Rapid progression of CD8 and CD4 T cells to cellular exhaustion and senescence during SARS-CoV2 infection.

Pedroso, Rodrigo Balsinha; Torres, Lícia; Ventura, Lucas Araújo; Camatta, Giovanna Caliman; Mota, Catarina; Mendes, Ana Catarina; Ribeiro, Filipa; Guimarães, Henrique Cerqueira; Barbuto, Rafael Calvão; Caixeta, Felipe; Nascimento, Leandro Souza; Oliveira, Mariana Almeida; Martins, Vinícius Dantas; Silveira-Nunes, Gabriela; Tupinambás, Unaí; Teixeira-Carvalho, Andrea; Graça, Luis; Faria, Ana Maria Caetano

Risk factors for the development of severe COVID-19 include several comorbidities, but age was the most striking one since elderly people were disproportionately affected by SARS-CoV-2 infection. Among the reasons for this markedly unfavorable response in the elderly, immunosenescence and inflammaging appear as major drivers of this outcome. A finding that was also notable was that hospitalized patients with severe COVID-19 have an accumulation of senescent T cells, suggesting that immunosenescence may be aggravated by SARS-CoV-2 infection. The present work was designed to examine whether these immunosenescence changes are characteristic of COVID-19 and whether it is dependent on disease severity using cross-sectional and longitudinal studies. Our cross-sectional data show that COVID-19, but not other respiratory infections, rapidly increased cellular senescence and exhaustion in CD4 and CD8 T cells during early infection. In addition, longitudinal analyses with patients from Brazil and Portugal provided evidence of increased frequencies of senescent and exhausted T cells over a 7-d period in patients with mild/moderate and severe COVID-19. Altogether, the study suggests that accelerated immunosenescence in CD4 and especially CD8 T-cell compartments may represent a common and unique outcome of SARS-CoV2 infection.

COVID-19; T-cell exhaustion; CELLULAR aging; OLDER people; T cells; IMMUNOSENESCENCE

Journal of Leukocyte Biology, 2024, Vol 116, Issue 6, p1385

0741-5400

Academic Journal

10.1093/jleuko/qiae180