) even after 7 days of incubation and three consecutive passages, nor the detection of MERS RNA compared to pretreatment samples which showed complete CPE within 2 to 3 days postinoculation and log viral RNA titer ranging from 9.48 to 10.22 copies/ mL in all three passages. Furthermore, inoculation of inactivated plasma on Vero E6 cells did not result in any cytopathic effect (CPE) even after 7 days of incubation and three consecutive passages, nor the detection of MERS RNA compared to pretreatment samples which showed complete CPE within 2 to 3 days postinoculation and log viral RNA titer ranging from 9.48 to 10.22 copies/ mL in all three passages. Similar to SARS-CoV, there is no proven evidence so far of transfusion-transmitted MERS-CoV infections, 25 but the presence of viral RNA in plasma and serum of acute patients raises this concern especially in endemic areas like Saudi Arabia.

title:
  Inactivation of Middle East respiratory syndrome‐coronavirus in human plasma using amotosalen and ultraviolet A light

abstract:
  BACKGROUND: Middle East respiratory syndrome‐coronavirus (MERS‐CoV) is a novel zoonotic pathogen. Although the potential for MERS‐CoV transmission through blood transfusion is not clear, MERS‐CoV was recognized as a pathogen of concern for the safety of the blood supply especially after its detection in whole blood, serum, and plasma of infected individuals. Here we investigated the efficacy of amotosalen and ultraviolet A light (UVA) to inactivate MERS‐CoV in fresh‐frozen plasma (FFP). STUDY DESIGN AND METHODS: Pooled FFP units were spiked with a recent clinical MERS‐CoV isolate. Infectious and genomic viral titers were determined in plasma before and after inactivation with amotosalen/UVA treatment by plaque assay and reverse transcription–quantitative polymerase chain reaction, respectively. In addition, residual replicating or live virus after inactivation was examined by passaging in the permissive Vero E6 cells. RESULTS: The mean MERS‐CoV infectious titer in pretreatment samples was 4.67 ± 0.25 log plaque‐forming units (pfu)/mL, which was reduced to undetectable levels after inactivation with amotosalen/UVA demonstrating a mean log reduction of more than 4.67 ± 0.25 pfu/mL. Furthermore, inoculation of inactivated plasma on Vero E6 cells did not result in any cytopathic effect (CPE) even after 7 days of incubation and three consecutive passages, nor the detection of MERS RNA compared to pretreatment samples which showed complete CPE within 2 to 3 days postinoculation and log viral RNA titer ranging from 9.48 to 10.22 copies/mL in all three passages. CONCLUSION: Our data show that amotosalen/UVA treatment is a potent and effective way to inactivate MERS‐CoV infectious particles in FFP to undetectable levels and to minimize the risk of any possible transfusion‐related MERS‐CoV transmission.


id: cord-306004-amv0los1
title: Host Determinants of MERS-CoV Transmission and Pathogenesis
author: Widagdo, W.
date: 2019-03-19
txt: ./txt/cord-306004-amv0los1.txt
cache: ./cache/cord-306004-amv0los1.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/30893947/
doi: 10.3390/v11030280
summary:
  Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic pathogen that causes respiratory infection in humans, ranging from asymptomatic to severe pneumonia. Differences in the behavior of the virus observed between individuals, as well as between humans and dromedary camels, highlight the role of host factors in MERS-CoV pathogenesis and transmission. MERS-CoV infection in these animals merely causes mild upper respiratory tract infection [17, 18] , but seroepidemiological studies showed that this virus has been circulating in dromedary camels for decades, suggesting the efficient transmission of MERS-CoV in this species [19] [20] [21] [22] . Given the fact that experimental in vivo infection studies and DPP4 expression analysis in different animal species revealed that dromedary camels are not the only animals in which MERS-CoV has an upper respiratory tract tropism [17, 18, 83, 84] , it is then relevant to question whether other animals can potentially spread MERS-CoV as well.

abstract:
  Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic pathogen that causes respiratory infection in humans, ranging from asymptomatic to severe pneumonia. In dromedary camels, the virus only causes a mild infection but it spreads efficiently between animals. Differences in the behavior of the virus observed between individuals, as well as between humans and dromedary camels, highlight the role of host factors in MERS-CoV pathogenesis and transmission. One of these host factors, the MERS-CoV receptor dipeptidyl peptidase-4 (DPP4), may be a critical determinant because it is variably expressed in MERS-CoV-susceptible species as well as in humans. This could partially explain inter- and intraspecies differences in the tropism, pathogenesis, and transmissibility of MERS-CoV. In this review, we explore the role of DPP4 and other host factors in MERS-CoV transmission and pathogenesis—such as sialic acids, host proteases, and interferons. Further characterization of these host determinants may potentially offer novel insights to develop intervention strategies to tackle ongoing outbreaks.


id: cord-306923-eujbxdqi
author: Ahmed, Anwar E.
date: 2018-04-25
txt: ./txt/cord-306923-eujbxdqi.txt
cache: ./cache/cord-306923-eujbxdqi.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/29624866/
doi: 10.1111/irv.12560
summary:
  Data on the time intervals between a patient''s presentation or admission to a healthcare facility and the first specimen sample have been limited in patients suspected and screened for MERS-CoV by a real-time reverse-transcription polymerase chain reaction (rRT-PCR) test, as it might correlate with recovery delay intervals. This chart review study was based on information from multicenters and a large sample size, and it provides valuable information on factors associated with prolonged or shorter recovery delay of patients suspected and screened for MERS-CoV by the rRT-PCR test. The study evidence supports that longer recovery delay was seen in patients with older age, MERS-CoV infection, ICU admission, and abnormal radiology findings in a sample of patients diagnosed by rRT-PCR. Factors associated with recovery delay in a sample of patients diagnosed by MERS-CoV rRT-PCR: A Saudi Arabian multicenter retrospective study

title:
  Factors associated with recovery delay in a sample of patients diagnosed by MERS‐CoV rRT‐PCR: A Saudi Arabian multicenter retrospective study

abstract:
  BACKGROUND: Research evidence exists that poor prognosis is common in Middle East respiratory syndrome coronavirus (MERS‐CoV) patients. OBJECTIVES: This study estimates recovery delay intervals and identifies associated factors in a sample of Saudi Arabian patients admitted for suspected MERS‐CoV and diagnosed by rRT‐PCR assay. METHODS: A multicenter retrospective study was conducted on 829 patients admitted between September 2012 and June 2016 and diagnosed by rRT‐PCR procedures to have MERS‐CoV and non‐MERS‐CoV infection in which 396 achieved recovery. Detailed medical charts were reviewed for each patient who achieved recovery. Time intervals in days were calculated from presentation to the initial rRT‐PCR diagnosis (diagnosis delay) and from the initial rRT‐PCR diagnosis to recovery (recovery delay). RESULTS: The median recovery delay in our sample was 5 days. According to the multivariate negative binomial model, elderly (age ≥ 65), MERS‐CoV infection, ICU admission, and abnormal radiology findings were associated with longer recovery delay (adjusted relative risk (aRR): 1.741, 2.138, 2.048, and 1.473, respectively). Camel contact and the presence of respiratory symptoms at presentation were associated with a shorter recovery delay (expedited recovery) (aRR: 0.267 and 0.537, respectively). Diagnosis delay is a positive predictor for recovery delay (r = .421; P = .001). CONCLUSIONS: The study evidence supports that longer recovery delay was seen in patients of older age, MERS‐CoV infection, ICU admission, and abnormal radiology findings. Shorter recovery delay was found in patients who had camel contact and respiratory symptoms at presentation. These findings may help us understand clinical decision making on directing hospital resources toward prompt screening, monitoring, and implementing clinical recovery and treatment strategies.


id: cord-307405-qk1ruj5q
title: Health Care Worker Contact with MERS Patient, Saudi Arabia
author: Hall, Aron J.
date: 2014-12-17
txt: ./txt/cord-307405-qk1ruj5q.txt
cache: ./cache/cord-307405-qk1ruj5q.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/25418612/
doi: 10.3201/eid2012.141211
summary:
  To investigate potential transmission of Middle East respiratory syndrome coronavirus (MERS-CoV) to health care workers in a hospital, we serologically tested hospital contacts of the index case-patient in Saudi Arabia, 4 months after his death. To investigate potential transmission of Middle East respiratory syndrome coronavirus (MERS-CoV) to health care workers in a hospital, we serologically tested hospital contacts of the index case-patient in Saudi Arabia, 4 months after his death. Hospital infection control staff administered a brief, standardized questionnaire to both groups of HCWs. Information was collected on HCW demographics, job duties, and symptoms of respiratory disease during June 15-July 4, 2012, which corresponds to the period when the case-patient was hospitalized and an incubation period of 2-10 days, based on MERS-CoV natural history information available at the time of investigation. In October 2013 (4 months after the case-patient''s death), a blood specimen (<20 mL) was collected from each HCW and transported first to the Ministry of Health Western Regional Laboratory in Saudi Arabia and then to the US Centers for Disease Control and Prevention for MERS-CoV testing.

abstract:
  To investigate potential transmission of Middle East respiratory syndrome coronavirus (MERS-CoV) to health care workers in a hospital, we serologically tested hospital contacts of the index case-patient in Saudi Arabia, 4 months after his death. None of the 48 contacts showed evidence of MERS-CoV infection.


id: cord-307995-8q7efrqk
title: Middle East respiratory syndrome coronavirus: current situation and travel-associated concerns
author: Al-Tawfiq, Jaffar A.
date: 2016-05-04
txt: ./txt/cord-307995-8q7efrqk.txt
cache: ./cache/cord-307995-8q7efrqk.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/s11684-016-0446-y
doi: 10.1007/s11684-016-0446-y
summary:
  Middle East respiratory syndrome coronavirus (MERS-CoV): summary and risk assessment of current situation in the Republic of Korea and China -as of 19 Screening for Middle East respiratory syndrome coronavirus infection in hospital patients and their healthcare worker and family contacts: a prospective descriptive study A family cluster of Middle East Respiratory syndrome coronavirus infections related to a likely unrecognized asymptomatic or mild case Community case clusters of Middle East respiratory syndrome coronavirus in Hafr Al-Batin, Kingdom of Saudi Arabia: a descriptive genomic study Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive genomic study KSA MERS-CoV Investigation Team.Hospital outbreak of Middle East respiratory syndrome coronavirus Middle East respiratory syndrome coronavirus: a case-control study of hospitalized patients Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study Ribavirin and interferon therapy in patients infected with the Middle East respiratory syndrome coronavirus: an observational study

abstract:
  The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 brought back memories of the occurrence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002. More than 1500 MERS-CoV cases were recorded in 42 months with a case fatality rate (CFR) of 40%. Meanwhile, 8000 cases of SARS-CoV were confirmed in six months with a CFR of 10%. The clinical presentation of MERS-CoV ranges from mild and non-specific presentation to progressive and severe pneumonia. No predictive signs or symptoms exist to differentiate MERS-CoV from community-acquired pneumonia in hospitalized patients. An apparent heterogeneity was observed in transmission. Most MERS-CoV cases were secondary to large outbreaks in healthcare settings. These cases were secondary to community-acquired cases, which may also cause family outbreaks. Travel-associated MERS infection remains low. However, the virus exhibited a clear tendency to cause large outbreaks outside the Arabian Peninsula as exemplified by the outbreak in the Republic of Korea. In this review, we summarize the current knowledge about MERS-CoV and highlight travel-related issues.


id: cord-309239-6lso1w0o
title: Inoculation of Goats, Sheep, and Horses with MERS-CoV Does Not Result in Productive Viral Shedding
author: Adney, Danielle R.
date: 2016-08-19
txt: ./txt/cord-309239-6lso1w0o.txt
cache: ./cache/cord-309239-6lso1w0o.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/27548203/
doi: 10.3390/v8080230
summary:
  The Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging pathogen first described from Saudi Arabia in 2012 [1] that can cause severe respiratory disease and death in roughly 36% of infected humans [2] . There is considerable field and experimental evidence that dromedary camels serve as an important reservoir host involved in transmission to humans [3] [4] [5] [6] [7] [8] , but whether other livestock such as goats, sheep, and horses play a role in transmission has only been assessed indirectly. The objective of this study was to determine if goats, sheep, and horses can be infected with MERS-CoV and assess their potential importance in viral transmission. Sheep, goat kids and horses were each inoculated intranasally with 1.4 × 10 6 to 1.9 × 10 6 plaque-forming units (PFU) of a low passage human isolate of MERS-CoV (strain HCoV-EMC/2012) propagated in Vero E6 cells as described previously [11] .

abstract:
  The Middle East respiratory syndrome coronavirus (MERS-CoV) was first recognized in 2012 and can cause severe disease in infected humans. Dromedary camels are the reservoir for the virus, although, other than nasal discharge, these animals do not display any overt clinical disease. Data from in vitro experiments suggest that other livestock such as sheep, goats, and horses might also contribute to viral transmission, although field data has not identified any seropositive animals. In order to understand if these animals could be infected, we challenged young goats and horses and adult sheep with MERS-CoV by intranasal inoculation. Minimal or no virus shedding was detected in all of the animals. During the four weeks following inoculation, neutralizing antibodies were detected in the young goats, but not in sheep or horses.


id: cord-309621-6jj19xpr
author: Yu, Pin
date: 2017-02-24
txt: ./txt/cord-309621-6jj19xpr.txt
cache: ./cache/cord-309621-6jj19xpr.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/28234937/
doi: 10.1371/journal.pone.0172093
summary:
  The main histopathological findings in the lungs of rhesus macaques and common marmosets were varying degrees of pulmonary lesions, including pneumonia, pulmonary oedema, haemorrhage, degeneration and necrosis of the pneumocytes and bronchial epithelial cells, and inflammatory cell infiltration. Although there have been several studies in animal models on the pathogenic mechanisms of MERS-CoV infection, little is known about the comparative pathology and inflammatory cell response in rhesus macaques or common marmosets infected with this virus. Pathological findings in the rhesus macaque tissues HE stained tissues from rhesus macaques experimentally infected with MERS-CoV demonstrate that MERS-CoV induces lesions that are primarily observed in the lungs, with varying degrees of inflammation, interstitial pneumonia (Fig 1A) , pulmonary oedema (Fig 1B) , haemorrhaging, degeneration and necrosis of pneumocytes and bronchial epithelial cells (Fig 1C) , and the infiltration of inflammatory cells. Using immunohistochemical techniques and an ISH analysis, we confirmed that MERS-CoV protein and viral RNA were distributed in the lungs of rhesus macaques and common marmosets and that they were primarily located in the pneumocytes and inflammatory cells.

title:
  Comparative pathology of rhesus macaque and common marmoset animal models with Middle East respiratory syndrome coronavirus

abstract:
  Middle East respiratory syndrome (MERS), which is caused by a newly discovered coronavirus (CoV), has recently emerged. It causes severe viral pneumonia and is associated with a high fatality rate. However, the pathogenesis, comparative pathology and inflammatory cell response of rhesus macaques and common marmosets experimentally infected with MERS-CoV are unknown. We describe the histopathological, immunohistochemical, and ultrastructural findings from rhesus macaque and common marmoset animal models of MERS-CoV infection. The main histopathological findings in the lungs of rhesus macaques and common marmosets were varying degrees of pulmonary lesions, including pneumonia, pulmonary oedema, haemorrhage, degeneration and necrosis of the pneumocytes and bronchial epithelial cells, and inflammatory cell infiltration. The characteristic inflammatory cells in the lungs of rhesus macaques and common marmosets were eosinophils and neutrophils, respectively. Based on these observations, the lungs of rhesus macaques and common marmosets appeared to develop chronic and acute pneumonia, respectively. MERS-CoV antigens and viral RNA were identified in type I and II pneumocytes, alveolar macrophages and bronchial epithelial cells, and ultrastructural observations showed that viral protein was found in type II pneumocytes and inflammatory cells in both species. Correspondingly, the entry receptor DDP4 was found in type I and II pneumocytes, bronchial epithelial cells, and alveolar macrophages. The rhesus macaque and common marmoset animal models of MERS-CoV can be used as a tool to mimic the oncome of MERS-CoV infections in humans. These models can help to provide a better understanding of the pathogenic process of this virus and to develop effective medications and prophylactic treatments.


id: cord-309734-m8miwtha
title: Middle East respiratory syndrome coronavirus experimental transmission using a pig model
author: Vergara‐Alert, J.
date: 2017-06-26
txt: ./txt/cord-309734-m8miwtha.txt
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extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/28653496/
doi: 10.1111/tbed.12668
summary:
  Dromedary camels are the main reservoir of Middle East respiratory syndrome coronavirus (MERS‐CoV), but other livestock species (i.e., alpacas, llamas, and pigs) are also susceptible to infection with MERS‐CoV. Virus was present in nasal swabs of infected animals, and limited amounts of viral RNA, but no infectious virus were detected in the direct contact pigs. However, other animal species such as non-human primates (rhesus macaques and common marmosets), members of the family Camelidae (alpacas and llamas), rabbits and pigs have been demonstrated to be susceptible to MERS-CoV infection (Crameri et al., 2016; Falzarano et al., 2014; Haagmans et al., 2015; Vergara-Alert, van den Brand, et al., 2017; de Wit et al., 2013 de Wit et al., , 2017 . To study whether MERS-CoV might be transmitted between pigs, an experimental transmission study in this animal model was designed and performed under direct and indirect contact settings.

