Ribavirin and Interferon Therapy for Critically Ill Patients With Middle East Respiratory Syndrome: A Multicenter Observational Study
Identifieur interne : 000B83 ( Pmc/Curation ); précédent : 000B82; suivant : 000B84Ribavirin and Interferon Therapy for Critically Ill Patients With Middle East Respiratory Syndrome: A Multicenter Observational Study
Auteurs : Yaseen M. Arabi [Arabie saoudite] ; Sarah Shalhoub [Canada] ; Yasser Mandourah ; Fahad Al-Hameed ; Awad Al-Omari ; Eman Al Qasim [Arabie saoudite] ; Jesna Jose [Arabie saoudite] ; Basem Alraddadi ; Abdullah Almotairi ; Kasim Al Khatib ; Ahmed Abdulmomen ; Ismael Qushmaq ; Anees A. Sindi ; Ahmed Mady [Arabie saoudite, Égypte] ; Othman Solaiman ; Rajaa Al-Raddadi ; Khalid Maghrabi ; Ahmed Ragab ; Ghaleb A. Al Mekhlafi ; Hanan H. Balkhy ; Abdulrahman Al Harthy [Arabie saoudite] ; Ayman Kharaba ; Jawaher A. Gramish ; Abdulsalam M. Al-Aithan [Arabie saoudite] ; Abdulaziz Al-Dawood [Arabie saoudite] ; Laura Merson [Royaume-Uni] ; Frederick G. Hayden [Royaume-Uni] ; Robert Fowler [Canada]Source :
- Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America [ 1058-4838 ] ; 2019.
Abstract
The objective of this study was to evaluate the effect of ribavirin and recombinant interferon (RBV/rIFN) therapy on the outcomes of critically ill patients with Middle East respiratory syndrome (MERS), accounting for time-varying confounders.
This is a retrospective cohort study of critically ill patients with laboratory-confirmed MERS from 14 hospitals in Saudi Arabia diagnosed between September 2012 and January 2018. We evaluated the association of RBV/rIFN with 90-day mortality and MERS coronavirus (MERS-CoV) RNA clearance using marginal structural modeling to account for baseline and time-varying confounders.
Of 349 MERS patients, 144 (41.3%) patients received RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-β1a; none received rIFN-β1b). RBV/rIFN was initiated at a median of 2 days (Q1, Q3: 1, 3 days) from intensive care unit admission. Crude 90-day mortality was higher in patients with RBV/rIFN compared to no RBV/rIFN (106/144 [73.6%] vs 126/205 [61.5%];
In this observational study, RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-β1a) therapy was commonly used in critically ill MERS patients but was not associated with reduction in 90-day mortality or in faster MERS-CoV RNA clearance.
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DOI: 10.1093/cid/ciz544
PubMed: 31925415
PubMed Central: 7108209
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Sarah Shalhoub<affiliation><nlm:aff id="AF0003"><institution>King Fahad Armed Forces Hospital</institution>, Jeddah</nlm:aff><wicri:noCountry code="subfield">Jeddah</wicri:noCountry></affiliation><affiliation><nlm:aff id="AF0004"><institution>Military Medical Services, Ministry of Defense, Prince Sultan Military Medical City</institution>, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation><affiliation><nlm:aff id="AF0005"><institution>Department of Intensive Care, College of Medicine, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center</institution>, King Abdulaziz Medical City, Jeddah</nlm:aff><wicri:noCountry code="subfield">Jeddah</wicri:noCountry></affiliation><affiliation><nlm:aff id="AF0006"><institution>Department of Intensive Care, College of Medicine, Alfaisal University, Dr Sulaiman Al-Habib Group Hospitals</institution>, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation><affiliation><nlm:aff id="AF0007"><institution>Department of Medicine, King Faisal Specialist Hospital and Research Center</institution>, Jeddah</nlm:aff><wicri:noCountry code="subfield">Jeddah</wicri:noCountry></affiliation><affiliation><nlm:aff id="AF0008"><institution>Department of Medicine, University of Jeddah</institution></nlm:aff></affiliation><affiliation><nlm:aff id="AF0009"><institution>Department of Critical Care Medicine, King Fahad Medical City</institution>, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation><affiliation><nlm:aff id="AF0010"><institution>Intensive Care Department, Al-Noor Specialist Hospital</institution>, Makkah</nlm:aff><wicri:noCountry code="subfield">Makkah</wicri:noCountry></affiliation><affiliation><nlm:aff id="AF0011"><institution>Department of Critical Care Medicine, King Saud University</institution>, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation><affiliation><nlm:aff id="AF0007"><institution>Department of Medicine, King Faisal Specialist Hospital and Research Center</institution>, Jeddah</nlm:aff><wicri:noCountry code="subfield">Jeddah</wicri:noCountry></affiliation><affiliation><nlm:aff id="AF0012"><institution>Department of Anesthesia and Critical Care, Faculty of Medicine, King Abdulaziz University</institution>, Jeddah</nlm:aff><wicri:noCountry code="subfield">Jeddah</wicri:noCountry></affiliation><affiliation><nlm:aff id="AF0015"><institution>Intensive Care Department, King Faisal Specialist Hospital and Research Center</institution>, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation><affiliation><nlm:aff id="AF0015"><institution>Intensive Care Department, King Faisal Specialist Hospital and Research Center</institution>, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation><affiliation><nlm:aff id="AF0017"><institution>Intensive Care Department, King Fahd Hospital</institution>, Jeddah</nlm:aff><wicri:noCountry code="subfield">Jeddah</wicri:noCountry></affiliation><affiliation><nlm:aff id="AF0019"><institution>Department of Infection Prevention and Control, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center</institution>, King Abdulaziz Medical City, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation><affiliation><nlm:aff id="AF0020"><institution>Department of Critical Care, King Fahad Hospital, Ohoud Hospital</institution>, Al-Madinah</nlm:aff><wicri:noCountry code="subfield">Al-Madinah</wicri:noCountry></affiliation><affiliation><nlm:aff id="AF0021"><institution>Pharmaceutical Care Department, College of Pharmacy, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center</institution>, King Abdulaziz Medical City, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation><affiliation><nlm:aff id="AF0024"><institution>Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine</institution>, Charlottesville</nlm:aff><wicri:noCountry code="subfield">Charlottesville</wicri:noCountry></affiliation>Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Ribavirin