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

Jinghao Nicholas Ngiam; Liang En Wee; Jue Tao Lim; Enoch Xueheng Loy; Matthew Chung Yi Koh; An Ting Tay; Huei Xin Lou; Phyllis Kim; Calvin J Chiew; Barnaby Edward Young; Shawn Vasoo; David Chien Boon Lye; Kelvin Bryan Tan

MBBS Jinghao Nicholas Ngiam, MBBS Liang En Wee, PhD Jue Tao Lim, MSc Enoch Xueheng Loy, Matthew Chung Yi Koh, An Ting Tay, Phyllis Huei Xin Lou, Phyllis Kim, PhD Calvin J Chiew, PhD Barnaby Edward Young, MBBS Shawn Vasoo, David Chien Boon Lye, Kelvin Bryan Tan

International Journal of Infectious Diseases, doi:10.1016/j.ijid.2026.108435

Objectives Post-acute sequelae of COVID-19 (PASC) are more common in unvaccinated or immunocompromised individuals. In Singapore, neutralising 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. Methods 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 postinfection, adjusted for demographics, vaccination status, and comorbidities. Results Of 19,689 eligible hospitalised individuals, 6.9% received early mAb therapy. While mAb treatment had no significant impact on overall post-acute sequelae (aHR for any sequelae:1.26[0.98-1.63]), we observed an increased risk of autoimmune ), particularly systemic lupus erythematosus and rheumatoid arthritis). There was also elevated risk of deep venous thrombosis (aHR=1. 83[1.03-3.22]), but this was no longer significant after adjusting for prior healthcare utilisation. Conclusions 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. Research in Context Evidence before this study We searched PubMed, Embase, and the Cochrane Library for studies published between Jan 1, 2020, and Dec 31, 2024, using the search terms ("COVID-19" OR "SARS-CoV-2") AND ("monoclonal antibody" OR "casirivimab" OR "imdevimab" OR "sotrovimab" OR "tixagevimab" OR "cilgavimab") AND ("long COVID" OR "post-acute sequelae" OR "PASC" OR "autoimmune" OR "thrombosis"), without language restrictions. We also reviewed reference lists of relevant articles. Prior studies have demonstrated that early treatment with neutralising monoclonal antibodies (mAbs) such as casirivimab/imdevimab, sotrovimab, or tixagevimab/cilgavimab reduced short-term outcomes such as hospitalisation or death in high-risk individuals with COVID-19. However, few studies have examined their long-term safety or the risk of post-acute sequelae of COVID-19 (PASC). Data on autoimmune or thrombotic complications following mAb treatment remain sparse and largely limited to pharmacovigilance reports or small case series. No large population-based studies have comprehensively assessed the association between early mAb use and subsequent risk of PASC across multiple organ systems. Added value of this study To our..

Declaration of Interest Statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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