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

Olga Lyudovyk; Justin Y. Kim; David Qualls; Madeline A. Hwee; Ya Hui Lin; Sawsan R. Boutemine; Yuval Elhanati; Alexander Solovyov; Melanie Douglas; Eunise Chen; N. Esther Babady; Lakshmi Ramanathan; Pallavi Vedantam; Chaitanya Bandlamudi; Sigrid Gouma; Philip Wong; Scott E. Hensley; Benjamin Greenbaum; Alexander C. Huang; Santosha A. Vardhana

doi:10.1016/j.ccell.2022.05.013

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

Olga Lyudovyk, Justin Y. Kim, David Qualls, Madeline A. Hwee, Ya Hui Lin, Sawsan R. Boutemine, Yuval Elhanati, Alexander Solovyov, Melanie Douglas, Eunise Chen, N. Esther Babady, Lakshmi Ramanathan, Pallavi Vedantam, Chaitanya Bandlamudi, Sigrid Gouma, Philip Wong, Scott E. Hensley, Benjamin Greenbaum, Alexander C. Huang, Santosha A. Vardhana

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	738-753.e5
Journal	Cancer Cell
Volume	40
Issue number	7
DOIs	https://doi.org/10.1016/j.ccell.2022.05.013
State	Published - 11 Jul 2022
Externally published	Yes

Keywords

CD20
COVID-19
SARS-CoV-2
T cell
cancer
convalescent
rituximab

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10.1016/j.ccell.2022.05.013

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Lyudovyk, O., Kim, J. Y., Qualls, D., Hwee, M. A., Lin, Y. H., Boutemine, S. R., Elhanati, Y., Solovyov, A., Douglas, M., Chen, E., Babady, N. E., Ramanathan, L., Vedantam, P., Bandlamudi, C., Gouma, S., Wong, P., Hensley, S. E., Greenbaum, B., Huang, A. C., & Vardhana, S. A. (2022). Impaired humoral immunity is associated with prolonged COVID-19 despite robust CD8 T cell responses. Cancer Cell, 40(7), 738-753.e5. https://doi.org/10.1016/j.ccell.2022.05.013

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

abstract = "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.",

keywords = "CD20, COVID-19, SARS-CoV-2, T cell, cancer, convalescent, rituximab",

author = "Olga Lyudovyk and Kim, {Justin Y.} and David Qualls and Hwee, {Madeline A.} and Lin, {Ya Hui} and Boutemine, {Sawsan R.} and Yuval Elhanati and Alexander Solovyov and Melanie Douglas and Eunise Chen and Babady, {N. Esther} and Lakshmi Ramanathan and Pallavi Vedantam and Chaitanya Bandlamudi and Sigrid Gouma and Philip Wong and Hensley, {Scott E.} and Benjamin Greenbaum and Huang, {Alexander C.} and Vardhana, {Santosha A.}",

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year = "2022",

month = jul,

day = "11",

doi = "10.1016/j.ccell.2022.05.013",

language = "English",

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Lyudovyk, O, Kim, JY, Qualls, D, Hwee, MA, Lin, YH, Boutemine, SR, Elhanati, Y, Solovyov, A, Douglas, M, Chen, E, Babady, NE, Ramanathan, L, Vedantam, P, Bandlamudi, C, Gouma, S, Wong, P, Hensley, SE, Greenbaum, B, Huang, AC & Vardhana, SA 2022, 'Impaired humoral immunity is associated with prolonged COVID-19 despite robust CD8 T cell responses', Cancer Cell, vol. 40, no. 7, pp. 738-753.e5. https://doi.org/10.1016/j.ccell.2022.05.013

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T1 - Impaired humoral immunity is associated with prolonged COVID-19 despite robust CD8 T cell responses

AU - Lyudovyk, Olga

AU - Kim, Justin Y.

AU - Qualls, David

AU - Hwee, Madeline A.

AU - Lin, Ya Hui

AU - Boutemine, Sawsan R.

AU - Elhanati, Yuval

AU - Solovyov, Alexander

AU - Douglas, Melanie

AU - Chen, Eunise

AU - Babady, N. Esther

AU - Ramanathan, Lakshmi

AU - Vedantam, Pallavi

AU - Bandlamudi, Chaitanya

AU - Gouma, Sigrid

AU - Wong, Philip

AU - Hensley, Scott E.

AU - Greenbaum, Benjamin

AU - Huang, Alexander C.

AU - Vardhana, Santosha A.

PY - 2022/7/11

Y1 - 2022/7/11

N2 - 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.

AB - 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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KW - T cell

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DO - 10.1016/j.ccell.2022.05.013

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C2 - 35679859

AN - SCOPUS:85131822300

SN - 1535-6108

VL - 40

SP - 738-753.e5

JO - Cancer Cell

JF - Cancer Cell

IS - 7

ER -

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

Abstract

Keywords

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