Rapid progression of CD8 and CD4 T cells to cellular exhaustion and senescence during SARS-CoV2 infection
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.
Authors
- Mariana de Almeida Oliveira (ORCID: https://orcid.org/0000-0001-7508-6679)
- Unaí Tupinambás (ORCID: https://orcid.org/0000-0001-6833-3870)
- Giovanna Caliman Camatta (ORCID: https://orcid.org/0000-0001-8278-773X)
- Andréa Teixeira‐Carvalho (ORCID: https://orcid.org/0000-0003-2814-5183)
- Ana Catarina Mendes
- Rodrigo Pedroso (ORCID: https://orcid.org/0000-0001-6266-8100)
- Rafael Calvão Barbuto (ORCID: https://orcid.org/0000-0001-6488-734X)
- Felipe Caixeta
- Catarina Pinheiro Mota (ORCID: https://orcid.org/0000-0003-1814-7425)
- Ana Maria Caetano Faria (ORCID: https://orcid.org/0000-0002-0604-8510)
- Leandro Souza Nascimento
- Lícia Torres (ORCID: https://orcid.org/0000-0002-2048-0318)
- Filipa Ribeiro (ORCID: https://orcid.org/0000-0001-7499-9062)
- Gabriela Silveira‐Nunes (ORCID: https://orcid.org/0000-0002-0557-2177)
- Vinícius Dantas Martins (ORCID: https://orcid.org/0000-0001-9994-5212)
- Luís Graça (ORCID: https://orcid.org/0000-0001-6935-8500)
- Henrique Cerqueira Guimarães (ORCID: https://orcid.org/0000-0002-6680-7099)
- Lucas Araújo Ventura
Institutions
- Universidade Federal de Juiz de Fora (BR)
- Universidade Federal de Minas Gerais (BR)
- University of Lisbon (PT)
- Instituto de Medicina Tropical (PY)
- Hospital Risoleta Tolentino Neves (BR)
- Fundação Oswaldo Cruz (BR)
- Universidade Nova de Lisboa (PT)
Publication Details
- Journal
- Journal of Leukocyte Biology
- Published
- 2024-09-19
- DOI
- https://doi.org/10.1093/jleuko/qiae180
- Citations
- 6
- Primary Topic
- COVID-19 Clinical Research Studies
- Type
- article
- Field-Weighted Citation Impact
- 2.33
Funders
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Merck Sharp and Dohme
- Fundação para a Ciência e a Tecnologia