abstract:
  Dromedary camels are the main reservoir of Middle East respiratory syndrome coronavirus (MERS‐CoV), but other livestock species (i.e., alpacas, llamas, and pigs) are also susceptible to infection with MERS‐CoV. Animal‐to‐animal transmission in alpacas was reported, but evidence for transmission in other species has not been proved. This study explored pig‐to‐pig MERS‐CoV transmission experimentally. Virus was present in nasal swabs of infected animals, and limited amounts of viral RNA, but no infectious virus were detected in the direct contact pigs. No virus was detected in the indirect contact group. Furthermore, direct and indirect contact pigs did not develop specific antibodies against MERS‐CoV. Therefore, the role of pigs as reservoir is probably negligible, although it deserves further confirmation.


id: cord-311937-6hadssmh
author: Sherbini, Nahid
date: 2016-06-11
txt: ./txt/cord-311937-6hadssmh.txt
cache: ./cache/cord-311937-6hadssmh.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S2210600615300927
doi: 10.1016/j.jegh.2016.05.002
summary:
  title: Middle East respiratory syndrome coronavirus in Al-Madinah City, Saudi Arabia: Demographic, clinical and survival data METHODS: A retrospective study was conducted of all confirmed MERS-CoV infections from March 2014 to May 2014 at two tertiary care hospitals in Al-Madinah region (Saudi Arabia). Epidemiology of Middle East respiratory syndrome coronavirus (MERS-CoV) was expanded after exploring the large hospital outbreak in Al-Hasa, Saudi Arabia [2] . We obtained data about demographic characteristics, clinical presentation, laboratory results, diagnosis, incubation period, smoking history, comorbidities, and history of contact with camels or MERS-CoV positive patients in regions within the Madinah area. Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study Screening for Middle East respiratory syndrome coronavirus infection in hospital patients and their healthcare worker and family contacts: a prospective descriptive study Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection

title:
  Middle East respiratory syndrome coronavirus in Al-Madinah City, Saudi Arabia: Demographic, clinical and survival data

abstract:
  BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV), is an emerging virus respiratory infection. It has a high mortality rate and a wide spectrum of clinical features. This study describes the clinical characteristics and outcome of MERS infected patients. METHODS: A retrospective study was conducted of all confirmed MERS-CoV infections from March 2014 to May 2014 at two tertiary care hospitals in Al-Madinah region (Saudi Arabia). We gathered data about demographic, clinical presentation, and factors associated with severity and mortality. RESULTS: A total of 29 cases were identified; 20 males (69%) and nine females (31%), age 45 ± 12 years. The death rate was higher for men (52%) than for women (23%). Initial presentation was fever in 22 (75%) cases, cough in 20 (69%) cases, and shortness of breath in 20 (69%) cases. Associated comorbidities were diabetes mellitus in nine (31%) patients and chronic kidney disease (CKD) in eight (27%) patients. Duration of symptoms before hospitalization ranged from 2.9 days to 5 days. Elevated liver enzymes were present in 14 (50%) patients and impaired renal profile present in eight (27%) patients. We also describe in this study radiological patterns and factors associated with mortality. CONCLUSION: MERS-CoV infection transmission continues to occur as clusters in healthcare facilities. The frequency of cases and deaths is higher among men than women and among patients with comorbidities.


id: cord-312692-jv3425w1
author: Iwata-Yoshikawa, Naoko
date: 2019-01-09
txt: ./txt/cord-312692-jv3425w1.txt
cache: ./cache/cord-312692-jv3425w1.txt
extension: .txt
mime: text/plain
url: https://jvi.asm.org/content/jvi/93/6/e01818-18.full.pdf
doi: 10.1128/jvi.01818-18
summary:
  Rodents are not susceptible to the virus because they do not express functional receptors; therefore, we generated a new animal model of MERS-CoV infection based on transgenic mice expressing human DPP4 (hDPP4). To assess innate immune responses in the lungs of Tg2, non-Tg, and C57BL/6 mice, all animals received intranasal administration of PBS with or without (B) Immunohistochemical analysis of hDPP4 expression in human, Tg2, and non-Tg mouse tissues stained with an anti-hDPP4 polyclonal antibody. Tg2 mice aged 10 and 25 weeks showed increased expression of cytokines and chemokines associated with migration of T cells and activation of macrophages, including IP-10, IL-6, IL-13, MCP-1, IFN-␥, MIP-1␣, MIG, and IL-12, in the lungs at day 5 and/or 7 p.i. This result is the same as that observed in a hDPP4 knock-in mouse model reported by Coleman et al.

title:
  Acute Respiratory Infection in Human Dipeptidyl Peptidase 4-Transgenic Mice Infected with Middle East Respiratory Syndrome Coronavirus

abstract:
  Middle East respiratory syndrome coronavirus (MERS-CoV) infection can manifest as a mild illness, acute respiratory distress, organ failure, or death. Several animal models have been established to study disease pathogenesis and to develop vaccines and therapeutic agents. Here, we developed transgenic (Tg) mice on a C57BL/6 background; these mice expressed human CD26/dipeptidyl peptidase 4 (hDPP4), a functional receptor for MERS-CoV, under the control of an endogenous hDPP4 promoter. We then characterized this mouse model of MERS-CoV. The expression profile of hDPP4 in these mice was almost equivalent to that in human tissues, including kidney and lung; however, hDPP4 was overexpressed in murine CD3-positive cells within peripheral blood and lymphoid tissues. Intranasal inoculation of young and adult Tg mice with MERS-CoV led to infection of the lower respiratory tract and pathological evidence of acute multifocal interstitial pneumonia within 7 days, with only transient loss of body weight. However, the immunopathology in young and adult Tg mice was different. On day 5 or 7 postinoculation, lungs of adult Tg mice contained higher levels of proinflammatory cytokines and chemokines associated with migration of macrophages. These results suggest that the immunopathology of MERS-CoV infection in the Tg mouse is age dependent. The mouse model described here will increase our understanding of disease pathogenesis and host mediators that protect against MERS-CoV infection. IMPORTANCE Middle East respiratory syndrome coronavirus (MERS-CoV) infections are endemic in the Middle East and a threat to public health worldwide. Rodents are not susceptible to the virus because they do not express functional receptors; therefore, we generated a new animal model of MERS-CoV infection based on transgenic mice expressing human DPP4 (hDPP4). The pattern of hDPP4 expression in this model was similar to that in human tissues (except lymphoid tissue). In addition, MERS-CoV was limited to the respiratory tract. Here, we focused on host factors involved in immunopathology in MERS-CoV infection and clarified differences in antiviral immune responses between young and adult transgenic mice. This new small-animal model could contribute to more in-depth study of the pathology of MERS-CoV infection and aid development of suitable treatments.


id: cord-312741-0au4nctt
title: Coronavirus in human diseases: Mechanisms and advances in clinical treatment
author: Lin, Panpan
date: 2020-10-01
txt: ./txt/cord-312741-0au4nctt.txt
cache: ./cache/cord-312741-0au4nctt.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/33173860/
doi: 10.1002/mco2.26
summary:
  160, 161 Once the PAMPs from invaded viruses are detected, RIG-I and MDA5 interact with the mitochondrial antiviral signaling protein (MAVs) that is a mitochondrial membrane-bound F I G U R E 2 Escape mechanisms of innate immune response of SARS-CoV and MERS-CoV adaptor molecule, followed by the activation of several kinase complexes and multiple subsequent transcription factors (IRF3, IRF7, and NF-κB). Antiviral peptides analogous derived from these regions exhibited inhibition to the spike protein-mediated cell-cell fusion and viral entry in viruses such as SARS-CoV, MERS-CoV, as well as HCoV-229E. Receptor-binding domain of severe acute respiratory syndrome coronavirus spike protein contains multiple conformation-dependent epitopes that induce highly potent neutralizing antibodies Characterization of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spike glycoprotein-mediated viral entry Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response Inhibition of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infectivity by peptides analogous to the viral spike protein

abstract:
  Coronaviruses (CoVs), a subfamily of coronavirinae, are a panel of single‐stranded RNA virus. Human coronavirus (HCoV) strains (HCoV‐229E, HCoV‐OC43, HCoV‐HKU1, HCoV‐NL63) usually cause mild upper respiratory diseases and are believed to be harmless. However, other HCoVs, associated with severe acute respiratory syndrome, Middle East respiratory syndrome, and COVID‐19, have been identified as important pathogens due to their potent infectivity and lethality worldwide. Moreover, currently, no effective antiviral drugs treatments are available so far. In this review, we summarize the biological characters of HCoVs, their association with human diseases, and current therapeutic options for the three severe HCoVs. We also highlight the discussion about novel treatment strategies for HCoVs infections.


id: cord-313054-w90eitw9
author: Mobaraki, Kazhal
date: 2019-04-27
txt: ./txt/cord-313054-w90eitw9.txt
cache: ./cache/cord-313054-w90eitw9.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/31029095/
doi: 10.1186/s12879-019-3987-2
summary:
  RESULTS: A total of 229 MERS-CoV cases, including 70 deaths (30.5%), were recorded in the disease outbreak news on world health organization website over the study period. Middle East respiratory syndrome coronavirus (MERS-CoV) infection is considered to cause a new viral epidemic [1] , and was first reported in a patient who died from a severe respiratory illness in a hospital in Jeddah, Saudi Arabia, in June 2012 [2, 3] . The occurrence of a large number of MERS-CoV cases and their associated deaths in the world indicate that this disease must be considered as a severe threat to public health [13] because millions of pilgrims from 184 countries converge in Saudi Arabia each year to perform Hajj and Umrah ceremony. Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study

title:
  Current epidemiological status of Middle East respiratory syndrome coronavirus in the world from 1.1.2017 to 17.1.2018: a cross-sectional study

abstract:
  BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) is considered to be responsible for a new viral epidemic and an emergent threat to global health security. This study describes the current epidemiological status of MERS-CoV in the world. METHODS: Epidemiological analysis was performed on data derived from all MERS-CoV cases recorded in the disease outbreak news on WHO website between 1.1.2017 and 17.1.2018. Demographic and clinical information as well as potential contacts and probable risk factors for mortality were extracted based on laboratory-confirmed MERS-CoV cases. RESULTS: A total of 229 MERS-CoV cases, including 70 deaths (30.5%), were recorded in the disease outbreak news on world health organization website over the study period. Based on available details in this study, the case fatality rate in both genders was 30.5% (70/229) [32.1% (55/171) for males and 25.8% (15/58) for females]. The disease occurrence was higher among men [171 cases (74.7%)] than women [58 cases (25.3%)]. Variables such as comorbidities and exposure to MERS-CoV cases were significantly associated with mortality in people affected with MERS-CoV infections, and adjusted odds ratio estimates were 2.2 (95% CI: 1.16, 7.03) and 2.3 (95% CI: 1.35, 8.20), respectively. All age groups had an equal chance of mortality. CONCLUSIONS: In today’s “global village”, there is probability of MERS-CoV epidemic at any time and in any place without prior notice. Thus, health systems in all countries should implement better triage systems for potentially imported cases of MERS-CoV to prevent large epidemics.


id: cord-313737-cob5hf5q
title: The inaugural Healthcare Infection Society Middle East Summit: ‘No action today. No cure tomorrow.’
author: Otter, J. A.
date: 2015-11-30
txt: ./txt/cord-313737-cob5hf5q.txt
cache: ./cache/cord-313737-cob5hf5q.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0195670115003059
doi: 10.1016/j.jhin.2015.06.021
abstract: nan
summary:
  1 The conference opened with Professor Tawfik Khoja outlining the challenges to infection prevention and control in the Middle East. Among the challenges he covered were public reporting and external scrutiny, hand hygiene, antibiotic resistance, the healthcare environment, surveillance and outbreaks, an increasingly elderly population, new threats [such as Ebola and Middle East respiratory syndrome coronavirus (MERS-CoV)], meticillinresistant Staphylococcus aureus (MRSA), C. Dr Phin highlighted a useful CDC toolkit providing advice on respiratory protection for healthcare workers, and also a recent BMJ review concluding that facemasks may help to prevent the spread of respiratory viruses in the community. As to which interventions we should use for each organism, this depends on organism and setting, although screening, isolation, stewardship, hand hygiene, and cleaning/ disinfection are the pillars of infection control. Dr Muhammad Halwani then gave an overview of infection control in the Middle East, focusing on acinetobacter and pseudomonas.


id: cord-314651-e4uaw5fy
author: Zhao, Guangyu
date: 2015-12-23
txt: ./txt/cord-314651-e4uaw5fy.txt
cache: ./cache/cord-314651-e4uaw5fy.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/26701103/
doi: 10.1371/journal.pone.0145561
summary:
  After intranasal inoculation with MERS-CoV, the mice rapidly developed severe pneumonia and multi-organ damage, with viral replication being detected in the lungs on day 5 and in the lungs, kidneys and brains on day 9 post-infection. To assess viral replication and histopathologic damage following MERS-CoV infection, mice were euthanized with overdose inhalational carbon dioxide, and tissues included lungs, kidneys, livers, spleens, intestines and brains were harvested on indicated time points. Although a transgenic mouse model expressing human DPP4 was also established, and its immune response was studied after infection with MERS-CoV [16] , the transgenic mice in the study died on day 6 with only progressive pneumonia and mild perivascular cuffing in brain, and no neurological disorder or other multi-organ damage was observed.

title:
  Multi-Organ Damage in Human Dipeptidyl Peptidase 4 Transgenic Mice Infected with Middle East Respiratory Syndrome-Coronavirus

abstract:
  The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe acute respiratory failure and considerable extrapumonary organ dysfuction with substantial high mortality. For the limited number of autopsy reports, small animal models are urgently needed to study the mechanisms of MERS-CoV infection and pathogenesis of the disease and to evaluate the efficacy of therapeutics against MERS-CoV infection. In this study, we developed a transgenic mouse model globally expressing codon-optimized human dipeptidyl peptidase 4 (hDPP4), the receptor for MERS-CoV. After intranasal inoculation with MERS-CoV, the mice rapidly developed severe pneumonia and multi-organ damage, with viral replication being detected in the lungs on day 5 and in the lungs, kidneys and brains on day 9 post-infection. In addition, the mice exhibited systemic inflammation with mild to severe pneumonia accompanied by the injury of liver, kidney and spleen with neutrophil and macrophage infiltration. Importantly, the mice exhibited symptoms of paralysis with high viral burden and viral positive neurons on day 9. Taken together, this study characterizes the tropism of MERS-CoV upon infection. Importantly, this hDPP4-expressing transgenic mouse model will be applicable for studying the pathogenesis of MERS-CoV infection and investigating the efficacy of vaccines and antiviral agents designed to combat MERS-CoV infection.


id: cord-315576-bgcqkz0p
author: Yamamoto, Naoki
date: 2020-08-05
txt: ./txt/cord-315576-bgcqkz0p.txt
cache: ./cache/cord-315576-bgcqkz0p.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0306987720314912?v=s5
doi: 10.1016/j.mehy.2020.110160
summary:
  The comparison of the numbers of cases and deaths due to SARS-CoV-2 / COVID-19 shows that people in Central Europe are much more affected than people in East Asia where the disease originally occurred. Trying to explain this difference, this communication presents four hypotheses that propose the following reasons for the observed findings: 1) Differences in social behaviors and cultures of people in the two regions; 2) Possible outbreak of virulent viruses in Central Europe due to multiple viral infection, and the involvement of immuno-virological factors associated with it, 3) Possibility of corona resistance gene mutation occurring among East Asians as a result of long-term co-evolution of virus and host, and 4) possible involvement of hygienic factors. For the analysis of the difference regarding the number of infected people and the death tolls due to COVID-19 between Central European and East Asian 5 countries, we have chosen Italy, Spain, France, Germany and UK from Central Europe and China, South Korea, Japan, and Taiwan from South East Asia.

title:
  Apparent difference in fatalities between Central Europe and East Asia due to SARS-COV-2 and COVID-19: Four hypotheses for possible explanation

abstract:
  The comparison of the numbers of cases and deaths due to SARS-CoV-2 / COVID-19 shows that people in Central Europe are much more affected than people in East Asia where the disease originally occurred. Trying to explain this difference, this communication presents four hypotheses that propose the following reasons for the observed findings: 1) Differences in social behaviors and cultures of people in the two regions; 2) Possible outbreak of virulent viruses in Central Europe due to multiple viral infection, and the involvement of immuno-virological factors associated with it, 3) Possibility of corona resistance gene mutation occurring among East Asians as a result of long-term co-evolution of virus and host, and 4) possible involvement of hygienic factors. Direct or indirect supportive evidences for each one of our hypotheses are presented and experimental approaches for their evaluation are discussed. Finally, we suggest that the dynamics of the pandemic also shows that the problems of the new coronavirus can be overcome due to people's awareness of the epidemics, rational viral diagnostics and a high level of medical care.


id: cord-317403-1wrsuoy7
title: Middle East Respiratory Syndrome in 3 Persons, South Korea, 2015
author: Yang, Jeong-Sun
date: 2015-11-17
txt: ./txt/cord-317403-1wrsuoy7.txt
cache: ./cache/cord-317403-1wrsuoy7.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/26488745/
doi: 10.3201/eid2111.151016
summary:
  In May 2015, Middle East respiratory syndrome coronavirus infection was laboratory confirmed in South Korea. For the index patient, MERS-CoV RNA was detectable in sputum, throat swab, and serum samples but not in a urine sample collected 9 days after symptom onset ( Table 1) . Because, to our knowledge, cases of MERS-CoV infection in South Korea have not been reported, we had to establish laboratory testing protocols to overcome vulnerabilities in the absence of appropriate epidemiologic support (i.e., generate positive controls to check for contamination and repeat testing). Although the source of infection for the index patient is unclear, phylogenetic analysis of the whole viral genome showed that the isolate from South Korea was closely related to the MERS-CoV strains isolated in Saudi Arabia in 2015. Probable transmission chains of Middle East respiratory syndrome coronavirus and the multiple generations of secondary infection in South Korea

abstract:
  In May 2015, Middle East respiratory syndrome coronavirus infection was laboratory confirmed in South Korea. Patients were a man who had visited the Middle East, his wife, and a man who shared a hospital room with the index patient. Rapid laboratory confirmation will facilitate subsequent prevention and control for imported cases.


