Role of the alpha-1 antitrypsin towards progression and severity of COVID- 19 infection among Saudi patients

Background Alpha-1 antitrypsin (A1AT) is involved in pathophysiology of severe COVID-19, including thrombosis expansion. A1AT has anti-inflammatory, tissue-protective, and anticoagulant capabilities. We aimed to screen frequencies of A1AT gene polymorphism among COVID-19 Saudi patients and its relation to severity. Methods Through cross-sectional study, we examined 100 COVID-19 Saudi patients to explore possible correlation between A1AT/interleukin 6 (IL-6) ratio and COVID-19 severity. The COVID-19 patients grouped as severe (31 patients) and non-severe (69 patients) cases. A1AT gene polymorphism was conducted using the PCR technique (ARMS) and ELISA. Results A1AT, IL-6, and vitamin D (VIT-D) showed extreme statistical significance among COVID-19 patients (severe, mild, and asymptomatic). The prevalence of A1AT gene mutation was higher among COVID-19 cases compared with non-mutated patients (56% vs. 44%). Moreover, serum A1AT levels were lower while serum IL-6 levels were higher than reference range and highly significant among mutated cases compared with non-mutated cases. Also, IL-6/A1AT ratio in severe COVID-19 patients (mean 1.4) was significantly higher compared with asymptomatic or moderate patients (0.16, 0.21; respectively). Strictly, all COVID-19 patients have severed deficiency of VIT-D level significant among mutated and non-mutated cases ( p <0.04 and p <0.03; respectively). The frequency of MM (wild type) was substantially high among asymptomatic cases compared with severe cases (67.2% vs. 16.1%). Heterozygous MS+MZ genotypes showed lower frequency among asymptomatic cases compared with severe and mild cases (27.6% vs. 48.4% and 72.7%; respectively). On the other hand, the more severe forms of SS+ZZ+SZ genotypes were all relatively rare with lower frequency among asymptomatic compared with mild and severe COVID-19 cases (5.2%, 27.3% and 35.5%; respectively). Interestingly, homozygous SS genotype elicited higher frequency among severe cases compared with mild or asymptomatic cases (22.6% vs. 0% and 5.2%). The more severe forms homozygous ZZ genotype vanished among asymptomatic and mild cases. This extensively illuminated that, severe COVID-19 patients have diminished A1AT response towards inflammation. Conclusion Two haplotypes (S) and (Z) alleles of A1AT have higher frequency and were clearly recognized among severe COVID-19 cases suggesting that SS and ZZ genotypes may be associated with an increased risk, while MM genotype may be protective against severe COVID-19 infection.