Persistence of specific T-cell response in patients with Long COVID and pulmonary sequelae

Background: A significant proportion of patients that survive COVID19 may develop LongCOVID or pulmonary sequelae(DLCO<80%).The mechanisms underlying these alterations are not described.Objectives:To determine if there is an association of the virus specific T cell response and the presence of LongCOVID or pulmonary sequelae at 12 months of convalescence. Methods: T lymphocytes were stimulated with specific SARSCoV2 peptides(N and S) in 40 patients (11 with LongCOVID, 17 pulmonary sequelae) at 12 months postCOVID.Tcell populations and IFNg production in stimulated lymphocytes were measured by flow cytometry. Lung function was measured at 6 and 12 months to evaluate the progression. Results: After comparing the prevalence of SARSCoV2 specific T cells(>2%IFNg+Tcells) across study groups at 12 months we observed that:1)50% of the recovered patients presented an in vitro Tcell response against SARSCoV2;2)72% of the patients with LongCOVID and 82% of the patients with lung sequelae responded.Th1 cells were increased in patients with LongCOVID in response to both peptides.Patients with pulmonary sequelae only presented an increase in Th1 in response to the S peptide. An in-depth characterization of the T lymphocytes in patients with LongCOVID,showed reduced expression of HLADR in CD4/CD8 T cells, and overall reduction of the frequencies of Th1 response.The frequency of CD4 HLADR,Th1,Th17,Th1/17 correlated with the change in DLCO in patients with pulmonary sequelae. Conclusions: Patients with LongCOVID or pulmonary sequelae have an increased persistence of virus specific Tcell response after 12 months. Findings suggest the presence of long-term altered immune profile in patients with LongCOVID.