Early administration of neutralizing monoclonal antibodies and post-acute sequelae of COVID-19

Post-acute sequelae of COVID-19 (PASC) are more common in unvaccinated or immunocompromised individuals. In Singapore, neutralizing monoclonal antibodies (mAbs) were offered early in the disease course to such high-risk patients. We evaluated the impact of early mAb use on the risk of post-acute multi-system complications and symptoms.

Using national COVID-19 registries and healthcare claims data, we conducted a retrospective cohort study including all Singaporeans who were unvaccinated, partially vaccinated, or immunocompromised at the time of SARS-CoV-2 infection between July 2021 and December 2022. Individuals were stratified by receipt of mAbs. Overlap weighting was applied to balance baseline characteristics. Competing risks regression was used to compare outcomes from 31 to 300 days post-infection, adjusted for demographics, vaccination status, and comorbidities.

Of 19,689 eligible hospitalized individuals, 6.9% received early mAb therapy. While mAb treatment had no significant impact on overall post-acute sequelae (adjusted hazard ratio [aHR] for any sequelae: 1.26 [0.98-1.63]), we observed an increased risk of autoimmune diseases (aHR = 2.20 [1.22-3.97]), particularly systemic lupus erythematosus and rheumatoid arthritis). There was also an elevated risk of deep venous thrombosis (aHR = 1.83 [1.03-3.22]), but this was no longer significant after adjusting for previous healthcare utilization.

Early mAb therapy did not significantly alter overall PASC risk but was associated with increased autoimmune complications. These findings may highlight the need for long-term safety monitoring in future mAb trials for SARS-CoV-2.