Why some people keep getting Covid – and others never at all

We all know somebody who seems untouchable while all around them fall ill, but that may be down to more than sheer luck

The Telegraph

Luke Minz

Gerry Gajadharsingh writes:

“Around May 2020 we started testing peoples IgG antibodies to see if they had actually had developed COVID-19 infection, due to the minimal antigen testing available when the pandemic broke in March and April 2020.  We had quite a few patient’s adamant that they had been exposed to the virus, with or without symptoms, because their partners had symptoms and subsequectly positive antibodies but they themselves had not developed antibodies. At the time I wrote several blogs about T cells and the innate part of the immune system. Around June 2021 TDL launched the T Spot test, checking for T-cell reactivity in relation to SARS CoV2. This gave us a more complete understanding of the immune response with COVID-19 infection and coupled with a new antibody test looking at spike protein antibodies,  gave us way of gauging whether COVID-19 vaccination was working to build immunity. Again, I have previously written several blogs about this.

With the Omicron variant so transmissible and so many people testing positive either with lateral flow or PCR tests over the past month or so, including repeat infections for some people, understanding the immune system is now back on the radar.

At the time of writing (January 2022) there’s something like 14.5 million people who have had confirmed COVID-19 infection, therefore it is highly likely that a significant amount of natural immunity has developed in those patients to protect them, at least from serious disease, if not from actually developing COVID-19 infection again. Coupled with the vaccination program and recently the addition of the third dose/booster, I’m not surprised that the talk is now about moving to an endemic as we come out of the pandemic, about time.

The article below discusses the possibility that there may be people (possibly quite a number of them) who seem to have a natural immunity to COVID-19.

The immune system is highly complex and I have previously blogged about the sort of things we can do to support and improve our immunity. However, exposure to infection also helps build the memory within our immune system, to be reactivated at a future date when we come exposed to another virus (usually of the same group).

I have been intrigued at my own personal situation, 58 years of age, mixed ethnicity, allergic asthma, occasional steroid inhaler, working in healthcare in central London throughout the entire pandemic over the past two years. Perhaps I have been extremely lucky, but touch wood, to date, have never tested positive for COVID-19 (take it from me I have been extensively tested, predominantly with PCR for the initial 18 months, which I paid for privately to protect my family and my patients).

Omicron, is obviously highly transmissible and I wondered whether or not my time had come. Just before Christmas I went to a football match with at least 50,000 people, soon after I went to a party down in Somerset, soon after many people tested positive for COVID 19 (with and without symptoms). Max my son went to a work party, someone tested positive, Max tested positive two days later around Christmas time, that’s another story as he is in a younger age group and had two doses of Astrazeneca and no booster and not a great antibody response), I was actually not surprised he picked up COVID-19. He stayed with us for the entire Christmas and New Year period. no one else in the family became infected. Anyway the good news is, I’ve not come across anyone who has developed very severe symptoms, thankfully.

Jessica my daughter, is my PA in London (so also exposed to many patients), we’ve all had the TDL spike protein antibody test, both with the maximum level > 2500, more importantly we both have reactive T cells. The vaccines that we received (Pfizer) seems to have built on the things we do anyway to support our immune systems and perhaps we have some immune memory from previous long-ago infection to another coronavirus.

An interesting thought from the article below.

When your T-cells learn how to fight one, they get better at fighting them all, it is thought.

This begs the more philosophical question, if we are aiming to produce vaccines to every single disease that happens to be out there, perhaps our immune system doesn’t really learn and ironically we may well become more susceptible to future problems. Food for thought. Researchers are looking at the massive increase of autoimmune problems over the past 20 to 30 years, some focusing on the correlation of the increase availability of eating fast food. I would’ve thought the chronology would probably also inside with the massive increase in general vaccination of the population, children and adults, over the past 20 to 30 years. I’ll leave it to others to draw their own conclusions.”

It’s the question on everyone’s lips. How come I’ve had Covid twice, despite being fully vaccinated? How has my neighbour – who spent the last month isolating with her fully-omicronned children – managed to avoid catching it? Why do some people fall foul of coronavirus again and again, and others remain steadfastly immune? Is it luck, genes, or what?

Yesterday, Sir Keir Starmer tested positive for Covid for the second time in just over two months. It came four weeks after the Labour leader received his third vaccine dose. It is the sixth time Sir Keir will have to self-isolate since the beginning of the pandemic. Few people in Britain have been locked in isolation as many times as Sir Keir.

There are people like Sarah, who in October last year, assumed Covid had finally come for her. The 25-year-old teacher had until that point managed to dodge the virus. But then a colleague at her central London primary school tested positive. Then another, and another. Eventually, the school had to close. Sarah had been in close contact with some of the positive cases, in meetings and in the staff room.

But curiously, her lateral flow tests kept returning negative results. Then, two months later, two of her three flatmates tested positive. Feulled by the omicron variant, Covid cases were exploding in London among Sarah’s age group during that week, ONS figures show. Every time she checked her phone, her social media was flooded with more positive results from friends. But still, Sarah’s test results remained stubbornly negative.

“I was just waiting to get it; I definitely felt like it was coming for us all,” she remembers.

We all know people like Sarah: the seemingly untouchable Covid “never-getters” who remain standing while everyone around them falls ill. Sebastian tells me he was the only person among his six flatmates not to fall ill last year. Hannah, 37, says she had a close dinner with her Covid-positive mother-in-law, then saw her partner fall ill. All the while, she stayed negative.

