Methods

The association between A1AT deficiency and SARS-COV-2 was explored using data from the Spanish COalition to Unlock Research on host GEnetics (SCOURGE) study on COVID-19 (https://www. scourge-covid. org)(10), which included 11,939 COVID-19 patients treated in 34 hospitals and research centers of Spain between March and December 2020. Clinical data was entered into the Research Electronic Data Capture (REDCap) database and classified according to five levels of severity {asymptomatic; mild (with symptoms but without pulmonary infiltrates or need for oxygen therapy); moderate (with pulmonary infiltrates affecting< 50% of the lungs or need for supplemental oxygen therapy); severe (hospitalized patients meeting any of the following criteria: PaO 2< 65 mmHg or SaO 2< 90%; PaO 2/FiO 2< 300, SaO 2/FiO 2< 440; dyspnea; respiratory frequency≥ 22 bpm; or infiltrates affecting> 50% of the lungs); and critical [admission to the intensive care unit or need for mechanical ventilation (invasive or non-invasive)]}(11). REDCap is a secure web application designed to support data capture for research studies that enables the collection and management of demographic, epidemiological and clinical variables, along with the results of laboratory analyses and imaging studies. Additionally, samples from the general population (untested for COVID-19) were also included in some analyses, with a total of 3,437 samples from the national DNA Bank and 2,506 control samples from the Genome Research at Fundación ACE (GR@ ACE-Consortium). General population controls were obtained through the Spanish national blood service (Servicio Nacional de Sangre), which provides blood from unrelated adult subjects that had reported to have a Spanish origin and confirmed the absence of any personal or familial history of disease, including infectious diseases, cancer, hematologic, circulatory or endocrine diseases; mental or behavioral illnesses; or visual, hearing, respiratory, immunologic, bone, congenital, skin or digestive diseases.