Exosomal miR-17-5p, miR-146a-3p, and miR-223-3p Correlate with Radiologic Sequelae in Survivors of COVID-19-Related Acute Respiratory Distress Syndrome

Abstract

We investigated the association between circulating microRNAs (miRNAs) potentially involved in the lung inflammatory process and fibrosis development among COVID-19-related acute respiratory distress syndrome (ARDS) survivors. At 4 ± 2 months from clinical recovery, COVID-19-related ARDS survivors matched for age, sex, and clinical characteristics underwent chest high-resolution computerized tomography (HRCT) and were selected based on imaging pattern evolution into fully recovered (N = normal), pulmonary opacities (PO) and fibrosis-like lesions (FL). Based on the previous literature, we performed plasma miRNA profiling of exosomal miRNAs belonging to the NLRP3-inflammasome platform with validated (miR-17-5p, miR-223-3p) and putative targets (miR-146a-5p), miRNAs involved in the post-transcriptional regulation of acute phase cytokines (miR128-3p, miR3168, miR125b-2-3p, miR106a-5p), miRNAs belonging to the NLRP4-inflammasome platform (miR-141-3p) and miRNAs related to post-transcriptional regulation of the fibrosis process (miR-21-5p). miR-17-5p, miR-223-3p, and miR-146a-5p were significantly down-regulated in patients with FL when compared to patients with PO. miR-146a-5p was also down-regulated in patients with FL than in N. The expression of the remaining miRNAs did not differ by group. In patients with long-term pulmonary radiological sequelae following COVID-19-related ARDS, a down-regulation of miR-17-5p, miR-146a-3p, and miR-223-3p correlated to fibrosis development in patients showing persistent hyper-reactivity to inflammatory stimulation. Our results support the hypothesis that NLRP3-Inflammasome could be implicated in the process of fibrotic evolution of COVID-19-associated ARDS.