AUTHOR=Martínez-Fleta Pedro , Vera-Tomé Paula , Jiménez-Fernández María , Requena Silvia , Roy-Vallejo Emilia , Sanz-García Ancor , Lozano-Prieto Marta , López-Sanz Celia , Vara Alicia , Lancho-Sánchez Ángel , Martín-Gayo Enrique , Muñoz-Calleja Cecilia , Alfranca Arantzazu , González-Álvaro Isidoro , Galván-Román José María , Aspa Javier , de la Fuente Hortensia , Sánchez-Madrid Francisco TITLE=A Differential Signature of Circulating miRNAs and Cytokines Between COVID-19 and Community-Acquired Pneumonia Uncovers Novel Physiopathological Mechanisms of COVID-19 JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.815651 DOI=10.3389/fimmu.2021.815651 ISSN=1664-3224 ABSTRACT=

Coronavirus Disease 2019 (COVID-19) pneumonia is a life-threatening infectious disease, especially for elderly patients with multiple comorbidities. Despite enormous efforts to understand its underlying etiopathogenic mechanisms, most of them remain elusive. In this study, we compared differential plasma miRNAs and cytokines profiles between COVID-19 and other community-acquired pneumonias (CAP). A first screening and subsequent validation assays in an independent cohort of patients revealed a signature of 15 dysregulated miRNAs between COVID-19 and CAP patients. Additionally, multivariate analysis displayed a combination of 4 miRNAs (miR-106b-5p, miR-221-3p, miR-25-3p and miR-30a-5p) that significantly discriminated between both pathologies. Search for targets of these miRNAs, combined with plasma protein measurements, identified a differential cytokine signature between COVID-19 and CAP that included EGFR, CXCL12 and IL-10. Significant differences were also detected in plasma levels of CXCL12, IL-17, TIMP-2 and IL-21R between mild and severe COVID-19 patients. These findings provide new insights into the etiopathological mechanisms underlying COVID-19.