Covid-19 induces senescence and exhaustion of t cells in patients with mild/moderate and severe disease during a seven-day interval

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. Major drivers that can explain this markedly unfavourable response in the elderly are inflammaging and immunosenescence. Recent reports have shown that the relationship between immunosenescence and COVID-19 can be bidirectional, since hospitalized patients with severe COVID-19 have an accumulation of senescent T cells suggesting that immunosenescence can be also exacerbated by SARS-CoV-2 infection. Therefore, the present work was designed to examine the emergence of immunosenescence in a longitudinal study in two distinct cohorts of COVID-19 patients, and to determine whether the senescence alterations were restricted to severe cases of the disease. Our data, with patients from Portugal and Brazil, identified their distinctive inflammatory profile and provided evidence of increased frequencies of senescent and exhausted T cells within a seven-day period in patients with mild to severe COVID-19. These results support the view that SARS-CoV2 infection can accelerate immunosenescence in both CD4 and CD8 T cell compartments in a short period of time. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was financially supported by grants from Fundacao para a Ciencia e a Tecnologia (FCT, Portugal, Research4covid_369), Merck Sharp & Dohme (MISP 42521) and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq, Brazil, APQ 407363/2021-1) RB Pedroso is funded by FCT (SFRH/BD/144372/2019) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Samples in Lisbon were collected, stored and provided by Biobanco iMM (Lisbon Academic Medical Center, Lisbon, Portugal) in coordination with a taskforce created at iMM for the collection of COVID 19 Research Samples Flow cytometry in Lisbon was performed at the Flow Cytometry Facility of iMM The research protocol was approved by the National Research Ethics Commission (CONEP # 5.190.260) of Brazil and by the Lisbon Academic Medical Center Ethics Committee (ref. no. 306/20). The study was conducted in accordance with the Helsinki Declaration for research involving humans. All participants, including healthy controls, agreed to participate voluntarily in this study without financial support and signed an informed consent. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors