Passive administration of SARS-CoV-2 neutralizing monoclonal antibodies (mAbs), such as CAS+IMD (Casirivimab + Imdevimab) antibody cocktail demonstrated beneficial effects on clinical outcomes in patients with COVID-19. However, little is known about their impact on the resolution of pathogenic inflammatory response and host immunity. We conducted an immunoprofiling study in 46 patients with longitudinal samples collected during October 2020 ~ April 2021, prior to the emergence of the Delta and Omicron variants and the use of COVID-19 vaccines. We examined the dynamic interplay of CAS+IMD with host immunity applying dimensional reduction approach on plasma proteomics and high dimensional flow cytometry data. Using an unbiased clustering method, we identified unique immunophenotypes associated with acute inflammation and disease resolution. Compared to placebo group, administration of CAS+IMD accelerated the transition from an acute inflammatory immunophenotype, to a less inflammatory or “resolving” immunophenotype, as characterized by reduced tissue injury, proinflammatory markers and restored lymphocyte/monocyte imbalance independent of baseline serostatus. Moreover, CAS+IMD did not impair the magnitude or the quality of host T cell immunity against SARS-CoV-2 spike protein. Our results indicate that administration of SARS-CoV-2 neutralizing antibodies can provide additional benefit by rapidly resolving inflammatory responses leading to a decreased requirement for systemic corticosteroids use, without impairing cellular antiviral immunity. 

Bei Wang is a researcher at Regeneron Pharmaceuticals, Inc. in Tarrytown, New York. Bei Wang contributes to innovative biopharmaceutical research, focusing on developing treatments and advancing healthcare solutions.