(T1130-04-24) Downregulated Expression Levels of miR-451a and miR-185-5p as Potential Biomarkers for Coronavirus Disease 2019 (COVID-19) Severity

Purpose: It is known that patients with coronavirus disease 2019 (COVID-19) can exhibit different symptoms, ranging from mild and moderate symptoms of the upper respiratory tract to severe acute respiratory syndrome, which can lead to multiple organ failure, culminating in death. Many efforts have been made to discover molecular biomarkers for the severity of COVID-19, such as microRNAs (miRNAs) [1]. Preliminary results of a study suggested that miR-451a and miR-185-5p could be potential biomarkers for the severity of COVID-19 [2]. Therefore, this study aimed to investigate the expression levels of two miRNAs (miR-451a and miR-185-5p) in patients with different severities of COVID-19.

Methods: This was an observational and multicenter study. miRNAs were extracted from the plasma of subjects with a positive nasopharyngeal swab Polymerase Chain Reaction (PCR) test for SARS-CoV-2, recruited during the first wave of the pandemic. They were classified by COVID-19 severity based on Falavigna et al. [3]: mild, moderate, severe, and critical COVID-19. miR-451a and miR-185-5p, as well as cel-miR-39 (exogenous control), were analyzed using real-time quantitative reverse transcription PCR (qRT-PCR). The expression level of miR-451a and miR-185-5p was calculated using the 2-∆CT method (∆CT = Ct of the miR of interest - Ct of cel-miR-39; Ct = cycle threshold). Student's t-test was used to compare the severity groups, and P < 0.05 was considered statistically significant.

Results: Eighty-five subjects were included in this study: 42 with severe/critical COVID-19 (59.5% male; 54.6 ± 14.3 years; 23.8% without comorbidities, 52.4% with hypertension, and 57.1% with obesity) and 43 with mild/moderate COVID-19 (44.2% male; 42.6 ± 11.3 years; 55.8% without comorbidities, 25.6% with hypertension, and 11.6% with obesity). Expression levels of miR-451a (p < 0.0001) and miR-185-5p (p < 0.0001) were significantly lower in the plasma samples of subjects with severe/critical COVID-19 (2-∆CT = 0.002 ± 0.004 and 0.00002 ± 0.00004, respectively) compared to subjects with mild/moderate COVID-19 (2-∆CT = 0.085 ± 0.093 and 0.001 ± 0.0008, respectively) (Figure 1).

Conclusion: miR-451a and miR-185-5p might be used as possible biomarkers for the severity of COVID-19. Moreover, these miRNAs may be potential targets for developing therapeutics to treat severe COVID-19.

References: [1] Visacri MB, Nicoletti AS, Pincinato EC, Loren P, Saavedra N, Saavedra K, Salazar LA, Moriel P. Role of miRNAs as biomarkers of COVID-19: a scoping review of the status and future directions for research in this field. Biomark Med. 2021;15(18):1785-1795.
[2] Nicoletti AS, Visacri MB, da Ronda CRDSC, Vasconcelos PEDNS, Quintanilha JCF, de Souza RN, Ventura DS, Eguti A, Silva LFS, Perroud Junior MW, Catharino RR, Reis LO, Dos Santos LA, Durán N, Fávaro WJ, Lancellotti M, da Costa JL, Moriel P, Pincinato EC. Differentially expressed plasmatic microRNAs in Brazilian patients with Coronavirus disease 2019 (COVID-19): preliminary results. Mol Biol Rep. 2022;49:6931-6943.
[3] Falavigna M, Colpani V, Stein C, Azevedo LCP, Bagattini AM, Brito GV, Chatkin JM, Cimerman S, Corradi MFDB, Cunha CAD, Medeiros FC, Oliveira Junior HA, Fritscher LG, Gazzana MB, Gräf DD, Marra LP, Matuoka JY, Nunes MS, Pachito DV, Pagano CGM, Parreira PCS, Riera R, Silva A Júnior, Tavares BM, Zavascki AP, Rosa RG, Dal-Pizzol F. Guidelines for the pharmacological treatment of COVID-19. The task-force/consensus guideline of the Brazilian Association of Intensive Care Medicine, the Brazilian Society of Infectious Diseases and the Brazilian Society of Pulmonology and Tisiology. Rev Bras Ter Intensiva. 2020;32(2):166-196.

Acknowledgements: This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES) [Finance Code 001—88881.504454/2020-01 and 88887.506965/2020-00], by São Paulo Research Foundation (FAPESP) [number 2021/04669-9], and by the National Council for Scientific and Technological Development (CNPq). This study was approved by the Research Ethics Committee of the School of Medical Sciences of the University of Campinas (UNICAMP) (numbers 36041420.0.000.5404 and 31049320.7.1001.5404).

Figure 1. Fold changes of miRNAs (miR-451a and miR-185-5p) in subjects with severe/critical and mild/moderate COVID-19.