and Interferon Therapy for Critically Ill Patients With Middle East Respiratory Syndrome: A Multicenter Observational Study</title><author><name sortKey="Arabi, Yaseen M" sort="Arabi, Yaseen M" uniqKey="Arabi Y" first="Yaseen M" last="Arabi">Yaseen M. Arabi</name><affiliation wicri:level="1"><nlm:aff id="AF0001"><institution>Intensive Care Department, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center</institution>, King Abdulaziz Medical City, Riyadh,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Shalhoub, Sarah" sort="Shalhoub, Sarah" uniqKey="Shalhoub S" first="Sarah" last="Shalhoub">Sarah Shalhoub</name><affiliation wicri:level="1"><nlm:aff id="AF0002"><institution>Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario</institution>, London,<country country="CA">Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation><nlm:aff id="AF0003"><institution>King Fahad Armed Forces Hospital</institution>, Jeddah</nlm:aff><wicri:noCountry code="subfield">Jeddah</wicri:noCountry></affiliation></author><author><name sortKey="Mandourah, Yasser" sort="Mandourah, Yasser" uniqKey="Mandourah Y" first="Yasser" last="Mandourah">Yasser Mandourah</name><affiliation><nlm:aff id="AF0004"><institution>Military Medical Services, Ministry of Defense, Prince Sultan Military Medical City</institution>, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation></author><author><name sortKey="Al Hameed, Fahad" sort="Al Hameed, Fahad" uniqKey="Al Hameed F" first="Fahad" last="Al-Hameed">Fahad Al-Hameed</name><affiliation><nlm:aff id="AF0005"><institution>Department of Intensive Care, College of Medicine, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center</institution>, King Abdulaziz Medical City, Jeddah</nlm:aff><wicri:noCountry code="subfield">Jeddah</wicri:noCountry></affiliation></author><author><name sortKey="Al Omari, Awad" sort="Al Omari, Awad" uniqKey="Al Omari A" first="Awad" last="Al-Omari">Awad Al-Omari</name><affiliation><nlm:aff id="AF0006"><institution>Department of Intensive Care, College of Medicine, Alfaisal University, Dr Sulaiman Al-Habib Group Hospitals</institution>, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation></author><author><name sortKey="Al Qasim, Eman" sort="Al Qasim, Eman" uniqKey="Al Qasim E" first="Eman" last="Al Qasim">Eman Al Qasim</name><affiliation wicri:level="1"><nlm:aff id="AF0001"><institution>Intensive Care Department, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center</institution>, King Abdulaziz Medical City, Riyadh,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Jose, Jesna" sort="Jose, Jesna" uniqKey="Jose J" first="Jesna" last="Jose">Jesna Jose</name><affiliation wicri:level="1"><nlm:aff id="AF0001"><institution>Intensive Care Department, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center</institution>, King Abdulaziz Medical City, Riyadh,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Alraddadi, Basem" sort="Alraddadi, Basem" uniqKey="Alraddadi B" first="Basem" last="Alraddadi">Basem Alraddadi</name><affiliation><nlm:aff id="AF0007"><institution>Department of Medicine, King Faisal Specialist Hospital and Research Center</institution>, Jeddah</nlm:aff><wicri:noCountry code="subfield">Jeddah</wicri:noCountry></affiliation><affiliation><nlm:aff id="AF0008"><institution>Department of Medicine, University of Jeddah</institution></nlm:aff></affiliation></author><author><name sortKey="Almotairi, Abdullah" sort="Almotairi, Abdullah" uniqKey="Almotairi A" first="Abdullah" last="Almotairi">Abdullah Almotairi</name><affiliation><nlm:aff id="AF0009"><institution>Department of Critical Care Medicine, King Fahad Medical City</institution>, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation></author><author><name sortKey="Al Khatib, Kasim" sort="Al Khatib, Kasim" uniqKey="Al Khatib K" first="Kasim" last="Al Khatib">Kasim Al Khatib</name><affiliation><nlm:aff id="AF0010"><institution>Intensive Care Department, Al-Noor Specialist Hospital</institution>, Makkah</nlm:aff><wicri:noCountry code="subfield">Makkah</wicri:noCountry></affiliation></author><author><name sortKey="Abdulmomen, Ahmed" sort="Abdulmomen, Ahmed" uniqKey="Abdulmomen A" first="Ahmed" last="Abdulmomen">Ahmed Abdulmomen</name><affiliation><nlm:aff id="AF0011"><institution>Department of Critical Care Medicine, King Saud University</institution>, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation></author><author><name sortKey="Qushmaq, Ismael" sort="Qushmaq, Ismael" uniqKey="Qushmaq I" first="Ismael" last="Qushmaq">Ismael Qushmaq</name><affiliation><nlm:aff id="AF0007"><institution>Department of Medicine, King Faisal Specialist Hospital and Research Center</institution>, Jeddah</nlm:aff><wicri:noCountry code="subfield">Jeddah</wicri:noCountry></affiliation></author><author><name sortKey="Sindi, Anees A" sort="Sindi, Anees A" uniqKey="Sindi A" first="Anees A" last="Sindi">Anees A. Sindi</name><affiliation><nlm:aff id="AF0012"><institution>Department of Anesthesia and Critical Care, Faculty of Medicine, King Abdulaziz University</institution>, Jeddah</nlm:aff><wicri:noCountry code="subfield">Jeddah</wicri:noCountry></affiliation></author><author><name sortKey="Mady, Ahmed" sort="Mady, Ahmed" uniqKey="Mady A" first="Ahmed" last="Mady">Ahmed Mady</name><affiliation wicri:level="1"><nlm:aff id="AF0013"><institution>Intensive Care Department, King Saud Medical City</institution>, Riyadh,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="AF0014"><institution>Tanta University Hospitals</institution>,<country country="EG">Egypt</country></nlm:aff><country xml:lang="fr">Égypte</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Solaiman, Othman" sort="Solaiman, Othman" uniqKey="Solaiman O" first="Othman" last="Solaiman">Othman Solaiman</name><affiliation><nlm:aff id="AF0015"><institution>Intensive Care Department, King Faisal Specialist Hospital and Research Center</institution>, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation></author><author><name sortKey="Al Raddadi, Rajaa" sort="Al Raddadi, Rajaa" uniqKey="Al Raddadi R" first="Rajaa" last="Al-Raddadi">Rajaa Al-Raddadi</name><affiliation><nlm:aff id="AF0016"><institution>Department of Community Medicine, Faculty of Medicine, King Abdulaziz University</institution></nlm:aff></affiliation></author><author><name sortKey="Maghrabi, Khalid" sort="Maghrabi, Khalid" uniqKey="Maghrabi