Biomarkers of Fibrosis in Patients with COVID-19 One Year After Hospital Discharge: A Prospective Cohort Study.

ABSTRACT

Beyond the acute infection of coronavirus disease (COVID-19), concern has arisen about long-term effects of SARS-CoV-2 infection. The aim of our study was to analyze if there is any biomarker of fibrogenesis in COVID-19 pneumonia patients capable of predicting post-COVID pulmonary sequelae. We conducted a multicenter, prospective, observational cohort study of patients admitted to hospital with bilateral COVID-19 pneumonia. We classified patients in two groups according to severity, and blood samples to measure MMP1, MMP7, periostin and VEGF, respiratory function tests and HRCT imaging were obtained at 2 and 12 months after hospital discharge. A total of 135 patients were evaluated at 12 months. Median age was 61 (IQR 19) years and 58.5% were men. We found between-group differences in age, radiological involvement, length of hospital stay and inflammatory laboratory parameters. Differences were found between 2 and 12 months in all functional tests, including improvements in FVC% (98.0 vs. 103.9; p=0.001) and DLCO<80% (60.9% vs. 39.7%; p=0.001). At 12 months, 63% of patients had complete HRTC resolution, but fibrotic changes persisted in 29.4%. Biomarker analysis demonstrated differences at 2 months in periostin (ng/mL) (0.8893 vs. 1.437; p<0.001) and MMP-7 (ng/mL) (8.7249 vs. 15.2181; p<0.001). No differences were found at 12 months. In multivariable analysis, only 2-month periostin was associated with 12-month fibrotic changes (OR 1.0013 95% CI 1.0006-1.00231; p=0.003) and 12-month DLCO impairment (OR 1.0006 95% CI 1.0000-1.0013; p=0.047). Our data suggest that early periostin post-discharge could predict the presence of fibrotic pulmonary changes.