Abstract: 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.
