Post-COVID-19 patients develop lung fibrotic-like changes: is there a role for IL-1alpha and TGF-beta?

ABSTRACT

Patients (around 40-50%) who were infected by SARS-CoV-2 develop a condition called as long-COVID-19 that lasted longer than the infection. One of the complications of post-COVID-19 (PC) is pulmonary fibrosis. T he purpose of this study was to identify blood biomarkers to predict PC patients undergoing pulmonary fibrosis. We analysed blood samples of healthy, anti-SARS-CoV-2 vaccinated subjects and PC patients, who were stratified according to the severity of the disease and chest computed tomography (CT) scan data that revealed fibrotic or non-fibrotic areas. PC patients had higher levels of the inflammatory C reactive protein (CRP), complement complex C5b-9, LDH, but not IL-6, independently of the severity of the disease and lung fibrotic areas. Interestingly, PC patients who presented signs of lung fibrosis were characterized by higher plasma levels of IL-1alpha, CXCL-10, TGF-beta, but not of IFN-beta, compared to healthy and vaccinated (VAX) subjects. In particular, 19 out of 23 (82.6%) severe PC and 8 out of 29 (27.6%) moderate PC patients presented signs of lung fibrosis, associated to lower levels of IFN-beta but higher IL-1alpha and TGF-beta. Instead, t he levels of IFN-beta were associated to the capability of the patient to respond to the infection without signs of lung fibrosis, implying a beneficial role of this cytokine. In conclusion, we found that higher plasma levels of IL-1alpha and TGF-beta, but not of IFN-beta, could predict an increased relative risk (RR=2.8) of lung fibrosislike changes in PC patients.