Expression features of miR-155 and miR-28 microRNAs in patients with long COVID and arterial hypertension

Post-COVID syndrome, known as long COVID, is characterized by prolonged systemic inflammation and vascular dysfunction, particularly in individuals with arterial hypertension. MicroRNAs, such as miR-155 and miR-28, are regarded as potential molecular markers of this pathological condition. This study aimed to evaluate the expression patterns of miR-155 and miR-28 in patients with long COVID depending on the presence of hypertension, and to evaluate their associations with markers of inflammation and vascular impairment. A total of 102 patients were examined at least four weeks after recovery from COVID-19. Two groups of patients were formed, i.e., individuals with or without arterial hypertension (respectively, 50 and 52 subjects). Plasma levels of miR-155 and miR-28 were measured using reverse transcription quantitative PCR. General statistical and correlation analyses were performed. The results demonstrated that patients with hypertension exhibited elevated expression of miR-155 and reduced levels of miR-28, along with increased concentrations of inflammatory markers such as C-reactive protein, interleukin-6, B-type natriuretic peptide, and fibrin degradation products. In contrast, normotensive patients showed more stable biomarker profiles. These findings suggest that miR-155 and miR-28 reflect the degree of inflammatory and vascular activation in long COVID. The association between hypertension and dysregulation of these microRNAs highlights their potential utility for risk stratification and post-infection monitoring in affected individuals.

1. Blüml S., Bonelli M., Niederreiter B., Puchner A., Mayr G., Hayer S., Koenders M.I., van den Berg W.B., Smolen J., Redlich K. Essential role of microRNA-155 in the pathogenesis of autoimmune arthritis in mice. Arthritis Rheum., 2011, Vol. 63, no. 5, pp. 1281-1288.

2. Charfeddine S., Ibn Hadjamor M., Jdidi J. Long COVID: impact on cardiovascular health and possible mechanisms. Clin. Res. Cardiol., 2022, Vol. 111, no. 10, pp. 1200-1210.

3. Chen W., Huang Y., Han J. miR-28 modulates the inflammatory response via targeting NF-κB signaling in endothelial cells. Cell Signal., 2017, Vol. 36, pp. 60-67.

4. Li C., Hu X., Li L., Li J.-H. Dysregulation of microRNA-155 and its potential role in pathogenesis of COVID-19. Front. Med. (Lausanne), 2020, Vol. 7, 576977. doi: 10.3389/fmed.2020.576977.

5. McGonagle D., O'Donnell J.S., Sharif K., Emery P., Bridgewood C. Immune mechanisms of pulmonary intravascular coagulopathy in COVID-19 pneumonia. Lancet Rheumatol., 2020, Vol. 2, iss. 7, e437-e445. doi: 10.1016/S2665-9913(20)30121-1.

6. O’Connell R.M., Kahn D., Gibson W.S.J., Round J.L., Scholz R.L., Chaudhuri A.A., Kahn M.E., Rao D.S., Baltimore D. MicroRNA-155 promotes autoimmune inflammation by enhancing inflammatory T cell development. Immunity, 2010, Vol. 33, no. 4, pp. 607-619.

7. Pretorius E., Vlok M., Venter C., Bezuidenhout J.A., Laubscher G.J., Steenkamp J., Kell D.B. Persistent clotting protein pathology in Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin. Cardiovasc. Diabetol., 2022, Vol. 21, no. 1, 148. doi: 10.1186/s12933-022-01546-1.

8. Reyes-Uribe P., Ramirez-Gonzalez J.E., Figueroa-Vega N. Circulating miRNAs in severe COVID-19: potential roles and challenges. Int. J. Mol. Sci., 2021, Vol. 22, no. 9, 4701.

9. Soriano J.B., Murthy S., Marshall J.C., Relan P., Diaz J.V. A clinical case definition of post-COVID-19 condition by a Delphi consensus. Lancet Infect. Dis., 2022, Vol. 22, no. 4, e102-e107. doi: 10.1016/S1473-3099(21)00703-9.

10. World Health Organization. A clinical case definition of post COVID-19 condition in children and adolescents by expert consensus, 16 February 2023. WHO, 2023. 102 p. Available at: https://iris.who.int/server/api/core/bitstreams/269e1f3a-5fa9-475b-a22d-ac4df32d9628/content.

11. Xie Y., Xu E., Bowe B., Al-Aly Z. Long-term cardiovascular outcomes of COVID-19. Nat. Med., 2022, Vol. 28, no. 3, pp. 583-590.

12. Yang Y., Tang H., Abernathy J. Cardiovascular comorbidities and COVID-19: a retrospective study in older adults. J. Am. Heart Assoc., 2022, Vol. 11, no. 4, e023012.

13. Zhao X., Wang K, Lyu P, et al. miR-28 controls endothelial barrier function via regulation of inflammatory signaling in hypoxic conditions. Cardiovasc. Res., 2021, Vol. 117, no. 4, pp. 1021-1032.

14. Zhou F., Yu T., Du R., Fan G., Liu Y., Liu Z., Xiang J., Wang Y., Song B., Gu X., Guan L., Wei Y., Li H., Wu X., Xu J., Tu S., Zhang Y., Chen H., Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet, 2020, Vol. 395, no. 10229, pp. 1054-1062.