Potential immunomodulatory effects of CAS+IMD monoclonal antibody cocktail in hospitalized patients with COVID-19

Bei Wang, Jacquelynn Golubov, Erin M. Oswald, Patrick Poon, Qiaozhi Wei, Clarissa Lett, Fadi Shehadeh, Matthew Kaczynski, Lewis Oscar Felix, Biswajit Mishra, Evangelia K. Mylona, Matthew F. Wipperman, Erica Chio, Sara C. Hamon, Andrea T. Hooper, Selin Somersan-Karakaya, Bret J. Musser, Christopher D. Petro, Jennifer D. Hamilton, Matthew A. SleemanGeorge D. Kalliolias, Eleftherios Mylonakis, Dimitris Skokos

Research output: Contribution to journalArticlepeer-review

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. 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.

Original languageEnglish (US)
Article number105334
Pages (from-to)105334
JournalEBioMedicine
Volume108
DOIs
StatePublished - Oct 2024

Keywords

  • COVID-19
  • SARS-CoV-2 neutralizing antibodies
  • Host immunity
  • Longitudinal immunophenotyping
  • Plasma proteomics
  • High dimensional flow cytometry
  • COVID-19 Drug Treatment
  • Immunization, Passive/methods
  • Humans
  • Middle Aged
  • Antibodies, Monoclonal, Humanized/therapeutic use
  • Antibodies, Monoclonal/therapeutic use
  • COVID-19/immunology
  • Male
  • Immunophenotyping
  • Hospitalization
  • Antibodies, Viral/immunology
  • SARS-CoV-2/immunology
  • Female
  • Adult
  • Aged
  • Antibodies, Neutralizing/immunology
  • Drug Combinations

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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