Immunosenescence profile is associated with increased susceptibility to severe COVID-19

Ventura, L. H. A., Torres, L., Camatta, G. C., Zamame, J., Coelho, M. M., Ramalho-Pinto, C. H., Gervazio, J., Caixeta, F., Nascimento, L., Oliveira, M. A., Martins, V. D., Oliveira, M. F., Costa, M. S., Sato, H. I., Guimaraes, H. C., Barbuto, R., Veiga, A. P., Ataide, N., Caetano, G. P., Rangon, S., Junior, M., Fortes, F. C., Zuccherato, L., Farias, E. S., Coelho, V., Avritchir, R., Souza, R., Ayupe, M. C., Loureiro, C., Neves, A. C. M., Passos, M. E., Leite, P., Teixeira, S., Tupinambas, U., Vilela, L. F., Silveira-Nunes, G., Maioli, T. U., Fonseca, D. M., Teixeira-Carvalho, A., Faria, A. M.

Departamento de Bioquimica e Imunologia-Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais · medrxiv

Paper

Abstract

In this study we tested the hypothesis that the immunosenescence profile could account for the disproportional susceptibility of the elderly to severe forms of COVID-19. The immunological profiles of volunteers residing in endemic and non-endemic areas for chronic infectious diseases were analyzed at early stage of SARS-CoV-2 infection. A unique signature of inflammatory plasma mediators was identified in COVID-19 volunteers when compared to individuals with other flu-like syndromes. COVID-19 severity correlated with high levels of inflammatory mediators; among them, CXCL9, a serum marker of aging. Patients who progressed to hospitalization displayed high frequencies of CD8+ and CD4+ T cells expressing exhaustion and senescence markers and showed reduced and more mature B cell repertoires, which are typical of senescence. They also had an acceleration of epigenetic age measured by DNA methylation. Therefore, severe COVID-19 correlated with phenotypic, functional, and epigenetic features of accelerated immunosenescence at onset of infection.

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Research summary

The paper investigates the relationship between immunosenescence and susceptibility to severe COVID-19, highlighting how aging-related immune changes can influence disease outcomes. This aligns with longevity research as it addresses the underlying mechanisms of aging and their implications for health in older adults. However, while the findings are solid and contribute to understanding the role of immunosenescence in disease severity, they do not present a transformative breakthrough or novel therapeutic approach to directly combat aging itself, thus limiting their overall impact.

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