Patients with alpha-1 antitrypsin deficiency (AATD) should be included in COVID-19 vaccine clinical trials, according to researchers in a new study published in the European Journal of Human Genetics.

“We believe that re-evaluation of the COVID-19 vaccine safety and immunogenicity in AATD patients will be fundamental to improving health outcomes in this high-risk population,” Chengliang Yang, from the Prevention of Organ Failure Centre of Excellence in Vancouver, Canada, and the coauthors wrote.

The alpha-1 antitrypsin protein, which is deficient in patients with AATD, plays a crucial role in protecting lung tissue from neutrophil elastase, which is secreted by macrophages and neutrophils in the presence of infection to destroy pathogens. However, neutrophil elastase can also damage the host tissue and lead to symptoms consistent with acute lung injury.

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Recent evidence suggests that alpha-1 antitrypsin also plays a crucial role in preventing SARS-CoV-2 infection, and therefore patients with AATD may be at a higher risk of being infected and developing COVID-19.

Moreover, the Alpha-1 Foundation reported that more than 32% of patients with AATD have been hospitalized or required critical care due to COVID-19; this is almost twice as many hospitalizations as the general public. The evidence also suggests that alpha-1 antitrypsin could be a promising therapeutic option for patients with COVID-19.

Patients with AATD may derive little benefit from the current vaccines available. However, no data are available since they have not been included in current clinical trials testing the vaccines. It is therefore important to conduct studies to evaluate the safety, immunogenicity, and efficacy of COVID-19 vaccines in patients with AATD.

“Re-evaluation of the COVID-19 vaccine safety and immunogenicity will further promote informed decision-making for vaccination in AATD individuals and contribute to reduce morbidity and mortality from COVID-19 infection,” the researchers concluded.


Yang C, Zhao H, Tebbutt SJ. Leave no one behind: inclusion of alpha-1 antitrypsin deficiency patients in COVID-19 vaccine trials. Eur J Hum Genet. Published online January 28, 2022. doi:10.1038/s41431-022-01047-4