id: cord-317688-mr851682
title: Middle East respiratory syndrome: what we learned from the 2015 outbreak in the Republic of Korea
author: Oh, Myoung-don
date: 2018-02-27
txt: ./txt/cord-317688-mr851682.txt
cache: ./cache/cord-317688-mr851682.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3904/kjim.2018.031
doi: 10.3904/kjim.2018.031
summary:
  Middle East Respiratory Syndrome coronavirus (MERS-CoV) was first isolated from a patient with severe pneumonia in 2012. Middle East respiratory syndrome coronavirus (MERS-CoV) was first isolated from a patient with severe pneumonia in September 2012 [1] . The first patient (index case) with MERS-CoV infection was a 68-year-old Korean man returning from the Middle East. Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in South Korea, 2015: epidemiology, characteristics and public health implications Risk factors for transmission of Middle East respiratory syndrome coronavirus infection during the 2015 outbreak in South Korea Clinical implications of 5 cases of Middle East respiratory syndrome coronavirus infection in a South Korean outbreak Renal complications and their prognosis in Korean patients with Middle East respiratory syndrome-coronavirus from the central MERS-CoV designated hospital Successful treatment of suspected organizing pneumonia in a patient with Middle East respiratory syndrome coronavirus infection: a case report

abstract:
  Middle East Respiratory Syndrome coronavirus (MERS-CoV) was first isolated from a patient with severe pneumonia in 2012. The 2015 Korea outbreak of MERSCoV involved 186 cases, including 38 fatalities. A total of 83% of transmission events were due to five superspreaders, and 44% of the 186 MERS cases were the patients who had been exposed in nosocomial transmission at 16 hospitals. The epidemic lasted for 2 months and the government quarantined 16,993 individuals for 14 days to control the outbreak. This outbreak provides a unique opportunity to fill the gap in our knowledge of MERS-CoV infection. Therefore, in this paper, we review the literature on epidemiology, virology, clinical features, and prevention of MERS-CoV, which were acquired from the 2015 Korea outbreak of MERSCoV.


id: cord-318181-xxc7vdnt
author: Ahmed, Anwar E.
date: 2018-03-14
txt: ./txt/cord-318181-xxc7vdnt.txt
cache: ./cache/cord-318181-xxc7vdnt.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/29550445/
doi: 10.1016/j.ijid.2018.03.005
summary:
  A total of 360 patients with confirmed pneumonia who were evaluated for MERS-CoV infection by real-time reverse transcription polymerase chain reaction (rRT-PCR) between September 1, 2012 and June 1, 2016 at King Abdulaziz Medical City in Riyadh and King Fahad General Hospital in Jeddah, were included. Nineteen predictive variables were included: age, sex, fever (temperature !38 C), one composite respiratory symptom (the presence of cough, bloody cough, shortness of breath, or chest pain), one composite gastrointestinal symptoms (the presence of diarrhea, vomiting, or nausea), seven MERS-CoV potential risk factors (contact with sick patients or camels, severe illness (defined according to the patient''s clinical status, ''yes/no'', which is based on clinical judgment), diabetes, lung disease, liver disease, renal disease, and heart disease), and seven laboratory measurements (white blood cell (WBC) count (Â10 9 /l), platelets (Â10 9 /l), creatinine (mmol/l), bilirubin (mmol/l), alanine aminotransferase (ALT; U/l), aspartate aminotransferase (AST; U/l), and albumin (g/ l)).

title:
  Early identification of pneumonia patients at increased risk of Middle East respiratory syndrome coronavirus infection in Saudi Arabia

abstract:
  BACKGROUND: The rapid and accurate identification of individuals who are at high risk of Middle East respiratory syndrome coronavirus (MERS-CoV) infection remains a major challenge for the medical and scientific communities. The aim of this study was to develop and validate a risk prediction model for the screening of suspected cases of MERS-CoV infection in patients who have developed pneumonia. METHODS: A two-center, retrospective case–control study was performed. A total of 360 patients with confirmed pneumonia who were evaluated for MERS-CoV infection by real-time reverse transcription polymerase chain reaction (rRT-PCR) between September 1, 2012 and June 1, 2016 at King Abdulaziz Medical City in Riyadh and King Fahad General Hospital in Jeddah, were included. According to the rRT-PCR results, 135 patients were positive for MERS-CoV and 225 were negative. Demographic characteristics, clinical presentations, and radiological and laboratory findings were collected for each subject. RESULTS: A risk prediction model to identify pneumonia patients at increased risk of MERS-CoV was developed. The model included male sex, contact with a sick patient or camel, diabetes, severe illness, low white blood cell (WBC) count, low alanine aminotransferase (ALT), and high aspartate aminotransferase (AST). The model performed well in predicting MERS-CoV infection (area under the receiver operating characteristics curves (AUC) 0.8162), on internal validation (AUC 0.8037), and on a goodness-of-fit test (p = 0.592). The risk prediction model, which produced an optimal probability cut-off of 0.33, had a sensitivity of 0.716 and specificity of 0.783. CONCLUSIONS: This study provides a simple, practical, and valid algorithm to identify pneumonia patients at increased risk of MERS-CoV infection. This risk prediction model could be useful for the early identification of patients at the highest risk of MERS-CoV infection. Further validation of the prediction model on a large prospective cohort of representative patients with pneumonia is necessary.


id: cord-318585-cp76qr9f
author: Matsuyama, Ryota
date: 2016-11-29
txt: ./txt/cord-318585-cp76qr9f.txt
cache: ./cache/cord-318585-cp76qr9f.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/27899100/
doi: 10.1186/s12889-016-3881-4
summary:
  BACKGROUND: While the risk of severe complications of Middle East respiratory syndrome (MERS) and its determinants have been explored in previous studies, a systematic analysis of published articles with different designs and populations has yet to be conducted. We identified older age, male sex and underlying medical conditions, including diabetes mellitus, renal disease, respiratory disease, heart disease and hypertension, as clinical predictors of death associated with MERS. PICO statement: Our study question is focused on laboratory confirmed cases of MERS regardless of their treatment status, and thus, involves only retrospective observational studies, measuring their risks of admission to Intensive Care Unit (ICU) and death and comparing those risks by age, gender and underlying comorbidities. The present study systematically reviewed the risk of severe manifestations and death by MERS by systematically searching and analyzing published articles from the KSA and the ROK and calculating not only the CFR but [16] . For Fig. 4 Estimated risks associated with Middle East respiratory syndrome (MERS) by study design.

title:
  Clinical determinants of the severity of Middle East respiratory syndrome (MERS): a systematic review and meta-analysis

abstract:
  BACKGROUND: While the risk of severe complications of Middle East respiratory syndrome (MERS) and its determinants have been explored in previous studies, a systematic analysis of published articles with different designs and populations has yet to be conducted. The present study aimed to systematically review the risk of death associated with MERS as well as risk factors for associated complications. METHODS: PubMed and Web of Science databases were searched for clinical and epidemiological studies on confirmed cases of MERS. Eligible articles reported clinical outcomes, especially severe complications or death associated with MERS. Risks of admission to intensive care unit (ICU), mechanical ventilation and death were estimated. Subsequently, potential associations between MERS-associated death and age, sex, underlying medical conditions and study design were explored. RESULTS: A total of 25 eligible articles were identified. The case fatality risk ranged from 14.5 to 100%, with the pooled estimate at 39.1%. The risks of ICU admission and mechanical ventilation ranged from 44.4 to 100% and from 25.0 to 100%, with pooled estimates at 78.2 and 73.0%, respectively. These risks showed a substantial heterogeneity among the identified studies, and appeared to be the highest in case studies focusing on ICU cases. We identified older age, male sex and underlying medical conditions, including diabetes mellitus, renal disease, respiratory disease, heart disease and hypertension, as clinical predictors of death associated with MERS. In ICU case studies, the expected odds ratios (OR) of death among patients with underlying heart disease or renal disease to patients without such comorbidities were 0.6 (95% Confidence Interval (CI): 0.1, 4.3) and 0.6 (95% CI: 0.0, 2.1), respectively, while the ORs were 3.8 (95% CI: 3.4, 4.2) and 2.4 (95% CI: 2.0, 2.9), respectively, in studies with other types of designs. CONCLUSIONS: The heterogeneity for the risk of death and severe manifestations was substantially high among the studies, and varying study designs was one of the underlying reasons for this heterogeneity. A statistical estimation of the risk of MERS death and identification of risk factors must be conducted, particularly considering the study design and potential biases associated with case detection and diagnosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12889-016-3881-4) contains supplementary material, which is available to authorized users.


id: cord-318872-0e5zjaz1
title: MERS transmission and risk factors: a systematic review
author: Park, Ji-Eun
date: 2018-05-02
txt: ./txt/cord-318872-0e5zjaz1.txt
cache: ./cache/cord-318872-0e5zjaz1.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/29716568/
doi: 10.1186/s12889-018-5484-8
summary:
  BACKGROUND: Since Middle East respiratory syndrome (MERS) infection was first reported in 2012, many studies have analysed its transmissibility and severity. The incubation period was reported to be 6.83-7 days in South Korea [4, 5] , but 5.5 in a study using data from multiple areas [6] and 5.2 in Saudi Arabia [7] . Although one study from Saudi Arabia reported longer than 17 days from onset to death [36] , Sha et al., comparing data between the Middle East and South Korea, reported similar periods of 11.5 and 11 days, respectively [29] . Mortality of MERS patients was found to be 20.4% in South Korea based on a report including all cases [27] , but most studies from Saudi Arabia reported higher rates, from 22 to 69.2% [7, 22, 33, [37] [38] [39] . Risk factors for transmission of Middle East respiratory syndrome coronavirus infection during the 2015 outbreak in South Korea

abstract:
  BACKGROUND: Since Middle East respiratory syndrome (MERS) infection was first reported in 2012, many studies have analysed its transmissibility and severity. However, the methodology and results of these studies have varied, and there has been no systematic review of MERS. This study reviews the characteristics and associated risk factors of MERS. METHOD: We searched international (PubMed, ScienceDirect, Cochrane) and Korean databases (DBpia, KISS) for English- or Korean-language articles using the terms “MERS” and “Middle East respiratory syndrome”. Only human studies with > 20 participants were analysed to exclude studies with low representation. Epidemiologic studies with information on transmissibility and severity of MERS as well as studies containing MERS risk factors were included. RESULT: A total of 59 studies were included. Most studies from Saudi Arabia reported higher mortality (22–69.2%) than those from South Korea (20.4%). While the R(0) value in Saudi Arabia was < 1 in all but one study, in South Korea, the R(0) value was 2.5–8.09 in the early stage and decreased to < 1 in the later stage. The incubation period was 4.5–5.2 days in Saudi Arabia and 6–7.8 days in South Korea. Duration from onset was 4–10 days to confirmation, 2.9–5.3 days to hospitalization, 11–17 days to death, and 14–20 days to discharge. Older age and concomitant disease were the most common factors related to MERS infection, severity, and mortality. CONCLUSION: The transmissibility and severity of MERS differed by outbreak region and patient characteristics. Further studies assessing the risk of MERS should consider these factors.


id: cord-319006-6f2sl0bp
author: Plipat, Tanarak
date: 2017-08-17
txt: ./txt/cord-319006-6f2sl0bp.txt
cache: ./cache/cord-319006-6f2sl0bp.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.2807/1560-7917.es.2017.22.33.30598
doi: 10.2807/1560-7917.es.2017.22.33.30598
summary:
  title: Imported case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection from Oman to Thailand, June 2015 Thailand reported the first Middle East respiratory syndrome (MERS) case on 18 June 2015 (day 4) in an Omani patient with heart condition who was diagnosed with pneumonia on hospital admission on 15 June 2015 (day 1). From 2012 to 21 July 2017, there have been 2,040 reported laboratory-confirmed cases and 712 deaths from Middle East respiratory syndrome coronavirus (MERS-CoV) infection in 27 countries [1] . A single imported case of Middle East respiratory syndrome (MERS) in South Korea, identified on 20 May 2015, resulted in 150 laboratory-confirmed cases, amplified by infection in hospitals and the transfer of patients within and between hospitals, and caused 15 deaths within 26 days, mainly among patients, visitors and healthcare personnel [2] .

title:
  Imported case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection from Oman to Thailand, June 2015

abstract:
  Thailand reported the first Middle East respiratory syndrome (MERS) case on 18 June 2015 (day 4) in an Omani patient with heart condition who was diagnosed with pneumonia on hospital admission on 15 June 2015 (day 1). Two false negative RT-PCR on upper respiratory tract samples on days 2 and 3 led to a 48-hour diagnosis delay and a decision to transfer the patient out of the negative pressure unit (NPU). Subsequent examination of sputum later on day 3 confirmed MERS coronavirus (MERS-CoV) infection. The patient was immediately moved back into the NPU and then transferred to Bamrasnaradura Infectious Disease Institute. Over 170 contacts were traced; 48 were quarantined and 122 self-monitored for symptoms. High-risk close contacts exhibiting no symptoms, and whose laboratory testing on the 12th day after exposure was negative, were released on the 14th day. The Omani Ministry of Health (MOH) was immediately notified using the International Health Regulation (IHR) mechanism. Outbreak investigation was conducted in Oman, and was both published on the World Health Organization (WHO) intranet and shared with Thailand’s IHR focal point. The key to successful infection control, with no secondary transmission, were the collaborative efforts among hospitals, laboratories and MOHs of both countries.


id: cord-319877-izn315hb
title: SARS and MERS: recent insights into emerging coronaviruses
author: de Wit, Emmie
date: 2016-06-27
txt: ./txt/cord-319877-izn315hb.txt
cache: ./cache/cord-319877-izn315hb.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1038/nrmicro.2016.81
doi: 10.1038/nrmicro.2016.81
summary:
  Scientific advancements since the 2002–2003 severe acute respiratory syndrome coronavirus (SARS-CoV) pandemic allowed for rapid progress in our understanding of the epidemiology and pathogenesis of MERS-CoV and the development of therapeutics. The downregulation of ACE2 results in the excessive production of angiotensin II by the related enzyme ACE, and it has been suggested that the stimulation of type 1a angiotensin II receptor and Middle East respiratory syndrome coronavirus (MERS-CoV) encode two large polyproteins, pp1a and pp1ab, which are proteolytically cleaved into 16 non-structural proteins (nsps), including papain-like protease (PLpro), 3C-like protease (3CLpro), RNA-dependent RNA polymerase (RdRp), helicase (Hel) and exonuclease (ExoN). Both severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) have developed mechanisms to interfere with these signalling pathways, as shown; these subversion strategies involve both structural proteins (membrane (M) and nucleocapsid (N)) and non-structural proteins (nsp1, nsp3b, nsp4a, nsp4b, nsp5, nsp6 and papain-like protease (PLpro); indicated in the figure by just their nsp numbers and letters).

abstract:
  The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 marked the second introduction of a highly pathogenic coronavirus into the human population in the twenty-first century. The continuing introductions of MERS-CoV from dromedary camels, the subsequent travel-related viral spread, the unprecedented nosocomial outbreaks and the high case-fatality rates highlight the need for prophylactic and therapeutic measures. Scientific advancements since the 2002–2003 severe acute respiratory syndrome coronavirus (SARS-CoV) pandemic allowed for rapid progress in our understanding of the epidemiology and pathogenesis of MERS-CoV and the development of therapeutics. In this Review, we detail our present understanding of the transmission and pathogenesis of SARS-CoV and MERS-CoV, and discuss the current state of development of measures to combat emerging coronaviruses. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrmicro.2016.81) contains supplementary material, which is available to authorized users.


id: cord-320709-2pnqpljt
title: Replication and shedding of MERS-CoV in Jamaican fruit bats (Artibeus jamaicensis)
author: Munster, Vincent J.
date: 2016-02-22
txt: ./txt/cord-320709-2pnqpljt.txt
cache: ./cache/cord-320709-2pnqpljt.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1038/srep21878
doi: 10.1038/srep21878
summary:
  The Mx1, ISG56 and RANTES gene expression in the lungs of Jamaican fruit bats was analyzed as an indicator of the induction of an innate immune response to MERS-CoV infection. The tissue tropism of MERS-CoV in Jamaican fruit bats is comparable to the respiratory tract tropism observed in dromedary camels and humans 49, 50 . MERS-CoV and related batCoV-HKU4 can inhibit innate immune signaling in a variety of human cell lines in vitro via the ORF4b-encoded accessory proteins 52 Lungs of Jamaican fruit bat 5 were stained with α -cytokeratin as an epithelial marker (purple) and with a polyclonal α -coronavirus antibody (brown-red) to demonstrate that viral antigen was located along the basement membrane of alveolar pneumocytes of bat 1 at 2 dpi (indicated by black arrows). Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels

abstract:
  The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) highlights the zoonotic potential of Betacoronaviruses. Investigations into the origin of MERS-CoV have focused on two potential reservoirs: bats and camels. Here, we investigated the role of bats as a potential reservoir for MERS-CoV. In vitro, the MERS-CoV spike glycoprotein interacted with Jamaican fruit bat (Artibeus jamaicensis) dipeptidyl peptidase 4 (DPP4) receptor and MERS-CoV replicated efficiently in Jamaican fruit bat cells, suggesting there is no restriction at the receptor or cellular level for MERS-CoV. To shed light on the intrinsic host-virus relationship, we inoculated 10 Jamaican fruit bats with MERS-CoV. Although all bats showed evidence of infection, none of the bats showed clinical signs of disease. Virus shedding was detected in the respiratory and intestinal tract for up to 9 days. MERS-CoV replicated transiently in the respiratory and, to a lesser extent, the intestinal tracts and internal organs; with limited histopathological changes observed only in the lungs. Analysis of the innate gene expression in the lungs showed a moderate, transient induction of expression. Our results indicate that MERS-CoV maintains the ability to replicate in bats without clinical signs of disease, supporting the general hypothesis of bats as ancestral reservoirs for MERS-CoV.


