Abstract
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).
| Original language | English (US) |
|---|---|
| Pages (from-to) | 624-634 |
| Number of pages | 11 |
| Journal | Journal of Infectious Diseases |
| Volume | 230 |
| Issue number | 3 |
| DOIs | |
| State | Published - Sep 15 2024 |
Funding
Financial support . This analysis used data from ACTT-1 (doi: 10.1056/nejmoa2007764 ). ACTT-1 was sponsored and primarily funded by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH). This trial has been funded in part with federal funds from the NIAID and the National Cancer Institute of the NIH (contract HHSN261200800001E 75N910D00024, task order 75N91019F00130/75N91020F00010) and by the Defense Health Program, Department of Defense. This trial has been supported in part by the NIAID of the NIH under awards UM1AI148684, UM1AI148576, UM1AI148573, UM1AI148575, UM1AI148452, UM1AI148685, UM1AI148450, and UM1AI148689. The trial has also been funded in part by the governments of Denmark, Japan, Mexico, and Singapore. The trial site in South Korea received funding from the Seoul National University Hospital. Support for the London International Coordinating Centre was also provided by the United Kingdom Medical Research Council (MRC_UU_12023/23). Collaborating investigators involved with collection of data during the ACTT-1 trial are noted in the .
Keywords
- COVID-19
- SARS-CoV-2
- antiviral efficacy
- clinical trial
- remdesivir
ASJC Scopus subject areas
- Immunology and Allergy
- Infectious Diseases
