A global medical mystery is being aggressively pursued by medical researchers. The core issue is that a relatively small fraction of people despite high exposure to COVID have not gotten ill with COVID infection. Think of health workers in hospitals in contact with many seriously ill COVID patients. Also, members of households that stood out because unlike others in the home who got ill with COVID they did not get infected. The mystery is what explains how highly exposed individuals did not get ill with COVID infection.
There are two main ways of explaining resistance to COVID. One is that some people have strengthened their immune systems by any of a number of actions taken before or during the pandemic. For example, some may have elevated levels of vitamin D in their blood by taking high doses of supplements. The other explanation that appeals to medical researchers is that some people have a genetic makeup that gives them total defense against COVID infection,
It is necessary to eliminate people who got infected but were asymptomatic and also those who practiced many safe behaviors to avoid COVID exposure. The group that merits investigation is people who were definitely highly exposed to COVID but escaped infection.
A small fraction of Americans has escaped COVID infection. CDC uses a figure of 60% for those infected; while the Institute for Health Metrics and Evaluation at the University of Washington says that 76% have been infected. The remainder may have escaped exposure or been exposed but escaped infection. The latter people are the subject of the medical mystery.
A very good April 2022 article is titled "Can people be naturally immune or resistant to COVID-19?"
Here are some excerpts.More than two years into the COVID-19 pandemic... there have been some rare cases in which certain unvaccinated people seem to have been able to dodge the virus despite being repeatedly exposed to it. This has raised the question of whether it is possible that some people are simply immune or resistant to COVID-19 without having had the virus or a vaccine...
"It's been a hard thing to talk about publicly because you say things and then people go, 'Oh, that must be me, because I haven't been infected yet,' when in fact, you know, you may not have been infected because you just got lucky so far," Shane Crotty, a virologist and professor at the La Jolla Institute for Immunology, said...
A simple potential explanation is that some of those who have not gotten COVID have just been lucky, Crotty said. It could also be that their behaviors, like wearing a mask properly or avoiding certain situations that would put them at risk of contracting the disease, may have kept them protected...
But scientifically speaking, Crotty said, there are two potential explanations that may explain why some people could have a much greater resistance to SARS-CoV-2, the virus that causes COVID-19, than others. One idea is that some people may clear the virus rapidly, before it reaches detectable levels, due to existing immunity to other coronaviruses like those that cause the common cold...
"The main idea there would be that there are T-cell responses that certain people happen to make in response to certain coronaviruses they've had before, that may provide a degree of protection that other people just don't happen to have," Crotty said...
Another study of health care workers in England published in November evaluated a group of U.K. health care workers during the first wave of the pandemic who were exposed to the virus but didn't develop COVID-19. Researchers found that the presence of cross-reactive memory T cells among some of the participants contributed to "the rapid clearance of SARS-CoV-2 and other coronavirus infections."
But, Crotty said, this is something that scientists need to continue to study. "There's no study that just nails it because it's a very hard study to do," the professor said. He and his team are determined to find some answers; they have enrolled people who have never been infected and have never been vaccinated, and they plan on monitoring them over time...
Another potential explanation for COVID-19 resistance is that some people may have innate immunity, meaning that there are genetic factors that protect them from a SARS-CoV-2 infection.
Neville Sanjana, an assistant professor of biology at New York University and a core faculty member at New York Genome Center, has been studying potential genetic factors underlying COVID-19 resistance. He says one place of interest that may provide some answers is the virus's entry mechanism, which in the case of SARS-CoV-2 is a specific protein that allows the virus to infect human cells called the angiotensin-converting enzyme 2, or ACE2 receptor.
Mutations in the ACE2 receptor, Sanjana says, will make it harder for the virus to get in. Viral resistance due to these types of mutations has already been demonstrated against other viruses such as HIV. "We know that there's an entry receptor similar to the one that we've identified for SARS-CoV-2, but it's a different gene," he said. "With HIV, the virus that causes AIDS, the entry receptor is CCR5, and we know that there are some people who naturally have a mutation that gets rid of CCR5 " and this leaves them virtually immune," he added.
Besides studying possible mutations in the entry receptor, Sanjana said, scientists have been looking at other genetic variations across the human genome. "The human genome has about 20,000 genes in it, and we really don't know which of those genes might influence key cells like the cells in our airway epithelium or in our lungs, which we think is the route of entry for SARS-CoV-2," he said, adding that some of those genes might make people more or less vulnerable to COVID-19.
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