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The aim was to evaluate which virus and host response factors were associated with mortality risk among participants in Therapeutics for Inpatients with COVID-19 (TICO\/ACTIV-3) trials.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A secondary analysis of 2625 adults hospitalized for acute SARS-CoV-2 infection randomized to 1 of 5 antiviral products or matched placebo in 114 centers on 4 continents. Uniform, site-level collection of participant baseline clinical variables was performed. Research laboratories assayed baseline upper respiratory swabs for SARS-CoV-2 viral RNA and plasma for anti\u2013SARS-CoV-2 antibodies, SARS-CoV-2 nucleocapsid antigen (viral Ag), and interleukin-6 (IL-6). Associations between factors and time to mortality by 90 days were assessed using univariate and multivariable Cox proportional hazards models.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Viral Ag \u22654500\u2005ng\/L (vs &amp;lt;200\u2005ng\/L; adjusted hazard ratio [aHR], 2.07; 1.29\u20133.34), viral RNA (&amp;lt;35 000\u2005copies\/mL [aHR, 2.42; 1.09\u20135.34], \u226535 000\u2005copies\/mL [aHR, 2.84; 1.29\u20136.28], vs below detection), respiratory support (&amp;lt;4 L O2 [aHR, 1.84; 1.06\u20133.22]; \u22654 L O2 [aHR, 4.41; 2.63\u20137.39], or noninvasive ventilation\/high-flow nasal cannula [aHR, 11.30; 6.46\u201319.75] vs no oxygen), renal impairment (aHR, 1.77; 1.29\u20132.42), and IL-6 &amp;gt;5.8\u2005ng\/L (aHR, 2.54 [1.74\u20133.70] vs \u22645.8\u2005ng\/L) were significantly associated with mortality risk in final adjusted analyses. Viral Ag, viral RNA, and IL-6 were not measured in real-time.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Baseline virus-specific, clinical, and biological variables are strongly associated with mortality risk within 90 days, revealing potential pathogen and host-response therapeutic targets for acute COVID-19 disease.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciad780","type":"journal-article","created":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T14:22:45Z","timestamp":1708438965000},"page":"1490-1503","source":"Crossref","is-referenced-by-count":15,"title":["Viral and Host Factors Are Associated With Mortality in Hospitalized Patients With COVID-19"],"prefix":"10.1093","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0922-8824","authenticated-orcid":false,"given":"Neil 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