K" first="Khalid" last="Maghrabi">Khalid Maghrabi</name><affiliation><nlm:aff id="AF0015"><institution>Intensive Care Department, King Faisal Specialist Hospital and Research Center</institution>, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation></author><author><name sortKey="Ragab, Ahmed" sort="Ragab, Ahmed" uniqKey="Ragab A" first="Ahmed" last="Ragab">Ahmed Ragab</name><affiliation><nlm:aff id="AF0017"><institution>Intensive Care Department, King Fahd Hospital</institution>, Jeddah</nlm:aff><wicri:noCountry code="subfield">Jeddah</wicri:noCountry></affiliation></author><author><name sortKey="Al Mekhlafi, Ghaleb A" sort="Al Mekhlafi, Ghaleb A" uniqKey="Al Mekhlafi G" first="Ghaleb A" last="Al Mekhlafi">Ghaleb A. Al Mekhlafi</name><affiliation><nlm:aff id="AF0018"><institution>Department of Intensive Care Services, Prince Sultan Military Medical City</institution></nlm:aff></affiliation></author><author><name sortKey="Balkhy, Hanan H" sort="Balkhy, Hanan H" uniqKey="Balkhy H" first="Hanan H" last="Balkhy">Hanan H. Balkhy</name><affiliation><nlm:aff id="AF0019"><institution>Department of Infection Prevention and Control, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center</institution>, King Abdulaziz Medical City, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation></author><author><name sortKey="Al Harthy, Abdulrahman" sort="Al Harthy, Abdulrahman" uniqKey="Al Harthy A" first="Abdulrahman" last="Al Harthy">Abdulrahman Al Harthy</name><affiliation wicri:level="1"><nlm:aff id="AF0013"><institution>Intensive Care Department, King Saud Medical City</institution>, Riyadh,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kharaba, Ayman" sort="Kharaba, Ayman" uniqKey="Kharaba A" first="Ayman" last="Kharaba">Ayman Kharaba</name><affiliation><nlm:aff id="AF0020"><institution>Department of Critical Care, King Fahad Hospital, Ohoud Hospital</institution>, Al-Madinah</nlm:aff><wicri:noCountry code="subfield">Al-Madinah</wicri:noCountry></affiliation></author><author><name sortKey="Gramish, Jawaher A" sort="Gramish, Jawaher A" uniqKey="Gramish J" first="Jawaher A" last="Gramish">Jawaher A. Gramish</name><affiliation><nlm:aff id="AF0021"><institution>Pharmaceutical Care Department, College of Pharmacy, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center</institution>, King Abdulaziz Medical City, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation></author><author><name sortKey="Al Aithan, Abdulsalam M" sort="Al Aithan, Abdulsalam M" uniqKey="Al Aithan A" first="Abdulsalam M" last="Al-Aithan">Abdulsalam M. Al-Aithan</name><affiliation wicri:level="1"><nlm:aff id="AF0022"><institution>Department of Medicine, Critical Care Division, King Abdulaziz Hospital</institution>, Al Ahsa,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Al Dawood, Abdulaziz" sort="Al Dawood, Abdulaziz" uniqKey="Al Dawood A" first="Abdulaziz" last="Al-Dawood">Abdulaziz Al-Dawood</name><affiliation wicri:level="1"><nlm:aff id="AF0001"><institution>Intensive Care Department, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center</institution>, King Abdulaziz Medical City, Riyadh,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Merson, Laura" sort="Merson, Laura" uniqKey="Merson L" first="Laura" last="Merson">Laura Merson</name><affiliation wicri:level="1"><nlm:aff id="AF0023"><institution>International Severe Acute Respiratory and Emerging Infection Consortium, Infectious Diseases Data Observatory, Oxford University</institution>,<country country="GB">United Kingdom</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hayden, Frederick G" sort="Hayden, Frederick G" uniqKey="Hayden F" first="Frederick G" last="Hayden">Frederick G. Hayden</name><affiliation wicri:level="1"><nlm:aff id="AF0023"><institution>International Severe Acute Respiratory and Emerging Infection Consortium, Infectious Diseases Data Observatory, Oxford University</institution>,<country country="GB">United Kingdom</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation><nlm:aff id="AF0024"><institution>Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine</institution>, Charlottesville</nlm:aff><wicri:noCountry code="subfield">Charlottesville</wicri:noCountry></affiliation></author><author><name sortKey="Fowler, Robert" sort="Fowler, Robert" uniqKey="Fowler R" first="Robert" last="Fowler">Robert Fowler</name><affiliation wicri:level="1"><nlm:aff id="AF0025"><institution>Institute of Health Policy Management and Evaluation, University of Toronto, Department of Critical Care Medicine and Department of Medicine, Sunnybrook Hospital</institution>, Ontario,<country country="CA">Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31925415</idno><idno type="pmc">7108209</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108209</idno><idno type="RBID">PMC:7108209</idno><idno type="doi">10.1093/cid/ciz544</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000B83</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000B83</idno><idno type="wicri:Area/Pmc/Curation">000B83</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000B83</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Ribavirin and Interferon Therapy for Critically Ill Patients With Middle East Respiratory Syndrome: A Multicenter Observational Study</title><author><name sortKey="Arabi, Yaseen M" sort="Arabi, Yaseen M" uniqKey="Arabi Y" first="Yaseen M" last="Arabi">Yaseen M. Arabi</name><affiliation wicri:level="1"><nlm:aff id="AF0001"><institution>Intensive Care Department, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center</institution>, King Abdulaziz Medical City, Riyadh,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Shalhoub, Sarah" sort="Shalhoub, Sarah" uniqKey="Shalhoub S" first="Sarah" last="Shalhoub">Sarah Shalhoub</name><affiliation wicri:level="1"><nlm:aff id="AF0002"><institution>Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario</institution>, London,<country country="CA">Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation><nlm:aff id="AF0003"><institution>King Fahad Armed Forces Hospital</institution>, Jeddah</nlm:aff><wicri:noCountry code="subfield">Jeddah</wicri:noCountry></affiliation></author><author><name sortKey="Mandourah, Yasser" sort="Mandourah, Yasser" uniqKey="Mandourah Y" first="Yasser" last="Mandourah">Yasser Mandourah</name><affiliation><nlm:aff id="AF0004"><institution>Military