Epidemiological correlation between COVID-19 epidemic and prevalence of α-1 antitrypsin deficiency in the world

Abstract

Among 68 countries in the world, severity of the COVID-19 epidemic was correlated with the prevalence of α-1 antitrypsin (AAT) deficiency. For the severe variant, PI*Z, the correlation coefficient (CC) was 0.8584 for the number of patients and 0.8713 for the number of deaths. For the milder variant, PI*S, it was 0.5818 and 0.6326, respectively. In Japan, the number of patients and deaths correlated with the population size with a CC of 0.6667 and 0.7074 respectively, and was proportional to the population size to the power of 1.65 and 1.54. The prevalence of AAT deficiency also correlated with the epidemiological pattern of COVID-19. In countries with high prevalence of AAT deficiency, after the initial rise, the daily number of patients and that of deaths ran parallel at a high level for more than 6 months without sign of abatement. In countries with a low prevalence of AAT deficiency, after the first wave of the epidemic, the number of the deaths decreased continuously while the number of patients remained the same or even increased resulting in a decreasing case-fatality rate. When the cumulative number of deaths was plotted on the y-axis against the cumulative number of patients on the x-axis, plots fell on a straight line in countries with a high prevalence of AAT deficiency; while in countries with low a prevalence of AAT deficiency, a break appeared, after which the plots fell on flatter slope indicating decreasing case-fatality rate. The observation suggests emergence of an attenuated variant in countries with a low prevalence of AAT deficiency.

Does Genetic Predisposition Contribute to the Exacerbation of COVID-19 Symptoms in Individuals with Comorbidities and Explain the Huge Mortality Disparity between the East and the West?

“…The pathomechanisms of comorbidities are closely related to chronic inflammation, and severe COVID-19 is characterized by an excessive inflammatory response, such as a cytokine storm. We and others have shown that some gene mutations, such as the ACE1 DD genotype and AAT-deficient alleles, may contribute to geographical disparities in COVID-19 severity and mortality [ 7 , 8 , 9 , 11 , 12 , 13 ]. Patients with several comorbidities experience more severe COVID-19 symptoms than patients without the ACE1 DD genotype or AAT-deficiency.…”

“…By contrast, there are data that suggest a role for AAT in preventing the exacerbation of COVID-19 [ 11 , 12 , 13 , 94 ]. When the SARS-CoV-2 spike (S) protein binds to the ACE2 receptor, it is coupled with the membrane protein TPMRSS2 and the endosomal cysteine proteases cathepsin B and L (CatB/L) [ 22 ].…”

“…Hatami et al also showed, in their meta-regression analysis, that ACE1 I/D polymorphism may affect COVID-19 recovery rate worldwide [ 10 ]. In addition, AAT-deficient alleles may contribute to national and global differences in COVID-19 infections and their associated severity and mortality [ 11 , 12 , 13 ]. As of the end of February, 2021, the numbers of deaths per million in Europe and the Americas were about 43 and 21 times higher than that in East Asia, respectively (data derived from the WHO Coronavirus Disease (COVID-19) Dashboard, 49T ) (accessed on 25 February 2021).…”

Insights into the potential role of alpha1‐antitrypsin in COVID‐19 patients: Mechanisms, current update, and future perspectives

“…With the mounting evidence of possible association between AATD and COVID‐19, 9 the logic consequence has been to validate if COVID‐19 patients could benefit from AAT supplementary therapy. Being an FDA‐approved drug with a remarkable clinical safety record, 10 AAT is currently tested in three registered interventional clinical trials as summarized in Table 2.…”

Immunological aspects of Alpha 1 Antitrypsin in COVID-19 infection among the Populace and Pregnant Women

“…Preclinical trials describe the gain in multiple sclerosis, rheumatoid arthritis, type 2 diabetes, acute myocardial infarction, and stroke. Being a hereditary disease, AATD has a geographic variation, with the greatest incidence rate in northern Italy, Spain, and Iran (13,14).…”