The Expression Levels of HIF-1a and the Long Non-Coding RNA HIF1A-AS1 in the Buffy Coat as Prognostic Markers for Severe COVID-19 Outcomes in Patients with Diabetes and Obesity

Objective — study of pathogenetic mechanisms and the search for effective prognostic markers for COVID-19 are highly relevant. Materials and methods. Thirty-six patients with comorbidities—obesity (BMI over 30), arterial hypertension, and subcompensated type 2 diabetes— were hospitalized in the infectious disease department of Kyiv City Clinical Hospital No. 4 after 7—12 days of outpatient treatment from the onset of the disease. All patients were confirmed to have COVID-19 by PCR. The control group included 7 practically healthy donors with a BMI < 25 and no signs of diabetes. The severity of the disease was assessed based on pulse oximetry and the duration of oxygen dependence according to WHO classification. According to these criteria, patients were divided into three groups by severity: mild (n = 8), moderate (n = 15), and severe (n = 13) according to the recommendations of the National Health Commission of Ukraine. The severity of COVID-19 was assessed at hospital discharge. Clinical analysis, RNA extraction from peripheral blood leukocytes, reverse transcription, real-time PCR, and the determination of HIF-1α and HIF1A-AS1 expression levels were conducted. Results and discussion. The expression level of HIF-1α in patients’ leukocytes varied widely from 6.8 arbitrary units to 146.9. In the control group, the expression level was (6.8 ± 3.2) a. u., which is 4.3 times lower than in the mild disease group ((29.4 ± 4.1) a. u.). In the moderate disease group, the expression level of HIF-1α almost doubled to (55.728 ± 16.8) a. u. In the severe disease group, the expression level was (146.9 ± 44.9) a. u., which is 5 times higher than in the mild group and 2.6 times higher than in the moderate group (p < 0.05). The expression level of the long non-coding RNA HIF1A-AS1 in the control group and patients with mild COVID-19 did not differ statistically (32.096 ± 7.9 and 29.3 ± 7.1). However, in the moderate disease group, the expression increased 5 times compared to the mild group, reaching 146.4 ± 37.4 (p < 0.05). In severe COVID-19, the expression level increased 9.8 times compared to the mild group (p < 0.05) and 1.9 times compared to the moderate group, reaching 286.7 ± 77.3. Conclusions. Our data demonstrate that the expression levels of HIF-1α and lnc RNA HIF1A-AS1 in blood leukocytes significantly increase in patients with moderate and severe COVID-19 at the pre-hospital stage, even before clinical deterioration occurs. This suggests that the expression levels of HIF-1α and lnc RNA HIF1A-AS1 can be considered important, complementary prognostic biomarkers for severe COVID-19 in high-risk groups with comorbid conditions, particularly in cases of metabolic disorders. The role of HIF1A-AS1 in the context of respiratory diseases requires further in-depth study and analysis. Targeting HIF-1α through its association with HIF1A-AS1 has the potential to become a therapeutic target in the treatment of severe respiratory diseases accompanied by ARDS.