id: cord-320746-iuzfexig
title: Middle East Respiratory Syndrome Coronavirus: Update for Clinicians
author: Rasmussen, Sonja A.
date: 2015-02-20
txt: ./txt/cord-320746-iuzfexig.txt
cache: ./cache/cord-320746-iuzfexig.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/25701855/
doi: 10.1093/cid/civ118
summary:
  Although much recent focus has been on the recognition of Ebola virus disease among travelers from West Africa, cases of Middle East respiratory syndrome coronavirus (MERS-CoV), including travel-associated cases, continue to be reported. Although much recent focus has been appropriately placed on the recognition of Ebola virus disease in travelers returning from West Africa, the recent increase in cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection (including travelassociated cases) is also of concern [1, 2] . Update on the epidemiology of Middle East respiratory syndrome coronavirus (MERS-CoV) infection, and guidance for the public, clinicians, and public health authorities First confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in the United States, updated information on the epidemiology of MERS-CoV infection, and guidance for the public, clinicians, and public health authorities

abstract:
  Although much recent focus has been on the recognition of Ebola virus disease among travelers from West Africa, cases of Middle East respiratory syndrome coronavirus (MERS-CoV), including travel-associated cases, continue to be reported. US clinicians need to be familiar with recommendations regarding when to suspect MERS-CoV, how to make a diagnosis, and what infection control measures need to be instituted when a case is suspected. Infection control is especially critical, given that most cases have been healthcare-associated. Two cases of MERS-CoV were identified in the United States in May 2014; because these cases were detected promptly and appropriate control measures were put in place quickly, no secondary cases occurred. This paper summarizes information that US clinicians need to know to prevent secondary cases of MERS-CoV from occurring in the United States.


id: cord-320921-eumuid3r
title: Lack of Middle East Respiratory Syndrome Coronavirus Transmission in Rabbits
author: Widagdo, W.
date: 2019-04-24
txt: ./txt/cord-320921-eumuid3r.txt
cache: ./cache/cord-320921-eumuid3r.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/31022948/
doi: 10.3390/v11040381
summary:
  Our data indicate that despite relatively high viral RNA levels produced, low levels of infectious virus are excreted in the upper respiratory tract of rabbits as compared to dromedary camels, thus resulting in a lack of viral transmission. Besides dromedary camels, other animal species, i.e. llamas, alpacas, and pigs have been shown to be susceptible and develop upper respiratory tract infection upon experimental intranasal MERS-CoV inoculation [9] [10] [11] . We found that rabbits inoculated with the MERS-CoV EMC strain and those with the Qatar15 strain developed an equally mild infection and shed similar levels of viral RNA in their nasal and throat swabs (Figure 3 ). We found that rabbits inoculated with the MERS-CoV EMC strain and those with the Qatar15 strain developed an equally mild infection and shed similar levels of viral RNA in their nasal and throat swabs (Figure 3 ).

abstract:
  Middle East respiratory syndrome coronavirus (MERS-CoV) transmission from dromedaries to humans has resulted in major outbreaks in the Middle East. Although some other livestock animal species have been shown to be susceptible to MERS-CoV, it is not fully understood why the spread of the virus in these animal species has not been observed in the field. In this study, we used rabbits to further characterize the transmission potential of MERS-CoV. In line with the presence of MERS-CoV receptor in the rabbit nasal epithelium, high levels of viral RNA were shed from the nose following virus inoculation. However, unlike MERS-CoV-infected dromedaries, these rabbits did not develop clinical manifestations including nasal discharge and did shed only limited amounts of infectious virus from the nose. Consistently, no transmission by contact or airborne routes was observed in rabbits. Our data indicate that despite relatively high viral RNA levels produced, low levels of infectious virus are excreted in the upper respiratory tract of rabbits as compared to dromedary camels, thus resulting in a lack of viral transmission.


id: cord-322760-tsxniu3j
author: Sha, Jianping
date: 2016-09-23
txt: ./txt/cord-322760-tsxniu3j.txt
cache: ./cache/cord-322760-tsxniu3j.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/27664026/
doi: 10.1007/s00705-016-3062-x
summary:
  Thus, older age, pre-existing concurrent diseases, and delayed confirmation increase the odds of a fatal outcome in nosocomial MERS-CoV outbreaks in the Middle East and South Korea. Information on all laboratory-confirmed MERS cases was obtained from various publicly available sources, including WHO Global Alert and Response updates, documents officially released by the local health bureau, news releases from Middle Eastern and South Korean authorities, the Weekly Epidemiological Record, ProMed posts, and literature published from 1 April 2012 to 29 June 2016 (http:// www.who.int/csr/don/archive/disease/coronavirus_infections/ en/). In this study, we compared the mortality risk factors in two different nosocomial outbreaks, based on 51 nosocomial outbreaks of MERS-CoV infection in the Middle East and one large outbreak identified in South Korea. The severity of nosocomial outbreaks and the risk of fatal infection in HCP were significantly lower than the overall rate in the Middle East and South Korea. Middle East respiratory syndrome coronavirus (MERS-CoV) nosocomial outbreak in South Korea: insights from modeling

title:
  Fatality risks for nosocomial outbreaks of Middle East respiratory syndrome coronavirus in the Middle East and South Korea

abstract:
  Middle East respiratory syndrome coronavirus (MERS-CoV) was first isolated in 2012. The largest known outbreak outside the Middle East occurred in South Korea in 2015. As of 29 June 2016, 1769 laboratory-confirmed cases (630 deaths; 35.6 % case fatality rate [CFR]) had been reported from 26 countries, particularly in the Middle East. However, the CFR for hospital outbreaks was higher than that of family clusters in the Middle East and Korea. Here, we compared the mortality rates for 51 nosocomial outbreaks in the Middle East and one outbreak of MERS-CoV in South Korea. Our findings showed the CFR in the Middle East was much higher than that in South Korea (25.9 % [56/216] vs. 13.8 % [24/174], p = 0.003). Infected individuals who died were, on average, older than those who survived in both the Middle East (64 years [25–98] vs. 46 years [2–85], p = 0.000) and South Korea (68 years [49–82] vs. 53.5 years [16–87], p = 0.000). Similarly, the co-morbidity rates for the fatal cases were statistically higher than for the nonfatal cases in both the Middle East (64.3 % [36/56] vs. 28.1 % [45/160], p = 0.000) and South Korea (45.8 % [11/24] vs. 12.0 % [18/150], p = 0.000). The median number of days from onset to confirmation of infection in the fatal cases was longer than that for survivors from the Middle East (8 days [1–47] vs. 4 days [0–14], p = 0.009). Thus, older age, pre-existing concurrent diseases, and delayed confirmation increase the odds of a fatal outcome in nosocomial MERS-CoV outbreaks in the Middle East and South Korea. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00705-016-3062-x) contains supplementary material, which is available to authorized users.


id: cord-323087-3cxyogor
title: Tissue Distribution of the MERS-Coronavirus Receptor in Bats
author: Widagdo, W.
date: 2017-04-26
txt: ./txt/cord-323087-3cxyogor.txt
cache: ./cache/cord-323087-3cxyogor.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/28446791/
doi: 10.1038/s41598-017-01290-6
summary:
  Middle East respiratory syndrome coronavirus (MERS-CoV) has been shown to infect both humans and dromedary camels using dipeptidyl peptidase-4 (DPP4) as its receptor. Apart from dromedary camels, insectivorous bats are suggested as another natural reservoir for MERS-like-CoVs. In order to gain insight on the tropism of these viruses in bats, we studied the DPP4 distribution in the respiratory and extra-respiratory tissues of two frugivorous bat species (Epomophorus gambianus and Rousettus aegyptiacus) and two insectivorous bat species (Pipistrellus pipistrellus and Eptesicus serotinus). The limited DPP4 expression in the respiratory tract of the two insectivorous bat species, particularly the common pipistrelle bat, is different from what has been reported for dromedary camels and humans. More importantly, the tissue distribution of DPP4 in insectivorous bats, believed to be one of the natural hosts for MERS-like-CoVs, is different to that in dromedary camels and humans.

abstract:
  Middle East respiratory syndrome coronavirus (MERS-CoV) has been shown to infect both humans and dromedary camels using dipeptidyl peptidase-4 (DPP4) as its receptor. The distribution of DPP4 in the respiratory tract tissues of humans and camels reflects MERS-CoV tropism. Apart from dromedary camels, insectivorous bats are suggested as another natural reservoir for MERS-like-CoVs. In order to gain insight on the tropism of these viruses in bats, we studied the DPP4 distribution in the respiratory and extra-respiratory tissues of two frugivorous bat species (Epomophorus gambianus and Rousettus aegyptiacus) and two insectivorous bat species (Pipistrellus pipistrellus and Eptesicus serotinus). In the frugivorous bats, DPP4 was present in epithelial cells of both the respiratory and the intestinal tract, similar to what has been reported for camels and humans. In the insectivorous bats, however, DPP4 expression in epithelial cells of the respiratory tract was almost absent. The preferential expression of DPP4 in the intestinal tract of insectivorous bats, suggests that transmission of MERS-like-CoVs mainly occurs via the fecal-oral route. Our results highlight differences in the distribution of DPP4 expression among MERS-CoV susceptible species, which might influence variability in virus tropism, pathogenesis and transmission route.


id: cord-323125-qtlevnbt
author: Al Hosani, Farida Ismail
date: 2019-02-01
txt: ./txt/cord-323125-qtlevnbt.txt
cache: ./cache/cord-323125-qtlevnbt.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/cid/ciy503
doi: 10.1093/cid/ciy503
summary:
  BACKGROUND: Although there is evidence of person-to-person transmission of Middle East respiratory syndrome coronavirus (MERS-CoV) in household and healthcare settings, more data are needed to describe and better understand the risk factors and transmission routes in both settings, as well as the extent to which disease severity affects transmission. METHODS: A seroepidemiological investigation was conducted among MERS-CoV case patients (cases) and their household contacts to investigate transmission risk in Abu Dhabi, United Arab Emirates. In this investigation, we use serological detection of MERS-CoV antibodies to evaluate if asymptomatic or mildly ill case patients had detectable MERS-CoV antibodies, estimate transmission rates from known cases to their household contacts, and identify potential risk factors. For each MERS-CoV case identified in the investigation, clinical information, including symptoms, was collected using the International Severe Acute Respiratory and Emerging Infection Consortium form, which was filled out in real time by healthcare providers and subsequently verified by retrospective chart review.

title:
  Serologic Follow-up of Middle East Respiratory Syndrome Coronavirus Cases and Contacts—Abu Dhabi, United Arab Emirates

abstract:
  BACKGROUND: Although there is evidence of person-to-person transmission of Middle East respiratory syndrome coronavirus (MERS-CoV) in household and healthcare settings, more data are needed to describe and better understand the risk factors and transmission routes in both settings, as well as the extent to which disease severity affects transmission. METHODS: A seroepidemiological investigation was conducted among MERS-CoV case patients (cases) and their household contacts to investigate transmission risk in Abu Dhabi, United Arab Emirates. Cases diagnosed between 1 January 2013 and 9 May 2014 and their household contacts were approached for enrollment. Demographic, clinical, and exposure history data were collected. Sera were screened by MERS-CoV nucleocapsid protein enzyme-linked immunosorbent assay and indirect immunofluorescence, with results confirmed by microneutralization assay. RESULTS: Thirty-one of 34 (91%) case patients were asymptomatic or mildly symptomatic and did not require oxygen during hospitalization. MERS-CoV antibodies were detected in 13 of 24 (54%) case patients with available sera, including 1 severely symptomatic, 9 mildly symptomatic, and 3 asymptomatic case patients. No serologic evidence of MERS-CoV transmission was found among 105 household contacts with available sera. CONCLUSIONS: Transmission of MERS-CoV was not documented in this investigation of mostly asymptomatic and mildly symptomatic cases and their household contacts. These results have implications for clinical management of cases and formulation of isolation policies to reduce the risk of transmission.


id: cord-323428-jd91k19z
author: Ababneh, Mustafa
date: 2019-10-11
txt: ./txt/cord-323428-jd91k19z.txt
cache: ./cache/cord-323428-jd91k19z.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.14202/vetworld.2019.1554-1562
doi: 10.14202/vetworld.2019.1554-1562
summary:
  CONCLUSION: The results of this study suggest that this recombinant adenovirus vaccine encoding the S1 subunit of MERS-CoV elicits potentially protective antigen-specific humoral and cellular immune responses in mice. Distribution and expression of the S1 subunit of the MERS-CoV spike protein in mice tissues were detected at weeks 3 and 5 post first immunization in the kidneys and lungs of the vaccinated group but not in control groups using conventional PCR (Figure-1 ). In contrast, IL-4 production in cell culture showed a significant increase in control animals after antigen stimulation, while the production of this cytokine was significantly decreased in the At week 4, the fold change in IFN-γ gene expression was significantly higher in the Ad-Middle East respiratory syndrome (MERS)-S1 group than that of both control groups (Ad-cytomegalovirus [CMV] and phosphate-buffered saline).

title:
  Recombinant adenoviral vaccine encoding the spike 1 subunit of the Middle East Respiratory Syndrome Coronavirus elicits strong humoral and cellular immune responses in mice

abstract:
  BACKGROUND AND AIM: Middle East respiratory syndrome coronavirus (MERS-CoV) has rapidly spread throughout the Middle East since its discovery in 2012. The virus poses a significant global public health threat with potentially devastating effects. In this study, a recombinant adenoviral-based vaccine encoding the spike 1 (S1) subunit of the MERS-CoV genome was constructed, and its humoral, and cellular immune responses were evaluated in mice. MATERIALS AND METHODS: Mice were immunized initially by intramuscular injection and boosted 3 weeks later by intranasal application. Expression of the S1 protein in the lungs and kidneys was detected using conventional polymerase chain reaction (PCR) and immunohistochemistry (IHC) targeting specific regions within the S1 subunit at weeks 3, 4, 5, and 6 after the first vaccination. Antigen-specific humoral and cellular immune responses were evaluated in serum and in cell culture following in vitro stimulation with a specific 9-mer epitope within the S1 protein (CYSSLILDY). RESULTS: S1 protein expression was only detected by IHC in the kidneys of the Ad-MERS-S1 group at week 6 from first immunization, and in both lungs and kidneys of Ad-MERS-S1 group by conventional PCR at weeks 3 and 5 post-prime. The vaccine elicited a specific S1-immunoglobulin G antibody response, which was detected in the sera of the vaccinated mice at weeks 4 and 6 from the onset of the first immunization. There was a significant increase in the amount of Th1-related cytokines (interferon-γ and interleukin [IL] 12), and a significant decrease in the Th2-related cytokine IL-4 in splenocyte cell culture of the vaccinated group compared with the control groups. CONCLUSION: The results of this study suggest that this recombinant adenovirus vaccine encoding the S1 subunit of MERS-CoV elicits potentially protective antigen-specific humoral and cellular immune responses in mice. This study demonstrates a promising vaccine for the control and/or prevention of MERS-CoV infection in humans.


id: cord-324324-8ybfiz8f
title: Novel human coronavirus (SARS-CoV-2): A lesson from animal coronaviruses
author: Decaro, Nicola
date: 2020-04-14
txt: ./txt/cord-324324-8ybfiz8f.txt
cache: ./cache/cord-324324-8ybfiz8f.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0378113520302935
doi: 10.1016/j.vetmic.2020.108693
summary:
  In addition, the close contact between human beings and different animal species sold at the wet markets of East Asia represents the optimal situation for the host species jump and adaptation to humans of potentially zoonotic agents like CoVs. It is not a coincidence that two of the most severe zoonoses of the last two decades (highly pathogenic H5N1 avian influenza and SARS) have emerged in the same Chinese province of Guangdong where the contact between humans and animals is closer (Lorusso et al., 2020) . All these viruses as well as analogous IBV-like CoVs detected in other birds including penguins, pigeons, peafowl, parrots, waterfowl, teal, quail, duck and whooper swan (Cavanagh et al., 2002; Circella et al., 2007; Domanska-Blicharz et al., 2014; Torres et al., 2013; Hughes et al., 2009; Liu et al., 2005; Wille et al., 2016; Jordan et al., 2015; Bande et al., 2016; Suryaman et al., 2019) have been assigned to the same viral species known as Avian coronavirus (ACoV) within the subgenus Igacovirus of genus Gammacoronavirus.

