Identification of circulating microRNA profiles associated with pulmonary function and radiologic features in survivors of SARS-CoV-2-induced ARDS

Abstract

There is a limited understanding of the pathophysiology of postacute pulmonary sequelae in severe COVID-19. The aim of current study was to define the circulating microRNA (miRNA) profiles associated with pulmonary function and radiologic features in survivors of SARS-CoV-2-induced ARDS. The study included patients who developed ARDS secondary to SARS-CoV-2 infection (n = 167) and a group of infected patients who did not develop ARDS (n = 33). Patients were evaluated 3 months after hospital discharge. The follow-up included a complete pulmonary evaluation and chest computed tomography. Plasma miRNA profiling was performed using RT-qPCR. Random forest was used to construct miRNA signatures associated with lung diffusing capacity for carbon monoxide (D LCO ) and total severity score (TSS). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were conducted. D LCO < 80% predicted was observed in 81.8% of the patients. TSS showed a median [P 25 ;P 75 ] of 5 [2;8]. The miRNA model associated with D LCO comprised miR-17-5p, miR-27a-3p, miR-126-3p, miR-146a-5p and miR-495-3p. Concerning radiologic features, a miRNA signature composed by miR-9-5p, miR-21-5p, miR-24-3p and miR-221-3p correlated with TSS values. These associations were not observed in the non-ARDS group. KEGG pathway and GO enrichment analyses provided evidence of molecular mechanisms related not only to profibrotic or anti-inflammatory states but also to cell death, immune response, hypoxia, vascularization, coagulation and viral infection. In conclusion, diffusing capacity and radiological features in survivors from SARS-CoV-2-induced ARDS are associated with specific miRNA profiles. These findings provide novel insights into the possible molecular pathways underlying the pathogenesis of pulmonary sequelae. Trial registration: . Trial registration: .

Genome-wide transcriptional profiling of pulmonary functional sequelae in ARDS- secondary to SARS-CoV-2 infection

“…Indeed, severe post-acute sequelae were associated with a complex alteration of cell death signaling, a key mechanism in immune response resolution. In consonance with recently published data from our group [31] , enrichment analysis revealed an overrepresentation of apoptotic pathways, including processes regulated and/or mediated by RUNX3 and FOXO and the downstream BIM apoptotic signaling pathway. The individual genes have been described in processes related to immune cell survival and depletion.…”

Residual pulmonary infiltrates, symptoms and diffusion impairment at 1‐year after severe COVID‐19 infection have different associated factors

“…García‐Hidalgo et al. reported that the diffusion capacity and radiological features of survivors of SARS‐CoV‐2‐induced acute respiratory distress syndrome were associated with specific miRNA profiles [24, 25].…”

“…SARS-CoV-2 pneumonia episodes with poorer SpO 2 /FiO 2 and CURB-65 ≥2 were independently associated with incomplete resolution. The effect of respiratory support was found to be increasingly dependent on the complexity of the requirement; the OR [24,25].…”

Study protocol for the epigenetic characterization of angor pectoris according to the affected coronary compartment: Global and comprehensive assessment of the relationship between invasive coronary physiology and microRNAs

“…miRNA profiling will be performed in the laboratory of the TRRM group of the IRBLleida by experienced personnel without access to clinical data. All experiments will be performed using the gold-standard technique; RT-qPCR, under standardized conditions in the same laboratory and according to the previous methodology used by the research group [ 17 , 18 ].…”