Baseline SARS-CoV-2 Viral Load Is Associated with Disease Severity and Clinical Outcomes in Hospitalised Patients with COVID-19: Post-Hoc Analyses of a Phase 2/3 Multicentre Trial

Background: Elucidating the relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and clinical outcomes is critical for understanding COVID-19. Methods: SARS-CoV-2 levels were analysed by quantitative real-time polymerase chain reaction (RT-qPCR) of naso- or oro-pharyngeal swab specimens collected at baseline and clinical outcomes were recorded over 60 days from 1362 COVID-19 hospitalised patients enrolled in a multi-center, randomized, placebo-controlled phase II/III trial of sarilumab for COVID-19 (NCT04315298). Findings: In post-hoc analyses, higher baseline viral load, measured by both RT-qPCR cycle threshold (Ct) and log10 copies/mL, was associated with greater supplemental oxygenation requirements and disease severity at study entry. Higher baseline viral load was associated with higher mortality, lower likelihood of improvement in clinical status and supplemental oxygenation requirements, and lower rates of hospital discharge. Viral load was not impacted by sarilumab treatment over time compared with placebo. Interpretation: These data support viral load as an important determinant of clinical outcomes in hospitalized patients with COVID-19 requiring supplemental oxygen or assisted ventilation. Trial Registration: NCT04315298 Funding Statement: Supported by Regeneron Pharmaceuticals, Inc. and Sanofi. Certain aspects of this project have been funded in whole or in part with federal funds from the Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority, under OT number: HHSO100201700020C. Declaration of Interests: All authors are employees or employees and shareholders of Regeneron Pharmaceuticals, Inc. Ethics Approval Statement: The local institutional review board or ethics committee at each centre oversaw trial conduct and documentation. All patients provided written informed consent before participation. Ethics approval was obtained from the following ethics review boards: WCG IRB, Puyallup, WA (IR0533); Oregon Health & Science University, Portland, OR (MOD00027616); Institutional Review Board University of Florida, Gainesville, FL (IRB202000779); Columbia University, Human Research Protection Office and IRBs, New York, NY (IRB-AAAS9615); Johns Hopkins Medicine, Office of Human Subjects Research, IRB, Baltimore, MD (IRB00246576/CIR00058074); NYU School Of Medicine, New York, NY (I20-00351_MOD03); Northwestern University IRB, Chicago, IL (STU00212239-MOD0012); Westchester Medical Center, NY Medical College, Office of Research Administration, Valhalla, NY (IRBReg#00000428); Portland Health and Services IRB Providence – St. Johns, Portland, OR (MOD2020001024); Cornell Weill Medicine IRB, New York, NY (IR9419); Providence St. Joseph IRB, Renton, WA (MOD2020001029); Providence Health and Services IRB, Portland, OR (MOD2020000519); Ascension St. John Hospital, Tulsa, OK (IRB#00001980); Geisinger IRB, Danville, PA (IRB#0008345).