Comorbid illnesses are associated with altered adaptive immune responses to SARS-CoV-2

Comorbid medical illnesses, such as obesity and diabetes, are associated with more severe COVID-19, hospitalization, and death. However, the role of the immune system in mediating these clinical outcomes has not been determined. We used multiparameter flow cytometry and systems serology to comprehen...

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Auteurs principaux: Yu, Krystle K.Q., Fischinger, Stephanie, Smith, Malisa T., Atyeo, Caroline, Cizmeci, Deniz, Wolf, Caitlin R., Layton, Erik D., Logue, Jennifer K., Aguilar, Melissa S., Shuey, Kiel, Loos, Carolin, Yu, Jingyou, Franko, Nicholas, Choi, Robert Y., Wald, Anna, Barouch, Dan, Koelle, David M., Lauffenburger, Douglas, Chu, Helen Y., Alter, Galit, Seshadri, Chetan
Autres auteurs: Ragon Institute of MGH, MIT and Harvard
Format: Article
Langue:English
Publié: American Society for Clinical Investigation 2021
Accès en ligne:https://hdl.handle.net/1721.1/130583
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author Yu, Krystle K.Q.
Fischinger, Stephanie
Smith, Malisa T.
Atyeo, Caroline
Cizmeci, Deniz
Wolf, Caitlin R.
Layton, Erik D.
Logue, Jennifer K.
Aguilar, Melissa S.
Shuey, Kiel
Loos, Carolin
Yu, Jingyou
Franko, Nicholas
Choi, Robert Y.
Wald, Anna
Barouch, Dan
Koelle, David M.
Lauffenburger, Douglas
Chu, Helen Y.
Alter, Galit
Seshadri, Chetan
author2 Ragon Institute of MGH, MIT and Harvard
author_facet Ragon Institute of MGH, MIT and Harvard
Yu, Krystle K.Q.
Fischinger, Stephanie
Smith, Malisa T.
Atyeo, Caroline
Cizmeci, Deniz
Wolf, Caitlin R.
Layton, Erik D.
Logue, Jennifer K.
Aguilar, Melissa S.
Shuey, Kiel
Loos, Carolin
Yu, Jingyou
Franko, Nicholas
Choi, Robert Y.
Wald, Anna
Barouch, Dan
Koelle, David M.
Lauffenburger, Douglas
Chu, Helen Y.
Alter, Galit
Seshadri, Chetan
author_sort Yu, Krystle K.Q.
collection MIT
description Comorbid medical illnesses, such as obesity and diabetes, are associated with more severe COVID-19, hospitalization, and death. However, the role of the immune system in mediating these clinical outcomes has not been determined. We used multiparameter flow cytometry and systems serology to comprehensively profile the functions of T cells and antibodies targeting spike, nucleocapsid, and envelope proteins in a convalescent cohort of COVID-19 subjects who were either hospitalized (n = 20) or not hospitalized (n = 40). To avoid confounding, subjects were matched by age, sex, ethnicity, and date of symptom onset. Surprisingly, we found that the magnitude and functional breadth of virus-specific CD4+ T cell and antibody responses were consistently higher among hospitalized subjects, particularly those with medical comorbidities. However, an integrated analysis identified more coordination between polyfunctional CD4+ T cells and antibodies targeting the S1 domain of spike among subjects who were not hospitalized. These data reveal a functionally diverse and coordinated response between T cells and antibodies targeting SARS-CoV-2, which is reduced in the presence of comorbid illnesses that are known risk factors for severe COVID-19.
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spelling mit-1721.1/1305832022-09-28T17:34:10Z Comorbid illnesses are associated with altered adaptive immune responses to SARS-CoV-2 Yu, Krystle K.Q. Fischinger, Stephanie Smith, Malisa T. Atyeo, Caroline Cizmeci, Deniz Wolf, Caitlin R. Layton, Erik D. Logue, Jennifer K. Aguilar, Melissa S. Shuey, Kiel Loos, Carolin Yu, Jingyou Franko, Nicholas Choi, Robert Y. Wald, Anna Barouch, Dan Koelle, David M. Lauffenburger, Douglas Chu, Helen Y. Alter, Galit Seshadri, Chetan Ragon Institute of MGH, MIT and Harvard Massachusetts Institute of Technology. Department of Biological Engineering Comorbid medical illnesses, such as obesity and diabetes, are associated with more severe COVID-19, hospitalization, and death. However, the role of the immune system in mediating these clinical outcomes has not been determined. We used multiparameter flow cytometry and systems serology to comprehensively profile the functions of T cells and antibodies targeting spike, nucleocapsid, and envelope proteins in a convalescent cohort of COVID-19 subjects who were either hospitalized (n = 20) or not hospitalized (n = 40). To avoid confounding, subjects were matched by age, sex, ethnicity, and date of symptom onset. Surprisingly, we found that the magnitude and functional breadth of virus-specific CD4+ T cell and antibody responses were consistently higher among hospitalized subjects, particularly those with medical comorbidities. However, an integrated analysis identified more coordination between polyfunctional CD4+ T cells and antibodies targeting the S1 domain of spike among subjects who were not hospitalized. These data reveal a functionally diverse and coordinated response between T cells and antibodies targeting SARS-CoV-2, which is reduced in the presence of comorbid illnesses that are known risk factors for severe COVID-19. Bill and Melinda Gates Foundation (Award 235730) NIAID (Grant U19 AI35995) U.S. Centers for Disease Control and Prevention (Grant CK000490) 2021-05-12T20:21:13Z 2021-05-12T20:21:13Z 2021-03 2020-11 2021-05-12T15:21:09Z Article http://purl.org/eprint/type/JournalArticle 2379-3708 https://hdl.handle.net/1721.1/130583 Yu, Krystle K.Q. et al. "Comorbid illnesses are associated with altered adaptive immune responses to SARS-CoV-2." JCI Insight 6, 6 (March 2021): e146242. © 2021 Yu et al. en http://dx.doi.org/10.1172/jci.insight.146242 JCI Insight Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf American Society for Clinical Investigation American Society for Clinical Investigation
spellingShingle Yu, Krystle K.Q.
Fischinger, Stephanie
Smith, Malisa T.
Atyeo, Caroline
Cizmeci, Deniz
Wolf, Caitlin R.
Layton, Erik D.
Logue, Jennifer K.
Aguilar, Melissa S.
Shuey, Kiel
Loos, Carolin
Yu, Jingyou
Franko, Nicholas
Choi, Robert Y.
Wald, Anna
Barouch, Dan
Koelle, David M.
Lauffenburger, Douglas
Chu, Helen Y.
Alter, Galit
Seshadri, Chetan
Comorbid illnesses are associated with altered adaptive immune responses to SARS-CoV-2
title Comorbid illnesses are associated with altered adaptive immune responses to SARS-CoV-2
title_full Comorbid illnesses are associated with altered adaptive immune responses to SARS-CoV-2
title_fullStr Comorbid illnesses are associated with altered adaptive immune responses to SARS-CoV-2
title_full_unstemmed Comorbid illnesses are associated with altered adaptive immune responses to SARS-CoV-2
title_short Comorbid illnesses are associated with altered adaptive immune responses to SARS-CoV-2
title_sort comorbid illnesses are associated with altered adaptive immune responses to sars cov 2
url https://hdl.handle.net/1721.1/130583
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