Medical Services, Ministry of Defense, Prince Sultan Military Medical City</institution>, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation></author><author><name sortKey="Al Hameed, Fahad" sort="Al Hameed, Fahad" uniqKey="Al Hameed F" first="Fahad" last="Al-Hameed">Fahad Al-Hameed</name><affiliation><nlm:aff id="AF0005"><institution>Department of Intensive Care, College of Medicine, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center</institution>, King Abdulaziz Medical City, Jeddah</nlm:aff><wicri:noCountry code="subfield">Jeddah</wicri:noCountry></affiliation></author><author><name sortKey="Al Omari, Awad" sort="Al Omari, Awad" uniqKey="Al Omari A" first="Awad" last="Al-Omari">Awad Al-Omari</name><affiliation><nlm:aff id="AF0006"><institution>Department of Intensive Care, College of Medicine, Alfaisal University, Dr Sulaiman Al-Habib Group Hospitals</institution>, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation></author><author><name sortKey="Al Qasim, Eman" sort="Al Qasim, Eman" uniqKey="Al Qasim E" first="Eman" last="Al Qasim">Eman Al Qasim</name><affiliation wicri:level="1"><nlm:aff id="AF0001"><institution>Intensive Care Department, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center</institution>, King Abdulaziz Medical City, Riyadh,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Jose, Jesna" sort="Jose, Jesna" uniqKey="Jose J" first="Jesna" last="Jose">Jesna Jose</name><affiliation wicri:level="1"><nlm:aff id="AF0001"><institution>Intensive Care Department, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center</institution>, King Abdulaziz Medical City, Riyadh,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Alraddadi, Basem" sort="Alraddadi, Basem" uniqKey="Alraddadi B" first="Basem" last="Alraddadi">Basem Alraddadi</name><affiliation><nlm:aff id="AF0007"><institution>Department of Medicine, King Faisal Specialist Hospital and Research Center</institution>, Jeddah</nlm:aff><wicri:noCountry code="subfield">Jeddah</wicri:noCountry></affiliation><affiliation><nlm:aff id="AF0008"><institution>Department of Medicine, University of Jeddah</institution></nlm:aff></affiliation></author><author><name sortKey="Almotairi, Abdullah" sort="Almotairi, Abdullah" uniqKey="Almotairi A" first="Abdullah" last="Almotairi">Abdullah Almotairi</name><affiliation><nlm:aff id="AF0009"><institution>Department of Critical Care Medicine, King Fahad Medical City</institution>, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation></author><author><name sortKey="Al Khatib, Kasim" sort="Al Khatib, Kasim" uniqKey="Al Khatib K" first="Kasim" last="Al Khatib">Kasim Al Khatib</name><affiliation><nlm:aff id="AF0010"><institution>Intensive Care Department, Al-Noor Specialist Hospital</institution>, Makkah</nlm:aff><wicri:noCountry code="subfield">Makkah</wicri:noCountry></affiliation></author><author><name sortKey="Abdulmomen, Ahmed" sort="Abdulmomen, Ahmed" uniqKey="Abdulmomen A" first="Ahmed" last="Abdulmomen">Ahmed Abdulmomen</name><affiliation><nlm:aff id="AF0011"><institution>Department of Critical Care Medicine, King Saud University</institution>, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation></author><author><name sortKey="Qushmaq, Ismael" sort="Qushmaq, Ismael" uniqKey="Qushmaq I" first="Ismael" last="Qushmaq">Ismael Qushmaq</name><affiliation><nlm:aff id="AF0007"><institution>Department of Medicine, King Faisal Specialist Hospital and Research Center</institution>, Jeddah</nlm:aff><wicri:noCountry code="subfield">Jeddah</wicri:noCountry></affiliation></author><author><name sortKey="Sindi, Anees A" sort="Sindi, Anees A" uniqKey="Sindi A" first="Anees A" last="Sindi">Anees A. Sindi</name><affiliation><nlm:aff id="AF0012"><institution>Department of Anesthesia and Critical Care, Faculty of Medicine, King Abdulaziz University</institution>, Jeddah</nlm:aff><wicri:noCountry code="subfield">Jeddah</wicri:noCountry></affiliation></author><author><name sortKey="Mady, Ahmed" sort="Mady, Ahmed" uniqKey="Mady A" first="Ahmed" last="Mady">Ahmed Mady</name><affiliation wicri:level="1"><nlm:aff id="AF0013"><institution>Intensive Care Department, King Saud Medical City</institution>, Riyadh,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="AF0014"><institution>Tanta University Hospitals</institution>,<country country="EG">Egypt</country></nlm:aff><country xml:lang="fr">Égypte</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Solaiman, Othman" sort="Solaiman, Othman" uniqKey="Solaiman O" first="Othman" last="Solaiman">Othman Solaiman</name><affiliation><nlm:aff id="AF0015"><institution>Intensive Care Department, King Faisal Specialist Hospital and Research Center</institution>, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation></author><author><name sortKey="Al Raddadi, Rajaa" sort="Al Raddadi, Rajaa" uniqKey="Al Raddadi R" first="Rajaa" last="Al-Raddadi">Rajaa Al-Raddadi</name><affiliation><nlm:aff id="AF0016"><institution>Department of Community Medicine, Faculty of Medicine, King Abdulaziz University</institution></nlm:aff></affiliation></author><author><name sortKey="Maghrabi, Khalid" sort="Maghrabi, Khalid" uniqKey="Maghrabi K" first="Khalid" last="Maghrabi">Khalid Maghrabi</name><affiliation><nlm:aff id="AF0015"><institution>Intensive Care Department, King Faisal Specialist Hospital and Research Center</institution>, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation></author><author><name sortKey="Ragab, Ahmed" sort="Ragab, Ahmed" uniqKey="Ragab A" first="Ahmed" last="Ragab">Ahmed Ragab</name><affiliation><nlm:aff id="AF0017"><institution>Intensive Care Department, King Fahd Hospital</institution>, Jeddah</nlm:aff><wicri:noCountry code="subfield">Jeddah</wicri:noCountry></affiliation></author><author><name sortKey="Al Mekhlafi, Ghaleb A" sort="Al Mekhlafi, Ghaleb A" uniqKey="Al Mekhlafi G" first="Ghaleb A" last="Al Mekhlafi">Ghaleb A. Al Mekhlafi</name><affiliation><nlm:aff id="AF0018"><institution>Department of Intensive Care Services, Prince Sultan Military Medical City</institution></nlm:aff></affiliation></author><author><name sortKey="Balkhy, Hanan H" sort="Balkhy, Hanan H" uniqKey="Balkhy H" first="Hanan H" last="Balkhy">Hanan H. Balkhy</name><affiliation><nlm:aff id="AF0019"><institution>Department of Infection Prevention and Control, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center</institution>, King Abdulaziz