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Impaired Humoral Immunity Is Associated With Prolonged COVID-19 Despite Robust CD8 T-Cell Responses

54 Pages Posted: 11 Mar 2022 Publication Status: Published

See all articles by Olga Lyudovyk

Olga Lyudovyk

Memorial Sloan Kettering Cancer Center

Justin Y. Kim

University of Pennsylvania

David Qualls

Memorial Sloan Kettering Cancer Center

Madeline A. Hwee

Memorial Sloan Kettering Cancer Center

Sawsan R. Boutemine

Memorial Sloan Kettering Cancer Center

Yuval Elhanati

Memorial Sloan Kettering Cancer Center - Computational Oncology Service

Alexander Solovyov

Memorial Sloan Kettering Cancer Center

Melanie Douglas

Memorial Sloan Kettering Cancer Center

Eunise Chen

University of Texas at Houston - McGovern Medical School

Ngolela Esther Babady

Memorial Sloan Kettering Cancer Center

Lakshmi Ramanathan

Memorial Sloan Kettering Cancer Center

Pallavi Vedantam

Memorial Sloan Kettering Cancer Center

Sigrid Gouma

University of Pennsylvania

Philip Wong

Memorial Sloan Kettering Cancer Center

Scott E. Hensley

University of Pennsylvania - Department of Microbiology

Benjamin D. Greenbaum

Memorial Sloan Kettering Cancer Center

Alexander Huang

University of Pennsylvania - Division of Hematology/Oncology; Parker Institute for Cancer Immunotherapy; Institute for Immunology and Immune Health; University of Pennsylvania - Department of Cancer Biology

Santosha Adipudi Vardhana

Memorial Sloan Kettering Cancer Center - Lymphoma Service

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Abstract

How host immune dysregulation affects recovery from COVID-19 infection in patients with cancer remains unclear.  We analyzed cellular and humoral immune responses in 103 patients with prior COVID-19 infection, over 20% of whom had delayed viral clearance. Patients with prolonged disease demonstrated loss of antibodies to nucleocapsid and spike proteins with a compensatory increase in IFN-γ production by COVID-specific T-cells. High-dimensional analysis of peripheral blood samples revealed increased CD8+ effector T-cell differentiation and a broad but poorly converged COVID-specific TCR repertoire in patients with prolonged disease, consistent with an ongoing CD8+ T-cell response to persistent viral antigen.  Conversely, patients with a CD4+ dominant immunophenotype had a much lower incidence of prolonged disease and exhibited a highly clonal TCR repertoire. These results identify a unique role for B-cells and CD4+ T-cells in promoting durable SARS-CoV-2 clearance, thereby underscoring the importance of coordinated cellular and humoral immunity in promoting long-term disease control.

Note:
Funding Information: ACH was funded by grant CA230157 from the NIH. ACH is supported by the Parker Institute for Cancer Immunotherapy which supports the Cancer Immunology program at the University of Pennsylvania. SV, OL, YE and BG are supported by funding from the Pershing Square Sohn Cancer Research Foundation and the Parker Institute for Cancer Immunotherapy. SV is supported by the Conrad Hilton Foundation.

Conflict of Interests: S.A.V. is on the advisory board for Immunai and has received consulting fees from ADC Therapeutics. ACH is a consultant for Immunai.

Ethical Approval: All data collection and analysis contained within this study was performed under Institutional Review Board (IRB) protocol #20-113, “High-Resolution immunophenotyping of body fluids from patients with nCOV-2019 infection,” approved by MSKCC’s IRB on 3/23/2020

Keywords: cancer, COVID-19, SARS-CoV-2, T-cell, B-cell, CD20, rituximab

Suggested Citation

Lyudovyk, Olga and Kim, Justin Y. and Qualls, David and Hwee, Madeline A. and Boutemine, Sawsan R. and Elhanati, Yuval and Solovyov, Alexander and Douglas, Melanie and Chen, Eunise and Babady, Ngolela Esther and Ramanathan, Lakshmi and Vedantam, Pallavi and Gouma, Sigrid and Wong, Philip and Hensley, Scott E. and Greenbaum, Benjamin D. and Huang, Alexander and Vardhana, Santosha Adipudi, Impaired Humoral Immunity Is Associated With Prolonged COVID-19 Despite Robust CD8 T-Cell Responses. Available at SSRN: https://ssrn.com/abstract=4047386 or http://dx.doi.org/10.2139/ssrn.4047386
This version of the paper has not been formally peer reviewed.

Olga Lyudovyk

Memorial Sloan Kettering Cancer Center ( email )

New York, NY 10065
United States

Justin Y. Kim

University of Pennsylvania ( email )

Philadelphia, PA 19104
United States

David Qualls

Memorial Sloan Kettering Cancer Center ( email )

New York, NY 10065
United States

Madeline A. Hwee

Memorial Sloan Kettering Cancer Center ( email )

New York, NY 10065
United States

Sawsan R. Boutemine

Memorial Sloan Kettering Cancer Center ( email )

New York, NY 10065
United States

Yuval Elhanati

Memorial Sloan Kettering Cancer Center - Computational Oncology Service ( email )

New York, NY
United States

Alexander Solovyov

Memorial Sloan Kettering Cancer Center ( email )

New York, NY 10065
United States

Melanie Douglas

Memorial Sloan Kettering Cancer Center ( email )

New York, NY 10065
United States

Eunise Chen

University of Texas at Houston - McGovern Medical School ( email )

7000 Fannin, Suite 1800
Houston, TX 76013
United States

Ngolela Esther Babady

Memorial Sloan Kettering Cancer Center ( email )

New York, NY 10065
United States

Lakshmi Ramanathan

Memorial Sloan Kettering Cancer Center ( email )

New York, NY 10065
United States

Pallavi Vedantam

Memorial Sloan Kettering Cancer Center ( email )

New York, NY 10065
United States

Sigrid Gouma

University of Pennsylvania

Philadelphia, PA 19104
United States

Philip Wong

Memorial Sloan Kettering Cancer Center ( email )

New York, NY 10065
United States

Scott E. Hensley

University of Pennsylvania - Department of Microbiology ( email )

Philadelphia, PA 19104
United States

Benjamin D. Greenbaum

Memorial Sloan Kettering Cancer Center ( email )

New York, NY 10065
United States

Alexander Huang

University of Pennsylvania - Division of Hematology/Oncology ( email )

Parker Institute for Cancer Immunotherapy ( email )

San Francisco, CA
United States

Institute for Immunology and Immune Health ( email )

United States

University of Pennsylvania - Department of Cancer Biology ( email )

Philadelphia, PA 19104
United States

Santosha Adipudi Vardhana (Contact Author)

Memorial Sloan Kettering Cancer Center - Lymphoma Service ( email )

New York, NY
United States

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