The HLA-G 14 bp insertion/deletion is associated with COVID-19 severity and exercise-induced oxygen desaturation in post-COVID subjects

The non-classical HLA-G molecule has been related to the lung inflammatory process. The 14 bp insertion/deletion (indel) in HLA-G has been associated with differential levels of the HLA-G molecule in plasma and with the severity of infectious diseases. We aimed to evaluate the association of the HLA-G variant 14 bp indel (rs371194629) with COVID-19 susceptibility and severity and the oxygen desaturation in the post-COVID condition. <bold>Methods:</bold> We evaluated 621 patients (median 55 years, 64% males) with severe COVID-19 hospitalized in the Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas (INER), Mexico City; 520 subjects Non-COVID (recruited previous to the COVID-19 pandemic, 53 years, 46% males); and 101 patients that were followed after discharge of COVID-19 (46.4% presenting exercise-induced oxygen desaturation, 58 years, 64% males) (Protocol approval No. B17-23). The severity of COVID-19 was evaluated through the invasive mechanical ventilation (IMV) requirement. HLA-G indel genotyping was determined by end-point PCR and agarose gel electrophoresis. The statistical analysis was performed on PLINK and RStudio. <bold>Results:</bold> The genotype DD was more frequent among patients requiring IMV than non-IMV (0.372 vs. 0.290, p=0.046, OR=1.45, CI 95%=1.01-2.08, recessive model). And this genotype was also associated with exercise-induced oxygen desaturation in post-COVID patients (0.435 vs 0.196, p=0.011, OR=3.15, CI 95%=1.28-7.79, recessive model). The allele and genotype frequencies were similar when COVID-19 and non-COVID subjects were compared. <bold>Conclusion:</bold> The HLA-G DD genotype is associated with severe COVID-19 and post-COVID condition.