HLA-G 14 bp variant is associated with exercise-induced oxygen desaturation in the post-COVID-19 condition

The HLA-G molecule has been related to the lung inflammatory process in respiratory diseases. A 14 pb insertion/deletion in the gene encoding HLA-G has been associated with differential levels of the HLA-G molecule in plasma and with the severity of infectious diseases. Therefore, this study evaluates the association of the HLA-G variant 14 pb insertion/deletion (rs371194629) with COVID-19 susceptibility, severity, and oxygen desaturation in the post-COVID condition. We included 621 patients with severe COVID-19 hospitalized in a third-level hospital; 520 subjects Non-COVID (recruited previous to the COVID-19 pandemic); and 101 patients that were followed after discharge of COVID-19 (46.4% presenting exercise-induced oxygen desaturation). The severity of COVID-19 was evaluated through the invasive mechanical ventilation (IMV) requirement. We found that the DD genotype was more frequent among patients requiring IMV than non-IMV (0.372 vs 0.290, p= 0.046, OR =1.45, 95%CI = 1.01-2.08, dominant model). 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, dominant model). The allele and genotype frequencies were similar when COVID-19 and non-COVID subjects were compared. Thus, the DD genotype of rs371194629 HLA-G was associated with COVID-19 severity and post-COVID condition.

Methods
The study was conducted according to the Declaration of Helsinki, and the protocol was approved by the local Research Ethics Committee. From each subject included in the study, a blood sample was collected in a tube with EDTA as an anticoagulant. Genomic DNA was isolated using standard techniques. HLA-G rs371194629 genotyping was determined by end-point PCR, employing the oligonucleotides reported by Ad’hiah et al. 2022 and agarose gel electrophoresis 2.5%. The 210 pb band indicated the deletion allele and the 224 band indicated the insertion of the 14 bp. The clinical and demographic data were obtained from the clinical records and questionnaires.