HIF-1α is Associated with Improved Survival in Acute Respiratory Distress Syndrome due to COVID-19: A Prospective Study

Background: Acute respiratory distress syndrome (ARDS) due to coronovirus disease 2019 (COVID-19) is accompanied by severe hypoxemia and hyperinflammation. Hypoxia-inducible factor (HIF) pathway plays a fundamental role in detecting the hypoxia and developing appropriate responses. Aim: The aim of this study was to evaluate the role of HIF-1α and PHD2 (prolyl hydroxylase domain2) genes in the pathophysiology of severe hypoxemia in COVID-19 patients. Methods: The study included 297 patients who developed ARDS due to COVID-19 infection and were admitted into the intensive care unit. APACHEII score, SOFA, vasopressor, dialysis and mechanical ventilation need during treatment, and 30-day mortality were recorded. DNA was isolated from the blood samples by the spin colon method with the QIAamp DNA MiniKit (Cat.No. 51106, QIAGEN, Germany). Results: Patients were divided into three groups according to their Hypoxia Inducible Factor-1α (C/T SNP [ 11549465 ]) genotypes. The frequencies were 71.13% for the homozygous CC genotype, 26.4% heterozygous CT genotype, and 2.36% for the homozygous TT genotype. The median age ( P = 0.631), APACHE II ( P = 0.205), and SOFA ( P = 0.077) scores were similar in all three groups. However, the need for dialysis, mechanical ventilation, and vasopressor was less in the homozygous TT-genotype group than in the other groups ( P < 0.05). The mortality rate was also lower in this group compared to other groups ( P < 0.05). Conclusion: In conclusion, we revealed the polymorphism in HIF-lα and PHD2 genes in ARDS patients due to COVID-19. The rate of HIF-lα polymorphism was 26.4% for heterozygous CT-genotype and 2.36% for homozygous TT-genotype. The 30-day mortality and adverse outcome (dialysis, vasopressor use, MV need) were significantly lower in TT homozygous. However, none of the polymorphisms in the PHD2 genes affected mortality and adverse outcome.