Antiviral therapy and interleukin-6 blockade associated with lower thrombotic risk in hospitalized COVID-19: a target trial emulation.

Thrombotic complications substantially contribute to morbidity and mortality in hospitalized patients with COVID-19, but the effect of antiviral and immune-targeted therapies on thrombotic risk remains uncertain. We conducted an observational cohort study embedded in a prospectively implemented hospital COVID-19 care protocol, including 2,524 patients hospitalized with PCR-confirmed COVID-19 between March 2020 and July 2022, with systematic ascertainment of thrombotic events within 28 days after admission under standardized thromboprophylaxis. Treatment effects of remdesivir, tocilizumab, and glucocorticoids were evaluated in a nested propensity score-matched cohort using time-varying Cox models and target trial emulation estimating intention-to-treat and per-protocol effects. In time-varying Cox models, tocilizumab and remdesivir were associated with lower thrombotic risk (average HR 0.40, 95% CI 0.25-0.65, and 0.44, 95% CI 0.24-0.78, respectively), whereas glucocorticoids showed no protective association. These effects were driven by a marked early benefit on day 3, with HRs of 0.23 (95% CI 0.12-0.42) for tocilizumab and 0.23 (95% CI 0.11-0.51) for remdesivir, which progressively attenuated over follow-up. In the target trial emulation, intention-to-treat analyses also showed lower thrombotic risk with tocilizumab (OR 0.39; 95% CI 0.17-0.87) and remdesivir (OR 0.44; 95% CI 0.21-0.93), with directionally consistent per-protocol estimates. These findings suggest a thrombotic benefit of antiviral therapy and interleukin-6 blockade beyond standard anticoagulation in selected high-risk patients.