Two genetic mutations responsible for the low production, and consequent deficiency, of a protein called Alpha 1 antitrypsin (AAT or A1AT), which has a protective action on the lungs and liver in inflammatory processes, may be associated with an increased risk of severe disease and mortality from covid-19.
The warning comes from a group of Israeli researchers from the University of Tel Aviv, led by David Gurwitz, Noam Shomron and Guy Shapira, who has just published the results of his research in the scientific journal FASEB Journal, from the Federation of American Societies for Experimental Biology.
“Our analysis reveals a strong correlation between these mutations and serious illness and increased mortality from covid-19,” say the researchers cited in a statement from their university.
If this cause-effect relationship is definitively confirmed by conducting clinical studies, researchers at the University of Tel Aviv believe that this opens the door to a new strategy against the pandemic: one that involves widespread testing of populations for mutations concerned and the protection in particular of persons identified as being at risk, as they carry the mutations.
Study covered almost 70 countries
The team collected data from 67 countries for the prevalence of the two genetic mutations, called PiZ and PiS, that occur in the SERPINA 1 gene, which encodes the AAT protein. And then he compared that information with coronavirus mortality data in the same 67 countries, finding that, even though the differences in health measures taken and other factors such as age are weighted, there is a strong correlation between the higher prevalence of the two mutations and increased mortality by covid-19.
This is very clear, for example, for the United States, the United Kingdom, Belgium, Spain or Italy, among others, as the authors emphasize.
Instead, the team also found that in many countries in Africa or Southeast Asia, where the prevalence of those two mutations is very low, mortality rates from covid-19 have been similarly lower – at least to date.
Test the population and protect those in need
Other studies, notably in Italy, had already shown that deficiency in the AAT protein was associated with more severe cases and a higher mortality rate due to covid-19. So the researchers at the University of Tel Aviv decided to follow that lead.
The data they collected shows a clear trend. For example, in Belgium, where 17 out of every thousand people have the PiZ mutation (the most frequent of the two evaluated in the study), mortality is 860 per million inhabitants. And in Spain, where there are the same 17 people in every thousand with the same mutation, the mortality figures for covid-19 do not go far: 640 per million inhabitants.
The trend is repeated in different countries. In the United States, where 15 in every thousand inhabitants carry the mutation, the mortality due to the coronavirus is 590 per million; in the United Kingdom, the mutation rate is 14 per thousand, and covid-19 mortality is 617 per million. And so on. In Italy the numbers are 13 and 620 respectively, and in Sweden 13 and 570.
Portugal, also evaluated in the study, and with a prevalence of that mutation identical to that of Spain, has a lower number of deaths per million (190), a situation that is not specifically addressed by the study.
The explanation may be related to other factors, such as the disparity in the measures taken by the countries, which is generally referred to by the researchers. In the case of Portugal, the measures taken early in the pandemic, with rapid and widespread confinement, may have been the key element in preventing a greater number of contagions and, consequently, of a heavier mortality at the moment.
Corroborating the pattern, the results of the study show that in countries like Japan, where mortality does not exceed 12 per million, the prevalence of those mutations is considered negligible – and the same for other countries, such as South Korea, Taiwan, Thailand , Vietnam or China itself.
In view of these results, the authors propose that in-depth studies on the issue should now be carried out and that, if this relationship is confirmed, move towards concrete measures.
“We call on the scientific community to test our hypothesis by studying clinical data, and on policy makers in each country to set up population surveys to identify people with the mutations,” write the researchers.
“These people should be given priority to administer vaccines against covid-19 when they are approved and, until then, they should be informed that they are at high risk and advised to remain in social isolation,” conclude the researchers.
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