Do gene-environment interactions play a role in COVID-19 distribution? The case of Alpha-1 Antitrypsin, air pollution and COVID-19

  • Nicola Murgia | Section of Occupational Medicine, Respiratory Diseases and Toxicology, University of Perugia, Italy.
  • Angelo Guido Corsico Center for Diagnosis of Inherited α1-Antitrypsin Deficiency, Department of Internal Medicine and Therapeutics, Pneumology Unit, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Italy.
  • Gennaro D'Amato Division of Respiratory and Allergic Diseases, Department of Chest Diseases, High Specialty A. Cardarelli Hospital, and Medical School of Specialization in Respiratory Diseases, Federico II University of Naples, Italy.
  • Cara Nichole Maesano INSERM and Sorbonne University, Epidemiology of Allergic and Respiratory Diseases Department, IPLESP, Paris, France.
  • Arturo Tozzi Center for Nonlinear Science, Department of Physics, University of North Texas, Denton TX, United States.
  • Isabella Annesi Maesano INSERM and Sorbonne University, Epidemiology of Allergic and Respiratory Diseases Department, IPLESP, Paris; Desbrest Institute of Epidemiology and Public Health, INSERM and Montpellier University, Montpellier, France.


Background: Gene-environment interactions are relevant for several respiratory diseases. This communication raises the hypothesis that the severity of COVID-19, a complex disease where the individual response to the infection may play a significant role, could partly result from a gene-environment interaction between air-pollution and Alpha-1 Antitrypsin (AAT) genes.
Methods: To evaluate the impact of the AAT and air pollution interaction on COVID-19, we introduced an AAT*air pollution global risk score summing together, in each country, an air pollution score (ozone, nitrogen dioxide and fine particulate matter) and an AAT score (which sums the ranked frequency of MZ, SZ, MS). We compared this global score with the ranking of European countries in terms of death number per million persons.
Results: The ranking of the AAT*air pollution global risk score matched the ranking of the countries in terms of the observed COVID-19 deaths per 1M inhabitants namely in the case of the first European countries:  Belgium, UK, Spain, Italy, Sweden, France. We observed parallelism between the number of COVID deaths and the AAT*air pollution global risk in Europe. AAT anti-protease, immune-modulating and coagulation-modulating activities may explain this finding, although very speculatively.
Conclusions: Even if further studies taking into account genetic background, population density, temporal dynamics of individual epidemics, access to healthcare, social disparities and immunological response to SARS-CoV2 are needed, our preliminary observation, urges to open a discussion on gene-environment interactions in COVID-19.



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Conflict of interest statement
The authors declare that they have no competing interests, and all authors confirm accuracy. IAM is an Associate Editor of Multidisciplinary Respiratory Medicine, GDA is a member of the Editorial Board of Multidisciplinary Respiratory Medicine
AAT, COVID-19, environment, air pollution
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How to Cite
Murgia, N., Corsico, A. G., D’Amato, G., Maesano, C. N., Tozzi, A., & Annesi Maesano, I. (2021). Do gene-environment interactions play a role in COVID-19 distribution? The case of Alpha-1 Antitrypsin, air pollution and COVID-19. Multidisciplinary Respiratory Medicine, 16.