Medical City, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation></author><author><name sortKey="Al Harthy, Abdulrahman" sort="Al Harthy, Abdulrahman" uniqKey="Al Harthy A" first="Abdulrahman" last="Al Harthy">Abdulrahman Al Harthy</name><affiliation wicri:level="1"><nlm:aff id="AF0013"><institution>Intensive Care Department, King Saud Medical City</institution>, Riyadh,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kharaba, Ayman" sort="Kharaba, Ayman" uniqKey="Kharaba A" first="Ayman" last="Kharaba">Ayman Kharaba</name><affiliation><nlm:aff id="AF0020"><institution>Department of Critical Care, King Fahad Hospital, Ohoud Hospital</institution>, Al-Madinah</nlm:aff><wicri:noCountry code="subfield">Al-Madinah</wicri:noCountry></affiliation></author><author><name sortKey="Gramish, Jawaher A" sort="Gramish, Jawaher A" uniqKey="Gramish J" first="Jawaher A" last="Gramish">Jawaher A. Gramish</name><affiliation><nlm:aff id="AF0021"><institution>Pharmaceutical Care Department, College of Pharmacy, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center</institution>, King Abdulaziz Medical City, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation></author><author><name sortKey="Al Aithan, Abdulsalam M" sort="Al Aithan, Abdulsalam M" uniqKey="Al Aithan A" first="Abdulsalam M" last="Al-Aithan">Abdulsalam M. Al-Aithan</name><affiliation wicri:level="1"><nlm:aff id="AF0022"><institution>Department of Medicine, Critical Care Division, King Abdulaziz Hospital</institution>, Al Ahsa,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Al Dawood, Abdulaziz" sort="Al Dawood, Abdulaziz" uniqKey="Al Dawood A" first="Abdulaziz" last="Al-Dawood">Abdulaziz Al-Dawood</name><affiliation wicri:level="1"><nlm:aff id="AF0001"><institution>Intensive Care Department, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center</institution>, King Abdulaziz Medical City, Riyadh,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Merson, Laura" sort="Merson, Laura" uniqKey="Merson L" first="Laura" last="Merson">Laura Merson</name><affiliation wicri:level="1"><nlm:aff id="AF0023"><institution>International Severe Acute Respiratory and Emerging Infection Consortium, Infectious Diseases Data Observatory, Oxford University</institution>,<country country="GB">United Kingdom</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hayden, Frederick G" sort="Hayden, Frederick G" uniqKey="Hayden F" first="Frederick G" last="Hayden">Frederick G. Hayden</name><affiliation wicri:level="1"><nlm:aff id="AF0023"><institution>International Severe Acute Respiratory and Emerging Infection Consortium, Infectious Diseases Data Observatory, Oxford University</institution>,<country country="GB">United Kingdom</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation><nlm:aff id="AF0024"><institution>Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine</institution>, Charlottesville</nlm:aff><wicri:noCountry code="subfield">Charlottesville</wicri:noCountry></affiliation></author><author><name sortKey="Fowler, Robert" sort="Fowler, Robert" uniqKey="Fowler R" first="Robert" last="Fowler">Robert Fowler</name><affiliation wicri:level="1"><nlm:aff id="AF0025"><institution>Institute of Health Policy Management and Evaluation, University of Toronto, Department of Critical Care Medicine and Department of Medicine, Sunnybrook Hospital</institution>, Ontario,<country country="CA">Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America</title><idno type="ISSN">1058-4838</idno><idno type="eISSN">1537-6591</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Abstract</title><sec id="s0100"><title>Background</title><p>The objective of this study was to evaluate the effect of ribavirin and recombinant interferon (RBV/rIFN) therapy on the outcomes of critically ill patients with Middle East respiratory syndrome (MERS), accounting for time-varying confounders.</p></sec><sec id="s0101"><title>Methods</title><p>This is a retrospective cohort study of critically ill patients with laboratory-confirmed MERS from 14 hospitals in Saudi Arabia diagnosed between September 2012 and January 2018. We evaluated the association of RBV/rIFN with 90-day mortality and MERS coronavirus (MERS-CoV) RNA clearance using marginal structural modeling to account for baseline and time-varying confounders.</p></sec><sec id="s0102"><title>Results</title><p>Of 349 MERS patients, 144 (41.3%) patients received RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-β1a; none received rIFN-β1b). RBV/rIFN was initiated at a median of 2 days (Q1, Q3: 1, 3 days) from intensive care unit admission. Crude 90-day mortality was higher in patients with RBV/rIFN compared to no RBV/rIFN (106/144 [73.6%] vs 126/205 [61.5%]; <italic>P</italic> = .02]. After adjusting for baseline and time-varying confounders using a marginal structural model, RBV/rIFN was not associated with changes in 90-day mortality (adjusted odds ratio, 1.03 [95% confidence interval {CI}, .73–1.44]; <italic>P</italic> = .87) or with more rapid MERS-CoV RNA clearance (adjusted hazard ratio, 0.65 [95% CI, .30–1.44]; <italic>P</italic> = .29).</p></sec><sec id="s0103"><title>Conclusions</title><p>In this observational study, RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-β1a) therapy was commonly used in critically ill MERS patients but was not associated with reduction in 90-day mortality or in faster MERS-CoV RNA clearance.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Arabi, Ym" uniqKey="Arabi Y">YM Arabi</name></author><author><name sortKey="Balkhy, Hh" uniqKey="Balkhy H">HH Balkhy</name></author><author><name sortKey="Hayden, Fg" uniqKey="Hayden F">FG Hayden</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Falzarano, D" uniqKey="Falzarano D">D Falzarano</name></author><author><name sortKey="De Wit, E" uniqKey="De Wit E">E de Wit</name></author><author><name sortKey="Martellaro, C" uniqKey="Martellaro C">C Martellaro</name></author><author><name sortKey="Callison, J" uniqKey="Callison J">J Callison</name></author><author><name sortKey="Munster, Vj" uniqKey="Munster V">VJ Munster</name></author><author><name sortKey="Feldmann, H" uniqKey="Feldmann H">H Feldmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Falzarano, D" uniqKey="Falzarano D">D Falzarano</name></author><author><name sortKey="De Wit, E" uniqKey="De Wit E">E de Wit</name></author><author><name sortKey="Rasmussen, Al" uniqKey="Rasmussen