Impact of immunosenescence in the outcome of COVID-19

The COVID-19 pandemic poses a significant challenge to science due to at-risk groups, including individuals with comorbidities and the elderly. However, in Brazil, 25% of deaths occur in individuals under 60 years old, without comorbidities considered risky in other countries. Additionally, not all elderly individuals develop severe forms of the disease, indicating complexities in the response to the virus. The study aimed to assess the immunological profile and senescence phenotype in individuals infected with SARS-CoV-2 in three cohorts (Belo Horizonte and Governador Valadares, MG, and São Paulo, SP, Brazil), divided into age groups (adults aged 20 to 60 and seniors above 60). The objective was to correlate these data with the clinical outcomes of the infection. The study adopted a cross-sectional approach where a total population of 806 individuals was collected in three centers. Volunteers were recruited from December 2020 to October 2021. Both individuals with flu-like illness with an unclear etiology and healthy individuals were included in the study. All participants underwent the RT-PCR (Real-Time Polymerase Chain Reaction) test to confirm the diagnosis of COVID-19, had their peripheral blood collected, and were monitored for clinical outcomes after 7 and 14 days. Clinical evolution information for hospitalized individuals was collected directly from their medical records. Participants were categorized into four distinct groups: Influenza-like Syndrome (with negative results for COVID-19 and mild respiratory infection of unknown origin), Mild COVID-19, and Hospitalized COVID-19, following the classification guidelines of the World Health Organization (WHO). The study revealed distinctive markers in COVID-19 patients, indicating a significant association between disease severity and specific immunological characteristics. Patients with severe forms showed higher expression of senescence markers in lymphocytes and NK cells, elevated inflammatory profile, more oligoclonal repertoire of B lymphocytes, dysbiosis in the intestinal microbiota, and increased DNA methylation rates, suggesting an advanced biological age. The correlation between biomarkers allowed the creation of an index reflecting immunosenescence associated with the severity of COVID-19. Comorbidities, especially chronic inflammatory diseases, influenced the immunosenescence profile, linking to a more severe disease progression. The study provided essential insights into the immunological and clinical aspects of COVID-19, contributing to future research in this field