Epidemiological studies have revealed that patients with alpha-1 antitrypsin deficiency (AATD) have a larger population in geographic areas which report a higher incidence of COVID-19 and mortality, according to a study published in the Journal of Clinical Medicine.

The geographical overlap between AATD patients and patients with COVID-19 suggests that there may be an association between the 2 diseases.

“The most common hereditary disorder in adults, [AATD], is characterized by reduced plasma levels or the abnormal functioning of α1-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,” Vianello and colleagues wrote.

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It has been further speculated that the disparity between geographic differences in COVID-19 infection and fatality rates could be explained by ethnic differences in SERPINA1 allele frequencies. “We examined epidemiological data on the correlation between the distribution of AATD, SARS-CoV-2 infection, and COVID-19 mortality rates,” the researchers wrote.

Based on the extensive range of data, the research team discovered a significant correlation between the frequency of Pi*Z and Pi*S alleles and mortality rates during the COVID-19 pandemic in 67 countries.

A potentially surprising result was that AAT could promote the host cell entry of the 614G virus by enhancing the spike protein and the inhibition of neutrophil elastase. Since AATD is more prevalent in North America and Europe, this could explain why the SARS-CoV-2 subtype 614G spread more easily there than in East Asian countries, for example. 

The researchers also identified a higher rate of COVID-19 infection in patients with AATD, compared to the control, while patients with severe COVID-19 had a relative risk of 8.8 for symptomatic COVID-19 compared to the control. 

“In conclusion, most epidemiological observations agree that there is a correlation between the SARS-CoV-2 epidemic, the clinical severity of COVID-19, and the prevalence of AATD,” the research team wrote.


Vianello A, Guarnieri G, Braccioni F, et al. Correlation between α1-antitrypsin deficiency and SARS-CoV-2 infection: epidemiological data and pathogenetic hypothesesJ Clin Med. Published online September 29, 2021. doi:10.3390/jcm10194493