TY - JOUR
T1 - Potential immunomodulatory effects of CAS+IMD monoclonal antibody cocktail in hospitalized patients with COVID-19
AU - Wang, Bei
AU - Golubov, Jacquelynn
AU - Oswald, Erin M.
AU - Poon, Patrick
AU - Wei, Qiaozhi
AU - Lett, Clarissa
AU - Shehadeh, Fadi
AU - Kaczynski, Matthew
AU - Felix, Lewis Oscar
AU - Mishra, Biswajit
AU - Mylona, Evangelia K.
AU - Wipperman, Matthew F.
AU - Chio, Erica
AU - Hamon, Sara C.
AU - Hooper, Andrea T.
AU - Somersan-Karakaya, Selin
AU - Musser, Bret J.
AU - Petro, Christopher D.
AU - Hamilton, Jennifer D.
AU - Sleeman, Matthew A.
AU - Kalliolias, George D.
AU - Mylonakis, Eleftherios
AU - Skokos, Dimitris
N1 - Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.
PY - 2024/10
Y1 - 2024/10
N2 - 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.
AB - 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.
KW - COVID-19
KW - SARS-CoV-2 neutralizing antibodies
KW - Host immunity
KW - Longitudinal immunophenotyping
KW - Plasma proteomics
KW - High dimensional flow cytometry
KW - COVID-19 Drug Treatment
KW - Immunization, Passive/methods
KW - Humans
KW - Middle Aged
KW - Antibodies, Monoclonal, Humanized/therapeutic use
KW - Antibodies, Monoclonal/therapeutic use
KW - COVID-19/immunology
KW - Male
KW - Immunophenotyping
KW - Hospitalization
KW - Antibodies, Viral/immunology
KW - SARS-CoV-2/immunology
KW - Female
KW - Adult
KW - Aged
KW - Antibodies, Neutralizing/immunology
KW - Drug Combinations
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U2 - 10.1016/j.ebiom.2024.105334
DO - 10.1016/j.ebiom.2024.105334
M3 - Article
C2 - 39270622
SN - 2352-3964
VL - 108
SP - 105334
JO - EBioMedicine
JF - EBioMedicine
M1 - 105334
ER -