Potential immunomodulatory effects of CAS+IMD monoclonal antibody cocktail in hospitalized patients with COVID-19Research in context
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. Sleeman,
George D. Kalliolias,
Eleftherios Mylonakis,
Dimitris Skokos
Affiliations
Bei Wang
Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY, 10591, USA
Jacquelynn Golubov
Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY, 10591, USA
Erin M. Oswald
Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY, 10591, USA
Patrick Poon
Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY, 10591, USA
Qiaozhi Wei
Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY, 10591, USA
Clarissa Lett
Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY, 10591, USA
Fadi Shehadeh
Division of Infectious Diseases, Department of Medicine, The Brown Alpert Medical School and the Miriam Hospital, Providence, RI, USA; Department of Medicine, Houston Methodist Academic Institute, Houston, TX, 77030, USA
Matthew Kaczynski
Division of Infectious Diseases, Department of Medicine, The Brown Alpert Medical School and the Miriam Hospital, Providence, RI, USA
Lewis Oscar Felix
Division of Infectious Diseases, Department of Medicine, The Brown Alpert Medical School and the Miriam Hospital, Providence, RI, USA; Department of Medicine, Houston Methodist Academic Institute, Houston, TX, 77030, USA
Biswajit Mishra
Division of Infectious Diseases, Department of Medicine, The Brown Alpert Medical School and the Miriam Hospital, Providence, RI, USA; Department of Medicine, Houston Methodist Academic Institute, Houston, TX, 77030, USA
Evangelia K. Mylona
Division of Infectious Diseases, Department of Medicine, The Brown Alpert Medical School and the Miriam Hospital, Providence, RI, USA; Department of Medicine, Houston Methodist Academic Institute, Houston, TX, 77030, USA
Matthew F. Wipperman
Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY, 10591, USA
Erica Chio
Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY, 10591, USA
Sara C. Hamon
Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY, 10591, USA
Andrea T. Hooper
Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY, 10591, USA
Selin Somersan-Karakaya
Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY, 10591, USA
Bret J. Musser
Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY, 10591, USA
Christopher D. Petro
Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY, 10591, USA
Jennifer D. Hamilton
Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY, 10591, USA
Matthew A. Sleeman
Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY, 10591, USA
George D. Kalliolias
Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY, 10591, USA
Eleftherios Mylonakis
Division of Infectious Diseases, Department of Medicine, The Brown Alpert Medical School and the Miriam Hospital, Providence, RI, USA; Department of Medicine, Houston Methodist Academic Institute, Houston, TX, 77030, USA
Dimitris Skokos
Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY, 10591, USA; Corresponding author.
Summary: 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.
