Why do some people get Covid while others don’t?

One of the great mysteries that has emerged from the Covid-19 pandemic — and one that’s still being investigated by infectious disease specialists — is why some people catch Covid and others don’t, even when they’re equally exposed to the virus.

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

Indeed, Danny Altmann, professor of immunology at Imperial College London, told CNBC that studies indicate the likelihood of becoming infected within a household once one case is positive is “not as high as you’d imagine.”

An increasing amount of research is being devoted to the reasons why some people never seem to get Covid — a so-called “never Covid” cohort.

Last month, new research was published by Imperial College London suggesting that people with higher levels of T cells (a type of cell in the immune system) from common cold coronaviruses were less likely to become infected with SARS-CoV-2, the virus that causes Covid-19.

Dr Rhia Kundu, first author of the study from Imperial’s National Heart & Lung Institute, said that “being exposed to the SARS-CoV-2 virus doesn’t always result in infection, and we’ve been keen to understand why.”

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

However she also cautioned that, “while this is an important discovery, it is only one form of protection, and I would stress that no one should rely on this alone. Instead, the best way to protect yourself against Covid-19 is to be fully vaccinated, including getting your booster dose.”

Lawrence Young, a professor of molecular oncology at Warwick University, told CNBC Wednesday that, “there’s much 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 themselves are resistant to infection.”

He said that early data suggests these individuals have naturally acquired immunity from previous infections with common cold coronaviruses. Around 20% of common cold infections are due to common cold coronaviruses, he said, “but why some individuals maintain levels of cross-reactive immunity remains unknown.”

As well as a degree of immunity provided by prior exposure to coronaviruses — a large family of viruses that cause illness ranging from the common cold to more severe diseases or infection — one’s Covid vaccination status is also likely to be a factor as to whether some people are more susceptible to Covid than others.

Covid vaccination is now widespread in most Western countries, albeit with variations among populaces in terms of which coronavirus vaccine was administered, and when.

Booster shots are also being deployed widely, and younger children are being vaccinated in many countries, as governments race to protect as many people as possible from the more transmissible, but less clinically severe, omicron variant.

Covid vaccines have been proven to reduce severe infections, hospitalizations and deaths and remain largely effective against known variants of the virus. However, they are not 100% effective in preventing infection and the immunity they provide wanes over time, and has been somewhat compromised by the omicron variant.

Andrew Freedman, an academic in infectious diseases at Cardiff University Medical School, told CNBC that why some people get Covid and others don’t “is a well recognized phenomenon and presumably relates to immunity from vaccination, previous infection or both.” 

“We know that many people have still caught (mostly mild) omicron infection despite being full vaccinated, including [having had] a booster. However, vaccination does still reduce the chance of catching omicron and responses do vary from person to person. So some people catch it and others don’t despite very significant exposure,” he said.

Warwick University’s Young said, when it comes to different immune responses to Covid, “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.”

Further studies into so-called “never Covid” individuals will help in developing a better understanding of the immune response to SARS-CoV-2, Young insisted, and “what facets of the cross-reactive response are most important, and how this information can be harnessed to generate universal variant-proof vaccines.”

Another question that has arisen during the pandemic is why two people with Covid may respond so differently to the infection; one could have heavy symptoms, for instance, and the other could be asymptomatic.

The answer might lie in our genes.

“It’s a really important question,” Imperial College’s Altmann told CNBC on Wednesday.

He said that he and his colleagues have conducted research, to be published soon, into immunogenetics (essentially, the relationship between genetics and the immune system) and Covid-19 infection, and have found that variations between people’s immune systems “makes a difference, at least to whether or not you get symptomatic disease.”

The research is focused on different HLA (Human leukocyte antigen) genes and is looking at how these can affect one’s response to Covid, with some HLA types more or less likely to experience a symptomatic, or asymptomatic, infection, he said.

“The key genes that control your immune response are called HLA genes. They matter for determining your response on encounter with SARS-CoV-2. For example, people with the gene HLA-DRB1*1302 are significantly more likely to have symptomatic infection,” Altmann added.

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, but only half of them actually 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.

Essentially all the trial volunteers they were given a low dose of the virus — introduced via drops up the nose — and then carefully monitored by clinical staff in a controlled environment over a two-week period.

Out of the 18 volunteers that became infected — one of only a few of its kind in the world — 16 went on to develop mild-to-moderate cold-like symptoms, including a stuffy or runny nose, sneezing, and a sore throat. 

The researchers conducting the study said it was the first to be able to provide detailed data on the early phase of infection, before and during the appearance of symptoms. Among the 18 infected participants, the average time from first exposure to the virus to viral detection and early symptoms (that is, the incubation period) was 42 hours, significantly shorter than existing estimates, which put the average incubation period at 5-6 days.

Following this period there was a steep rise in the amount of virus (viral load) found in swabs taken from participants’ nose or throat. These levels peaked at around five days into infection on average, but high levels of viable (infectious) virus were still picked up in lab tests up to nine days after inoculation on average, and up to a maximum of 12 days for some.

Also interesting was where the most virus was found. While the virus was detected first in the throat, and significantly earlier than in the nose (40 hours in the throat compared to 58 hours in the nose), virus levels were lower and peaked sooner in the throat. Peak levels of 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.

They noted that while there is a possibility of “missing infectious virus early in the course of infection, particularly if only the nose is tested,” the researchers said the findings overall support continued use of lateral flow tests to identify people likely to be infectious.

“We found that overall, lateral flow tests correlate very well with the presence of infectious virus,” said Professor Christopher Chiu, the chief investigator on the trial. “Even though in the first day or two they may be less sensitive, if you use them correctly and repeatedly, and act on them if they read positive, this will have a major impact on interrupting viral spread.”