Author Interviews, COVID -19 Coronavirus, FASEB, Genetic Research / 25.09.2020
COVID-19: Genetics Helps Explain National Differences in Infection Rate, Severity and Mortality
MedicalResearch.com Interview with:
David Gurwitz, PhD
Associate Professor
Department of Human Molecular Genetics and Biochemistry
Sackler Faculty of Medicine
Tel-Aviv University, Tel-Aviv Israel
MedicalResearch.com: 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.
Dr. David Katz[/caption]
MedicalResearch.com Interview with:
David L. Katz, MD, MPH, FACPM, FACP, FACLM
Director, Yale University Prevention Research Center
Griffin Hospital
President, American College of Lifestyle Medicine
Founder, True Health Initiative
Medical Research: What is the background for this study? What are the main findings?
Dr. Katz: the evidence that nuts in general, and walnuts in particular, have health promoting properties is vast and conclusive. In our own prior research, we have shown that daily ingestion of walnuts ameliorates overall cardiac risk in type 2 diabetics (
Dr. Wopereis[/caption]
MedicalResearch.com Interview with:
Suzan Wopereis, Ph.D.
TNO, Microbiology and Systems Biology Group
Zeist, The Netherlands
Medical Research: What is the background for this study? What are the main findings?
Dr. Wopereis: For the first time we could demonstrate the very subtle start of negative health effects caused by a high calorie snack diet in healthy men. We already knew about the negative consequences of such diets from so called epidemiologic studies. In such studies, scientists compare large populations (thousands of people) to better understand disease development. For example, by comparing obese populations to a lean population, scientists could define various steps in the disease development related to obesity, like high cholesterol, onset of inflammation, high blood pressure, high glucose, etc. Yet, the early deviations from health were difficult to study because human metabolism (the way we digest and metabolize our meals from a biochemical viewpoint) is very flexible and able to efficiently deal with all kinds of daily stressors, such as a meal or intensive exercise. So, at TNO we decided to exploit this flexibility by giving our healthy volunteers a ‘challenge test’, in the form of a high-fat milkshake. Next, we studied how multiple aspects of their metabolism react to such a challenge test. We showed that a snack diet for 4 weeks reduced many aspects of flexibility of our healthy men, thus indicating very early changes in health. Both the high-fat challenge test and the integral study of many different outcomes form a novel approach of what “healthy” really means.
In the study we used two groups of male volunteers. One group of 10 healthy male volunteers and one group of 9 male volunteers with Metabolic Syndrome, who had a combination of 2 or more risk factors that raises your risk for heart disease and other health problems (unhealthy cholesterol levels, high blood pressure, high blood sugar, high blood lipids, and abdominal fat). In other words, subjects with Metabolic Syndrome have a suboptimal health condition. Both groups received a high-fat milk-shake, and before and up to 8 hours after consumption of this metabolic challenge-test, blood samples were taken. In these blood samples, 61 different biomarkers were measured, such as cholesterol and blood sugar. These 61 biomarkers were used for a thorough health assessment of these 2 groups in response to the challenge test. We noted that biochemical processes related to sugar metabolism, fat metabolism and inflammation function abnormal in subjects with Metabolic Syndrome. The next step was to provide the 10 healthy male volunteers with a snack diet for 4 weeks. On top of their normal diet they had to consume an additional 1300 kcal per day, in the form of sweets and savory products such as candy bars, tarts, peanuts, and crisps. After these 4 weeks the response of the same 61 biomarkers to the challenge test was evaluated. Here, we observed that signaling molecules such as hormones regulating the control of sugar and fat metabolism and inflammation were changed, resembling the very subtle start of negative health effects. Without the use of the challenge test, we would not have been able to observe that even this short period of overfeeding induces changes in the metabolism of healthy people that resemble what happens in people with metabolic syndrome.
