2025/07/22 by Anca Streinu‐Cercel, Antonella Castagna, Shan‐Chwen Chang +21 · 1 voice · 1 citation
Medicine · #SARS-CoV-2 and COVID-19 Research #COVID-19 Clinical Research Studies #Long-Term Effects of COVID-19
paper · pdf · doi:10.1093/cid/ciaf406
openalex publication_date 2025/07/22 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/31
BACKGROUND: Obeldesivir is an oral nucleoside analog prodrug inhibitor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: Nonhospitalized adults with risk factors for developing severe coronavirus disease 2019 (COVID-19) were enrolled ≤5 days from COVID-19 symptom onset and randomized 1:1 to receive obeldesivir 350 mg or placebo twice daily for 5 days. The primary end point was COVID-19-related hospitalization or all-cause death by day 29. Other end points included time to symptom alleviation by day 15, change in SARS-CoV-2 viral RNA copy number and infectious viral titer, and incidence of adverse events and laboratory abnormalities. RESULTS: Four hundred and sixty five participants were randomized and received ≥1 dose of study drug. Baseline characteristics were generally balanced between groups. Overall, 58% had received ≥1 COVID-19 vaccination, and 92% were seropositive for SARS-CoV-2 antibodies. COVID-19-related hospitalization or all-cause death by day 29 was reported in 0 of 211 (0%) participants with obeldesivir and 1 of 207 (0.5%) participants with placebo (log-rank P = .32). Time to COVID-19 symptom alleviation was numerically shorter with obeldesivir versus placebo. Obeldesivir reduced viral RNA copy number at day 5 and infectious titer at days 3 and 5 versus placebo. The safety profile was generally comparable across arms. CONCLUSIONS: Although underpowered in the context of a changing COVID-19 landscape, obeldesivir in nonhospitalized adults with targeted risk factors did not improve COVID-19-related hospitalization or all-cause death. Obeldesivir reduced viral RNA copy number and infectious titer, demonstrating its ability to inhibit SARS-CoV-2 replication, and resulted in numerically faster symptom alleviation. CLINICAL TRIALS REGISTRATION: NCT05603143; EudraCT 2022-002741-18.