NAT2 Gene Variants as a Provocative Factor for the Severe Course of COVID-19 Pneumonia in Ukrainian Patients

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Abstract
Background: Previous studies indicate a close relationship between the severity of COVID-19 and oxidative stress. N-acetyltransferase 2 (NAT2) is an enzyme that metabolizes a wide range of xenobiotics and plays an important role in the regulation of reactive oxygen species, consequently contributing to the development of oxidative stress. Aim: To determine the impact of NAT2 gene variants on the risk of developing and the progression of severe COVID-19-associated pneumonia in patients from the Poltava region of Ukraine. Methods: The study included 117 patients who were diagnosed with severe COVID-19 pneumonia and received treatment in the intensive care unit. The NAT2 gene variants were identified through the PCR-RFLP method. Results: The presence of the AA genotype of the A803G variant in patients with severe COVID-19 pneumonia is associated with an almost 3-fold reduction in the risk of lethal outcomes. The presence of the TT genotype of the C481T variant was associated with the need for artificial lung ventilation. Patients in the study group with a heterozygous GA genotype of the G590A variant demonstrated a notable rise in the risk of developing systemic inflammatory response syndrome and acute respiratory distress syndrome, with a nearly 2.5-fold and 3-fold increase, respectively. The G857A variant was not associated with the risk of developing the above-- mentioned complications in the examined patients. Conclusion: The obtained results suggested that the NAT2 gene variants might influence the incidence, course, and adverse consequences of COVID-19.

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