HIF-1α is Associated with Improved Survival in ARDS due to COVID-19: A Prospective Study

Abstract

Abstract Background Acute respiratory distress syndrome(ARDS) due to COVID-19 is accompanied by severe hypoxemia and hyperinflammation. Hypoxia-inducible factor(HIF) pathway plays a fundamental role in detecting hypoxia and developing appropriate responses. The epidemiological report claimed a lower rate of disease in the population living at high altitudes and hypothesized that adaptation to hypoxia might be advantageous for SARS-CoV-2 infection. This study was designed to examine the frequency of polymorphisms in the HIF-1α and PHD2(prolyl hydroxylase domain 2) genes, which are involved in the adaptation to hypoxia, and the relationship of existing polymorphisms with survival in the ARDS clinic developed due to COVID-19. Methods The study included 297 patients who developed ARDS due to COVID-19 infection and were admitted to the tertiary intensive care unit. Age, gender, hospitalization diagnosis, arterial blood pressure, heart rate, APACHEII score, SOFA laboratory parameters during hospitalization, vasopressor, dialysis and mechanical ventilation need during treatment, length of hospital stay, and 30-day mortality status were recorded. DNA was isolated from the blood samples by spin colon method with the QIAamp DNA MiniKit (Cat.No.51106, QIAGEN, Germany). Results Patients were divided into 3 groups according to their Hypoxia Inducible Factor-1α (C/T SNP [11549465]) genotypes. Frequencies were 71.13% for the homozygous CC genotype, 26.4% heterozygous CT genotype, and 2.36% for the homozygous TT genotype. 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). PND2 (C/T SNP [480902] and [516651]) polymorphism, clinical and laboratory features were similar in all groups. Moreover, 30-day mortality did not differ between the groups. Conclusion In conclusion, we revealed polymorphism in HIF-lα and PHD2 genes in ARDS patients due to COVID-19. The rate of HIF-lα polymorphism was 26.4% heterozygous CT-genotype and 2.36% for homozygous TT-genotype. 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.