A">AL Rasmussen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Momattin, H" uniqKey="Momattin H">H Momattin</name></author><author><name sortKey="Mohammed, K" uniqKey="Mohammed K">K Mohammed</name></author><author><name sortKey="Zumla, A" uniqKey="Zumla A">A Zumla</name></author><author><name sortKey="Memish, Za" uniqKey="Memish Z">ZA Memish</name></author><author><name sortKey="Al Tawfiq, Ja" uniqKey="Al Tawfiq J">JA Al-Tawfiq</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hart, Bj" uniqKey="Hart B">BJ Hart</name></author><author><name sortKey="Dyall, J" uniqKey="Dyall J">J Dyall</name></author><author><name sortKey="Postnikova, E" uniqKey="Postnikova E">E Postnikova</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Khalid, M" uniqKey="Khalid M">M Khalid</name></author><author><name sortKey="Al Rabiah, F" uniqKey="Al Rabiah F">F Al Rabiah</name></author><author><name sortKey="Khan, B" uniqKey="Khan B">B Khan</name></author><author><name sortKey="Al Mobeireek, A" uniqKey="Al Mobeireek A">A Al Mobeireek</name></author><author><name sortKey="Butt, Ts" uniqKey="Butt T">TS Butt</name></author><author><name sortKey="Al Mutairy, E" uniqKey="Al Mutairy E">E Al Mutairy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Al Tawfiq, Ja" uniqKey="Al Tawfiq J">JA Al-Tawfiq</name></author><author><name sortKey="Momattin, H" uniqKey="Momattin H">H Momattin</name></author><author><name sortKey="Dib, J" uniqKey="Dib J">J Dib</name></author><author><name sortKey="Memish, Za" uniqKey="Memish Z">ZA Memish</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shalhoub, S" uniqKey="Shalhoub S">S Shalhoub</name></author><author><name sortKey="Farahat, F" uniqKey="Farahat F">F Farahat</name></author><author><name sortKey="Al Jiffri, A" uniqKey="Al Jiffri A">A Al-Jiffri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Omrani, As" uniqKey="Omrani A">AS Omrani</name></author><author><name sortKey="Saad, Mm" uniqKey="Saad M">MM Saad</name></author><author><name sortKey="Baig, K" uniqKey="Baig K">K Baig</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Al Ghamdi, M" uniqKey="Al Ghamdi M">M Al Ghamdi</name></author><author><name sortKey="Alghamdi, Km" uniqKey="Alghamdi K">KM Alghamdi</name></author><author><name sortKey="Ghandoora, Y" uniqKey="Ghandoora Y">Y Ghandoora</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Suissa, S" uniqKey="Suissa S">S Suissa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Suissa, S" uniqKey="Suissa S">S Suissa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Arabi, Ym" uniqKey="Arabi Y">YM Arabi</name></author><author><name sortKey="Shalhoub, S" uniqKey="Shalhoub S">S Shalhoub</name></author><author><name sortKey="Al Omari, A" uniqKey="Al Omari A">A Al Omari</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Arabi, Ym" uniqKey="Arabi Y">YM Arabi</name></author><author><name sortKey="Al Omari, A" uniqKey="Al Omari A">A Al-Omari</name></author><author><name sortKey="Mandourah, Y" uniqKey="Mandourah Y">Y Mandourah</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Corman, Vm" uniqKey="Corman V">VM Corman</name></author><author><name sortKey="Muller, Ma" uniqKey="Muller M">MA Muller</name></author><author><name sortKey="Costabel, U" uniqKey="Costabel U">U Costabel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Arabi, Ym" uniqKey="Arabi Y">YM Arabi</name></author><author><name sortKey="Alothman, A" uniqKey="Alothman A">A Alothman</name></author><author><name sortKey="Balkhy, Hh" uniqKey="Balkhy H">HH Balkhy</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Vincent, Jl" uniqKey="Vincent J">JL Vincent</name></author><author><name sortKey="De Mendonca, A" uniqKey="De Mendonca A">A de Mendonça</name></author><author><name sortKey="Cantraine, F" uniqKey="Cantraine F">F Cantraine</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Arabi, Ym" uniqKey="Arabi Y">YM Arabi</name></author><author><name sortKey="Mandourah, Y" uniqKey="Mandourah Y">Y Mandourah</name></author><author><name sortKey="Al Hameed, F" uniqKey="Al Hameed F">F Al-Hameed</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Delaney, Jw" uniqKey="Delaney J">JW Delaney</name></author><author><name sortKey="Pinto, R" uniqKey="Pinto R">R Pinto</name></author><author><name sortKey="Long, J" uniqKey="Long J">J Long</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hernan, Ma" uniqKey="Hernan M">MA Hernán</name></author><author><name sortKey="Brumback, B" uniqKey="Brumback B">B 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Sheahan</name></author><author><name sortKey="Sims, Ac" uniqKey="Sims A">AC Sims</name></author><author><name sortKey="Graham, Rl" uniqKey="Graham R">RL Graham</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Beigel, Jh" uniqKey="Beigel J">JH Beigel</name></author><author><name sortKey="Voell, J" uniqKey="Voell J">J Voell</name></author><author><name sortKey="Kumar, P" uniqKey="Kumar P">P Kumar</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Clin Infect Dis</journal-id><journal-id journal-id-type="iso-abbrev">Clin. Infect. Dis</journal-id><journal-id journal-id-type="publisher-id">cid</journal-id><journal-title-group><journal-title>Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America</journal-title></journal-title-group><issn pub-type="ppub">1058-4838</issn><issn pub-type="epub">1537-6591</issn><publisher><publisher-name>Oxford University Press</publisher-name><publisher-loc>US</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31925415</article-id><article-id pub-id-type="pmc">7108209</article-id><article-id pub-id-type="doi">10.1093/cid/ciz544</article-id><article-id pub-id-type="publisher-id">ciz544</article-id><article-categories><subj-group subj-group-type="heading"><subject>Major Article</subject></subj-group></article-categories><title-group><article-title>Ribavirin and Interferon Therapy for Critically Ill Patients With Middle East Respiratory Syndrome: A Multicenter Observational Study</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Arabi</surname><given-names>Yaseen M</given-names></name><xref ref-type="aff" rid="AF0001">1</xref><xref ref-type="corresp" rid="c1"></xref><pmc-comment>arabi@ngha.med.sa </pmc-comment>
