The Journal of infectious diseases · 2024
SARS-CoV-2 RNA and Nucleocapsid Antigen Are Blood Biomarkers Associated With Severe Disease Outcomes That Improve in Response to Remdesivir.
СтатьяРандомизированное исследованиеМногоцентровое исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Singh Kanal, Rubenstein Kevin, Callier Viviane, Shaw-Saliba Katy, Rupert Adam, Dewar Robin, Laverdure Sylvain, Highbarger Helene, Lallemand Perrine, Huang Meei-Li, Jerome Keith R, Sampoleo Reigran, Mills Margaret G, Greninger Alexander L, Juneja Kavita, Porter Danielle, Benson Constance A, Dempsey Walla, El Sahly Hana M, Focht Chris, Jilg Nikolaus, Paules Catharine I, Rapaka Rekha R, Uyeki Timothy M, Clifford Lane H, Beigel John, Dodd Lori E, Adaptive COVID-19 Treatment Trial (ACTT-1) Study Group Members
Аннотация
BACKGROUND: Although 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.
METHODS: Longitudinal 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.
RESULTS: Higher 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.
CONCLUSIONS: Reductions in SARS-CoV-2 RNA and antigen levels in blood correlated with clinical benefit from antiviral therapy.
CLINICAL TRIAL REGISTRATION: NCT04280705 (ClinicalTrials.gov).
METHODS: Longitudinal 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.
RESULTS: Higher 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.
CONCLUSIONS: Reductions in SARS-CoV-2 RNA and antigen levels in blood correlated with clinical benefit from antiviral therapy.
CLINICAL TRIAL REGISTRATION: NCT04280705 (ClinicalTrials.gov).