Potential immunomodulatory effects of CAS+IMD monoclonal antibody cocktail in hospitalized patients with COVID-19
eBioMedicine, 2024
Wang B., Golubov J., Oswald E., Poon P., Wei Q., Lett C., Shehadeh F., Kaczynski M., Felix L., Mishra B., Mylona E., Wipperman M., Chio E., Hamon S., Hooper A., Somersan-Karakaya S., Musser B., Petro C., Hamilton J., Sleeman M., Kalliolias G., Mylonakis E., Skokos D.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Infectious Diseases | Pathophysiology | Plasma | O Olink Explore 3072/384 |
Abstract
Background
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 hospitalized patients with COVID-19 who were seronegative at baseline and outpatients. However, little is known about their impact on the host immunophenotypes.
Methods
We conducted an immunoprofiling study in 46 patients from a single site of a multi-site trial of CAS + IMD in hospitalized patients. We collected longitudinal samples during October 2020 ∼ April 2021, prior to the emergence of the Delta and Omicron variants and the use of COVID-19 vaccines. All collected samples were analyzed without exclusion and post-hoc statistical analysis was performed. We examined the dynamic interplay of CAS + IMD with host immunity applying dimensional reduction approach on plasma proteomics and high dimensional flow cytometry data.
Findings
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.
Interpretation
Our results identified immunophenotypic changes indicative of a possible SARS-CoV-2 neutralizing antibodies-induced anti-inflammatory effect, without an evident impairment of cellular antiviral immunity, suggesting that further studies of Mabs effects on SAS-CoV-2 or other viral mediated inflammation are warranted.