3.1 Baseline laboratory data
Baseline laboratory data included ESR and total and absolute counts of WBC (granulocytes, lymphocytes, and monocytes). COVID-19 patients showed a significantly increased median (IQR) ESR compared to HC (45 [37-55] vs . 13 [9-16] mm/h; p < 0.001). Likewise, the total count of WBC was significantly higher in patients than in HC (7.8 [6.2-9.8] vs . 7 [6.0-8.1] × 109/L; p = 0.001), but the count in both groups was within the reference range. Granulocytes were significantly elevated in patients compared to HC (5.2 [4.0-6.9] vs . 3.8 [3.1-4.8] × 109/L; p < 0.001), while lymphocytes were significantly lower in patients (1.8 [1.4-2.4] vs . 2.5 [2.2-3.1] × 109/L;p < 0.001). Monocyte counts showed no significant difference between patients and HC (p = 0.567). GLR was significantly higher in patients than in HC (2.3 [1.8-4.5]vs . 1.6 [1.3-1.8]; p < 0.001), while LMR decreased significantly in patients (3.5 [3.0-4.3] vs . 4.8 [3.7-5.6]; p < 0.001) (Table 2).
3.2 IFIH1 SNPs
HWE analysis demonstrated that genotype frequencies of both SNPs (rs1990760 and rs2111485) did not deviate significantly from HWE in the HC group (p = 0.523 and 0.253, respectively). Association analysis was conducted under five genetic models; allele, recessive, dominant, over-dominant, and co-dominant. For SNP rs1990760, the genotype frequencies of CC, CT, and TT were 4.4, 37.8, and 57.8%, respectively, in COVID-19 patients. The corresponding frequencies in HC were significantly different (24.4, 53.3, and 22.2%, respectively;p < 0.001). Under the allele model (T vs .C ), the mutant T allele was associated with a significantly increased risk of COVID-19 (OR = 3.44; 95% CI = 2.19-5.39; p < 0.001; pc < 0.001). A higher risk of infection with COVID-19 was associated with the mutant TT genotype under recessive (TT vs . CC+CT: OR = 4.86; 95% CI = 2.52-9.38; p < 0.001; pc < 0.001) and co-dominant (OR = 14.59; 95% CI = 4.42-48.19; p < 0.001; pc < 0.001) models. Under dominant model (CT+TTvs . CC), the CT+TT genotypes were also associated with an increased risk of COVID-19 (OR = 6.95; 95 CI = 2.27-21.28; p = 0.001; pc = 0.005). Under over-dominant model (CT vs . CC+TT), there was no significant risk of COVID-19 associated with SNP rs1990760 (p = 0.035; pc = 0.175) (Table 3).
In the case of SNP rs2111485, genotype frequencies (AA, AG, and GG) showed significant differences between COVID-19 patients and HC (6.7, 64.4 and 28.9% vs . 42.2, 41.1 and 16.7%, respectively; p< 0.001). The mutant G allele (allele model; Gvs . A ) and GG genotype (co-dominant model; GG vs . AA) were associated with a higher risk of COVID-19 (OR = 2.65, 95% CI =1.73-4.05, p < 0.001, pc < 0.001; OR = 10.72, 95% CI = 3.66-31.40, p < 0.001, pc< 0.001, respectively). Under dominant (AG+GG vs . AA: OR = 10.15; 95% CI = 4.01-25.69; p < 0.001; pc< 0.001) and over-dominant (AG vs . AA+GG: OR: 2.62; 95% CI = 1.43-4.80); p = 0.002; pc = 0.01) models, a significant increased risk of COVID-19 was also associated with SNP rs2111485. Under recessive model (GG vs . AA+AG), there was no significant risk of COVID-19 associated with SNP rs2111485 (p = 0.063; pc = 0.315) (Table 3).
To further explore the association of IFIH1 SNPs with COVID-19, haplotype analysis of the two SNPs was conducted (haplotype: rs1990760-rs2111485). Four haplotypes were encountered (T-A, T-G, C-A, and C-G) with frequencies of 22.2, 54.4, 16.7 and 6.7%, respectively, in COVID-19 patients, and 20.6, 28.3, 42.2 and 8.9%, respectively, in HC. The T-G haplotype was significantly associated with an increased risk of the disease (OR = 3.02; 95% CI = 1.95-4.68; p< 0.001; pc < 0.001), while the C-A haplotype was associated with a significantly decreased risk of contracting COVID-19 (OR = 0.27; 95% CI = 0.18-0.45; p < 0.001;pc < 0.001). The T-A and C-G and haplotypes showed no association with COVID-19 risk (Table 3). LD analysis revealed that the rs1990760 and rs2111485 polymorphisms were moderately linked as indicated by the LD coefficient (D’) of 0.57 and correlation coefficient (R2) of 0.18 (Figure 1).