</contrib><contrib contrib-type="author"><name><surname>Shalhoub</surname><given-names>Sarah</given-names></name><xref ref-type="aff" rid="AF0002">2</xref><xref ref-type="aff" rid="AF0003">3</xref></contrib><contrib contrib-type="author"><name><surname>Mandourah</surname><given-names>Yasser</given-names></name><xref ref-type="aff" rid="AF0004">4</xref></contrib><contrib contrib-type="author"><name><surname>Al-Hameed</surname><given-names>Fahad</given-names></name><xref ref-type="aff" rid="AF0005">5</xref></contrib><contrib contrib-type="author"><name><surname>Al-Omari</surname><given-names>Awad</given-names></name><xref ref-type="aff" rid="AF0006">6</xref></contrib><contrib contrib-type="author"><name><surname>Al Qasim</surname><given-names>Eman</given-names></name><xref ref-type="aff" rid="AF0001">1</xref></contrib><contrib contrib-type="author"><name><surname>Jose</surname><given-names>Jesna</given-names></name><xref ref-type="aff" rid="AF0001">1</xref></contrib><contrib contrib-type="author"><name><surname>Alraddadi</surname><given-names>Basem</given-names></name><xref ref-type="aff" rid="AF0007">7</xref><xref ref-type="aff" rid="AF0008">8</xref></contrib><contrib contrib-type="author"><name><surname>Almotairi</surname><given-names>Abdullah</given-names></name><xref ref-type="aff" rid="AF0009">9</xref></contrib><contrib contrib-type="author"><name><surname>Al Khatib</surname><given-names>Kasim</given-names></name><xref ref-type="aff" rid="AF0010">10</xref></contrib><contrib contrib-type="author"><name><surname>Abdulmomen</surname><given-names>Ahmed</given-names></name><xref ref-type="aff" rid="AF0011">11</xref></contrib><contrib contrib-type="author"><name><surname>Qushmaq</surname><given-names>Ismael</given-names></name><xref ref-type="aff" rid="AF0007">7</xref></contrib><contrib contrib-type="author"><name><surname>Sindi</surname><given-names>Anees A</given-names></name><xref ref-type="aff" rid="AF0012">12</xref></contrib><contrib contrib-type="author"><name><surname>Mady</surname><given-names>Ahmed</given-names></name><xref ref-type="aff" rid="AF0013">13</xref><xref ref-type="aff" rid="AF0014">14</xref></contrib><contrib contrib-type="author"><name><surname>Solaiman</surname><given-names>Othman</given-names></name><xref ref-type="aff" rid="AF0015">15</xref></contrib><contrib contrib-type="author"><name><surname>Al-Raddadi</surname><given-names>Rajaa</given-names></name><xref ref-type="aff" rid="AF0016">16</xref></contrib><contrib contrib-type="author"><name><surname>Maghrabi</surname><given-names>Khalid</given-names></name><xref ref-type="aff" rid="AF0015">15</xref></contrib><contrib contrib-type="author"><name><surname>Ragab</surname><given-names>Ahmed</given-names></name><xref ref-type="aff" rid="AF0017">17</xref></contrib><contrib contrib-type="author"><name><surname>Al Mekhlafi</surname><given-names>Ghaleb A</given-names></name><xref ref-type="aff" rid="AF0018">18</xref></contrib><contrib contrib-type="author"><name><surname>Balkhy</surname><given-names>Hanan H</given-names></name><xref ref-type="aff" rid="AF0019">19</xref></contrib><contrib contrib-type="author"><name><surname>Al Harthy</surname><given-names>Abdulrahman</given-names></name><xref ref-type="aff" rid="AF0013">13</xref></contrib><contrib contrib-type="author"><name><surname>Kharaba</surname><given-names>Ayman</given-names></name><xref ref-type="aff" rid="AF0020">20</xref></contrib><contrib contrib-type="author"><name><surname>Gramish</surname><given-names>Jawaher A</given-names></name><xref ref-type="aff" rid="AF0021">21</xref></contrib><contrib contrib-type="author"><name><surname>Al-Aithan</surname><given-names>Abdulsalam M</given-names></name><xref ref-type="aff" rid="AF0022">22</xref></contrib><contrib contrib-type="author"><name><surname>Al-Dawood</surname><given-names>Abdulaziz</given-names></name><xref ref-type="aff" rid="AF0001">1</xref></contrib><contrib contrib-type="author"><name><surname>Merson</surname><given-names>Laura</given-names></name><xref ref-type="aff" rid="AF0023">23</xref></contrib><contrib contrib-type="author"><name><surname>Hayden</surname><given-names>Frederick G</given-names></name><xref ref-type="aff" rid="AF0023">23</xref><xref ref-type="aff" rid="AF0024">24</xref></contrib><contrib contrib-type="author"><name><surname>Fowler</surname><given-names>Robert</given-names></name><xref ref-type="aff" rid="AF0025">25</xref></contrib><on-behalf-of>for the Saudi Critical Care Trials Group</on-behalf-of></contrib-group><aff id="AF0001"><label>1</label><institution>Intensive Care Department, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center</institution>, King Abdulaziz Medical City, Riyadh,<country country="SA">Saudi Arabia</country></aff><aff id="AF0002"><label>2</label><institution>Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario</institution>, London,<country country="CA">Canada</country></aff><aff id="AF0003"><label>3</label><institution>King Fahad Armed Forces Hospital</institution>, Jeddah</aff><aff id="AF0004"><label>4</label><institution>Military Medical Services, Ministry of Defense, Prince Sultan Military Medical City</institution>, Riyadh</aff><aff id="AF0005"><label>5</label><institution>Department of Intensive Care, College of Medicine, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center</institution>, King Abdulaziz Medical City, Jeddah</aff><aff id="AF0006"><label>6</label><institution>Department of Intensive Care, College of Medicine, Alfaisal University, Dr Sulaiman Al-Habib Group Hospitals</institution>, Riyadh</aff><aff id="AF0007"><label>7</label><institution>Department of Medicine, King Faisal Specialist Hospital and Research Center</institution>, Jeddah</aff><aff id="AF0008"><label>8</label><institution>Department of Medicine, University of Jeddah</institution></aff><aff id="AF0009"><label>9</label><institution>Department of Critical Care Medicine, King Fahad Medical City</institution>, Riyadh</aff><aff id="AF0010"><label>10</label><institution>Intensive Care Department, Al-Noor Specialist Hospital</institution>, Makkah</aff><aff id="AF0011"><label>11</label><institution>Department of Critical Care Medicine, King Saud University</institution>, Riyadh</aff><aff id="AF0012"><label>12</label><institution>Department of Anesthesia and Critical Care, Faculty of Medicine, King Abdulaziz University</institution>, Jeddah</aff><aff id="AF0013"><label>13</label><institution>Intensive Care Department, King Saud Medical City</institution>, Riyadh,<country country="SA">Saudi Arabia</country></aff><aff id="AF0014"><label>14</label><institution>Tanta University