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
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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.
AbstractList 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.
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.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.
Author Bandlamudi, Chaitanya
Hensley, Scott E
Huang, Alexander C
Hwee, Madeline A
Qualls, David
Kim, Justin Y
Douglas, Melanie
Greenbaum, Benjamin
Babady, N Esther
Vedantam, Pallavi
Wong, Philip
Lin, Ya-Hui
Lyudovyk, Olga
Elhanati, Yuval
Chen, Eunise
Ramanathan, Lakshmi
Gouma, Sigrid
Vardhana, Santosha A
Solovyov, Alexander
Boutemine, Sawsan R
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  givenname: Olga
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  organization: Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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  surname: Kim
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  organization: Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
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  givenname: Yuval
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  organization: Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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  fullname: Douglas, Melanie
  organization: Lymphoma Service, Division of Hematologic Malignancies, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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  givenname: Eunise
  surname: Chen
  fullname: Chen, Eunise
  organization: University of Texas Health Science Center at Houston, McGovern Medical School, Houston, TX, USA
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  givenname: N Esther
  surname: Babady
  fullname: Babady, N Esther
  organization: Infectious Diseases Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Clinical Microbiology Service, Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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  givenname: Lakshmi
  surname: Ramanathan
  fullname: Ramanathan, Lakshmi
  organization: Clinical Chemistry Service, Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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  organization: Memorial Sloan Kettering Cancer Center, New York, NY, USA
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  surname: Bandlamudi
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  organization: Memorial Sloan Kettering Cancer Center, New York, NY, USA
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  givenname: Sigrid
  surname: Gouma
  fullname: Gouma, Sigrid
  organization: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
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  surname: Wong
  fullname: Wong, Philip
  organization: Memorial Sloan Kettering Cancer Center, New York, NY, USA
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  givenname: Scott E
  surname: Hensley
  fullname: Hensley, Scott E
  organization: Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
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  givenname: Benjamin
  surname: Greenbaum
  fullname: Greenbaum, Benjamin
  email: greenbab@mskcc.org
  organization: Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Physiology, Biophysics & Systems Biology, Weill Cornell Medicine, Weill Cornell Medical College, New York, NY, USA. Electronic address: greenbab@mskcc.org
– sequence: 19
  givenname: Alexander C
  surname: Huang
  fullname: Huang, Alexander C
  email: alexander.huang@pennmedicine.upenn.edu
  organization: Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA. Electronic address: alexander.huang@pennmedicine.upenn.edu
– sequence: 20
  givenname: Santosha A
  surname: Vardhana
  fullname: Vardhana, Santosha A
  email: vardhans@mskcc.org
  organization: Lymphoma Service, Division of Hematologic Malignancies, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA. Electronic address: vardhans@mskcc.org
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Keywords CD20
COVID-19
convalescent
SARS-CoV-2
T cell
cancer
rituximab
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Snippet How immune dysregulation affects recovery from COVID-19 infection in patients with cancer remains unclear. We analyzed cellular and humoral immune responses in...
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SubjectTerms CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
COVID-19
Humans
Immunity, Cellular
Immunity, Humoral
Immunologic Memory
Receptors, Antigen, T-Cell
SARS-CoV-2
Title Impaired humoral immunity is associated with prolonged COVID-19 despite robust CD8 T cell responses
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