Identification of Specific Biomarkers for Selective Clinical Interventions in Post- COVID-19 Patients

Background: In COVID-19 clinical symptoms can persist even after negativization. Currently, there are no specific diagnostic tests that characterize the complexity of post COVID-19 and address specific, interventions. We here investigated the biomarkers that define the post-COVID-19 clinical state.Methods: We investigated the exhaled breath condensate (EBC) of 38 post COVID-19 patients and 38 sex and age-matched healthy controls via nuclear magnetic resonance (NMR)-based metabolomics. Predicted gene-modulated microRNAs (miRNAs) related to COVID-19 were quantified from EBC of 6 patients and 6 controls. Finally, clinical parameters from all post-COVID19 patients were correlated with metabolomic data.Findings: Post-COVID-19 patients and controls showed different metabolic phenotype ('metabotype'), due to persistent inflammation. From them, by using enrichment analysis, we identified miR146a, miR-126 and miR-223, which resulted up-regulated (miR146a) and downregulated (miR-126 and miR-223) in post-COVID-19. Correlation of metabolites with clinical data confirmed that patients and controls presented different metabotypes, and that post-COVID-19 before rehabilitation is still characterized by persistent inflammation, dysregulation of liver, endovascular thrombotic and pulmonary processes, and physical impairment.Interpretation: Joining EBC metabolomics, miRNAs and clinical data, we described the altered condition of post-COVID-19 patients. They are characterized by several pathophysiological processes, which should be primarily targeted to contrast the post-acute sequelae of COVID-19.Funding Information: This work was partially supported by the “Ricerca corrente” funding scheme of the Ministry of Health, Italy.Declaration of Interests: All the authors wish to declare no conflict of interest.Ethics Approval Statement: We followed the STROBE reporting guidelines, 7 in line with the 1975 Declaration of Helsinki. The Ethic Committee of Istituto Nazionale Tumori, Fondazione Pascale, Naples, Italy approved the study (n. ICS 3/20). All study participants provided written informed consent.