abstract:
  The recent pandemic caused by the novel human coronavirus, referrred to as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), not only is having a great impact on the health care systems and economies in all continents but it is also causing radical changes of common habits and life styles. The novel coronavirus (CoV) recognises, with high probability, a zoonotic origin but the role of animals in the SARS-CoV-2 epidemiology is still largely unknown. However, CoVs have been known in animals since several decades, so that veterinary coronavirologists have a great expertise on how to face CoV infections in animals, which could represent a model for SARS-CoV-2 infection in humans. In the present paper, we provide an up-to-date review of the literature currently available on animal CoVs, focusing on the molecular mechanisms that are responsible for the emergence of novel CoV strains with different antigenic, biologic and/or pathogenetic features. A full comprehension of the mechanisms driving the evolution of animal CoVs will help better understand the emergence, spreading, and evolution of SARS-CoV-2.


id: cord-327867-1wkbjtji
author: Da''ar, Omar B.
date: 2018-06-11
txt: ./txt/cord-327867-1wkbjtji.txt
cache: ./cache/cord-327867-1wkbjtji.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1017/s0950268818001541
doi: 10.1017/s0950268818001541
summary:
  title: Underlying trend, seasonality, prediction, forecasting and the contribution of risk factors: an analysis of globally reported cases of Middle East Respiratory Syndrome Coronavirus This study set out to identify and analyse trends and seasonal variations of monthly global reported cases of the Middle East respiratory syndrome coronavirus (MERS-CoV). This study set out to identify trends and seasonal variations; made a prediction based on the globally reported cases of the Middle East respiratory syndrome coronavirus (MERS-CoV), extrapolated into the future by forecasting the trend and assessed contributions of various risk factors for the MERS-CoV cases. Using linear time series models and their application to the modelling and prediction of the globally reported MERS-CoV data, the present study identified trends, analysed seasonality, predicted and forecast evolution of MERS-CoV cases and assessed the contribution of various risk factors.

title:
  Underlying trend, seasonality, prediction, forecasting and the contribution of risk factors: an analysis of globally reported cases of Middle East Respiratory Syndrome Coronavirus

abstract:
  This study set out to identify and analyse trends and seasonal variations of monthly global reported cases of the Middle East respiratory syndrome coronavirus (MERS-CoV). It also made a prediction based on the reported and extrapolated into the future by forecasting the trend. Finally, the study assessed contributions of various risk factors in the reported cases. The motivation for this study is that MERS-CoV remains among the list of blueprint priority and potential pandemic diseases globally. Yet, there is a paucity of empirical literature examining trends and seasonality as the available evidence is generally descriptive and anecdotal. The study is a time series analysis using monthly global reported cases of MERS-CoV by the World Health Organisation between January 2015 and January 2018. We decomposed the series into seasonal, irregular and trend components and identified patterns, smoothened series, generated predictions and employed forecasting techniques based on linear regression. We assessed contributions of various risk factors in MERS-CoV cases over time. Successive months of the MERS-CoV cases suggest a significant decreasing trend (P = 0.026 for monthly series and P = 0.047 for Quarterly series). The MERS-CoV cases are forecast to wane by end 2018. Seasonality component of the cases oscillated below or above the baseline (the centred moving average), but no association with the series over time was noted. The results revealed contributions of risk factors such as camel contact, male, old age and being from Saudi Arabia and Middle East regions to the overall reported cases of MERS-CoV. The trend component and several risk factors for global MERS-CoV cases, including camel contact, male, age and geography/region significantly affected the series. Our statistical models appear to suggest significant predictive capacity and the findings may well inform healthcare practitioners and policymakers about the underlying dynamics that produced the globally reported MERS-CoV cases.


id: cord-328298-tm7gds8h
author: Gardner, Lauren M.
date: 2016-09-05
txt: ./txt/cord-328298-tm7gds8h.txt
cache: ./cache/cord-328298-tm7gds8h.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/27601536/
doi: 10.1093/jtm/taw063
summary:
  In order to prevent global outbreaks such as the one seen in South Korea, it is critical for high-risk countries to be prepared and have appropriate screening and triage protocols in place to identify travel-related cases of MERS-CoV. The results provide a country level ranking and corresponding expected relative risk, which can be used by public health authorities in each country to ensure the appropriate screening and triage protocols are in place to identify travel-related cases of MERS-coronavirus. The proposed model quantifies the relative risk of disease spread by MERS-CoV-infected travellers departing from the Middle East and arriving at any given world airport. The analysis quantifies the relative expected risk of MERS-CoV-infected (air travel) passengers arriving at airports based on a set of active transmission regions, the outbreak size at each and travel patterns; the model does not include the potential importation of infected intermediary hosts or intermediary host by-products since the influence of that possibility is yet to be established.

title:
  Risk of global spread of Middle East respiratory syndrome coronavirus (MERS-CoV) via the air transport network

abstract:
  Background: Middle East respiratory syndrome coronavirus (MERS-CoV) emerged from the Kingdom of Saudi Arabia (KSA) in 2012 and has since spread to 26 countries. All cases reported so far have either been in the Middle East or linked to the region through passenger air travel, with the largest outbreak outside KSA occurring in South Korea. Further international spread is likely due to the high travel volumes of global travel, as well as the occurrence of large annual mass gathering such as the Haj and Umrah pilgrimages that take place in the region. Methods: In this study, a transport network modelling framework was used to quantify the risk of MERS-CoV spreading internationally via air travellers. All regions connected to MERS-CoV affected countries via air travel are considered, and the countries at highest risk of travel-related importations of MERS-CoV were identified, ranked and compared with actual spread of MERS cases. Results: The model identifies all countries that have previously reported a travel acquired case to be in the top 50 at-risk countries. India, Pakistan and Bangladesh are the highest risk countries which have yet to report a case, and should be prepared for the possibility of (pilgrims and general) travellers returning infected with MERS-CoV. In addition, the UK, Egypt, Turkey and the USA are at risk of more cases. Conclusions: We have demonstrated a risk-analysis approach, using travel patterns, to prioritize countries at highest risk for MERS-CoV importations. In order to prevent global outbreaks such as the one seen in South Korea, it is critical for high-risk countries to be prepared and have appropriate screening and triage protocols in place to identify travel-related cases of MERS-CoV. The results from the model can be used by countries to prioritize their airport and hospital screening and triage protocols.


id: cord-329190-kv9n2qj3
title: A review of candidate therapies for Middle East respiratory syndrome from a molecular perspective
author: Rabaan, Ali A.
date: 2017-09-01
txt: ./txt/cord-329190-kv9n2qj3.txt
cache: ./cache/cord-329190-kv9n2qj3.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1099/jmm.0.000565
doi: 10.1099/jmm.0.000565
summary:
  The current therapies have mainly been adapted from severe acute respiratory syndrome (SARS-CoV) treatments, including broad-spectrum antibiotics, corticosteroids, interferons, ribavirin, lopinavir–ritonavir or mycophenolate mofetil, and have not been subject to well-organized clinical trials. The Medline database was searched using combinations and variations of terms, including ''Middle East respiratory syndrome coronavirus'', ''MERS-CoV'', ''SARS'', ''therapy'', ''molecular'', ''vaccine'', ''prophylactic'', ''S protein'', ''DPP4'', ''heptad repeat'', ''protease'', ''inhibitor'', ''anti-viral'', ''broad-spectrum'', ''interferon'', ''convalescent plasma'', ''lopinavir ritonavir'', ''antibodies'', ''antiviral peptides'' and ''live attenuated viruses''. A position paper on the evidence base for specific MERS-CoV therapies, published by Public Health England (PHE) and the World Health Organization-International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC-WHO), suggested that benefit was likely to exceed risk for convalescent plasma, lopinavir-ritonavir, IFNs and monoclonal/polyclonal antibodies, while, by contrast, for ribavirin monotherapy and corticosteroids it was considered that the risks would outweigh the benefits [42] .

abstract:
  There have been 2040 laboratory-confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) in 27 countries, with a mortality rate of 34.9 %. There is no specific therapy. The current therapies have mainly been adapted from severe acute respiratory syndrome (SARS-CoV) treatments, including broad-spectrum antibiotics, corticosteroids, interferons, ribavirin, lopinavir–ritonavir or mycophenolate mofetil, and have not been subject to well-organized clinical trials. The development of specific therapies and vaccines is therefore urgently required. We examine existing and potential therapies and vaccines from a molecular perspective. These include viral S protein targeting; inhibitors of host proteases, including TMPRSS2, cathepsin L and furin protease, and of viral M(pro) and the PL(pro) proteases; convalescent plasma; and vaccine candidates. The Medline database was searched using combinations and variations of terms, including ‘Middle East respiratory syndrome coronavirus’, ‘MERS-CoV’, ‘SARS’, ‘therapy’, ‘molecular’, ‘vaccine’, ‘prophylactic’, ‘S protein’, ‘DPP4’, ‘heptad repeat’, ‘protease’, ‘inhibitor’, ‘anti-viral’, ‘broad-spectrum’, ‘interferon’, ‘convalescent plasma’, ‘lopinavir ritonavir’, ‘antibodies’, ‘antiviral peptides’ and ‘live attenuated viruses’. There are many options for the development of MERS-CoV-specific therapies. Currently, MERS-CoV is not considered to have pandemic potential. However, the high mortality rate and potential for mutations that could increase transmissibility give urgency to the search for direct, effective therapies. Well-designed and controlled clinical trials are needed, both for existing therapies and for prospective direct therapies.


id: cord-330343-p7a8chn4
title: An updated roadmap for MERS-CoV research and product development: focus on diagnostics
author: Kelly-Cirino, Cassandra
date: 2019-02-01
txt: ./txt/cord-330343-p7a8chn4.txt
cache: ./cache/cord-330343-p7a8chn4.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1136/bmjgh-2018-001105
doi: 10.1136/bmjgh-2018-001105
summary:
  ► Diagnostic research and development (R&D) needs to include point-of-care testing options, syndromic panels for differential diagnosis, a greater understanding of viral and antibody kinetics, improved access to clinical specimens, and establishment of international reference standards. Diagnostics play a central role in the early detection and control of outbreaks and can enable a more nuanced understanding of the disease kinetics and risk factors for the Middle East respiratory syndrome-coronavirus (MERS-CoV), one of the high-priority pathogens identified by the WHO. Diagnostics play a central role in the early detection and control of outbreaks and can enable a more nuanced understanding of the disease kinetics and risk factors for the Middle East respiratory syndrome-coronavirus (MERS-CoV), one of the high-priority pathogens identified by the WHO. In this review we identified sources for molecular and serological diagnostic tests used in MERS-CoV detection, case management and outbreak investigations, as well as surveillance for humans and animals (camels), and summarised the performance of currently available tests, diagnostic needs, and associated challenges for diagnostic test development and implementation.

abstract:
  Diagnostics play a central role in the early detection and control of outbreaks and can enable a more nuanced understanding of the disease kinetics and risk factors for the Middle East respiratory syndrome-coronavirus (MERS-CoV), one of the high-priority pathogens identified by the WHO. In this review we identified sources for molecular and serological diagnostic tests used in MERS-CoV detection, case management and outbreak investigations, as well as surveillance for humans and animals (camels), and summarised the performance of currently available tests, diagnostic needs, and associated challenges for diagnostic test development and implementation. A more detailed understanding of the kinetics of infection of MERS-CoV is needed in order to optimise the use of existing assays. Notably, MERS-CoV point-of-care tests are needed in order to optimise supportive care and to minimise transmission risk. However, for new test development, sourcing clinical material continues to be a major challenge to achieving assay validation. Harmonisation and standardisation of laboratory methods are essential for surveillance and for a rapid and effective international response to emerging diseases. Routine external quality assessment, along with well-characterised and up-to-date proficiency panels, would provide insight into MERS-CoV diagnostic performance worldwide. A defined set of Target Product Profiles for diagnostic technologies will be developed by WHO to address these gaps in MERS-CoV outbreak management.


id: cord-331228-wbd0s4fo
title: Middle East respiratory syndrome coronavirus: a comprehensive review
author: Shehata, Mahmoud M.
date: 2016-01-20
txt: ./txt/cord-331228-wbd0s4fo.txt
cache: ./cache/cord-331228-wbd0s4fo.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/26791756/
doi: 10.1007/s11684-016-0430-6
summary:
  authors: Shehata, Mahmoud M.; Gomaa, Mokhtar R.; Ali, Mohamed A.; Kayali, Ghazi Role of the spike glycoprotein of human Middle East respiratory syndrome coronavirus (MERS-CoV) in virus entry and syncytia formation Middle East respiratory syndrome coronavirus (MERS-CoV)-Saudi Arabia Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study First cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infections in France, investigations and implications for the prevention of human-to-human transmission Clinical features and viral diagnosis of two cases of infection with Middle East respiratory syndrome coronavirus: a report of nosocomial transmission Middle East respiratory syndrome coronavirus infection in dromedary camels in Saudi Arabia

abstract:
  The Middle East respiratory syndrome coronavirus was first identified in 2012 and has since then remained uncontrolled. Cases have been mostly reported in the Middle East, however travel-associated cases and outbreaks have also occurred. Nosocomial and zoonotic transmission of the virus appear to be the most important routes. The infection is severe and highly fatal thus necessitating rapid and efficacious interventions. Here, we performed a comprehensive review of published literature and summarized the epidemiology of the virus. In addition, we summarized the virological aspects of the infection and reviewed the animal models used as well as vaccination and antiviral tested against it.


id: cord-331714-2qj2rrgd
title: Single-Stranded RNA Viruses
author: Lvov, Dimitry Konstantinovich
date: 2015-05-29
txt: ./txt/cord-331714-2qj2rrgd.txt
cache: ./cache/cord-331714-2qj2rrgd.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/B9780128017425000088
doi: 10.1016/b978-0-12-801742-5.00008-8
summary:
  Among them are viruses associated with sporadic cases or outbreaks of human disease, such as hemorrhagic fever with renal syndrome (viruses of the genus Hantavirus), Crimean–Congo hemorrhagic fever (CCHFV, Nairovirus), California encephalitis (INKV, TAHV, and KHATV; Orthobunyavirus), sandfly fever (SFCV and SFNV, Phlebovirus), Tick-borne encephalitis (TBEV, Flavivirus), Omsk hemorrhagic fever (OHFV, Flavivirus), West Nile fever (WNV, Flavivirus), Sindbis fever (SINV, Alphavirus) Chikungunya fever (CHIKV, Alphavirus) and others. Artashat virus (ARTSV, strain LEIV-2236Ar) was originally isolated from Ornithodoros alactagalis ticks (family Argasidae) collected in the burrows of a small five-toed jerboa (Allactaga elater) near Arevashat village (40 02 absence of antigenic relationships with any known viruses, it was referred to as an "unclassified bunyavirus." 1À3 Taxonomy.

abstract:
  In this chapter, we describe 73 zoonotic viruses that were isolated in Northern Eurasia and that belong to the different families of viruses with a single-stranded RNA (ssRNA) genome. The family includes viruses with a segmented negative-sense ssRNA genome (families Bunyaviridae and Orthomyxoviridae) and viruses with a positive-sense ssRNA genome (families Togaviridae and Flaviviridae). Among them are viruses associated with sporadic cases or outbreaks of human disease, such as hemorrhagic fever with renal syndrome (viruses of the genus Hantavirus), Crimean–Congo hemorrhagic fever (CCHFV, Nairovirus), California encephalitis (INKV, TAHV, and KHATV; Orthobunyavirus), sandfly fever (SFCV and SFNV, Phlebovirus), Tick-borne encephalitis (TBEV, Flavivirus), Omsk hemorrhagic fever (OHFV, Flavivirus), West Nile fever (WNV, Flavivirus), Sindbis fever (SINV, Alphavirus) Chikungunya fever (CHIKV, Alphavirus) and others. Other viruses described in the chapter can cause epizootics in wild or domestic animals: Geta virus (GETV, Alphavirus), Influenza A virus (Influenzavirus A), Bhanja virus (BHAV, Phlebovirus) and more. The chapter also discusses both ecological peculiarities that promote the circulation of these viruses in natural foci and factors influencing the occurrence of epidemic and epizootic outbreaks


id: cord-332237-8oykgp0h
author: Omrani, Ali S
date: 2014-09-29
txt: ./txt/cord-332237-8oykgp0h.txt
cache: ./cache/cord-332237-8oykgp0h.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S147330991470920X
doi: 10.1016/s1473-3099(14)70920-x
summary:
  title: Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study We aimed to compare ribavirin and interferon alfa-2a treatment for patients with severe MERS-CoV infection with a supportive therapy only. INTERPRETATION: In patients with severe MERS-CoV infection, ribavirin and interferon alfa-2a therapy is associated with significantly improved survival at 14 days, but not at 28 days. 8 We aimed to assess outcomes of a treatment programme for patients with severe MERS-CoV infection that consisted of oral ribavirin and subcutaneous pegylated interferon alfa-2a. In critically ill patients with severe MERS-CoV infection, our study shows that ribavirin and pegylated interferon alfa-2a therapy is associated with a signifi cant 14-day survival benefi t compared with standard treatment. 18 In another report, 19 a patient with severe MERS-CoV infection received ribavirin and interferon therapy with good clinical response and no signifi cant adverse eff ects.

