Lower Circulating Interferon-Gamma Is a Risk Factor for Lung Fibrosis in COVID-19 Patients

Cytokine storm resulting from SARS-CoV-2 infection is one of the leading causes of acute respiratory distress syndrome (ARDS) and lung fibrosis. We investigated the effect of inflammatory molecules to identify any marker that is related to lung fibrosis in coronavirus disease 2019 (COVID-19). Seventy-six COVID-19 patients who were admitted to Youan Hospital between January 21 and March 20, 2020 and recovered were recruited for this study. Pulmonary fibrosis, represented as fibrotic volume on chest CT images, was computed by an artificial intelligence (AI)-assisted program. Plasma samples were collected from the participants shortly after admission, to measure the basal inflammatory molecules levels. At discharge, fibrosis was present in 46 (60.5%) patients whose plasma interferon-gamma (IFN-gamma) levels were twofold lower than those without fibrosis (p> 0.05). The multivariate-adjusted logistic regression analysis demonstrated the inverse association risk of having lung fibrosis and basal circulating IFN-gamma levels with an estimate of 0.43 (p= 0.02). Per the 1-SD increase of basal IFN-gamma level in circulation, the fibrosis volume decreased by 0.070% (p= 0.04) at the discharge of participants. The basal circulating IFN-gamma levels were comparable with c-reactive protein in the discrimination of the occurrence of lung fibrosis among COVID-19 patients at discharge, unlike circulating IL-6 levels. In conclusion, these data indicate that decreased circulating IFN-gamma is a risk factor of lung fibrosis in COVID-19.