Hospitals</institution>,<country country="EG">Egypt</country></aff><aff id="AF0015"><label>15</label><institution>Intensive Care Department, King Faisal Specialist Hospital and Research Center</institution>, Riyadh</aff><aff id="AF0016"><label>16</label><institution>Department of Community Medicine, Faculty of Medicine, King Abdulaziz University</institution></aff><aff id="AF0017"><label>17</label><institution>Intensive Care Department, King Fahd Hospital</institution>, Jeddah</aff><aff id="AF0018"><label>18</label><institution>Department of Intensive Care Services, Prince Sultan Military Medical City</institution></aff><aff id="AF0019"><label>19</label><institution>Department of Infection Prevention and Control, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center</institution>, King Abdulaziz Medical City, Riyadh</aff><aff id="AF0020"><label>20</label><institution>Department of Critical Care, King Fahad Hospital, Ohoud Hospital</institution>, Al-Madinah</aff><aff id="AF0021"><label>21</label><institution>Pharmaceutical Care Department, College of Pharmacy, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center</institution>, King Abdulaziz Medical City, Riyadh</aff><aff id="AF0022"><label>22</label><institution>Department of Medicine, Critical Care Division, King Abdulaziz Hospital</institution>, Al Ahsa,<country country="SA">Saudi Arabia</country></aff><aff id="AF0023"><label>23</label><institution>International Severe Acute Respiratory and Emerging Infection Consortium, Infectious Diseases Data Observatory, Oxford University</institution>,<country country="GB">United Kingdom</country></aff><aff id="AF0024"><label>24</label><institution>Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine</institution>, Charlottesville</aff><aff id="AF0025"><label>25</label><institution>Institute of Health Policy Management and Evaluation, University of Toronto, Department of Critical Care Medicine and Department of Medicine, Sunnybrook Hospital</institution>, Ontario,<country country="CA">Canada</country></aff><author-notes><corresp id="c1">Correspondence: Y. Arabi, Intensive Care Department, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, MC 1425, PO Box 22490, Riyadh 11426, Saudi Arabia (<email>arabi@ngha.med.sa</email>). </corresp></author-notes><pub-date pub-type="epub" iso-8601-date="2019-06-25"><day>25</day><month>6</month><year>2019</year></pub-date><pub-date pub-type="pmc-release"><day>25</day><month>6</month><year>2020</year></pub-date><pmc-comment> PMC Release delay is 12 months and
0 days and was based on the
<elocation-id>ciz544</elocation-id><history><date date-type="received"><day>03</day><month>12</month><year>2018</year></date><date date-type="accepted"><day>21</day><month>6</month><year>2019</year></date></history><permissions><copyright-statement>© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.</copyright-statement><copyright-year>2019</copyright-year><license license-type="publisher-standard" xlink:href="https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model"><license-p>This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (<ext-link ext-link-type="uri" xlink:href="https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model">https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model</ext-link>)</license-p></license><license><license-p>This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.</license-p></license></permissions><self-uri xlink:href="ciz544.pdf"></self-uri><abstract><title>Abstract</title><sec id="s0100"><title>Background</title><p>The objective of this study was to evaluate the effect of ribavirin and recombinant interferon (RBV/rIFN) therapy on the outcomes of critically ill patients with Middle East respiratory syndrome (MERS), accounting for time-varying confounders.</p></sec><sec id="s0101"><title>Methods</title><p>This is a retrospective cohort study of critically ill patients with laboratory-confirmed MERS from 14 hospitals in Saudi Arabia diagnosed between September 2012 and January 2018. We evaluated the association of RBV/rIFN with 90-day mortality and MERS coronavirus (MERS-CoV) RNA clearance using marginal structural modeling to account for baseline and time-varying confounders.</p></sec><sec id="s0102"><title>Results</title><p>Of 349 MERS patients, 144 (41.3%) patients received RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-β1a; none received rIFN-β1b). RBV/rIFN was initiated at a median of 2 days (Q1, Q3: 1, 3 days) from intensive care unit admission. Crude 90-day mortality was higher in patients with RBV/rIFN compared to no RBV/rIFN (106/144 [73.6%] vs 126/205 [61.5%]; <italic>P</italic> = .02]. After adjusting for baseline and time-varying confounders using a marginal structural model, RBV/rIFN was not associated with changes in 90-day mortality (adjusted odds ratio, 1.03 [95% confidence interval {CI}, .73–1.44]; <italic>P</italic> = .87) or with more rapid MERS-CoV RNA clearance (adjusted hazard ratio, 0.65 [95% CI, .30–1.44]; <italic>P</italic> = .29).</p></sec><sec id="s0103"><title>Conclusions</title><p>In this observational study, RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-β1a) therapy was commonly used in critically ill MERS patients but was not associated with reduction in 90-day mortality or in faster MERS-CoV RNA clearance.</p></sec></abstract><abstract abstract-type="teaser"><p>In this observational study accounting for baseline and time-varying confounders, ribavirin and recombinant interferon (rIFN-α2a, rIFN-α2b, or rIFN-β1a) therapy was not associated with reduction in 90-day mortality or in faster MERS-CoV RNA clearance.</p></abstract><kwd-group><kwd>coronavirus</kwd><kwd>Middle East respiratory syndrome</kwd><kwd>pneumonia</kwd><kwd>ribavirin</kwd><kwd>interferon</kwd></kwd-group><funding-group><award-group award-type="grant"><funding-source><named-content content-type="funder-name">National Institutes of Health</named-content><named-content content-type="funder-identifier">10.13039/100000002</named-content></funding-source></award-group></funding-group><counts><page-count count="8"></page-count></counts><custom-meta-group><custom-meta><meta-name>article-lifecycle</meta-name><meta-value>PAP</meta-value></custom-meta><custom-meta><meta-name>edited-state</meta-name><meta-value>corrected-proof</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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