On the other side of the coin are those unlucky souls who seem to catch Covid again and again. For a long time, the question of why some caught the virus more than others was written off as a consequence of sheer luck. Whether or not you catch Covid can be explained by something as random as whether you talk to a certain person at a party, or whether you sit near an open window on a bus, virologists say. Testing issues are also a factor; some people are simply better than others at swabbing their nose and throat.

But now, top immunologists suspect it might have a more profound explanation. Researchers in Britain and Brazil are looking at whether some people might possess a natural immunity to the virus. Even before the pandemic began, their immune systems already knew how to fight the virus, it is believed. If their blood and cells are studied carefully, this fortunate few could give scientists crucial insights into the nature of immunity. And they might just hold the key to the holy grail of pandemic research: a universal Covid vaccine, with the ability to knock out any variant.

We tend to think of immunity as something of an absolute – either we’re immune to a virus, or we’re not. But that hides a world of complications, says Danny Altmann, professor of medicine and immunology at Imperial College London. The genes that control our immunity are among the most diverse in the human body, he says, differing hugely from person to person.

When thinking about something like your blood type, he says, “there’s a very limited chequerboard” of gene combinations. But for immunity, “I’m talking about thousands of possibilities on your chequerboard; no two people will ever look the same.”

As a result, we shouldn’t be surprised that some are more prone to catching viruses than others. We can see this happening in real-time in the laboratory. Researchers at Oxford University and Imperial College London are currently carrying out “challenge studies”, where volunteers are deliberately exposed to Covid, usually through a liquid solution sniffed into their nose, then kept in isolation and observed for two weeks.

All volunteers have received the same number of vaccines, and all are exposed to exactly the same quantity of Sars-Cov-2 (the virus that causes Covid), in exactly the same way. And yet, if it’s anything like previous challenge studies, scientists expect volunteers will mount notably different immune responses. Some will see their antibody and T-cells burst into action; others will not.

We can also see this playing out in hospitals. At the beginning of the pandemic, researchers at University College London recruited a large cohort of London-based healthcare staff for their COVIDSortium study. All of the volunteers were probably exposed to Sars-Cov-2 during their jobs. Their test results were monitored thoroughly. At the end of the trial, about 20 per cent of the healthcare staff showed signs of a clear-cut Covid infection, whilst 65 per cent had clearly not been infected.

But most interesting was the remaining 15 per cent. Members of this third group appeared to have experienced low-level “abortive infections”, not picked up on PCR tests. They didn’t have Covid antibodies in their blood, but they had a much higher T-cell count than average, with particularly high levels of the specific T-cell known to combat Covid. Essentially, their T-cells had nipped the virus in the bud before it ever got the chance to set up camp inside their bodies. It looked as though their immune systems already knew how to fight Covid, even though it was still the early days of the pandemic.

“They didn’t completely resist the infection, but they eliminated it so rapidly that it couldn’t be picked up by the standard test,” says Mala Maini, a professor of viral immunology at University College London, and lead author of the study.

Here was clear evidence that some people may be naturally immune to Covid. Prof Altmann, who was not involved in the study, says the results look “convincing”.

But what explains this natural immunity? The most likely theory is that these people’s immune systems have already been exposed to similar viruses, years or decades earlier. Sars-CoV2 is one of a family of seven coronaviruses, most of which cause the common cold. All of these viruses look fairly similar. When your T-cells learn how to fight one, they get better at fighting them all, it is thought.

Testing issues are a factor; some people are simply better than others at swabbing their nose and throat

Another, less well-researched answer lies in our genes. Some people might simply be born with an immunity to certain viruses, scientists suspect. This possibility emerged in 2008, when virologists in Kenya found a group of sex workers who had never caught HIV, despite having unprotected sex with numerous positive cases. It turns out their cells lacked a crucial receptor – the same receptor used by HIV particles to break into our cells.

“Big studies are going on now to see if something similar might be happening in some people with Covid, but there’s no clear evidence for that yet,” says Prof Maini.

Indeed, at the University of São Paulo, researchers are recruiting 100 cohabiting couples. In each case, one half of the couple tested positive for symptomatic Covid, whilst the other stayed Covid-free (with blood tests confirming they had no Covid-specific antibodies). All 200 will have their DNA analysed to search for genetic differences.

If it turns out that some people are indeed naturally immune to Covid, it’s wonderful news for them. But it might also help the rest of us, speeding up development of a pan-coronavirus vaccine capable of defeating any variant. The current generation of Covid vaccines were all designed to target the spike protein, on the virus’s outer edge. But the spike protein also changes frequently, each time the virus mutates. This means vaccines are slightly less effective against each new variant.

But natural immunity appears to work differently. In the UCL trial, researchers looked carefully at the blood of those volunteers who seemed to have pre-existing immunity to the virus. Rather than targeting the spike protein, their T-cells were targeting proteins at the centre of the virus. These proteins are much less likely to change from mutation to mutation. In fact, they tend to be found in most coronaviruses, not just Sars-Cov-2. If a vaccine could be built to target these inner proteins, it might just be able to defeat all variants – as well as a range of other coronaviruses.

Experts stress that the science is still in progress. Nobody should “go around feeling Teflon-coated in some way”, Prof Altmann urges. But as we enter our third year of the pandemic, it’s certainly a hopeful sign.