Publication date: Feb 06, 2025

Passive immunotherapy, including monoclonal antibodies and neutralizing proteins, were used for the treatment of patients with COVID-19 during the pandemic. ACTIV-3/TICO was a multinational, randomized placebo-controlled platform trial that evaluated the effectiveness of multiple passive immunotherapy agents in patients hospitalized with COVID-19. Given the long half-life of some agents studied, participants were followed for an extended period to assess the long-term efficacy and sustained safety of these agents. We conducted a pooled analysis of individual participant data from four trials of ACTIV-3/TICO: sotrovimab, amubarvimab-romlusevimab, tixagevimab-cilgavimab, and ensovibep. Cox proportional hazards models were conducted to compare time to mortality and time to mortality or rehospitalization between participants receiving active agents versus placebo through 18 months. A total of 2311 participants were enrolled between December 16, 2020 and November 15, 2021. Overall, 56. 9% (1315/2311) received an active agent and 77. 2% (1784/2311) of participants were unvaccinated for SARS-CoV-2. Median duration between symptom onset and enrollment was 8 days (IQR 6 – 10), and most participants received remdesivir (92. 1% [2129/2311]) and corticosteroids (70. 4% [1627/2311]) prior to enrollment. There was no difference in mortality across all active (11. 9% [157/1315]) versus placebo (14. 0% [139/996]) arms (HR 0. 87 [95% CI 0. 70 – 1. 08]). Furthermore, there was no difference in combined mortality or rehospitalization across all active (31. 7% [417/1315]) versus placebo (32. 1% [320/996]) arms (HR 0. 96 [95% CI 0. 84 – 1. 10]). In our large study of long half-life passive immunotherapy for hospitalized patients with COVID-19, we did not find evidence of a long-term effect on either mortality or rehospitalization. NCT04501978.

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