Abstract
A high incidence of thromboembolic events associated with high mortality has been reported in severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infections with respiratory failure. The present study characterized post-transcriptional gene regulation by global microRNA (miRNA) expression in relation to activated coagulation and inflammation in 21 critically ill SARS-CoV-2 patients. The cohort consisted of patients with moderate respiratory failure (n = 11) and severe respiratory failure (n = 10) at an acute stage (day 0–3) and in the later course of the disease (>7 days). All patients needed supplemental oxygen and severe patients were defined by the requirement of positive pressure ventilation (intubation). Levels of D-dimers, activated partial thromboplastin time (aPTT), C-reactive protein (CRP), and interleukin (IL)-6 were significantly higher in patients with severe compared with moderate respiratory failure. Concurrently, next generation sequencing (NGS) analysis demonstrated increased dysregulation of miRNA expression with progression of disease severity connected to extreme downregulation of miR-320a, miR-320b and miR-320c. Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis revealed involvement in the Hippo signaling pathway, the transforming growth factor (TGF)-β signaling pathway and in the regulation of adherens junctions. The expression of all miR-320 family members was significantly correlated with CRP, IL-6, and D-dimer levels. In conclusion, our analysis underlines the importance of thromboembolic processes in patients with respiratory failure and emphasizes miRNA-320s as potential biomarkers for severe progressive SARS-CoV-2 infection.
Highlights
IntroductionThe ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) global pandemic is one of the greatest threats to our health and to economic and social stability creativecommons.org/licenses/by/ 4.0/)
Four patients from the group with severe respiratory failure died during the treatment
MiRNAs critical in the pathogenesis of inflamm lung diseases, buthave they emerged play aas crucial roleregulators in the immune response to respiratory lung diseases, but they play a crucial role in the immune response to respiratory viral infections [18,19,20]
Summary
The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) global pandemic is one of the greatest threats to our health and to economic and social stability creativecommons.org/licenses/by/ 4.0/). The severe course of SARS-CoV-2 infection with lung failure is usually triggered by sepsis, pneumonia, or organ failure [1,6]. Many patients with severe ARDS show massively increased levels of leukocytes, C-reactive protein (CRP), interleukin (IL)-6, and D-dimers in response to the viral infection [5]. In a recent case series of autopsies, thrombotic events were observed in at least one major organ in all autopsies, predominantly in the lung (89%), heart (56%), and kidneys (44%) of nine patients [11]
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