The Immunological Factors Predisposing to Severe Covid-19 Are Already Present in Healthy Elderly and Men
Male sex and old age are risk factors for COVID-19 severity, but the underlying causes are unknown. A possible explanation for this might be the differences in immunological profiles in males and the elderly before the infection. With this in mind, we analyzed the abundance of circulating proteins a...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.720090/full |
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| author | Gizem Kilic Ozlem Bulut Martin Jaeger Rob ter Horst Rob ter Horst Valerie A. C. M. Koeken Valerie A. C. M. Koeken Simone J. C. F. M. Moorlag Vera P. Mourits Charlotte de Bree Jorge Domínguez-Andrés Leo A. B. Joosten Mihai G. Netea Mihai G. Netea |
| author_facet | Gizem Kilic Ozlem Bulut Martin Jaeger Rob ter Horst Rob ter Horst Valerie A. C. M. Koeken Valerie A. C. M. Koeken Simone J. C. F. M. Moorlag Vera P. Mourits Charlotte de Bree Jorge Domínguez-Andrés Leo A. B. Joosten Mihai G. Netea Mihai G. Netea |
| author_sort | Gizem Kilic |
| collection | DOAJ |
| description | Male sex and old age are risk factors for COVID-19 severity, but the underlying causes are unknown. A possible explanation for this might be the differences in immunological profiles in males and the elderly before the infection. With this in mind, we analyzed the abundance of circulating proteins and immune populations associated with severe COVID-19 in 2 healthy cohorts. Besides, given the seasonal profile of COVID-19, the seasonal response against SARS-CoV-2 could also be different in the elderly and males. Therefore, PBMCs of female, male, young, and old subjects in different seasons of the year were stimulated with heat-inactivated SARS-CoV-2 to investigate the season-dependent anti-SARS-CoV-2 immune response. We found that several T cell subsets, which are known to be depleted in severe COVID-19 patients, were intrinsically less abundant in men and older individuals. Plasma proteins increasing with disease severity, including HGF, IL-8, and MCP-1, were more abundant in the elderly and males. Upon in vitro SARS-CoV-2 stimulation, the elderly produced significantly more IL-1RA and had a dysregulated IFNγ response with lower production in the fall compared with young individuals. Our results suggest that the immune characteristics of severe COVID-19, described by a differential abundance of immune cells and circulating inflammatory proteins, are intrinsically present in healthy men and the elderly. This might explain the susceptibility of men and the elderly to SARS-CoV-2 infection. |
| first_indexed | 2024-12-17T01:35:36Z |
| format | Article |
| id | doaj.art-659d0e3a1f5440459e7f1fbbad9c4fb6 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-17T01:35:36Z |
| publishDate | 2021-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-659d0e3a1f5440459e7f1fbbad9c4fb62022-12-21T22:08:27ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-08-011210.3389/fimmu.2021.720090720090The Immunological Factors Predisposing to Severe Covid-19 Are Already Present in Healthy Elderly and MenGizem Kilic0Ozlem Bulut1Martin Jaeger2Rob ter Horst3Rob ter Horst4Valerie A. C. M. Koeken5Valerie A. C. M. Koeken6Simone J. C. F. M. Moorlag7Vera P. Mourits8Charlotte de Bree9Jorge Domínguez-Andrés10Leo A. B. Joosten11Mihai G. Netea12Mihai G. Netea13Department of Internal Medicine and Radboud Centre for Infectious Diseases, Radboud University Medical Centre, Nijmegen, NetherlandsDepartment of Internal Medicine and Radboud Centre for Infectious Diseases, Radboud University Medical Centre, Nijmegen, NetherlandsDepartment of Internal Medicine and Radboud Centre for Infectious Diseases, Radboud University Medical Centre, Nijmegen, NetherlandsDepartment of Internal Medicine and Radboud Centre for Infectious Diseases, Radboud University Medical Centre, Nijmegen, NetherlandsCeMM Research Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, AustriaDepartment of Internal Medicine and Radboud Centre for Infectious Diseases, Radboud University Medical Centre, Nijmegen, NetherlandsDepartment of