Long-term immune changes after COVID-19 and the effect of BCG vaccination and latent infections on disease severity

Abstract

BackgroundSeveral years after the COVID-19 pandemic, the role of trained immunity in COVID-19 remains controversial, and questions regarding the long-term effects of COVID-19 on immune cells remain unresolved. We investigated the roles of Bacillus Calmette-Guerin (BCG) vaccination and latent infections in the progression of COVID-19 and sepsis. MethodsWe conducted a prospective analysis of 97 individuals recovering from mild-to-critical COVID-19 and 64 sepsis patients. Immune cell frequencies, expression of functional markers, and plasma titres of anti-Toxoplasma gondii/cytomegalovirus/BCG antibodies were assessed and their impact on disease severity and outcomes were determined. To examine monocyte responses to secondary challenge, monocytes isolated from COVID-19 convalescent patients, BCG vaccinated and unvaccinated volunteers were stimulated with SARS-CoV-2 and LPS. ResultsPost COVID-19 patients showed immune dysregulation regardless of disease severity characterized mainly by altered expression of activation and functional markers in myeloid (CD39, CD64, CD85d, CD11b) and lymphoid cells (CD39, CD57, TIGIT). Strikingly, post-critical COVID-19 patients showed elevated expression of CD57 in CD8+ T cells compared to other severity groups. Additionally, a higher frequency of CMV and T. gondii seropositive-alongside a lower frequency of BCG seropositive-patients were associated with severe and critical COVID-19. However, the monocyte response to stimulation was unaffected by the severity of COVID-19. ConclusionThese findings highlight the long-term alterations of immune cells in post-COVID-19 patients emphasizing the substantial impact of COVID-19 on immune function. However, our data showed no relationship between previous BCG vaccination and protection against SARS-CoV-2 infection.