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

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.

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.

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).

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).

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.