Why do some people get Covid when others don't? Here’s what we know so far

One of the great mysteries of the Covid-19 pandemic — and one that infectious disease specialists are still looking into — is why some people get Covid and others don't while being equally exposed to the virus.

Many of us know entire households who caught Covid and had to isolate over the pandemic. Still, there are also multiple anecdotes of couples, families, and colleagues where some people saw the virus — but not everyone.

Indeed, according to research, the chances of becoming infected inside a family once one case is positive are "not as high as you'd imagine," according to Danny Altmann, professor of immunology at Imperial College London.

‘Never Covid’ people.

Some people never seem to obtain Covid — the so-called never Covid cohort — are the focus of an increasing amount of research.

People with more significant numbers of T cells (a type of immune cell) from common cold coronaviruses were less likely to become infected with SARS-CoV-2. This virus causes Covid-19, according to new research published last month by Imperial College London.

"Being exposed to the SARS-CoV-2 virus doesn't always result in infection, and we've been keen to understand why," said Dr. Rhia Kundu of Imperial's College National Heart and Lung Institute.

“We observed that high levels of pre-existing T cells, formed by the body when infected with other human coronaviruses like the common cold, can protect against Covid-19 infection,” she said.

"While this is an important discovery, it is only one kind of protection," Kundu cautioned, "and I would stress that no one should rely on this alone." Instead, getting fully vaccinated, including your booster dose, is the most excellent method to protect yourself against Covid-19."

“There's a lot of interest in these cases of so-called ‘never Covid' – individuals who have clearly been exposed to close contacts in their household who are infected, but who are immune to infection,” said Lawrence Young, a molecular oncology professor at Warwick University.

According to him, early evidence suggests that these people had naturally acquired immunity from previous infections with common cold coronaviruses. "Why some individuals maintain levels of cross-reactive immunity is unknown," he said, "but around 20% of common cold infections are caused to common cold coronaviruses."

In addition to prior exposure to coronaviruses — a large family of viruses that can cause diseases ranging from the common cold to more severe conditions and illnesses — one's Covid vaccination status is likely to play a role in whether some people are more susceptible to Covid than others.

The role of vaccines

Covid vaccination is now widely used in most Western countries, albeit there are variations in how and when the coronavirus vaccine is given to different populations.

In many countries, booster shots are frequently used, and younger children are vaccinated as governments race to protect as many people as possible from the more transmissible but less clinically severe omicron variant.

Vaccines against Covid have been shown to prevent severe infections, hospitalizations, and deaths, and they are still mainly effective against known virus variants. However, they are not 100% effective in preventing disease, and the immunity they provide wanes over time and has been somewhat compromised by the omicron variant.

Professor Andrew Freedman of Cardiff University Medical School, specializing in infectious diseases, said  that some people get Covid and others don't "is a well-recognized phenomenon presumably related to protection from vaccination, a past infection, or both."

"We know that despite being fully vaccinated, including getting a booster, several persons have still caught (mostly mild) omicron infection." Vaccination does, however, reduce the risk of catching omicron, and responses differ from person to person. So, despite significant exposure, some people see it, and some don't," he explained.

"Certainly, cross-reactive immunity from previous infections with common cold coronavirus is likely to be a major contributor, particularly as these individuals may have additional immune benefits from also having been vaccinated," Young of Warwick University said when it comes to different immune responses to Covid.

Young claimed that more research into "never Covid" people will aid in developing a better understanding of the immune response to SARS-CoV-2, as well as "what facets of the cross-reactive response are most important, and how this information can be harnessed to generate universal variant-proof vaccines."

The genetic factor

Another question that has arisen during the pandemic is why two people with Covid may respond to the infection differently; one may have severe symptoms while the other stays asymptomatic.

The answer might lie in our genes.

Imperial College's Altmann said, "It's a really serious question."

He and his colleagues conducted research into immunogenetics (basically, the relationship between genetics and the immune system) and Covid-19 infection, which will be published soon, and found that differences in people's immune systems "makes a difference, at least to whether or not you get symptomatic disease," he said.

The study looks at how different HLA (human leukocyte antigen) genes affect a person's response to Covid. He Explained that some HLA types are more or less likely to have an asymptomatic or asymptomatic infection.

"HLA genes are the key genes that control your immune response, and they're important in determining how you'll react if you come into contact with SARS-CoV-2. "People with the gene HLA-DRB1*1302 are significantly more likely to have an asymptomatic infection," said Altmann.

Could it be the tests?

The professor also pointed to the first results released Wednesday of a British human challenge trial, carried out by Imperial and several other research bodies, in which 36 healthy young adults were deliberately exposed to Covid. Still, only half of them became infected with the virus.

“How is it that you pipette an identical dose of virus into people’s nostrils and 50% become infected, the other 50% not?,” Altmann asked, referring to the method used in the trial to expose the participants to the virus.

All trial participants were given a low dose of the virus via nose drops and were then closely monitored by clinical staff in a controlled environment for two weeks.

16 of the 18 infected volunteers experienced mild to moderate cold-like symptoms, such as a stuffy or runny nose, sneezing, and a sore throat.

The researchers conducting the study said it was the first to provide detailed data on the early phase of infection, before and during the appearance of symptoms. The average time from first exposure to the virus to viral detection and early signs (that is, the incubation period) was 42 hours among the 18 infected subjects, significantly lower than previous estimates of five to six days.

Following this time, the amount of virus (viral load) found in swabs taken from participants' noses or throats increased significantly. These levels peaked about five days after infection on average. However, lab testing showed high amounts of viable (infectious) viruses up to nine days after inoculation on average and up to 12 days for some.

It was also interesting to see where the most virus was found. Virus levels were lower and peaked sooner in the throat, despite being found first in the throat and much earlier than in the nose (40 hours in the throat vs. 58 hours in the nose). Peak levels of the virus were significantly higher in the nose than in the throat, indicating a potentially greater risk of the virus being shed from the nose than the mouth.

While there is a risk of "missing infectious virus early in the course of infection, particularly if just the nose is tested," the researchers concluded that the findings support lateral flow tests to identify people who are likely to be infectious.

"Overall, we found that lateral flow tests correlate very well with the presence of infectious virus," said Christopher Chiu, professor of infectious diseases at Imperial College London's Institute of Infection and the trial's chief investigator. "Even though they may be less sensitive in the first day or two, if you use them correctly and repeatedly, and act on them if they read positive, you can greatly decrease viral spread."

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