Analysis of serum microRNAs and rs2910164 GC single-nucleotide polymorphism of miRNA-146a in COVID-19 patients

ABSTRACT

Alteration of micro-RNAs (miRNAs) expression, including miRNA-122a, −146a and −205 family members, can have profound effects on inflammatory and IFN pathways (miRNA-146a), known as hallmarks of COVID-19. SARS-CoV-2-infected patients were recruited at Policlinico Umberto I Hospital of Sapienza University of Rome (Italy). MiRNA‐122a, ‐146a, ‐205 and IFI27 (Interferon Alpha Inducible Protein 27) levels were screened in SARS-CoV-2 patients (n = 14) and healthy controls (n = 10) by real‐time RT‐PCR assays. Then, miRNA-146a rs2910164 GC single-nucleotide polymorphism (SNP) was genotyped in a larger group of COVID-19 patients (n = 129), and its relationship with severe disease [Intensive Care Unit (ICU) support or survival/death] was assessed. SARS-CoV-2-positive patients had increased PCR, D-Dimer and Fibrinogen levels compared to healthy controls (p < .05 for all measurements). MiRNA-122a and -146a serum levels were upregulated in COVID-19 patients (miRNA-122a: p = .002; miRNA-146a: p < .001). Decreased IFI27 levels were observed in COVID-19 patients with higher miRNA-146a levels (p = .047). Moreover, miRNA-146a rs2910164 C/G genotypes distributions were similar in COVID-19 patients and in validated European healthy subjects (n = 37,214). MiRNA-146a SNP was not associated with severe COVID-19 outcome (ICU or death). MiRNA-122a and -146a levels were elevated in SARS-CoV-2 infected patients, with miRNA-146a upregulation possibly contributing to IFN pathways dysregulation (e.g., reduced IFI27 levels) observed in severe COVID-19, although there is no evidence for the involvement of rs2910164 SNP.

KEYWORDS:

• COVID-19
• miRNA-122a
• miRNA-146a and miRNA-205
• SARS-CoV-2
• inflammation
• IFN response
• ISG
• IFI27
• miRNA-146a rs2910164 SNP

Acknowledgments

We gratefully acknowledge the participating members of Virology and Infectious Diseases COVID-19 Study Group of Sapienza University.

Author contributions

Conceptualization, C.P. and C.S.; investigation, M.S., L.S, F.F, L.S., C.B, G.O., A.V., F.M.C; molecular data curation, L.C.; clinical and biochemical data curation, G.C.; writing—original draft preparation, C.P. and C.S.; writing—review and editing, C.S. and G.d.E; editing, C.M.M. and G.A.; visualization, supervision and project administration, C.S. and G.d.E. jointly share senior authorship. All authors have read and agreed to the published version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was supported by an intramural grant to G.A. from Sapienza University of Rome [Progetti finanziati anno 2020, progetti H2020, Antonelli Guido, COVID-19: Approaches for antiviral drug development B MEDICINA MOLECOLARE] and from the Italian Ministry of Health: COVID-2020-12371817 and by an intramural grant to C.S. from Sapienza University of Rome [Progetti finanziati anno 2019 and 2020 (progetti medi)].