SARS-CoV-2 RNA and Nucleocapsid Antigen Are Blood Biomarkers Associated With Severe Disease Outcomes That Improve in Response to Remdesivir.
Singh K., Rubenstein K., Callier V., Shaw-Saliba K., Rupert A., Dewar R., Laverdure S., Highbarger H., Lallemand P., Huang M-L., Jerome KR., Sampoleo R., Mills MG., Greninger AL., Juneja K., Porter D., Benson CA., Dempsey W., El Sahly HM., Focht C., Jilg N., Paules CI., Rapaka RR., Uyeki TM., Clifford Lane H., Beigel J., Dodd LE., Adaptive COVID-19 Treatment Trial (ACTT-1) Study Group Members None.
BackgroundAlthough antivirals remain important for the treatment COVID-19, methods to assess treatment efficacy are lacking. Here, we investigated the impact of remdesivir on viral dynamics and their contribution to understanding antiviral efficacy in the multicenter Adaptive COVID-19 Treatment Trial 1, which randomized patients to remdesivir or placebo.MethodsLongitudinal specimens collected during hospitalization from a substudy of 642 patients with COVID-19 were measured for viral RNA (upper respiratory tract and plasma), viral nucleocapsid antigen (serum), and host immunologic markers. Associations with clinical outcomes and response to therapy were assessed.ResultsHigher baseline plasma viral loads were associated with poorer clinical outcomes, and decreases in viral RNA and antigen in blood but not the upper respiratory tract correlated with enhanced benefit from remdesivir. The treatment effect of remdesivir was most pronounced in patients with elevated baseline nucleocapsid antigen levels: the recovery rate ratio was 1.95 (95% CI, 1.40-2.71) for levels >245 pg/mL vs 1.04 (95% CI, .76-1.42) for levels <245 pg/mL. Remdesivir also accelerated the rate of viral RNA and antigen clearance in blood, and patients whose blood levels decreased were more likely to recover and survive.ConclusionsReductions in SARS-CoV-2 RNA and antigen levels in blood correlated with clinical benefit from antiviral therapy.Clinical trial registrationNCT04280705 (ClinicalTrials.gov).