ANALYSIS: Until a week ago, when my family and I dropped like flies, I thought I might just be one of “those” people: the unicorns referred to as “never Covid people”, who test negative despite having been exposed to the virus.

Are these people paragons of health? Have they been listening to Trump and other Ivermectin-promoting types and been taking their daily dose of horse wormer? (Obviously I jest – this is not recommended, preventatively or otherwise.)

The answer is neither. Nor are they necessarily as resistant to the virus as they might think.

“It may be that at least some people have been exposed and contracted Covid but had only minimal or no symptoms,” says Professor John Christendom, the director of the Genetics Research Theme at Murdoch Children’s Research Institute in Australia.

Beyond those who have had Covid without realising, there is a cohort who do appear to be resistant to catching it. The size of this cohort is hard to tell exactly because of global differences in vaccination, genetic differences in ancestry groups and environmental factors. But there are enough “never Covid” types to have piqued the interest of researchers around the world who hope these people hold clues for treating everyone else.

A widely reported Imperial College London study, published in Nature in January, found that high levels of pre-existing T cells (a type of white blood cell that targets specific antigens), created by the body when infected with other human coronaviruses like the common cold, can protect against Covid-19 infection.

READ MORE

• What happens if you’ve got long Covid and can’t work?
• Expert warns of reinfection as new variants emerge
• New Zealand seeks reassurance from China children can stay with parents during COVID isolation amid reports of separation
• New XE variant possibly most transmissible yet - WHO

“The immune system is good at recognising viruses that aren’t exactly the same but come from the same family,” says immunologist Stuart Tangye from the Garvan Institute of Medical Research. “Studies from 2020 found that 25-45% of people who were studied and had not previously been infected with SARS-CoV2 had detectable levels of T cells that cross-reacted with SARS-CoV2.”

However, resistance to Covid is more than just T-cells.

A separate study published in Nature Medicine in March, also by Imperial College researchers, took 36 healthy, unvaccinated male and female volunteers aged between 18 and 30 and infected them with a low dose of Covid.

While the purpose of the study was to track the trajectory of the virus (they found incubation is only about 42 hours not five days as previously thought and that the virus appears first in the throat and then the nose), they made another unintended discovery: only half the participants became infected.

It could be in their genes, posits Tangye. “Genetic influences are either making people vulnerable to really severe disease … but may also contribute to resistance … There are populations of people who probably should have been infected and sick but weren’t.”

Exactly which genes have a protective effect is part of an international research project called the Covid Human Genetic Effort, which Christodoulou is involved with.

“We are collecting information and DNA from individuals who have been ‘hyperexposed’ to Covid but who don’t seem to contract Covid – for example, living in a household where multiple family members were infected, but one member of the household wasn’t – to see if genetic factors can be identified that might offer protection against Covid infection,” says Christodoulou, who is also the chairperson of Genomic Medicine at the University of Melbourne.

While researchers keep searching for the genetic clues, a new study published at the end of April found booster shots can increase the range of immune cells, called memory B cells, making them more effective at “neutralising” Covid.

With any infection or vaccination, our body responds and then forgets the virus, explains Tangye, but becomes better at responding with repeated exposure. “The first and second doses are like the training, getting your immune system into good shape and ready to take off and the third really gives you the protection … You are primed and ready to go.”

So if someone who has recently been vaccinated is exposed to Covid, they may be protected. If they have been boosted, this may provide even more protection, at least for a time.

The degree of exposure – how long we were in contact with someone and whether we were inside or out – will also make a difference, as will our behaviour.

“People have become much more cognisant of social distancing and washing their hands and wearing masks. There are those non-pharmaceutical interventions people have embraced,” Tangye says.

As for how healthy you are generally, that unfortunately won’t make us resistant to catching Covid.

“We regularly hear of otherwise young, fit and healthy individuals contracting very severe Covid,” says Christodoulou.

“For those otherwise healthy people, we know that there are some factors that are associated with this, for example having so-called auto-antibodies to type 1 interferons (type 1 interferons are the first line of defence against Covid) or having mutations in genes that are involved in production and function of type 1 interferons.”

Interestingly, Tangye adds that there are people who naturally have this type 1 interferon pathway “turned up a little bit”.

“That can be pathogenic – they can get these inflammatory diseases that don’t have a defined trigger …these non-infectious, spontaneous flares for no good reason – but people with those conditions may well have some resistance to Covid just because they have that innate immune response primed.”

These people account for only a fraction of never Covids. For the rest, it seems to come down to a combination of immunity, genetics, environment and luck.

“Being healthy all round puts you in better shape against infectious diseases and lifestyle disease,” says Tangye. “Being healthy is good. But healthy people are still getting sick. It’s not a panacea.”

Most of us may not be able to do much to avoid the virus, but we can still look to never Covids for some answers.

“If we can identify genetic reasons why people don’t get Covid, it may help inform ways by which SARS COV2 enters or attacks our cells. Remember, viruses are hopeless on their own. They need all the machinery of our cells to be disease-causing,” explains Tangye.

“So if we can disrupt the ‘human cell processes’ without too many adverse events, we could be better at stopping viral infection.”