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Background Elucidating the relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and clinical outcomes is critical for understanding coronavirus disease 2019 (COVID-19). Methods The SARS-CoV-2 levels were analyzed by quantitative real-time polymerase chain reaction (RT-qPCR) of nasopharyngeal or oropharyngeal swab specimens collected at baseline, and clinical outcomes were recorded over 60 days from 1362 COVID-19 hospitalized patients enrolled in a multicenter, randomized, placebo-controlled phase 2/3 trial of sarilumab for COVID-19 (ClinicalTrials.gov NCT04315298). Results In post hoc analyses, higher baseline viral load, measured by both RT-qPCR cycle threshold 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 versus placebo. Conclusions These data support viral load as an important determinant of clinical outcomes in hospitalized patients with COVID-19 requiring supplemental oxygen or assisted ventilation.

BACKGROUNDSarilumab (anti-interleukin-6 receptor-α monoclonal antibody) may attenuate the inflammatory response in Covid-19.METHODSWe performed an adaptive, phase 2/3, randomized, double-blind, placebo-controlled trial of intravenous sarilumab 200 mg or 400 mg in adults hospitalized with Covid-19. The phase 3 primary analysis population (cohort 1) was patients with critical Covid-19 receiving mechanical ventilation (MV) randomized to sarilumab 400 mg or placebo. The primary end point for phase 3 was the proportion of patients with ≥1-point improvement in clinical status from baseline to day 22.RESULTSFour-hundred fifty-seven (457) and 1365 patients were randomized and treated in phases 2 and 3, respectively. Among phase 3 critical patients receiving MV (n=289; 34.3% on corticosteroids), the proportion with ≥1-point improvement in clinical status (alive not receiving MV) at day 22 was 43.2% in sarilumab 400 mg and 35.5% in placebo (risk difference [RD] +7.5%; 95% confidence interval [CI], –7.4 to 21.3; P=0.3261), representing a relative risk improvement of 21.7%. Day 29 all-cause mortality was 36.4% in sarilumab 400 mg versus 41.9% in placebo (RD –5.5%; 95% CI, –20.2 to 8.7; relative risk reduction 13.3%). In post hoc analyses pooling phase 2 and 3 critical patients receiving MV, the hazard ratio (HR) for death in sarilumab 400 mg compared with placebo was 0.76 (95% CI, 0.51 to 1.13) overall, improving to 0.49 (95% CI, 0.25 to 0.94) in patients receiving corticosteroids at baseline.CONCLUSIONIn hospitalized patients with Covid-19 receiving MV, numerical benefits with sarilumab did not achieve statistical significance, but benefit may be greater in patients receiving corticosteroids. A larger study is required to confirm this observed numerical benefit.(ClinicalTrials.gov number, NCT04315298)