Correlation between α1-Antitrypsin Deficiency and SARS-CoV-2 Infection: Epidemiological Data and Pathogenetic Hypotheses

The most common hereditary disorder in adults, alpha 1-antitrypsin deficiency (AATD), is characterized by reduced plasma levels or the abnormal functioning of alpha 1-antitrypsin (AAT), a major human blood serine protease inhibitor, which is encoded by the SERine Protein INhibitor-A1 (SERPINA1) gene and produced in the liver. Recently, it has been hypothesized that the geographic differences in COVID-19 infection and fatality rates may be partially explained by ethnic differences in SERPINA1 allele frequencies. In our review, we examined epidemiological data on the correlation between the distribution of AATD, SARS-CoV-2 infection, and COVID-19 mortality rates. Moreover, we described shared pathogenetic pathways that may provide a theoretical basis for our epidemiological findings. We also considered the potential use of AAT augmentation therapy in patients with COVID-19.

Automated summary

This review examines the correlation between alpha 1-antitrypsin deficiency, SARS-CoV-2 infection, and COVID-19 mortality rates, suggesting that ethnic differences in SERPINA1 allele frequencies may partially explain the geographic disparities. Shared pathogenetic pathways are also discussed as theoretical basis for the epidemiological findings, along with the potential use of AAT augmentation therapy in patients with COVID-19.