Association of serum HIF-1α levels with mortality and ICU admission in hospitalized patients with SARS-CoV-2 infection: a prospective cohort study

Aims: SARS-CoV-2 infection can trigger a dysregulated immune response, including cytokine storm syndrome (CSS), which exacerbates respiratory failure through heightened pro-inflammatory mediators and hypoxemia. Hypoxia-inducible factor-1α (HIF-1α) orchestrates cellular adaptation to hypoxia by shifting metabolism toward glycolysis. Prior studies present varying evidence regarding HIF-1α’s role in acute inflammatory states. The purpose of this study was to investigate the role of hypoxia inducible factor 1a (HIF-1a) in predicting mortality, ward and intensive care unit (ICU) admission requirements. Methods: The study was performed as a single center prospective study in a tertiary center. Hospitalized patients with at least one positive nasopharyngeal COVID-19 reverse transcription-polymerase chain reaction test were included in the study. White blood cell count, thrombocyte count, lactate levels, fibrinogen, D-dimer, brain natriuretic peptide (BNP), C-reactive protein (CRP), procalcitonin, ferritin, interleukin 6 (IL-6) troponin, partial oxygen, and partial carbon dioxide pressure from arterial blood gas sampling were recorded. Results: Of 127 screened, 80 participants completed the study (mean age 66.1±17.2 years; 54% male). Thirty-day mortality was 21.3% (n=17). Median BNP (529 vs. 1,957 pg/ml), ferritin (256 vs. 598.5 ng/ml), and IL-6 (14 vs. 101 pg/ml) were significantly higher in non-survivors (p=0.043, 0.003, and 0.001, respectively). Survivors exhibited lower median HIF-1α (0.85 vs. 1.20 ng/ml), but this difference was not statistically significant (p>0.05). Subgroup analyses by CURB-65 and ICU status similarly revealed no significant HIF-1α differences. HIF-1α did not correlate with any inflammatory markers. HIF-1α levels at admission did not significantly predict ICU care or mortality. This may reflect HIF-1α’s pro- and anti-inflammatory roles and variability in sampling timing relative to disease onset. Current literature suggests both protective and detrimental HIF-1α effects, complicating its prognostic utility. Conclusion: Admission HIF-1α alone does not predict clinical outcomes in hospitalized COVID-19. Studies incorporating serial measurements and baseline controls are warranted to evaluate HIF-1α’s involvement in COVID-19 pathophysiology.