Genetic factors that naturally protect against severe COVID-19

Genetic factors that naturally protect against severe COVID-19

Brazilian investigators have worked to identify certain genetic factors that may grant people protection against COVID-19 infection or severe disease progression.

In the study, investigators looked at 87 “super-old” adults (90 years and older) who were unvaccinated and had mild or no symptoms of COVID-19 after confirmed infection. The average age of this group was 94 years old, one woman, aged 114, was the oldest person documented to have recovered from COVID-19 in Brazil.

This primary cohort was compared to a group of 55 people under the age of 60 with severe or fatal COVID-19 disease, as well as a general population of older people. The researchers performed whole-exome sequencing and in-depth analysis of polymorphisms in the major histocompatibility complex (MHC) of chromosome 6, a region associated with COVID-19 outcome.

They found that the resilient super-elderly group had a higher frequency of certain missense variants in the MUC22 embarrassed. This was one of the strongest signals in their CMH region, compared to the younger severe COVID-19 group and the general older control population. Specifically, this study found missense variant rs62399430 to MUC22 was twice as common in the resilient super-old (p = 0.00002).

The MUC22 The gene is part of the mucin family and is associated with the production of mucus. Mucus serves to protect and lubricate the airways, but an overproduction of mucus leads to the lung inflammation commonly seen in patients with severe COVID-19.

It is well documented that the basal pro-inflammatory state in the elderly may increase susceptibility to severe COVID-19, the researchers concluded that MUC22 has the potential to provide crucial protection against severe COVID-19 by inhibiting the overactive immune response typically seen in older adults.

The study authors also hypothesized that higher expression of miR-6891-5p associated with all MUC22 protective variants may serve to reduce viral reproduction in cells, resulting in less severe COVID-19 symptoms during infection.

“If we can truly prove that certain genes promote resistance to SARS-CoV-2, perhaps the same is true for other viruses,” said Mayana Zatz, professor of human and medical genetics at the Institute of Biosciences and Biological Sciences from the University of São Paulo. a lead author of the studies.

“Further research can then be based on these findings to try to understand the mechanisms underlying this resilience and develop drugs that improve protection against viral infections.”

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