Impaired Humoral Immunity Is Associated With Prolonged COVID-19 Despite Robust CD8 T-Cell Responses
54 Pages Posted: 11 Mar 2022 Publication Status: Published
More...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
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