Article
Author: Hamon, Sara C. ; Hamon, Sara C ; Sleeman, Matthew A ; Somersan-Karakaya, Selin ; Oswald, Erin M ; Mishra, Biswajit ; Mylonakis, Eleftherios ; Mylona, Evangelia K. ; Wei, Qiaozhi ; Kalliolias, George D. ; Hooper, Andrea T ; Oswald, Erin M. ; Musser, Bret J. ; Felix, Lewis Oscar ; Wipperman, Matthew F ; Wang, Bei ; Petro, Christopher D ; Kalliolias, George D ; Poon, Patrick ; Golubov, Jacquelynn ; Shehadeh, Fadi ; Skokos, Dimitris ; Musser, Bret J ; Hooper, Andrea T. ; Mylona, Evangelia K ; Chio, Erica ; Kaczynski, Matthew ; Hamilton, Jennifer D. ; Wipperman, Matthew F. ; Hamilton, Jennifer D ; Sleeman, Matthew A. ; Lett, Clarissa ; Petro, Christopher D.
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.
FUNDING:Regeneron Pharmaceuticals Inc and federal funds from the Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority, under OT number: HHSO100201700020C.