Why Do Some People Escape Infection That Sickens Others?

Even in the conditions of COVID-19 pandemic, we have seen cases when whole families get sick except for one or two fortunate family members. And at so-called superspreader events that infect many, a lucky few typically walk away with their health intact. Did the virus never enter their bodies? Or do some people have a natural resistance to pathogens they've never been exposed to before encoded in their genes?

The study of innate resistance is a very important issue. This is more than just scientific curiosity, and studying how it works can be a path to curb future outbreaks.. Understanding these different forms of resistance can help scientists develop vaccines and treatments.

Spaan is part of an international effort to identify genetic variations that spare people from becoming infected with SARS-CoV-2, the virus that causes COVID-19.

However, SARC-COV-2 is not the only infection in the history of science against which certain groups of people have a natural resistance barrier. Perhaps the strongest example of how odd genes of just a few people can inspire treatments to help many comes from research on the human immunodeficiency virus (HIV).

Interesting facts

In the mid-1990s, several groups of researchers independently identified a mutation in a gene called CCR5 linked to resistance to HIV infection.

The gene encodes a protein on the surface of some white blood cells that help set up the movement of other immune cells to fight infections. HIV, meanwhile, uses the CCR5 protein to help it enter the white blood cells that it infects.

The mutation, known as delta 32, results in a shorter than usual protein that doesn't reach the surface of the cell. People who carry two copies of the delta 32 forms of CCR5 do not have any CCR5 protein on the outside of their white blood cells.

Researchers, led by molecular immunologist Philip Murphy, MD, at the National Institute of Allergy and Infectious Diseases in Bethesda, MD, showed in 1997 that people with two copies of the mutation were unusually common among a group of men who were at especially high risk of HIV exposure, but had never contracted the virus. And out of more than 700 HIV-positive people, none carried two copies of CCR5 delta 32.

Pharmaceutical companies used these insights to develop drugs to block CCR5 and delay the development of AIDS. For instance, the drug maraviroc, marketed by Pfizer, was approved for use in HIV-positive people in 2007.

An interesting example of natural resistance is known in tuberculosis, which in the first years of its existence led to mass mortality. Caused by Mycobacterium tuberculosis.

Some 85%-95% of people with intact immune systems who are infected with TB control the infection and never get active lung disease. The subjects of the study were individuals who lived or worked with infected people and were at high risk of infection.

Covid-19

Groups of researchers studied resistance to COVID-19 infection, suggesting that reduced risk of contracting the virus is tied to certain blood group factors. People with Type O blood appear to be at a slightly reduced risk of infection, for example.

But the studies done so far are designed to find common genetic variations, which generally have a small effect on resistance. Now, genetic researchers are launching an effort to identify genetic resistance factors with a big effect, even if they are vanishingly rare.

The group plans to study individuals who were at high risk for infection but did not become ill. Genome sequencing of these groups and additional laboratory studies are planned to determine the cause of what caused the virus resistance.

Their research is inspired by existing examples. Modern technologies simplify research and make it intense.

The diversity of Covid-19 mutational strains indicates that it will be among us for a long time, which highlights the need for these studies.

source: medscape.com