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The Immunological Factors Predisposing to Severe Covid-19 Are Already Present in Healthy Elderly and Men
Gizem Kilic1, Ozlem Bulut1, Martin Jaeger1
1Department of Internal Medicine and Radboud Centre for Infectious Diseases, Radboud University Medical Centre, Nijmegen, Netherlands.
Insights
Healthy men and older individuals have pre-existing immune differences that increase COVID-19 severity risk. These immunological profiles, including lower T cell counts and higher inflammatory proteins, may explain their susceptibility to SARS-CoV-2 infection.
Area of Science:
- Immunology
- Virology
- Gerontology
Background:
- Male sex and advanced age are established risk factors for severe COVID-19.
- The immunological underpinnings of this increased susceptibility in these demographic groups remain largely unknown.
- Pre-existing differences in immune profiles may predispose certain individuals to worse outcomes following SARS-CoV-2 infection.
Purpose of the Study:
- To investigate intrinsic immunological differences in healthy males and the elderly compared to young females.
- To explore potential season-dependent variations in anti-SARS-CoV-2 immune responses.
- To identify circulating proteins and immune cell populations associated with COVID-19 severity in at-risk groups.
Main Methods:
- Analysis of circulating proteins and immune cell populations in two healthy cohorts.
- Stimulation of peripheral blood mononuclear cells (PBMCs) from diverse age and sex groups with heat-inactivated SARS-CoV-2.
- Assessment of season-specific immune responses against SARS-CoV-2 in vitro.
Main Results:
- Healthy males and older individuals exhibited lower intrinsic abundance of specific T cell subsets crucial for combating severe COVID-19.
- Elevated levels of plasma proteins, including HGF, IL-8, and MCP-1, associated with disease severity, were observed in elderly and male subjects.
- Elderly individuals showed increased IL-1RA production and a dysregulated, season-dependent interferon-gamma (IFNγ) response to SARS-CoV-2 stimulation.
Conclusions:
- Intrinsic immunological characteristics, including immune cell distribution and inflammatory protein levels, are present in healthy men and the elderly.
- These pre-existing immune variations may contribute to the heightened susceptibility of males and older adults to severe COVID-19.
- Understanding these baseline immune differences is critical for predicting and potentially mitigating severe SARS-CoV-2 outcomes.
Abstract:
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.
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