Podcast Episode · ID:IOTS - Infectious Disease Insight Of Two Specialists · 19/11/2025 · 42m

Immunocompromised patients, especially those receiving B–cell–depleting therapy (BCDT), remain at high risk for severe coronavirus disease 2019 (COVID–19). Although monoclonal antibodies showed benefit pre–Omicron, the real–world effectiveness of the oral antivirals in BCDT recipients is unclear.MethodsWe emulated a target trial using the Cleveland Clinic electronic health record. Adult patients (≥18 years) with immune–mediated inflammatory diseases who received rituximab or ocrelizumab and tested positive for severe acute respiratory syndrome coronavirus 2 between 19 December 2021 and 30 June 2025 were eligible. The primary endpoint was hospitalization or death within 21 days; the secondary endpoint was death within 90 days. Propensity scores adjusted for confounding, and Weighted Cox regression models were used to evaluated treatment effects.ResultsAmong 255 853 COVID–19 cases, 876 met criteria for the nirmatrelvir/ritonavir cohort (411 treated, 465 untreated) and 566 for the molnupiravir cohort (91 treated, 475 untreated). In the nirmatrelvir/ritonavir cohort, 18 (4.4%) of treated versus 43 (9.2%) of untreated patients were hospitalized or died within 21 days. After weighting, nirmatrelvir/ritonavir reduced the hazard by 44% (hazard ratio [HR], 0.56; 95% confidence interval [CI],  0.31–0.99). In the molnupiravir cohort, 6 (6.6%) of treated and 46 (9.7%) of untreated patients met the primary endpoint; the weighted HR was 0.56 (95% CI, 0.24–1.33), not statistically significant.ConclusionsEarly outpatient nirmatrelvir/ritonavir significantly lowers the risk of COVID–19–related hospitalization or death in patients on BCDT. Molnupiravir showed a nonsignificant trend toward benefit. These findings support prioritizing nirmatrelvir/ritonavir for high–risk immunocompromised populations.

Amid the ongoing shutdown, the HHS secretary wiped out entire offices that investigate disease outbreaks, manage infectious disease responses and collect data.

Amid the ongoing shutdown, the HHS secretary wiped out entire offices that investigate disease outbreaks, manage infectious disease responses and collect data.

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