Impaired humoral immunity is associated with prolonged COVID-19 despite robust CD8 T cell responses

How 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, more than 20% of whom had delayed viral clearance. Delayed clearance was associated with loss of...

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Published in:Cancer cell Vol. 40; no. 7; p. 738
Main Authors: Lyudovyk, Olga, Kim, Justin Y, Qualls, David, Hwee, Madeline A, Lin, Ya-Hui, Boutemine, Sawsan R, Elhanati, Yuval, Solovyov, Alexander, Douglas, Melanie, Chen, Eunise, Babady, N Esther, Ramanathan, Lakshmi, Vedantam, Pallavi, Bandlamudi, Chaitanya, Gouma, Sigrid, Wong, Philip, Hensley, Scott E, Greenbaum, Benjamin, Huang, Alexander C, Vardhana, Santosha A
Format: Journal Article
Language:English
Published: United States 11.07.2022
Subjects:
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
COVID-19
Humans
Immunity, Cellular
Immunity, Humoral
Immunologic Memory
Receptors, Antigen, T-Cell
SARS-CoV-2
CD20
COVID-19
convalescent
SARS-CoV-2
T cell
cancer
rituximab
ISSN:1878-3686, 1878-3686
Online Access:Get more information
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Summary:How 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, more than 20% of whom had delayed viral clearance. Delayed clearance was associated with loss of antibodies to nucleocapsid and spike proteins with a compensatory increase in functional T cell responses. High-dimensional analysis of peripheral blood samples demonstrated increased CD8 effector T cell differentiation and a broad but poorly converged COVID-specific T cell receptor (TCR) repertoire in patients with prolonged disease. Conversely, patients with a CD4 dominant immunophenotype had a lower incidence of prolonged disease and exhibited a deep and highly select COVID-associated TCR repertoire, consistent with effective viral clearance and development of T cell memory. These results highlight the importance of B cells and CD4 T cells in promoting durable SARS-CoV-2 clearance and the significance of coordinated cellular and humoral immunity for long-term disease control.
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ISSN:1878-3686
1878-3686
DOI:10.1016/j.ccell.2022.05.013