HuffPost UK reader Charlie asked: “Why does Covid affect people differently?”
If there’s one thing we know about Covid-19, it’s that no two people seem to be impacted in the same way.
Some people can become infected but not have any symptoms whatsoever (it’s thought one in three experience this), others can end up with a runny nose and sore throat, while family or flatmates in the same household end up breathless, coughing and unable to get out of bed.
Some have headaches, others have diarrhoea. Children can be completely unaffected, or come out in rashes and a raging fever. Both young and old can end up hospitalised – with some ending up on ventilation.
But why does it impact us all so differently? Is it to do with our immune systems, genetics, viral load or something else entirely?
“All infectious diseases affect different people to a different extent,” Professor Charles Bangham, chair of immunology and co-director of the Institute of Infection at Imperial College London, tells HuffPost UK.
“I might suffer badly when I get influenza, whereas you might have a mild or even completely asymptomatic infection, even if we can detect some virus in swabs from your respiratory tract. But with a different virus, I might have a milder infection than you.”
The main reason for these differences between individuals is that each of us has a unique set of genes that control the efficiency of the immune response, he explains.
When Covid-19 enters the body, it attaches to our cells, hijacks them, and then creates copies of itself to invade even more cells. Our immune system kicks in to try and stop this, sending out its frontline defence – the ‘innate immune response’ – to deal with the intruder.
This is the default response to any virus entering the body. As part of this initial response, inflammatory proteins called ‘interferons’ are released, which have antiviral functions. The aim is to stop the virus in its tracks – though we don’t actually know how well this first response works in fending off infection.
While the innate immune system is trying (and sometimes failing) to fight off the virus, it also ‘talks’ to the more specific ‘adaptive’ immune response. This is your body’s tailor-made solution for dealing with Covid-19, and involves the release of B-cells, which produce antibodies, as well as T-cells, which kill infected cells.
It’s been speculated that some people might generate immunity that helps fight against Covid-19 after previously being infected by another coronavirus, which *could* help explain why some people don’t get it as bad.
The main genes that control the efficiency of the immune response are the tissue type genes – the HLA genes – which also control whether a transplanted organ can be accepted, says Prof Bangham. There are hundreds of slightly different variants of these genes, which is why finding a match for transplants can be so hard.
“This gene variation is also why each of us can respond so differently to infections,” he explains. “Fortunately, each of us has several of these genes and each one gives us a chance to make a good immune response to a different range of viruses – or bacteria or other infectious agents.”
Professor Lawrence Young, an expert in molecular oncology at Warwick Medical School, agrees that the immune response plays a key role. If you are male, you might notice your female partner seemed to have milder symptoms – and the immune response is probably behind this too.
“The immune response is a major factor particularly in relation to sex differences,” says Prof Young. We know that men are more likely to suffer from severe symptoms than women and also have a greater risk of death.
“Many studies show that women have a more robust immune response to SARS-CoV-2 infection,” Prof Young continues. “There is both a genetic and hormonal impact of female gender on the way the immune system responds to infection.”
We also know that underlying health conditions can weaken the immune system and that age is also an important factor linked both to the effectiveness of the immune system (“as we get older our immune systems become less efficient,” says Prof Young) and to other co-morbidities.
This helps explain why those aged 60 and over, as well as those with certain health conditions, are deemed more vulnerable to the effects of Covid and need to be prioritised for vaccination.
And the amount of virus you’re exposed to – does that play a part? It’s possible, says Prof Young. “This is certainly the case for other respiratory infections such as flu where initial exposure to a lower dose of virus results in fewer and shorter symptoms.”
But Prof Bangham is less convinced. “It is much less likely that the difference in severity of the infection is due to a difference in the infecting dose of virus. The reason for this is simple: once the virus gets into the body, it replicates exponentially,” he says. “So it doesn’t take long for the virus to reach a high level in the body, even if it started from a lower dose.”
We know people from ethnic backgrounds are more at risk of severe illness. This could be down to genetic or biological reasons.
Researchers at the University of Colorado are hoping to explore this further – and, more broadly, answer the question of why Covid-19 affects people differently, by analysing blood samples from patients who tested positive for Covid-19 as well as from those who tested negative.
“Covid-19 is not one entity,” said Dr Joaquin Espinosa, professor of pharmacology at the University of Colorado School of Medicine, who is leading the study.
“It manifests itself in very different ways in every individual,” he adds. “If you have 100 people infected with the same virus, you have a wide range of outcomes,” said Dr Espinosa. “Every person is different. Some will not get sick at all, some will die, and everything in between. What are the mechanisms driving this massive diversity?”
The study will analyse the samples from a broad variety of biological perspectives to identify specific patterns – changes in proteins, red blood cells or immune response – that can shed some more light on the the mechanisms underlying the diverse ways the virus affects people.
Experts are still learning about Covid-19. The information in this story is what was known or available at the time of publication, but guidance could change as scientists discover more about the virus. To keep up to date with health advice and cases in your area, visit gov.uk/coronavirus and nhs.uk.