title:
  Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study

abstract:
  BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) infection is associated with high mortality and has no approved antiviral therapy. We aimed to compare ribavirin and interferon alfa-2a treatment for patients with severe MERS-CoV infection with a supportive therapy only. METHODS: In this retrospective cohort study, we included adults (aged ≥16 years) with laboratory-confirmed MERS-CoV infection and pneumonia needing ventilation support, diagnosed between Oct 23, 2012, and May 1, 2014, at the Prince Sultan Military Medical City (Riyadh, Saudi Arabia). All patients received appropriate supportive care and regular clinical and laboratory monitoring, but patients diagnosed after Sept 16, 2013, were also given oral ribavirin (dose based on calculated creatinine clearance, for 8–10 days) and subcutaneous pegylated interferon alfa-2a (180 μg per week for 2 weeks). The primary endpoint was 14-day and 28-day survival from the date of MERS-CoV infection diagnosis. We used χ(2) and Fischer's exact test to analyse categorical variables and the t test to analyse continuous variables. FINDINGS: We analysed 20 patients who received ribavirin and interferon (treatment group; initiated a median of 3 days [range 0–8] after diagnosis) and 24 who did not (comparator group). Baseline clinical and laboratory characteristics were similar between groups, apart from baseline absolute neutrophil count, which was significantly lower in the comparator group (5·88 × 10(9)/L [SD 3·95] vs 9·88 × 10(9)/L [6·63]; p=0·023). 14 (70%) of 20 patients in the treatment group had survived after 14 days, compared with seven (29%) of 24 in the comparator group (p=0·004). After 28 days, six (30%) of 20 and four (17%) of 24, respectively, had survived (p=0·054). Adverse effects were similar between groups, apart from reduction in haemoglobin, which was significantly greater in the treatment group than in the comparator group (4·32 g/L [SD 2·47] vs 2·14 g/L [1·90]; p=0·002). INTERPRETATION: In patients with severe MERS-CoV infection, ribavirin and interferon alfa-2a therapy is associated with significantly improved survival at 14 days, but not at 28 days. Further assessment in appropriately designed randomised trials is recommended. FUNDING: None.


id: cord-332952-d5l60cgc
title: MERS: Progress on the global response, remaining challenges and the way forward
author: nan
date: 2018-09-17
txt: ./txt/cord-332952-d5l60cgc.txt
cache: ./cache/cord-332952-d5l60cgc.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/30236531/
doi: 10.1016/j.antiviral.2018.09.002
summary:
  Typical of an emerging zoonosis, Middle East respiratory syndrome coronavirus (MERS-CoV) has an animal reservoir, i.e. dromedary camels in which the virus causes little to no disease (Mohd et al., 2016) . For example, studies of respiratory pathogens (Yu et al., 2007; Tran et al., 2012; Thompson et al., 2013) and MERS-CoV conducted in the Middle East (Assiri et al., 2013; Oboho et al., 2015; Hunter et al., 2016; Balkhy et al., 2016) and the Republic of Korea (Bin et al., 2016; Kim et al., 2016a Kim et al., , 2016b Nam et al., 2017) illustrate that aerosol-generating procedures and non-invasive ventilation, combined with inappropriate infection prevention and control practices and lack of adherence to standard practices had an important role in facilitating human-to-human transmission in health care settings. The critical care response to a hospital outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection: an observational study Sero-prevalence of Middle East respiratory syndrome coronavirus (MERS-CoV) specific antibodies in dromedary camels in Tabuk, Saudi Arabia

abstract:
  This article summarizes progress in research on Middle East Respiratory Syndrome (MERS) since a FAO-OIE-WHO Global Technical Meeting held at WHO Headquarters in Geneva on 25–27 September 2017. The meeting reviewed the latest scientific findings and identified and prioritized the global activities necessary to prevent, manage and control the disease. Critical needs for research and technical guidance identified during the meeting have been used to update the WHO R&D MERS-CoV Roadmap for diagnostics, therapeutics and vaccines and a broader public health research agenda. Since the 2017 meeting, progress has been made on several key actions in animal populations, at the animal/human interface and in human populations. This report also summarizes the latest scientific studies on MERS since 2017, including data from more than 50 research studies examining the presence of MERS-CoV infection in dromedary camels.


id: cord-337066-pztrwvib
title: Clinical Presentation and Outcomes of Middle East Respiratory Syndrome in the Republic of Korea
author: Choi, Won Suk
date: 2016-06-30
txt: ./txt/cord-337066-pztrwvib.txt
cache: ./cache/cord-337066-pztrwvib.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3947/ic.2016.48.2.118
doi: 10.3947/ic.2016.48.2.118
summary:
  CONCLUSION: The clinical features of MERS-CoV infection in the Republic of Korea were similar to those of previous outbreaks in the Middle East. This retrospective observational study focused on the clinical characteristics of confirmed cases of MERS-CoV infection in the Republic of Korea. All patients with laboratory-confirmed MERS-CoV infection were identified during the outbreak in the Republic of Korea, during which confirmatory tests were performed only for suspected cases. We described the clinical characteristics of all 186 patients with confirmed MERS-CoV infection during the outbreak in the Republic of Korea (Table 1) . The proportions of patients with underlying medical conditions such as diabetes (18.8%), chronic lung disease (10.2%), or chronic kidney disease (4.8%) were smaller in this study, which might explain why cases with complicating respiratory or renal failure were relatively uncommon in the outbreak in the Republic of Korea, compared to those reported in Saudi Arabia.

abstract:
  BACKGROUND: From May to July 2015, the Republic of Korea experienced the largest outbreak of Middle East respiratory syndrome (MERS) outside the Arabian Peninsula. A total of 186 patients, including 36 deaths, had been diagnosed with MERS-coronavirus (MERS-CoV) infection as of September 30th, 2015. MATERIALS AND METHODS: We obtained information of patients who were confirmed to have MERS-CoV infection. MERS-CoV infection was diagnosed using real-time reverse-transcriptase polymerase chain reaction assay. RESULTS: The median age of the patients was 55 years (range, 16 to 86). A total of 55.4% of the patients had one or more coexisting medical conditions. The most common symptom was fever (95.2%). At admission, leukopenia (42.6%), thrombocytopenia (46.6%), and elevation of aspartate aminotransferase (42.7%) were observed. Pneumonia was detected in 68.3% of patients at admission and developed in 80.8% during the disease course. Antiviral agents were used for 74.7% of patients. Mechanical ventilation, extracorporeal membrane oxygenation, and convalescent serum were employed for 24.5%, 7.1%, and 3.8% of patients, respectively. Older age, presence of coexisting medical conditions including diabetes or chronic lung disease, presence of dyspnea, hypotension, and leukocytosis at admission, and the use of mechanical ventilation were revealed to be independent predictors of death. CONCLUSION: The clinical features of MERS-CoV infection in the Republic of Korea were similar to those of previous outbreaks in the Middle East. However, the overall mortality rate (20.4%) was lower than that in previous reports. Enhanced surveillance and active management of patients during the outbreak may have resulted in improved outcomes.


id: cord-337825-ujq9mxk7
title: Overview of lethal human coronaviruses
author: Chen, Bin
date: 2020-06-10
txt: ./txt/cord-337825-ujq9mxk7.txt
cache: ./cache/cord-337825-ujq9mxk7.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1038/s41392-020-0190-2
doi: 10.1038/s41392-020-0190-2
summary:
  Coronaviruses are the largest +ssRNA viruses and contain at least 14 ORFs, 16 protein combines with viral RNA to form a nucleocapsid, which is involved in the replication of SARS-CoV and is the most abundant protein in virus-infected cells. MERS-CoV can infect T-cells from human lymphoid organs and causes the peripheral blood inducing apoptosis by intrinsic and extrinsic pathways, thus avoiding host immune response detection method, Nanopore Targeted Sequencing, also has the potential for efficiently detecting viruses in a reasonable time. The structural and accessory proteins M, ORF 4a, ORF 4b, and ORF 5 of Middle East respiratory syndrome coronavirus (MERS-CoV) are potent interferon antagonists Middle East respiratory syndrome coronavirus (MERS-CoV) entry inhibitors targeting spike protein Identification of a receptor-binding domain in the S protein of the novel human coronavirus Middle East respiratory syndrome coronavirus as an essential target for vaccine development Receptor-binding domain of SARS-CoV spike protein induces highly potent neutralizing antibodies: implication for developing subunit vaccine

abstract:
  Coronavirus infections of multiple origins have spread to date worldwide, causing severe respiratory diseases. Seven coronaviruses that infect humans have been identified: HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1, SARS-CoV, MERS-CoV, and SARS-CoV-2. Among them, SARS-CoV and MERS-CoV caused outbreaks in 2002 and 2012, respectively. SARS-CoV-2 (COVID-19) is the most recently discovered. It has created a severe worldwide outbreak beginning in late 2019, leading to date to over 4 million cases globally. Viruses are genetically simple, yet highly diverse. However, the recent outbreaks of SARS-CoV and MERS-CoV, and the ongoing outbreak of SARS-CoV-2, indicate that there remains a long way to go to identify and develop specific therapeutic treatments. Only after gaining a better understanding of their pathogenic mechanisms can we minimize viral pandemics. This paper mainly focuses on SARS-CoV, MERS-CoV, and SARS-CoV-2. Here, recent studies are summarized and reviewed, with a focus on virus–host interactions, vaccine-based and drug-targeted therapies, and the development of new approaches for clinical diagnosis and treatment.


id: cord-338057-ycmr9prw
author: Lee, Jae Hoon
date: 2015-07-15
txt: ./txt/cord-338057-ycmr9prw.txt
cache: ./cache/cord-338057-ycmr9prw.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/26240502/
doi: 10.3346/jkms.2015.30.8.1207
abstract: nan
summary:
  title: An Appropriate Lower Respiratory Tract Specimen Is Essential for Diagnosis of Middle East Respiratory Syndrome (MERS) He briefly summarized the ongoing status of the Middle East Respiratory Syndrome (MERS) outbreak and emphasized close monitoring of medical staffs, patients, and visitors, and timely well-designed briefings to mass media. Some reasons that could be considered for the delayed diagnosis of MERS include: 1) low initial viral load and shedding, and 2) poor sample collection in patients with "no cough" or dry cough. In re-evaluating the patient''s diagnostic history, his viral load could have been low due to the early phase of disease and/or could have been falsely negative due to inadequate dry coughlinked respiratory samples. Middle East respiratory syndrome coronavirus (MERS-CoV) causes transient lower respiratory tract infection in rhesus macaques Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission

title:
  An Appropriate Lower Respiratory Tract Specimen Is Essential for Diagnosis of Middle East Respiratory Syndrome (MERS)


id: cord-339762-lh8czr0a
author: Ng, Dianna L.
date: 2016-03-31
txt: ./txt/cord-339762-lh8czr0a.txt
cache: ./cache/cord-339762-lh8czr0a.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0002944015006471
doi: 10.1016/j.ajpath.2015.10.024
summary:
  title: Clinicopathologic, Immunohistochemical, and Ultrastructural Findings of a Fatal Case of Middle East Respiratory Syndrome Coronavirus Infection in the United Arab Emirates, April 2014 Middle East respiratory syndrome coronavirus (MERS-CoV) infection causes an acute respiratory illness and is associated with a high case fatality rate; however, the pathogenesis of severe and fatal MERS-CoV infection is unknown. Middle East respiratory syndrome coronavirus (MERS-CoV) infection causes an acute respiratory illness and is associated with a high case fatality rate; however, the pathogenesis of severe and fatal MERS-CoV infection is unknown. Middle East respiratory syndrome coronavirus (MERS-CoV) was initially isolated from a sputum specimen of a patient who died of respiratory and renal failure in Saudi Arabia in 2012. Although the pathogenesis of severe and fatal MERS-CoV infection is unknown, these postmortem findings provide critical insights, including evidence that pneumocytes are important targets, suggesting that direct cytopathic effects contribute to MERS-CoV respiratory symptoms.

title:
  Clinicopathologic, Immunohistochemical, and Ultrastructural Findings of a Fatal Case of Middle East Respiratory Syndrome Coronavirus Infection in the United Arab Emirates, April 2014

abstract:
  Middle East respiratory syndrome coronavirus (MERS-CoV) infection causes an acute respiratory illness and is associated with a high case fatality rate; however, the pathogenesis of severe and fatal MERS-CoV infection is unknown. We describe the histopathologic, immunohistochemical, and ultrastructural findings from the first autopsy performed on a fatal case of MERS-CoV in the world, which was related to a hospital outbreak in the United Arab Emirates in April 2014. The main histopathologic finding in the lungs was diffuse alveolar damage. Evidence of chronic disease, including severe peripheral vascular disease, patchy cardiac fibrosis, and hepatic steatosis, was noted in the other organs. Double staining immunoassays that used anti–MERS-CoV antibodies paired with immunohistochemistry for cytokeratin and surfactant identified pneumocytes and epithelial syncytial cells as important targets of MERS-CoV antigen; double immunostaining with dipeptidyl peptidase 4 showed colocalization in scattered pneumocytes and syncytial cells. No evidence of extrapulmonary MERS-CoV antigens were detected, including the kidney. These results provide critical insights into the pathogenesis of MERS-CoV in humans.


id: cord-340836-eb5a9ln3
author: Aghazadeh-Attari, Javad
date: 2018-04-06
txt: ./txt/cord-340836-eb5a9ln3.txt
cache: ./cache/cord-340836-eb5a9ln3.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/29670390/
doi: 10.2147/ijgm.s160741
summary:
  METHODS: Full details of MERS-CoV cases available on the disease outbreak news section of the World Health Organization official website from January 2013 to November 2016 were retrieved; demographic and clinical information, global distribution status, potential contacts, and probable risk factors for the mortality of laboratory-confirmed MERS-CoV cases were extracted and analyzed by following standard statistical methods. From September 23, 2012, to November 11, 2016, the occurrence of 1,879 laboratory-confirmed cases of MERS-CoV infection, including 659 deaths, was reported to WHO by the National IHR Focal Points of 27 countries in Europe, North Africa, the Middle East, the United States of America, and Asia. The comparison of characteristics of the cases and the effect of various potential risk factors on the final outcome (dead/survived) of laboratory-confirmed MERS-CoV cases in the world (Table 2) reveal that two factors, namely, morbid case being native and travel history, are considered significant in a unifactorial analysis (P-values are <0.05) and with the potential of bearing on the dynamics of the disease.

title:
  Epidemiological factors and worldwide pattern of Middle East respiratory syndrome coronavirus from 2013 to 2016

abstract:
  BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging threat to global health security with high intensity and lethality. This study was conducted to investigate epidemiological factors and patterns related to this disease. METHODS: Full details of MERS-CoV cases available on the disease outbreak news section of the World Health Organization official website from January 2013 to November 2016 were retrieved; demographic and clinical information, global distribution status, potential contacts, and probable risk factors for the mortality of laboratory-confirmed MERS-CoV cases were extracted and analyzed by following standard statistical methods. RESULTS: Details of 1,094 laboratory-confirmed cases were recorded, including 421 related deaths. Significant differences were observed in the presentation of the disease from year to year, and all studied parameters differed during the years under study (all P-values <0.05). Evaluation of the effects of various potential risk factors of the final outcome (dead/survived) revealed that two factors, namely, the morbid case being native and travel history, are significant based on a unifactorial analysis (P <0.05). From 2013 to 2016, these factors remained important. However, factors that were significant in predicting mortality varied in different years. CONCLUSION: These findings point to interesting potential dimensions in the dynamic of this disease. Furthermore, effective national and international preparedness plans and actions are essential to prevent, control, and predict such viral outbreaks; improve patient management; and ensure global health security.


id: cord-341795-zbqfs77n
author: Sikkema, R. S.
date: 2019-02-21
txt: ./txt/cord-341795-zbqfs77n.txt
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extension: .txt
mime: text/plain
url: https://doi.org/10.1017/s095026881800345x
doi: 10.1017/s095026881800345x
summary:
  This systematic review aims to compile and analyse all published data on MERS-coronavirus (CoV) in the global camel population to provide an overview of current knowledge on the distribution, spread and risk factors of infections in dromedary camels. In the field surveys included in this review, MERS-CoV RNA has been described in rectal swab samples, although other field studies report negative results [3, [22] [23] [24] and when viral RNA can be detected, the positivity rate of rectal swabs is lower compared with nasal swab samples [19, [25] [26] [27] . Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study Longitudinal study of Middle East respiratory syndrome coronavirus infection in dromedary camel herds in Saudi Arabia Middle East respiratory syndrome coronavirus (MERS-CoV) RNA and neutralising antibodies in milk collected according to local customs from dromedary camels

title:
  Global status of Middle East respiratory syndrome coronavirus in dromedary camels: a systematic review

abstract:
  Dromedary camels have been shown to be the main reservoir for human Middle East respiratory syndrome (MERS) infections. This systematic review aims to compile and analyse all published data on MERS-coronavirus (CoV) in the global camel population to provide an overview of current knowledge on the distribution, spread and risk factors of infections in dromedary camels. We included original research articles containing laboratory evidence of MERS-CoV infections in dromedary camels in the field from 2013 to April 2018. In general, camels only show minor clinical signs of disease after being infected with MERS-CoV. Serological evidence of MERS-CoV in camels has been found in 20 countries, with molecular evidence for virus circulation in 13 countries. The seroprevalence of MERS-CoV antibodies increases with age in camels, while the prevalence of viral shedding as determined by MERS-CoV RNA detection in nasal swabs decreases. In several studies, camels that were sampled at animal markets or quarantine facilities were seropositive more often than camels at farms as well as imported camels vs. locally bred camels. Some studies show a relatively higher seroprevalence and viral detection during the cooler winter months. Knowledge of the animal reservoir of MERS-CoV is essential to develop intervention and control measures to prevent human infections.


