Correlation between α1-Antitrypsin Deficiency and SARS-CoV-2 Infection: Epidemiological Data and Pathogenetic Hypotheses

Abstract

The most common hereditary disorder in adults, α1-antitrypsin deficiency (AATD), is characterized by reduced plasma levels or the abnormal functioning of α1-antitrypsin (AAT), a major human blood serine protease inhibitor, which is encoded by the SERine Protein INhibitor-A1 (SERPINA1) gene and produced in the liver. Recently, it has been hypothesized that the geographic differences in COVID-19 infection and fatality rates may be partially explained by ethnic differences in SERPINA1 allele frequencies. In our review, we examined epidemiological data on the correlation between the distribution of AATD, SARS-CoV-2 infection, and COVID-19 mortality rates. Moreover, we described shared pathogenetic pathways that may provide a theoretical basis for our epidemiological findings. We also considered the potential use of AAT augmentation therapy in patients with COVID-19.

Systematic evaluation of plasma signaling cascades by functional proteomics approaches: SARS‐CoV‐2 infection as model

“…The treatments indicated in patients with COVID-19 are based on preventive anticoagulant therapies such as heparin and the use of corticosteroids such as dexamethasone as anti-inflammatory drugs [49,50], which agrees with the pattern of APRs described in this work.…”

“…In the case of pulmonary sepsis, it seems that the most significant variations are more focused on the coagulation cascade. The treatments indicated in patients with COVID‐19 are based on preventive anticoagulant therapies such as heparin and the use of corticosteroids such as dexamethasone as anti‐inflammatory drugs [49, 50], which agrees with the pattern of APRs described in this work. However, the administration of drugs with more specific targets on some APRs could lead to an improvement in the treatment of severe cases.…”

Low Prevalence of Mild Alpha-1-Antitrypsin Deficiency in Hospitalized COVID-19-Patients

“… 6–8 In addition, a recent review further highlighted theoretical pathogenic pathways in patients with AATD that could impact COVID-19-severity, including decreased inhibition of neutrophil extracellular traps, decreased inhibitory effect on thrombin and potentially an increase in thrombus formation. 9 …”