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...
| Auteurs principaux: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Langue: | English |
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American Society for Clinical Investigation
2021
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| Accès en ligne: | https://hdl.handle.net/1721.1/130583 |
| _version_ | 1826208046178631680 |
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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. |
| first_indexed | 2024-09-23T13:59:40Z |
| format | Article |
| id | mit-1721.1/130583 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T13:59:40Z |
| publishDate | 2021 |
| publisher | American Society for Clinical Investigation |
| record_format | dspace |
| 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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