id: cord-343184-kptkmgdm
author: Crameri, Gary
date: 2016-06-17
txt: ./txt/cord-343184-kptkmgdm.txt
cache: ./cache/cord-343184-kptkmgdm.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3201/eid2206.160007
doi: 10.3201/eid2206.160007
summary:
  title: Experimental Infection and Response to Rechallenge of Alpacas with Middle East Respiratory Syndrome Coronavirus We conducted a challenge/rechallenge trial in which 3 alpacas were infected with Middle East respiratory syndrome coronavirus. However, the alpaca, a close relative within the Camelidae family, may provide a temperamentally suitable and valuable animal model for MERS-CoV infection, particularly for developing and testing vaccine candidates for camels. We found no previous MERS-CoV challenge trial reported in alpacas, so we chose a preliminary dose and rechallenge time on the basis of our experience with other virus infection trials for other emerging infectious diseases (8) . Our challenge/rechallenge trial was planned as a first stage in the assessment of the alpaca as a potential surrogate for camels for MERS-CoV vaccine testing. Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study Infection, replication, and transmission of Middle East respiratory syndrome coronavirus in alpacas

title:
  Experimental Infection and Response to Rechallenge of Alpacas with Middle East Respiratory Syndrome Coronavirus

abstract:
  We conducted a challenge/rechallenge trial in which 3 alpacas were infected with Middle East respiratory syndrome coronavirus. The alpacas shed virus at challenge but were refractory to further shedding at rechallenge on day 21. The trial indicates that alpacas may be suitable models for infection and shedding dynamics of this virus.


id: cord-343302-g9vcchrh
author: Agrawal, Anurodh Shankar
date: 2016-08-19
txt: ./txt/cord-343302-g9vcchrh.txt
cache: ./cache/cord-343302-g9vcchrh.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1038/srep31629
doi: 10.1038/srep31629
summary:
  title: Passive Transfer of A Germline-like Neutralizing Human Monoclonal Antibody Protects Transgenic Mice Against Lethal Middle East Respiratory Syndrome Coronavirus Infection Here, we further characterized this novel human mAb in our Tg mouse model of MERS-CoV infection and showed prophylactic and therapeutic protection of mice treated with m336 before and after a lethal challenge with the virus, respectively. In our studies, we noted that passively transferred with 1 mg and 0.1 mg of m336 monoclonal antibodies to individual mice 12 h prior to challenge with 1,000 LD 50 of MERS-CoV resulted in 100% and 75% protection against lethality, respectively (Fig. 1) , suggesting that using 0.1 mg m336/mouse as a prophylaxis is suboptimal to completely neutralize viral infection, thereby allowing residual viruses to replicate within lungs during the course of infection.

title:
  Passive Transfer of A Germline-like Neutralizing Human Monoclonal Antibody Protects Transgenic Mice Against Lethal Middle East Respiratory Syndrome Coronavirus Infection

abstract:
  Middle East Respiratory Syndrome coronavirus (MERS-CoV) has repeatedly caused outbreaks in the Arabian Peninsula. To date, no approved medical countermeasures (MCM) are available to combat MERS-CoV infections. Several neutralizing human monoclonal antibodies (mAbs), including m336, a germline-like human mAb, have been chosen as promising MCM for MERS-CoV. However, their clinical development has been hindered by the lack of a robust animal model that recapitulate the morbidity and mortality of human infections. We assessed the prophylactic and therapeutic efficacy of m336 by using well-characterized transgenic mice shown to be highly sensitive to MERS-CoV infection and disease. We found that mice treated with m336 prior to or post lethal MERS-CoV challenging were fully protected, compared to control mice which sufferered from profound weight loss and uniform death within days after infection. Taken together, these results support further development of m336 and other human monoclonal antibodies as potential therapeutics for MERS-CoV infection.


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-345046-str19r9a
author: Al Ghamdi, Mohammed
date: 2016-04-21
txt: ./txt/cord-345046-str19r9a.txt
cache: ./cache/cord-345046-str19r9a.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/27097824/
doi: 10.1186/s12879-016-1492-4
summary:
  title: Treatment outcomes for patients with Middle Eastern Respiratory Syndrome Coronavirus (MERS CoV) infection at a coronavirus referral center in the Kingdom of Saudi Arabia In this recent cohort, when comparing survivors to nonsurvivors, survival was associated with male gender, vomiting on admission, elevated respiratory rate, abnormal lung exam on physical exam, working as a healthcare worker, history of hypertension, elevated ALT, clearance of MERS CoV on repeat PCR testing, and receiving mycophenolate mofetil or beta interferon (Table 1 ). In analyzing the relationship between severity of illness and treatments administered, beta interferon and mycophenolate mofetil were given to less severely ill patients (Table 3) Discussion MERS-CoV is an emerging disease for which the initial epidemiology has been described, but in-depth clinical studies and the role of therapy in incompletely understood. We present data from a retrospective cohort of ill patients with Mers-CoV and the results of the evaluation of the clinical efficacy of beta interferon beta, alpha interferon, ribavirin and mycophenolate mofetil in addition to routine supportive care.

title:
  Treatment outcomes for patients with Middle Eastern Respiratory Syndrome Coronavirus (MERS CoV) infection at a coronavirus referral center in the Kingdom of Saudi Arabia

abstract:
  BACKGROUND: Middle Eastern Respiratory Syndrome coronavirus (MERS-CoV) is a poorly understood disease with no known treatments. We describe the clinical features and treatment outcomes of patients with laboratory confirmed MERS-CoV at a regional referral center in the Kingdom of Saudi Arabia. METHODS: In 2014, a retrospective chart review was performed on patients with a laboratory confirmed diagnosis of MERS-CoV to determine clinical and treatment characteristics associated with death. Confounding was evaluated and a multivariate logistic regression was performed to assess the independent effect of treatments administered. RESULTS: Fifty-one patients had an overall mortality of 37 %. Most patients were male (78 %) with a mean age of 54 years. Almost a quarter of the patients were healthcare workers (23.5 %) and 41 % had a known exposure to another person with MERS-CoV. Survival was associated with male gender, working as a healthcare worker, history of hypertension, vomiting on admission, elevated respiratory rate, abnormal lung exam, elevated alanine transaminase (ALT), clearance of MERS-CoV on repeat PCR polymerase chain reaction (PCR) testing, and mycophenolate mofetil treatment. Survival was reduced in the presence of coronary artery disease, hypotension, hypoxemia, CXR (chest X-ray) abnormalities, leukocytosis, creatinine >1 · 5 mg/dL, thrombocytopenia, anemia, and renal failure. In a multivariate analysis of treatments administered, severity of illness was the greatest predictor of reduced survival. CONCLUSIONS: Care for patients with MERS-CoV remains a challenge. In this retrospective cohort, interferon beta and mycophenolate mofetil treatment were predictors of increased survival in the univariate analysis. Severity of illness was the greatest predictor of reduced survival in the multivariate analysis. Larger randomized trials are needed to better evaluate the efficacy of these treatment regimens for MERS-CoV.


id: cord-345081-15s2i6f0
title: Middle East respiratory syndrome in children: Dental considerations
author: Al-Sehaibany, Fares S.
date: 2017-04-17
txt: ./txt/cord-345081-15s2i6f0.txt
cache: ./cache/cord-345081-15s2i6f0.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.15537/smj.2017.4.15777
doi: 10.15537/smj.2017.4.15777
summary:
  As of January 2016, 1,633 laboratory-confirmed cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection and 587 MERS-related deaths have been reported by the World Health Organization globally. Middle East Respiratory Syndrome Coronavirus may also spread through aerosols generated during various dental treatments, resulting in transmission between patients and dentists. 1, 17 Viral infections, such as severe acute respiratory syndrome Saudi Med J 2017; Vol. 38 (4) www.smj.org.sa (SARS-CoV), may be transmitted to healthcare workers from infected patients through aerosols. 19 This review is an attempt to discuss MERS-CoV infection among children and those providing dental treatment to them, including precautions and considerations pertaining to the practice of pediatric dentistry. In pediatric dental practice, effective infection control measures for the prevention or minimization of viral infection transmission can be implemented by a) controlling the gag or cough reflex; b) reducing aerosol/ splatter generation; c) managing contaminated air and; d) improving personal protection.

abstract:
  As of January 2016, 1,633 laboratory-confirmed cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection and 587 MERS-related deaths have been reported by the World Health Organization globally. Middle East Respiratory Syndrome Coronavirus may occur sporadically in communities or may be transmitted within families or hospitals. The number of confirmed MERS-CoV cases among healthcare workers has been increasing. Middle East Respiratory Syndrome Coronavirus may also spread through aerosols generated during various dental treatments, resulting in transmission between patients and dentists. As MERS-CoV cases have also been reported among children, pediatric dentists are at risk of MERS-CoV infection. This review discusses MERS-CoV infection in children and healthcare workers, especially pediatric dentists, and considerations pertaining to pediatric dentistry. Although no cases of MERS-CoV transmission between a patient and a dentist have yet been reported, the risk of MERS-CoV transmission from an infected patient may be high due to the unique work environment of dentists (aerosol generation).


id: cord-345591-zwh1xj5u
author: Al-Dorzi, Hasan M.
date: 2016-10-24
txt: ./txt/cord-345591-zwh1xj5u.txt
cache: ./cache/cord-345591-zwh1xj5u.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/27778310/
doi: 10.1186/s13613-016-0203-z
summary:
  title: The critical care response to a hospital outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection: an observational study BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) has caused several hospital outbreaks, including a major outbreak at King Abdulaziz Medical City, a 940-bed tertiary-care hospital in Riyadh, Saudi Arabia (August–September 2015). Eight HCWs had MERS requiring ICU admission (median stay = 28 days): Seven developed acute respiratory distress syndrome, four were treated with prone positioning, four needed continuous renal replacement therapy and one had extracorporeal membrane oxygenation. The Middle East respiratory syndrome (MERS) coronavirus is a recently identified virus that is closely related to the severe acute respiratory syndrome coronavirus (SARS-CoV) [1] , causes severe hypoxemic respiratory failure with multiorgan failure and frequently requires admission to the intensive care unit (ICU) [2, 3] .

title:
  The critical care response to a hospital outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection: an observational study

abstract:
  BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) has caused several hospital outbreaks, including a major outbreak at King Abdulaziz Medical City, a 940-bed tertiary-care hospital in Riyadh, Saudi Arabia (August–September 2015). To learn from our experience, we described the critical care response to the outbreak. METHODS: This observational study was conducted at the Intensive Care Department which covered 5 ICUs with 60 single-bedded rooms. We described qualitatively and, as applicable, quantitatively the response of intensive care services to the outbreak. The clinical course and outcomes of healthcare workers (HCWs) who had MERS were noted. RESULTS: Sixty-three MERS patients were admitted to 3 MERS-designated ICUs during the outbreak (peak census = 27 patients on August 25, 2015, and the last new case on September 13, 2015). Most patients had multiorgan failure. Eight HCWs had MERS requiring ICU admission (median stay = 28 days): Seven developed acute respiratory distress syndrome, four were treated with prone positioning, four needed continuous renal replacement therapy and one had extracorporeal membrane oxygenation. The hospital mortality of ICU MERS patients was 63.4 % (0 % for the HCWs). In response to the outbreak, the number of negative-pressure rooms was increased from 14 to 38 rooms in 3 MERS-designated ICUs. Patients were managed with a nurse-to-patient ratio of 1:0.8. Infection prevention practices were intensified. As a surrogate, surface disinfectant and hand hygiene gel consumption increased by ~30 % and 17 N95 masks were used per patient/day on average. Family visits were restricted to 2 h/day. Although most ICU staff expressed concerns about acquiring MERS, all reported to work normally. During the outbreak, 27.0 % of nurses and 18.4 % of physicians working in the MERS-designated ICUs reported upper respiratory symptoms, and were tested for MERS-CoV. Only 2/196 (1.0 %) ICU nurses and 1/80 (1.3 %) physician tested positive, had mild disease and recovered fully. The total sick leave duration was 138 days for nurses and 30 days for physicians. CONCLUSIONS: Our hospital outbreak of MERS resulted in 63 patients requiring organ support and prolonged ICU stay with a high mortality rate. The ICU response required careful facility and staff management and proper infection control and prevention practices.


id: cord-348821-2u6ki9dv
author: Xu, Ping
date: 2020-03-10
txt: ./txt/cord-348821-2u6ki9dv.txt
cache: ./cache/cord-348821-2u6ki9dv.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1101/2020.03.08.20032821
doi: 10.1101/2020.03.08.20032821
summary:
  The aim of this study, therefore, is to perform a systematic review to compare epidemiological, clinical and laboratory features of COVID-19 and MERS-COV population. Thus, the purpose of this study is to perform a systematic review of epidemiological, clinical and laboratory characteristics of patients infected by COVID-19 or MERS-COV disease, and to compare COVID-19 and MERS-COV in the context of their incubation, laboratory features, admission rate of intensive cure unit (ICU) and rate of discharge and fatality, which will provide a comprehensive reference for clinical physicians in treatment of coronavirus diseases. https://doi.org/10.1101/2020.03.08.20032821 doi: medRxiv preprint 5 The study that met following criteria were included: (1) reporting clinical characteristics of COVID-19 or MERS-COV disease, (2) minimum sample size of five, (3) confirmed COVID-19 or MERS-COV disease, (4) English literature. Clinical predictors of mortality of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection: A cohort study Clinical outcomes among hospital patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection

title:
  Clinical Characteristics of Two Human to Human Transmitted Coronaviruses: Corona Virus Disease 2019 versus Middle East Respiratory Syndrome Coronavirus.

abstract:
  After the outbreak of the middle east respiratory syndrome (MERS) worldwide in 2012. Currently, a novel human coronavirus has caused a major disease outbreak, and named corona virus disease 2019 (COVID-19). The emergency of MRES-COV and COVID-19 has caused global panic and threatened health security. Unfortunately, the similarities and differences between the two coronavirus diseases remain to be unknown. The aim of this study, therefore, is to perform a systematic review to compare epidemiological, clinical and laboratory features of COVID-19 and MERS-COV population. We searched PubMed, EMBASE and Cochrane Register of Controlled Trials database to identify potential studies reported COVID-19 or MERS-COV. Epidemiological, clinical and laboratory outcomes, the admission rate of intensive cure unit (ICU), discharge rate and fatality rate were evaluated using GraphPad Prism software. Thirty-two studies involving 3770 patients (COVID-19 = 1062, MERS-COV = 2708) were included in this study. The present study revealed that compared with COVID-19 population, MERS-COV population had a higher rate of ICU admission, discharge and fatality and longer incubation time. It pointed out that fever, cough and generalised weakness and myalgia were main clinical manifestations of both COVID-19 and MERS-COV, whereas ARDS was main complication. The most effective drug for MERS-COV is ribavirin and interferon.


id: cord-349010-n4s8dzgp
title: Update on therapeutic options for Middle East Respiratory Syndrome Coronavirus (MERS-CoV)
author: Al-Tawfiq, Jaffar A.
date: 2016-12-24
txt: ./txt/cord-349010-n4s8dzgp.txt
cache: ./cache/cord-349010-n4s8dzgp.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/27937060/
doi: 10.1080/14787210.2017.1271712
summary:
  The Middle East respiratory syndrome coronavirus (MERS-CoV) emerged as an important virus in 2012 and since then has caused multiple outbreaks in hospitals especially in the Kingdom of Saudi Arabia and outside the Arabian Peninsula [1] [2] [3] . Based on analysis of SARS data, interferon-ribavirin combination was suggested as a possible therapeutic option for the treatment of MERS-CoV infections [5] . Ribavirin and interferon therapy in patients infected with the Middle East respiratory syndrome coronavirus: an observational study Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study Inhibition of Middle East respiratory syndrome coronavirus (MERS-CoV) infection by anti-CD26 monoclonal antibody Feasibility, safety, clinical, and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol Towards the prophylactic and therapeutic use of human neutralizing monoclonal antibodies for Middle East respiratory syndrome coronavirus (MERS-CoV)

abstract:
  Introduction: The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is an important emerging respiratory pathogen. MERS-CoV resulted in multiple hospital outbreaks within and outside the Arabian Peninsula. The disease has a high case fatality rate, with the need for a therapeutic option. Areas covered: In this review, we provide an overview of the progress in the development of therapeutic strategies for MERS. We searched PubMed, Embase, Cochrane, Scopus, and Google Scholar, using the following terms: ‘MERS’, ‘MERS-CoV’, ‘Middle East respiratory syndrome’ in combination with ‘treatment’ or ‘therapy’. Expert commentary: There are multiple agents tried in vitro and in vivo. None of these agents were used in large clinical studies. Available clinical studies are limited to the use of the combination of interferon and other agents. These clinical studies are based solely on case reports and case series. There are no prospective or randomized trials. There is a need to have prospective and randomized clinical trials for the therapy of MERS-CoV. However, this strategy might be hampered by the sporadic cases outside the large hospital outbreaks.


