IMPACT OF SINGLE-NUCLEOTIDE POLYMORPHISMS ON PULMONARY OUTCOMES AND LONG-TERM SYMPTOM PERSISTENCE IN COVID-19 PATIENTS

COVID-19 presents a strong immune response, and single-nucleotide polymorphisms (SNPs) in genes related to host immunity and cellular function may contribute to clinical variability. Polymorphisms in genes involved in viral entry, immune response, and renal functions are linked to COVID-19 severity. Therefore, our hypothesis is that SNPs are associated with symptom persistence in the post-COVID period. We aim to investigate the influence of SNPs in cytokine genes, pathogen recognition receptors (such as Toll-like receptors), and components of the renin-angiotensin-aldosterone system in persistent post-COVID symptoms. A group of 84 post-COVID-19 patients was included based on pulmonary function parameters and radiological findings. The study has ethics committee approval (CAAE: # 59213722.5.0000.5243). SNPs in cytokine genes were considered (TNF rs1800629, IL8 rs4073, IL1A rs1800587), renin-angiotensin-aldosterone system (ACE2 rs2285666) and Toll-like receptors (TLR7 rs179008 and TLR9 rs5743836 and rs352140). Logistic regression analyses evaluated associations between SNPs and specific outcomes, estimating corresponding odds ratios (ORs) and 95% confidence intervals (OR [95% CI]). Radiological and pulmonary function data were analyzed in this cohort (mean age 55.4 ± 14.4 years). The A allele of ACE2 rs2285666 was associated with dyspnea status in women (p = 0.044). Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) levels were associated with TLR9 rs352140. The dominant model of the T-allele (CC vs CT+TT) (OR = 3.36 [1.13 - 9.97], p = 0.028) and the T allele (OR = 1.99 [1.02 - 3.89], p = 0.043) were associated with reduced DLCO levels. Regarding radiological findings, the GA genotype in TNF rs1800629 (OR = 5.23 [1.43 - 19.16], p = 0.012) and the A allele (OR = 3.61 [1.016 - 12.83], p = 0.047) were associated with air trapping + ground-glass opacities in the lung. Our results suggest that ACE2 variants were implicated with dyspnea in women, while the TNF A allele was associated with alterations in pulmonary function parameters and specific radiological findings. Additionally, the TLR9 rs352140 polymorphism was associated with altered pulmonary function parameters, suggesting that cytokines and TLR SNPs polymorphisms contribute to the persistence of pulmonary alterations in the post-COVID period.