Cytokines profile in COVID-19 patients during and following hospitalization

<bold>Introduction:</bold> Patients surviving COVID-19 can experience a spectrum of respiratory symptoms and residual lung damage. <bold>Aim:</bold> characterize specific cytokines profiles that reflect lung fibrosis, endothelial damage, thrombosis and inflammation among COVID-19 survivors and understand their relationship to disease severity. <bold>Methods:</bold> We enrolled 73 hospitalized COVID-19 patients. Patients who survived hospitalization were invited to a follow-up outpatient clinic visit. We measured levels of pulmonary fibrosis, inflammation and endothelial damage biomarkers: MMP-2, MMP-7, MMP-9, KL-6, angiopoietin-2, thrombomodulin, IL-6, TNF-α and hyaluronan in plasma obtained during admission and at follow-up. Clinical and imaging data were retrieved at baseline and at follow-up while pulmonary function tests were performed during follow-up visits. Control samples were obtained from 12 healthy subjects. <bold>Results:</bold> of the 73 patients, 60 (82.2%) had severe disease, and 14 (19.2%) died within 90 days. 18 patients were evaluated at follow-up. Dyspnea and fatigue were the most common symptoms at follow-up. MMP-2 and MMP-7 were significantly increased at follow-up compared to baseline, while angiopoietin-2, IL-6, and hyaluronan decreased. Higher MMP-7 at follow up was negatively correlated with FVC and DLCO (R=-0.1 and -0.45, respectively). A machine learning approach showed that MMP-2 at follow-up was the most important cytokine associated with FVC variability, while TNF-α, MMP-9 and MMP-7 were among the variables associated with DLCO variability. <bold>Conclusion:</bold> Cytokines profiling of severe COVID-19 survivors may reflect lung fibrosis and repair.