Ethnic differences in alpha‐1 antitrypsin deficiency allele frequencies may partially explain national differences in COVID‐19 fatality rates

Shapira, Guy; Shomron, Noam; Genevieve, David

doi:10.1096/fj.202002097

Cited by 49 publications

(50 citation statements)

References 29 publications

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“… 7 A significant positive correlation was reported between the combined frequencies of the PI*SZ genotype in 67 countries and their reported COVID‐19 mortality. 8 These observations are intriguing, but interpretations are challenged by many confounding factors (eg, socioeconomic status and ethnicity) and further investigations are required.…”

mentioning

confidence: 99%

α1-Antitrypsin deficiency and the risk of COVID-19: an urgent call to action

Yang

Chapman

Wong

et al. 2021

The Lancet Respiratory Medicine

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mentioning

confidence: 99%

α1-Antitrypsin deficiency and the risk of COVID-19: an urgent call to action

Yang

Chapman

Wong

et al. 2021

The Lancet Respiratory Medicine

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“…Moreover, the underlying mechanisms of A1AT on anti-viral, anti-inflammation, anti-cell death, antiproteases, and anti-coagulation should be studied. Furthermore, Shapira et al found a significant positive correlation between the combined frequencies of the A1AT deficiency alleles in 67 countries and their reported COVID-19 mortality rates (Shapira et al, 2020). Given the important role that A1AT plays in the prevention and treatment of the pathological process of SARS-CoV-2 infection, patients with A1AT deficiency may be more susceptible to SARS-CoV-2 viral infection with worse clinical outcomes.…”

Section: Research Agendamentioning

confidence: 99%

Alpha-1 Antitrypsin for COVID-19 Treatment: Dual Role in Antiviral Infection and Anti-Inflammation

2020

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Many drugs have been approved for clinical trials for the treatment of COVID-19 disease, focusing on either antiviral or anti-inflammatory approaches. Combining antiviral and anti-inflammatory drugs or therapies together may be more effective. Human alpha-1 antitrypsin (A1AT) is a blood circulating glycoprotein that is best known as a protease inhibitor. It has been used to treat emphysema patients with A1AT deficiency for decades. We and others have demonstrated its role in reducing acute lung injury by inhibiting inflammation, cell death, coagulation, and neutrophil elastase activation. Recently, A1AT has been found to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by inhibiting transmembrane serine protease 2 (TMPRSS2), a protease involved in the entry of SARS-CoV-2 into host cells. This dual role of both antiviral infection and anti-inflammation makes A1AT a unique and excellent candidate for COVID-19 treatment. Three clinical trials of A1AT for COVID-19 treatment have recently been approved in several countries. It is important to determine whether A1AT can prevent the progress from moderate to severe lung injury and eventually to be used to treat COVID-19 patients with acute respiratory distress syndrome.

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“…AAT impedes SARS-CoV2 cellular entry and prevents the main clinical complications of severe COVID-19, such as acute inflammation and acute respiratory failure [41]. Therefore, it could be hypothesized that the geographical distribution of pathogenic variants of AAT protein is to a certain extent linked to differences in COVID-19 epidemiology and severity throughout Europe [42]. Furthermore, a Food and Drug Administration-approved AAT augmentation therapy, used for patients with AATD and emphysema, has potential value in managing SARS-CoV-2 infection and an aberrant immune response.…”

Section: Protease Complexed and Cleaved Forms Of Aatmentioning

confidence: 99%

Post-Translational Modifications of Circulating Alpha-1-Antitrypsin Protein

Lechowicz¹,

Rudzinski²,

Jezela‐Stanek³

et al. 2020

IJMS

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Alpha-1-antitrypsin (AAT), an acute-phase protein encoded by the SERPINA1 gene, is a member of the serine protease inhibitor (SERPIN) superfamily. Its primary function is to protect tissues from enzymes released during inflammation, such as neutrophil elastase and proteinase 3. In addition to its antiprotease activity, AAT interacts with numerous other substances and has various functions, mainly arising from the conformational flexibility of normal variants of AAT. Therefore, AAT has diverse biological functions and plays a role in various pathophysiological processes. This review discusses major molecular forms of AAT, including complex, cleaved, glycosylated, oxidized, and S-nitrosylated forms, in terms of their origin and function.

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Ethnic differences in alpha‐1 antitrypsin deficiency allele frequencies may partially explain national differences in COVID‐19 fatality rates

Abstract: This article was fast-tracked under a recently instituted interim policy in which editors may, at their discretion, accept coronavirus-related manuscripts submitted for the Review, Perspectives, and Hypotheses categories without additional review.

Cited by 49 publications

References 29 publications

α1-Antitrypsin deficiency and the risk of COVID-19: an urgent call to action

α1-Antitrypsin deficiency and the risk of COVID-19: an urgent call to action

Alpha-1 Antitrypsin for COVID-19 Treatment: Dual Role in Antiviral Infection and Anti-Inflammation

Post-Translational Modifications of Circulating Alpha-1-Antitrypsin Protein

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