id: cord-349262-gnqbyc6t
author: Hemida, Maged Gomaa
date: 2020-10-14
txt: ./txt/cord-349262-gnqbyc6t.txt
cache: ./cache/cord-349262-gnqbyc6t.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1017/s0950268820002459
doi: 10.1017/s0950268820002459
summary:
  title: The Middle East respiratory syndrome coronavirus in the breath of some infected dromedary camels (Camelus dromedarius) Dromedary camels remain the currently identified reservoir for the Middle East respiratory syndrome coronavirus (MERS-CoV). We tested nasal swabs, breath samples from animals within this herd by the real-time PCR. However, the nasal swabs are still the sample of choice in the diagnosis of MERS-CoV among the infected dromedary camel population. Detection of the virus in the air of positive camel''s herd [5, 6] may suggest the virus is excreted in the breath of the infected animals in high concentration. The aim of our study was to test the possibility of MERS-CoV shedding in the breath of the infected dromedary camels. Longitudinal study of Middle East respiratory syndrome coronavirus infection in dromedary camel herds in Saudi Arabia Dromedary camels and the transmission of Middle East respiratory syndrome coronavirus (MERS-CoV)

title:
  The Middle East respiratory syndrome coronavirus in the breath of some infected dromedary camels (Camelus dromedarius)

abstract:
  Dromedary camels remain the currently identified reservoir for the Middle East respiratory syndrome coronavirus (MERS-CoV). The virus is released in the secretions of the infected camels, especially the nasal tract. The virus shedding curve through the nasal secretions was studied. Although human transmission of the virus through the respiratory tract of close contact people with dromedary reported previously, the exact mechanism of transmission is still largely unknown. The main goal of this study was to check the possibility of MERS-CoV shedding in the exhaled air of the infected camels. To achieve this goal, we conducted a follow-up study in one of the dromedary camel herds, December 2018–April 2019. We tested nasal swabs, breath samples from animals within this herd by the real-time PCR. Our results showed that some of the tested nasal swabs and breath were positive from 24 March 2019 until 7 April 2019. The phylogenetic analysis of the obtained S and N gene sequences revealed the detected viruses are clustering together with some human and camel samples from the eastern region, especially from Al-Hufuf city, as well as some samples from Qatar and Jordon. These results are clearly showing the possibility of shedding of the virus in the breath of the infected camels. This could explain, at least in part, the mechanism of transmission of MERS-CoV from animals to humans. This study is confirming the shedding of MERS-CoV in the exhaled air of the infected camels. Further studies are needed for a better understanding of the MERS-CoV.


id: cord-349287-mwj2qby4
title: MERS coronavirus: diagnostics, epidemiology and transmission
author: Mackay, Ian M.
date: 2015-12-22
txt: ./txt/cord-349287-mwj2qby4.txt
cache: ./cache/cord-349287-mwj2qby4.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1186/s12985-015-0439-5
doi: 10.1186/s12985-015-0439-5
summary:
  The first known cases of Middle East respiratory syndrome (MERS), associated with infection by a novel coronavirus (CoV), occurred in 2012 in Jordan but were reported retrospectively. Most human cases of MERS have been linked to lapses in infection prevention and control (IPC) in healthcare settings, with approximately 20 % of all virus detections reported among healthcare workers (HCWs) and higher exposures in those with occupations that bring them into close contact with camels. Since asymptomatic zoonoses have been posited [72] , an absence of antibodies to MERS-CoV among some humans who have regular and close contact with camels may reflect the rarity of actively infected animals at butcheries, a limited transmission risk associated with slaughtering DCs [70] , a pre-existing cross-protective immune status or some other factor(s) resulting in a low risk of disease and concurrent seroconversion developing after exposure in this group. First cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infections in France, investigations and implications for the prevention of human-tohuman transmission

abstract:
  The first known cases of Middle East respiratory syndrome (MERS), associated with infection by a novel coronavirus (CoV), occurred in 2012 in Jordan but were reported retrospectively. The case first to be publicly reported was from Jeddah, in the Kingdom of Saudi Arabia (KSA). Since then, MERS-CoV sequences have been found in a bat and in many dromedary camels (DC). MERS-CoV is enzootic in DC across the Arabian Peninsula and in parts of Africa, causing mild upper respiratory tract illness in its camel reservoir and sporadic, but relatively rare human infections. Precisely how virus transmits to humans remains unknown but close and lengthy exposure appears to be a requirement. The KSA is the focal point of MERS, with the majority of human cases. In humans, MERS is mostly known as a lower respiratory tract (LRT) disease involving fever, cough, breathing difficulties and pneumonia that may progress to acute respiratory distress syndrome, multiorgan failure and death in 20 % to 40 % of those infected. However, MERS-CoV has also been detected in mild and influenza-like illnesses and in those with no signs or symptoms. Older males most obviously suffer severe disease and MERS patients often have comorbidities. Compared to severe acute respiratory syndrome (SARS), another sometimes- fatal zoonotic coronavirus disease that has since disappeared, MERS progresses more rapidly to respiratory failure and acute kidney injury (it also has an affinity for growth in kidney cells under laboratory conditions), is more frequently reported in patients with underlying disease and is more often fatal. Most human cases of MERS have been linked to lapses in infection prevention and control (IPC) in healthcare settings, with approximately 20 % of all virus detections reported among healthcare workers (HCWs) and higher exposures in those with occupations that bring them into close contact with camels. Sero-surveys have found widespread evidence of past infection in adult camels and limited past exposure among humans. Sensitive, validated reverse transcriptase real-time polymerase chain reaction (RT-rtPCR)-based diagnostics have been available almost from the start of the emergence of MERS. While the basic virology of MERS-CoV has advanced over the past three years, understanding of the interplay between camel, environment, and human remains limited. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-015-0439-5) contains supplementary material, which is available to authorized users.


id: cord-349643-jtx7ni9b
title: Development of Medical Countermeasures to Middle East Respiratory Syndrome Coronavirus
author: Uyeki, Timothy M.
date: 2016-07-17
txt: ./txt/cord-349643-jtx7ni9b.txt
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url: https://doi.org/10.3201/eid2207.160022
doi: 10.3201/eid2207.160022
summary:
  Preclinical development of and research on potential Middle East respiratory syndrome coronavirus (MERS-CoV) medical countermeasures remain preliminary; advancements are needed before most countermeasures are ready to be tested in human clinical trials. Research priorities include standardization of animal models and virus stocks for studying disease pathogenesis and efficacy of medical countermeasures; development of MERS-CoV diagnostics; improved access to nonhuman primates to support preclinical research; studies to better understand and control MERS-CoV disease, including vaccination studies in camels; and development of a standardized clinical trial protocol. F rom September 2012 through April 27, 2016, a total of 1,728 laboratory-confirmed Middle East respiratory syndrome coronavirus (MERS-CoV) infections, leading to 624 deaths (36% case-fatality proportion), had been reported to the World Health Organization (WHO) (1) . Prophylaxis with a Middle East respiratory syndrome coronavirus (MERS-CoV)-specific human monoclonal antibody protects rabbits from MERS-CoV infection

abstract:
  Preclinical development of and research on potential Middle East respiratory syndrome coronavirus (MERS-CoV) medical countermeasures remain preliminary; advancements are needed before most countermeasures are ready to be tested in human clinical trials. Research priorities include standardization of animal models and virus stocks for studying disease pathogenesis and efficacy of medical countermeasures; development of MERS-CoV diagnostics; improved access to nonhuman primates to support preclinical research; studies to better understand and control MERS-CoV disease, including vaccination studies in camels; and development of a standardized clinical trial protocol. Partnering with clinical trial networks in affected countries to evaluate safety and efficacy of investigational therapeutics will strengthen efforts to identify successful medical countermeasures.


id: cord-351685-n70tkf38
author: Altamimi, Asmaa
date: 2020-02-19
txt: ./txt/cord-351685-n70tkf38.txt
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mime: text/plain
url: https://doi.org/10.1155/2020/9629747
doi: 10.1155/2020/9629747
summary:
  title: Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory METHODS: It was a surveillance system-based study, for which data from a total of 23,646 suspected patients in Riyadh and Al Qassim regions were analyzed from January 2017 until December 2017 to estimate the prevalence of MERS-CoV among suspected cases and to determine potential demographic risk factors related to the confirmation of the diagnosis. During the study period, i.e., the year 2017, only 119 confirmed cases were reported, which means that the number of MERS-CoV infection cases has decreased in Riyadh and Al-Qassim regions in comparison to that of the last three years. Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study

title:
  Demographic Variations of MERS-CoV Infection among Suspected and Confirmed Cases: An Epidemiological Analysis of Laboratory-Based Data from Riyadh Regional Laboratory

abstract:
  Introduction. Middle East respiratory syndrome coronavirus was first recognized in September 2012 in Saudi Arabia. The clinical presentations of MERS and non-MERS SARI are often similar. Therefore, the identification of suspected cases that may have higher chances of being diagnosed as cases of MERS-CoV is essential. However, the real challenge is to flag these patients through some demographic markers. The nature of these markers has not previously been investigated in Saudi Arabia, and hence, this study aims to identify them. METHODS: It was a surveillance system-based study, for which data from a total of 23,646 suspected patients in Riyadh and Al Qassim regions were analyzed from January 2017 until December 2017 to estimate the prevalence of MERS-CoV among suspected cases and to determine potential demographic risk factors related to the confirmation of the diagnosis. RESULTS: Of 23,646 suspected cases, 119 (0.5%) were confirmed by laboratory results. These confirmed cases (67.2% of which were males) had a mean age of 43.23 years (SD ± 22.8). Around 42.2% of the confirmed cases were aged between 41 and 60 years and about 47% of confirmed cases had their suspected specimen tested in the summer. The study identified three significant and independent predictors for confirmation of the disease: an age between 41 and 60 years, male gender, and summer season admission. CONCLUSION: The study provides evidence that the MERS-CoV epidemic in the subject regions has specific characteristics that might help future plans for the prevention and management of such a contagious disease. Future studies should aim to confirm such findings in other regions of Saudi Arabia as well and explore potential preventable risk factors.


id: cord-352527-eeyqh9nc
title: Advances in MERS-CoV Vaccines and Therapeutics Based on the Receptor-Binding Domain
author: Zhou, Yusen
date: 2019-01-14
txt: ./txt/cord-352527-eeyqh9nc.txt
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url: https://www.ncbi.nlm.nih.gov/pubmed/30646569/
doi: 10.3390/v11010060
summary:
  A number of MERS vaccines have been developed based on viral RBD, including nanoparticles, virus-like particles (VLPs), and recombinant proteins, and their protective efficacy has been evaluated in animal models, including mice with adenovirus 5 (Ad5)-directed expression of human DPP4 (Ad5/hDPP4), hDPP4-transgenic (hDPP4-Tg) mice, and non-human primates (NHPs) [88] [89] [90] [91] [92] [93] [94] . Receptor usage of a novel bat lineage C Betacoronavirus reveals evolution of Middle East respiratory syndrome-related coronavirus spike proteins for human dipeptidyl peptidase 4 binding Recombinant receptor-binding domains of multiple Middle East respiratory syndrome coronaviruses (MERS-CoVs) induce cross-neutralizing antibodies against divergent human and camel MERS-CoVs and antibody escape mutants A conformation-dependent neutralizing monoclonal antibody specifically targeting receptor-binding domain in Middle East respiratory syndrome coronavirus spike protein A novel nanobody targeting Middle East respiratory syndrome coronavirus (MERS-CoV) receptor-binding domain has potent cross-neutralizing activity and protective efficacy against MERS-CoV

abstract:
  Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) is an infectious virus that was first reported in 2012. The MERS-CoV genome encodes four major structural proteins, among which the spike (S) protein has a key role in viral infection and pathogenesis. The receptor-binding domain (RBD) of the S protein contains a critical neutralizing domain and is an important target for development of MERS vaccines and therapeutics. In this review, we describe the relevant features of the MERS-CoV S-protein RBD, summarize recent advances in the development of MERS-CoV RBD-based vaccines and therapeutic antibodies, and illustrate potential challenges and strategies to further improve their efficacy.


id: cord-354272-99vw735a
author: DARLING, N. D.
date: 2017-10-24
txt: ./txt/cord-354272-99vw735a.txt
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url: https://www.ncbi.nlm.nih.gov/pubmed/29061208/
doi: 10.1017/s0950268817002345
summary:
  title: Retrospective, epidemiological cluster analysis of the Middle East respiratory syndrome coronavirus (MERS-CoV) epidemic using open source data In an effort to better understand the patterns of transmission, a retrospective analysis of epidemiological clusters identified throughout the ongoing MERS-CoV epidemic was conducted using open-source data. Several key search terms were utilized to capture all cluster-related literature, including ''MERS-CoV'', ''nosocomial'', ''cluster'', ''transmission'', ''superspreader'', ''contact tracing'', and ''healthcare worker''. An exported cluster was defined as any cluster that resulted from verified travel of an index case (from an area of known MERS-CoV transmission) within one incubation period (14 days) of symptom onset. If a case was reported from the city during the estimated time in which there was ongoing nosocomial transmission, had no travel or camel exposure in the 14 days prior to illness onset, and had no known household contact with a confirmed MERS-CoV case, the case was included in the case count for that particular nosocomial cluster.

title:
  Retrospective, epidemiological cluster analysis of the Middle East respiratory syndrome coronavirus (MERS-CoV) epidemic using open source data

abstract:
  The Middle East respiratory syndrome coronavirus (MERS-CoV) is caused by a novel coronavirus discovered in 2012. Since then, 1806 cases, including 564 deaths, have been reported by the Kingdom of Saudi Arabia (KSA) and affected countries as of 1 June 2016. Previous literature attributed increases in MERS-CoV transmission to camel breeding season as camels are likely the reservoir for the virus. However, this literature review and subsequent analysis indicate a lack of seasonality. A retrospective, epidemiological cluster analysis was conducted to investigate increases in MERS-CoV transmission and reports of household and nosocomial clusters. Cases were verified and associations between cases were substantiated through an extensive literature review and the Armed Forces Health Surveillance Branch's Tiered Source Classification System. A total of 51 clusters were identified, primarily nosocomial (80·4%) and most occurred in KSA (45·1%). Clusters corresponded temporally with the majority of periods of greatest incidence, suggesting a strong correlation between nosocomial transmission and notable increases in cases.


id: cord-354302-l2kywzro
title: Replication and Shedding of MERS-CoV in Upper Respiratory Tract of Inoculated Dromedary Camels
author: Adney, Danielle R.
date: 2014-12-17
txt: ./txt/cord-354302-l2kywzro.txt
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mime: text/plain
url: https://doi.org/10.3201/eid2012.141280
doi: 10.3201/eid2012.141280
summary:
  Epidemiologic investigations identified dromedary camels as the likely source of zoonotic transmission of Middle East respiratory syndrome coronavirus (MERS-CoV). Epidemiologic investigations identified dromedary camels as the likely source of zoonotic transmission of Middle East respiratory syndrome coronavirus (MERS-CoV). We inoculated 3 adult camels with a human isolate of MERS-CoV and a transient, primarily upper respiratory tract infection developed in each of the 3 animals. We inoculated 3 adult camels with a human isolate of MERS-CoV and a transient, primarily upper respiratory tract infection developed in each of the 3 animals. T he Middle East respiratory syndrome coronavirus (MERS-CoV) was first recognized in 2012 related to a fatal human case of pneumonia in Saudi Arabia (1) . MERS-CoV shedding started during 1-2 dpi, as detected by the presence of infectious virus and viral RNA by qPCR in nasal swab samples. Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels

abstract:
  In 2012, a novel coronavirus associated with severe respiratory disease in humans emerged in the Middle East. Epidemiologic investigations identified dromedary camels as the likely source of zoonotic transmission of Middle East respiratory syndrome coronavirus (MERS-CoV). Here we provide experimental support for camels as a reservoir for MERS-CoV. We inoculated 3 adult camels with a human isolate of MERS-CoV and a transient, primarily upper respiratory tract infection developed in each of the 3 animals. Clinical signs of the MERS-CoV infection were benign, but each of the camels shed large quantities of virus from the upper respiratory tract. We detected infectious virus in nasal secretions through 7 days postinoculation, and viral RNA up to 35 days postinoculation. The pattern of shedding and propensity for the upper respiratory tract infection in dromedary camels may help explain the lack of systemic illness among naturally infected camels and the means of efficient camel-to-camel and camel-to-human transmission.


id: cord-356113-hmj0qu0v
title: Korean MERS: A new cross continent emerging infectious disease
author: Wiwanitkit, Somsri
date: 2015-10-31
txt: ./txt/cord-356113-hmj0qu0v.txt
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mime: text/plain
url: https://api.elsevier.com/content/article/pii/S2222180815609410
doi: 10.1016/s2222-1808(15)60941-0
summary:
  Abstract Middle East respiratory syndrome is a new emerging infectious disease that was firstly detected in the Middle East. However, the new emergence of this infection is in Korea and Korean Middle East respiratory syndrome becomes the new concern in public health. Middle East respiratory syndrome (MERS) is a new emerging infectious disease that was firstly detected in the Middle East [1] [2] [3] . Clinical features and viral diagnosis of two cases of infection with Middle East respiratory syndrome coronavirus: a report of nosocomial transmission Clinical and laboratory findings of the first imported case of Middle East respiratory syndrome coronavirus to the United States Complete genome sequence of Middle East respiratory syndrome coronavirus (MERS-CoV) from the first imported MERS-CoV case in China Genomic sequencing and analysis of the first imported Middle East respiratory syndrome coronavirus (MERS CoV) in China Imported case of MERS-CoV infection identified in China

abstract:
  Abstract Middle East respiratory syndrome is a new emerging infectious disease that was firstly detected in the Middle East. This disease can cause severe respiratory illness and was proved to be a coronavirus infection. The infection was firstly confined within the Middle East. However, the new emergence of this infection is in Korea and Korean Middle East respiratory syndrome becomes the new concern in public health. In this brief article, the authors discuss on this new cross continent emerging infectious disease.


