Abstract

Background: Most patients fully recover from coronavirus disease 2019 (COVID-19) but, due to unknown mechanisms, a subset of them can develop chronic lung sequelae. We hypothesized that these sequelae are related to alterations of their immune response.

Objectives: To explore the association between the long term lung sequelae and abnormalities of the immune response.

Methods: Lung function and blood samples of COVID19 patients were obtained at months 6 and 12 post hospital discharge. Pulmonary sequelae were defined as DLCO < 80%. In plasma of n= 166 patients we determined n=188 inflammation and organ damage proteins (by Olink) and the presence of autoantibodies; and in a subset (n=40) we assessed the presence of virus specific T cells.

Results: At 12 months, patients with lung sequelae presented: (1) increased levels of plasma inflammatory mediators (i.e. KIM1, PTN, IL6, ADGRG1, CXCL9, NPPC, CALCA, CCL3, EN-RAGE, IFNg, CCL19), of those, the expression of CCL19, CCL3 and EN-RAGE was higher at 12 than 6 months; (2) increased frequency of autoreactive autoantibodies, specifically the antinuclear ones; (3) higher proportion of virus specific T cells vs fully recovered patients (82% vs. 50%) and (4) under stimulation, the proportion of exhausted CD8 CD28- cells correlated with a worsening of DLCO from 6 to 12 months.

Conclusions: Patients with pulmonary sequelae had evidence of immune abnormalities, including plasma inflammatory mediators, autoantibodies and persistence of virus specific T cell.