The Immunological Factors Predisposing To Severe COVID-19 Are Already Present In Healthy Elderly And Men

Kilic, G.; Bulut, O.; Jaeger, M.; ter Horst, R.; Koeken, V.; Moorlag, S. J. C. F. M.; Mourits, V.; de Bree, C.; Dominguez-Andres, J.; Joosten, L. A. B.; Netea, M.

doi:10.1101/2021.04.30.442229

bioRxiv · 10.1101/2021.04.30.442229

The Immunological Factors Predisposing To Severe COVID-19 Are Already Present In Healthy Elderly And Men

Kilic, G.·Bulut, O.·Jaeger, M.·ter Horst, R.·Koeken, V.·Moorlag, S. J. C. F. M.·Mourits, V.·de Bree, C.·Dominguez-Andres, J.·Joosten, L. A. B.·Netea, M.

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Abstract

BackgroundMale 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. Given the seasonal profile of COVID-19, the seasonal response against SARS-CoV-2 could also be different in these groups. MethodsThe abundance of circulating proteins and immune populations associated with severe COVID-19 was analyzed in 2 healthy cohorts. PBMCs of female, male, young, and old subjects in different seasons of the year were stimulated with heat-inactivated SARS-CoV-2. ResultSeveral 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. The elderly produced significantly more IL-1RA and had a dysregulated IFN{gamma} response with lower production in the summer compared with young individuals. ConclusionsThe 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. SummaryImmunological profile of severe COVID-19, characterized by altered immune cell populations and inflammatory plasma proteins is intrinsically present in healthy men and the elderly. Different age and sex groups show distinct seasonal responses to SARS-CoV-2.

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Kilic, G., Bulut, O., Jaeger, M., ter Horst, R., Koeken, V., Moorlag, S. J. C. F. M., Mourits, V., de Bree, C., Dominguez-Andres, J., Joosten, L. A. B., Netea, M.. 2021-05-04. The Immunological Factors Predisposing To Severe COVID-19 Are Already Present In Healthy Elderly And Men. https://doi.org/10.1101/2021.04.30.442229

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