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Covid, discovered a genetic factor that increases mortality

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Covid, discovered a genetic factor that increases mortality

The clinical outcomes of Covid19 are extremely heterogeneous, today we know some factors that can increase mortality: age, sex, presence of comorbidities. However, there are also silent genetic factors that can increase the risk of severe consequences in case of Sars-CoV2 infection.

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Our genetic code is defined by the union of our parents’ DNA. For each of our characters, for example the color of the eyes, we have at least 2 copies of the same gene (alleles, one of maternal origin and one paternal, the Mendelian rules establish how the different genes are expressed (black eyes are dominant over blue eyes for example However, there is a variability between the various alleles within the population, in fact for some genes there are several variants that slightly alter the function of that gene.

A well-known example is the gene that produces Apolipoprotein E (APOE), which exists in several variants within the world population: APOE2, APOE3 and APOE4. The most common form is the APOE3, in fact in 77.9% of the population there is at least one copy while the APOE4 in 13.7% and the APOE2 only in 8.4%.

People with Alzheimer’s have more APOE4

Alzheimer’s patients have a higher percentage of APOE4 than the general population, in fact about 37% of Alzheimer’s patients have this specific variant. The presence of the APOE4 variant in the Alzheimer’s population is not only coincidental: it has been observed that the APOE4 variant creates more favorable conditions for the development of neuro-degenerative diseases, such as Alzheimer’s. It should be emphasized that the presence of both APOE4 alleles is not a sufficient condition for the development of Alzheimer’s disease as it is a multi-factorial disease, therefore with not only genetic elements.

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The different APOE variants influence the mortality of Covid19

A team of researchers infected genetically modified mice with the Sars-Cov2 virus, the goal of the experiment was to understand if there is a correlation between mortality from Covid19 and the different variants of APOE. The experiment showed that mice with the APOE4 variant (that of Alzheimer’s) and to a lesser extent APOE2 have a higher risk of death in case of infection with Sars-CoV2.

APOE involved in the immune response

The researchers wondered the reason for this correlation and found that APOE is involved in the immune response, specifically they observed that APOE4 mice had a reduced immune response compared to APOE3 mice. A lower innate response could explain why some people, all other things being equal, experience a more severe disease than others. The researchers analyzed the frequency of APOE variants in the population and confirmed the correlation observed in mice, in fact, subjects with the APOE4 variant have a significantly higher risk of death than the other 2 variants.

Who has the APOE4 variant at risk of dying from Covid19?

The presence of the APOE4 variant alone is not able to determine the mortality of Covid19, in fact other factors have a greater weight in determining the outcome of the disease such as age, sex, presence of auto-antibodies and previous pathologies for example. Furthermore, there are protective genetic factors that, on the contrary, reduce the mortality of Covid19. Finally, the outcome of the disease is strongly influenced by the vaccination status, in fact we know that vaccines offer very high protection against death and serious consequences of the disease.

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New possible strategies

This study is very important at the epidemiological and pharmacological level: in the first case it helps us to understand how different populations, also from a genetic point of view, have responded to the pandemic and secondly because it opens the way to possible strategies to prevent severe Covid in some patients. at risk.

REF:

https://www.nature.com/articles/s41586-022-05344-2

https://www.lescienze.it/news/2018/06/04/news/alzheimer_apoe4_accumulazione_amiloide_microglia-4006189/

https://www.salute.eu/2022/08/22/news/covid_gravita_anziani_cause-362244452/

Aureliano Stingi, doctor in molecular biology works in the field of precision oncology. He collaborates with the World Health Organization in the battle against Covid19-themed fake news

Instagram: Aureliano _Turn it off Twitter: @AurelianoStingi

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