corona virus-Covid19

COVID-19: Genetics Helps Explain National Differences in Infection Rate, Severity and Mortality Interview with:
David Gurwitz, PhD

Associate Professor
Department of Human Molecular Genetics and Biochemistry
Sackler Faculty of Medicine
Tel-Aviv University, Tel-Aviv Israel What is the background for this study?

Response: We closely followed the news on COVID-19 epidemiology since it was declared a pandemic, and were puzzled by the low fatality rates reported in nearly all East Asian countries, even that clearly this was in part due to fast response; for example, Taiwan remains the best example for combatting the pandemic.

My past research on serpins (serine protease inhibitors) made me wonder if ethnic differences in some of them are in part related to the relatively low COVID-19 morbidities and fatalities, as serine proteases, in particular TMPPRSS2, are strongly implicated in the SARS-CoV-2 respiratory track cell entry and infection.

Additionally, serine proteases such as neutrophil elastase are highly implicated in inflammatory tissue damage. Guy Shapira, a graduate student of my colleague Professor Noam Shomron, examined mutation records in different ethnic groups for the entire human serpin gene family. He came up with the findings we report regarding a close correlation between national records of the frequencies of the two mutations PiZ and PiS, underlying alpha-1 antitrypsin deficiency, in 67 countries on the global scale, and the current COVID-19 fatalities in the same 67 countries. What should readers take away from your report?

Response: Our message is clearly summarized in our closing statements. We urge the biomedical community to study our hypothesis so that it can be validated or refuted. If validated, it has far-reaching consequences for protecting individuals likely to have severe COVID-19 outcomes, including fatal outcomes. What recommendations do you have for future research as a result of this work?

Response: If validated by clinical studies, as we state in our article, population-wide screening efforts should be considered for identifying individuals who are carriers of the PiZ or PiS mutations (the most common mutations causing  alpha-1 antitrypsin deficiency).

Next, such individuals should be advised to observe strict social distancing, until a vaccine is approved. Once a vaccine becomes available, they should be among those prioritized to be offered a vaccine, while explaining to them that they might be at higher risk than the general population in their country.

We are aware that some people will object a vaccine due to fears of side effects, or fears of conspiracy theories circulated on social media. Therefore, the risk should be assessed, and if found true, should be explained with the highest possible transparency by national healthcare providers Is there anything else you would like to add?

Response: We do not have any conflict of interest. We are driven by the wish to reduce the high health and economic burden of COVID-19.

We are also concerned that even once a COVID-19 vaccine is approved, the global supply will not be able to meet the global demand, and in low income countries, and poor people in any country without national health insurance, may be left behind. 


Shapira, G, Shomron, N, Gurwitz, D. Ethnic differences in alpha‐1 antitrypsin deficiency allele frequencies may partially explain national differences in COVID‐19 fatality rates. The FASEB Journal. 2020; 00: 1– 6.



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Last Updated on September 25, 2020 by Marie Benz MD FAAD