AFTER two and a half years of Covid and the evolution of ever-more infectious strains of the virus, it might seem improbable that anyone could have avoided it.

Yet a minority of the population have - and scientists are keen to understand why.

According to YouGov, who have been carrying out a regular coronavirus public attitudes tracker on behalf of the Scottish Government since the beginning of the pandemic, 16 per cent of adults in Scotland believe they “definitely haven’t had” Covid.

This is based on an online survey of 1000 people in Scotland between August 23 and 25, so it is possible that some of these individuals were infected at some point without experiencing any symptoms.

However, it roughly corresponds with similar estimates from the UK Health Security Agency (UKHSA) that around three in 20 people in England (15%) had never had Covid as of July this year.

READ MORE: One in 45 have Covid as Scotland sees infection rate rise again

The most obvious explanation is behavioural: people who are retired or who work from home, for example, are better placed to curtail their contacts than those in working in retail, factory or healthcare-based occupations.

Unsurprisingly then, 27% of retired people in Scotland say they have never had Covid compared to 9% of those working full-time.

Likewise, those most worried about getting Covid are more likely to have reduced their risk through caution. Notably, the YouGov survey found that 31% of over-75s (the highest risk age group) believe they have never had Covid compared to 5% of adults aged 25 to 34.

HeraldScotland: Scientists want to analyse the genomes of unvaccinated people who have been exposed to Covid without becoming infectedScientists want to analyse the genomes of unvaccinated people who have been exposed to Covid without becoming infected

But beyond what science magazine Wired described this week as “judicious caution, sheer luck, or a lack of friends”, the much more interesting angle for scientists is to identify those individuals - especially unvaccinated, or pre-vaccinated, individuals - who have almost certainly been exposed to the virus but whose own immune system appears to have batted it off.

The thinking is that these people contain genetic clues to resistance which could be used in future to develop more effective vaccines against infection.

Researchers involved in the Covid Human Genetic Effort (CHGE)- a global network of scientists whose original aim was to discover why some people experience only mild disease and others die from the infection, despite apparently similar health and demographic profiles - have become increasingly intrigued by a small number of people who appear never to have caught it at all despite very clear exposure.

For example, spouses who shared a bed while their partner had a confirmed and symptomatic infection, or healthcare workers repeatedly exposed to Covid positive patients.

In October last year, scientists in the New York arm of the CHGE project issued an appeal via Nature Immunology inviting applications from around the world from people who met a fairly narrow criteria.

READ MORE: Why Covid reinfections could be a bigger problem than expected 

In addition to a negative PCR test and a history of prolonged, unprotected exposure to the virus through household contact with a confirmed case, candidates’ blood would also be analysed.

Only those with no Covid antibodies and a negative T cell response, indicating no prior infection or vaccination, could be included.

To date the study has been inundated with 15,000 applications, but only around 800 to 1000 ticked the necessary boxes. Many more fell by the wayside as the ultra-transmissible Omicron wave took off.

On the plus side, the scientists believe that those who continued to remain so-called "Covid virgins" at a time when many others were experiencing their second, third or even fourth bouts of the infection lend credence to the theory of some sort innate, gene-based immunity.

HeraldScotland: Participants will be tested for signs of antibodies and T cellsParticipants will be tested for signs of antibodies and T cells

In Ireland, scientists at Trinity College who are also taking part in CHGE, lost around half their recruits - healthcare workers at a Dublin hospital - once Omicron struck, but bolstered their pool of potential candidates following a national appeal which attracted 16,000 applicants.

The team hopes to extract 100 to 200 suitable candidates from this cohort before carrying out a genetic analysis: first to identify any recurring mutations among participants which might be important, and secondly to cross-reference their genomes against an existing list of genes associated with immunity and resistance.

The process, which will be repeated in dozens of participating labs worldwide, will take around four to six months with the expectation that - in the end - the number of people genuinely naturally resistant to Covid will be rare.

READ MORE: The Edinburgh scientists unravelling why some people are more likely to get sepsis than others 

Nonetheless, the phenomenon is neither new nor unique to Covid.

In 1999, a biochemist in North Carolina, Zheng Cui, discovered a mouse so genetically-resistant to cancer that even when he injected it with a million times the normal lethal dose of cancer cells, it survived. A mutation in its DNA coded for white blood cells capable of destroying a tumour at the earliest stage.

When he extracted and transferred these white blood cells into rodents from the same species, but without this mutation, they too became resistant.

Furthermore, when Cui sampled human volunteers he found that 10-15% had similar "super cancer-fighting" white blood cells, potentially explaining why some people never get the disease.

More recently, Cui has been working to develop a bank of cancer-killing granulocytes - a type of white blood cell - as a potential cure for pancreatic cancer.

HeraldScotland: At one point, as many as one in 11 people in Scotland were estimated to be infected with Covid - yet some have still never been infected at allAt one point, as many as one in 11 people in Scotland were estimated to be infected with Covid - yet some have still never been infected at all

HIV therapies have already been developed off the back of genetic anomalies: in the 1990s, a group of sex workers in Nairobi, Kenya who had inexplicably swerved the virus were found to share a genetic mutation which meant that their bodies produced an abnormal version of a protein called CCR5, which HIV relies on to latch onto human cells and replicate.

Carriers of this mutation can effectively "block" the infection and, most significantly, when two HIV-positive patients received stem cell transplants from donors with this mutation they too became HIV free.

It remains to be seen, but our own DNA might also contain a cure for Covid.