Alpha-1 antitrypsin deficiency severity and the risk of COVID-19: A Portuguese cohort

Abstract

Alpha-1 antitrypsin deficiency (AATD) is highly prevalent in Portugal. It is estimated that 1:5249 individuals have a ZZ genotype, and 1:281 have a SZ genotype [1]. Patients with AATD have recently been proposed as a susceptible population for COVID-19 and disease severity [2]. Data from an Italian registry of AATD revealed a geographical distribution of AATD similar to that of . A significant positive correlation was reported between the combined frequencies of the PI*SZ genotype in 67 countries and their reported COVID-19 mortality [4]. In January 2021, Portugal presented one of the highest incidences of SARS-CoV-2 infection and mortality in the world [5].Based on these assumptions and in an attempt to address the risk of COVID-19 infection in a Portuguese cohort, we gathered data from all AATD patients followed at Pulmonology consultation in our tertiary hospital in Porto. In Portugal there is a national COVID-19 status database where all SARS-CoV-2 swab results are registered. We checked all our AATD patients' SARS-CoV-2 positive results until the end of January 2021. AATD patients with a diagnosis of COVID-19 were compared with the remaining AATD cohort regarding pre-infection α1-antitrypsin

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

“…The Pi*ZZ genotype was significantly associated with greater COVID-19 incidence (33.3%, p = 0.012), followed by Pi*MS (14.3%) and Pi*SZ (10.0%). Moreover, the baseline AAT levels were significantly lower in patients with COVID-19 (42.9 ± 12.1 vs. 65.5 ± 2.8 mg/dL; p = 0.012) [ 31 ].…”

SARS-CoV-2 infection in alpha1-antitrypsin deficiency

“…The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is a leading cause of death in many countries and because of that, it is of utmost importance to identify subjects susceptible to a life-threatening SARS-CoV-2 infection in order to protect them and to prioritize them in vaccination programs. Several lines of evidence suggest that individuals with alpha1-antitrypsin deficiency (AATD) may constitute such a population 1 , 2 , 3 . AATD arises due to mutations in alpha1-antitrypsin (AAT) gene and represents the most prominent genetic predisposition to chronic obstructive pulmonary disease and emphysema 4 , 5 .…”

“…This finding is in line with their overall risk for lung-related mortality that is not substantially elevated 4 . On the other hand, individuals with severe AATD should remain cautious given that the current data are scarce and a small study from Portugal suggested an increased risk 1 .…”

Advances in the development of therapeutic strategies against COVID-19 and perspectives in the drug design for emerging SARS-CoV-2 variants

“…A statistical study based on 500,000 people shows that mild α1-Antitrypsin deficiency (AATD) genotypes were not associated with increased SARS-CoV-2 infection rates or fatalities [41] . For the lack of α1AT makes it easier to activate TMPRSS2, severe AATD patients may be susceptible to SARS-CoV-2 [42] , [43] . There have been four trials recruited or completed to test whether α1AT can be used for the treatment of COVID-19 patients [44] .…”