Unraveling the Dynamic Interplay of SARS-CoV-2 Neutralizing Monoclonal Antibodies and Host Immunity in Hospitalized Patients with COVID-19 2264
Abstract Description Passive administration of SARS-CoV-2 neutralizing monoclonal antibodies, such as the CAS+IMD (REGEN-COV®, Ronapreve, REGN-COV2) antibody cocktail, benefits viral load, mortality rate, and clinical course in COVID-19 patients. However, their impact on resolving pathogenic inflammatory response and host immunity is less understood. This study examined CAS+IMD’s interaction with host immunity using longitudinal plasma proteomics and high-dimensional flow cytometry data. Unbiased clustering identified unique immunophenotypes linked to acute inflammation and disease resolution. Compared to the placebo group, CAS+IMD accelerated the shift from an acute inflammatory to a less inflammatory or “resolving” immunophenotype, marked by reduced tissue injury, lower proinflammatory markers, and restored lymphocyte/monocyte balance, regardless of baseline serostatus. Additionally, CAS+IMD did not impair the magnitude or quality of host T cell immunity against the SARS-CoV-2 spike protein. These findings suggest that SARS-CoV-2 neutralizing antibodies can rapidly resolve inflammatory responses, reducing the need for systemic steroids, without compromising cellular antiviral immunity. Funding Sources Supported Regeneron Pharmaceuticals and Department of Health and human service under OT number: HHSO100201700020C. Topic Categories Translational and Interventional Immunology (TI)
Authors
- Matthew F. Wipperman (ORCID: https://orcid.org/0000-0003-1436-3366)
- Andrea T. Hooper (ORCID: https://orcid.org/0000-0003-1131-1229)
- George D. Kalliolias (ORCID: https://orcid.org/0000-0002-4427-8245)
- Clarissa Lett (ORCID: https://orcid.org/0000-0002-9361-8357)
- Sara Hamon (ORCID: https://orcid.org/0000-0002-2413-2302)
- Matthew Kaczynski (ORCID: https://orcid.org/0009-0002-0573-4508)
- Biswajit Mishra (ORCID: https://orcid.org/0000-0001-6288-5383)
- Jennifer D. Hamilton (ORCID: https://orcid.org/0000-0003-1236-5245)
- Erica Chio (ORCID: https://orcid.org/0009-0002-9001-6892)
- Christopher D. Petro
- Matthew A. Sleeman (ORCID: https://orcid.org/0000-0003-2945-0315)
- Qiaozhi Wei (ORCID: https://orcid.org/0000-0003-3062-5071)
- Bret J. Musser (ORCID: https://orcid.org/0000-0003-2949-211X)
- Evangelia K. Mylona (ORCID: https://orcid.org/0000-0002-5365-5348)
- Selin Somersan-Karakaya (ORCID: https://orcid.org/0000-0003-2000-2700)
- Bei Wang (ORCID: https://orcid.org/0000-0002-1639-584X)
- Patrick Poon (ORCID: https://orcid.org/0000-0003-2243-8436)
- Jacquelynn Golubov (ORCID: https://orcid.org/0000-0003-2382-657X)
- Fadi Shehadeh (ORCID: https://orcid.org/0000-0002-9552-4004)
- Dimitris Skokos (ORCID: https://orcid.org/0000-0003-1196-3139)
- Lewis Oscar Felix (ORCID: https://orcid.org/0000-0003-2170-3162)
- Eleftherios Mylonakis
Institutions
- Regeneron (United States) (US)
- Rhode Island Hospital (US)
- Methodist Hospital (US)
Publication Details
- Journal
- The Journal of Immunology
- Published
- 2025-11-01
- DOI
- https://doi.org/10.1093/jimmun/vkaf283.201
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00