COVID-19 infection in severe Alpha 1-antitrypsin deficiency: Looking for a rationale

Respir Med. 2021 Jul;183:106440. doi: 10.1016/j.rmed.2021.106440. Epub 2021 Apr 30.


The clinical manifestations of COVID-19 are heterogeneous: 46.4% of patients admitted into hospital reported to have at least one comorbidity. Comorbidities such as COPD, diabetes, hypertension and malignancy predispose patients with Covid-19 to adverse clinical outcomes. Alpha 1-antitrypsin deficiency (AATD) is a genetic disorder caused by pathological mutation(s) in the SERPINA1 gene resulting in an imbalance in proteinase activity which may lead to premature emphysema and COPD. Our aim was to investigate whether people with severe AAT deficiency (AATD) have an increased risk of (severe) COVID-19 infection. We collected data on COVID-19 symptoms, laboratory-confirmed infection, hospitalization and treatment by means of a telephone survey, directly administered to Italian severe AATD subjects in May 2020. We then compared our findings with data collected by the Istituto Superiore di Sanità on the total population in Italy during the same period. We found an higher frequency of SARS-CoV-2 infection in our cohort (3.8%) compared to national data regarding infection, thus giving severe AATD a relative risk of 8. 8 (95%CI 5.1-20,0; p<0.0001) for symptomatic SARS-CoV-2 infection. Moreover, the relative risk (RR) was higher in AATD patients with pre-existing lung diseases (RR 13.9; 95%CI 8.0-33.6; p<0.001), but with a similar death rate (1 in 8, 12.5%) compared to the general population (13.9%; RR 0.9). These preliminary findings highlight the importance of close surveillance in the spread of COVID-19 in patients with severe AATD and underlines the need for further studies into the role of the antiprotease shield in preventing SARS-Cov-2 infection.

Keywords: Alpha1-antitrypsin; COVID-19; Infectious disease; Rare disease.

Publication types

  • Review

MeSH terms

  • Biomarkers / blood
  • COVID-19 / blood
  • COVID-19 / epidemiology*
  • Comorbidity
  • Global Health
  • Humans
  • Pandemics*
  • Peptide Hydrolases / blood
  • SARS-CoV-2*
  • Severity of Illness Index
  • alpha 1-Antitrypsin Deficiency / blood
  • alpha 1-Antitrypsin Deficiency / epidemiology*


  • Biomarkers
  • Peptide Hydrolases