A new review reports that α1-proteinase inhibitor (α1-PI) therapy, already used for patients with alpha-1 antitrypsin deficiency (AATD), may be effective against poor outcomes from coronavirus disease 2019 (COVID-19) infection, which appear to be more severe among patients with AATD.

The study, published in Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry, suggests that α1-PI could be a diagnostic marker of poor prognosis in COVID-19.

“α1-PI drugs are already used for treating patients with genetic α1-antitrypsin deficiency,” the authors wrote. “α1-PI has antiviral, anti-inflammatory, anticoagulant and antiapoptotic properties, which makes it a potential drug for targeted therapy and is a basis for translational studies under the conditions of hyperproteolysis, in particular, in case of COVID-19.”


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α1-PI is naturally present in serum, and increased concentrations exert anti-inflammatory and antiviral effects as well as tissue-protective properties. It has been shown to inhibit the penetration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in human cells.

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Given that proteinase activation is key to infection by SARS-CoV-2, it has been hypothesized that patients with AATD and reduced proteinase levels would be more susceptible to poor outcomes from COVID-19. The authors speculate that the development of α1-PIs, such as those used for AATD, might also be effective against COVID-19 in these patients and in those with a nongenetic or acquired form of α1-PI deficiency.

Further supporting this hypothesis, 4 clinical trials employing α1-PI therapies for patients with COVID-19 are currently underway.

However, the authors caution that it is unknown whether all patients will experience an anti-COVID-19 effect from α1-PI treatments, and there has been no study yet of the association between α1-PI use and complications or outcomes. Further investigation of the role of α1-PI in COVID-19 infections is needed.

Reference

Akbasheva OE, Spirina LV, Dyakov DA, Masunova NV. Proteolysis and deficiency of α1-proteinase inhibitor in SARS-CoV-2 infection. Biochem Mosc Suppl B Biomed Chem. 2022;16(4):271-291. doi:10.1134/S1990750822040035