Computational Biology for Individualised Infection Medicine, Centre for Individualised Infection Medicine (CiiM) & TWINCORE, Joint Ventures Between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, GermanyDepartment of Internal Medicine and Radboud Centre for Infectious Diseases, Radboud University Medical Centre, Nijmegen, NetherlandsDepartment of Internal Medicine and Radboud Centre for Infectious Diseases, Radboud University Medical Centre, Nijmegen, NetherlandsDepartment of Internal Medicine and Radboud Centre for Infectious Diseases, Radboud University Medical Centre, Nijmegen, NetherlandsDepartment of Internal Medicine and Radboud Centre for Infectious Diseases, Radboud University Medical Centre, Nijmegen, NetherlandsDepartment of Internal Medicine and Radboud Centre for Infectious Diseases, Radboud University Medical Centre, Nijmegen, NetherlandsDepartment of Internal Medicine and Radboud Centre for Infectious Diseases, Radboud University Medical Centre, Nijmegen, NetherlandsDepartment of Immunology and Metabolism, Life & Medical Sciences Institute, University of Bonn, Bonn, GermanyMale sex and old age are risk factors for COVID-19 severity, but the underlying causes are unknown. A possible explanation for this might be the differences in immunological profiles in males and the elderly before the infection. With this in mind, we analyzed the abundance of circulating proteins and immune populations associated with severe COVID-19 in 2 healthy cohorts. Besides, given the seasonal profile of COVID-19, the seasonal response against SARS-CoV-2 could also be different in the elderly and males. Therefore, PBMCs of female, male, young, and old subjects in different seasons of the year were stimulated with heat-inactivated SARS-CoV-2 to investigate the season-dependent anti-SARS-CoV-2 immune response. We found that several T cell subsets, which are known to be depleted in severe COVID-19 patients, were intrinsically less abundant in men and older individuals. Plasma proteins increasing with disease severity, including HGF, IL-8, and MCP-1, were more abundant in the elderly and males. Upon in vitro SARS-CoV-2 stimulation, the elderly produced significantly more IL-1RA and had a dysregulated IFNγ response with lower production in the fall compared with young individuals. Our results suggest that the immune characteristics of severe COVID-19, described by a differential abundance of immune cells and circulating inflammatory proteins, are intrinsically present in healthy men and the elderly. This might explain the susceptibility of men and the elderly to SARS-CoV-2 infection.https://www.frontiersin.org/articles/10.3389/fimmu.2021.720090/fullCOVID-19agingsex differencesseasonalitySARS-CoV-2infection |
| spellingShingle | Gizem Kilic Ozlem Bulut Martin Jaeger Rob ter Horst Rob ter Horst Valerie A. C. M. Koeken Valerie A. C. M. Koeken Simone J. C. F. M. Moorlag Vera P. Mourits Charlotte de Bree Jorge Domínguez-Andrés Leo A. B. Joosten Mihai G. Netea Mihai G. Netea The Immunological Factors Predisposing to Severe Covid-19 Are Already Present in Healthy Elderly and Men Frontiers in Immunology COVID-19 aging sex differences seasonality SARS-CoV-2 infection |
| title | The Immunological Factors Predisposing to Severe Covid-19 Are Already Present in Healthy Elderly and Men |
| title_full | The Immunological Factors Predisposing to Severe Covid-19 Are Already Present in Healthy Elderly and Men |
| title_fullStr | The Immunological Factors Predisposing to Severe Covid-19 Are Already Present in Healthy Elderly and Men |
| title_full_unstemmed | The Immunological Factors Predisposing to Severe Covid-19 Are Already Present in Healthy Elderly and Men |
| title_short | The Immunological Factors Predisposing to Severe Covid-19 Are Already Present in Healthy Elderly and Men |
| title_sort | immunological factors predisposing to severe covid 19 are already present in healthy elderly and men |
| topic | COVID-19 aging sex differences seasonality SARS-CoV-2 infection |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.720090/full |
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