Coronavirus in numbers

Coronavirus: How ‘viral load’ and genetics could explain why young people have died from Covid-19

Scientists are racing to build database of DNA research to find any genetic reasons people may be more or less susceptible to deadly virus

Harry Cockburn
Tuesday 07 April 2020 07:42

The coronavirus pandemic has hit older people far harder than those who are younger, but scientists are yet to fully understand why this is.

Many of the elderly people who have died have had pre-existing health conditions such as heart disease, lung disease and diabetes, all of which make fighting the virus more difficult, but many have not had any such health problems, and occasionally the virus has caused the deaths of younger, apparently healthy people.

Researchers around the world are racing to learn how the virus behaves, which health factors put people most at risk, and are trying to work out whether there may be genetic traits that could mean some people respond to the infection differently to others.

There are various theories to suggest why the virus is so unusually — and devastatingly — selective.

Some scientists have suggested the greater the amount of virus that infects an individual — known as the “viral load” — could make a large difference to how the body is able to respond to infection.

Put simply, the larger the dose of the virus a person gets, the worse the infection is, and the least promising the outcome.

A parallel school of thought is that genetic variations between humans — differences in our DNA — could affect how susceptible an individual is to the virus.

And another candidate for why apparently healthy young people are dying is they may have a highly reactive immune system, which is sent into overdrive fighting off the virus. In such a scenario, a huge inflammation storm could inadvertently overwhelm vital organs such as the lungs.

None of the theories compete with one another, and aspects of all of them, as well as innumerable other factors, could be at play in an individual case.

Viral load

Dr Edward Parker of the London School of Hygiene and Tropical Medicine, explained how a high viral load can impact humans. He said: “After we are infected with a virus, it replicates in our body’s cells. The total amount of virus a person has inside them is referred to as their ‘viral load’. For Covid-19, early reports from China suggest the viral load is higher in patients with more severe disease, which is also the case for Sars and influenza.

“The amount of virus we are exposed to at the start of an infection is referred to as the ‘infectious dose’. For influenza, we know that that initial exposure to more virus — or a higher infectious dose — appears to increase the chance of infection and illness. Studies in mice have also shown that repeated exposure to low doses may be just as infectious as a single high dose.”

He added: “So all in all, it is crucial for us to limit all possible exposures to Covid-19, whether these are to highly symptomatic individuals coughing up large quantities of virus or to asymptomatic individuals shedding small quantities. And if we are feeling unwell, we need to observe strict self-isolation measures to limit our chance of infecting others.”

Professor Wendy Barclay, the head of the Department of Infectious Disease at Imperial College London, said existing knowledge of viral load means healthcare workers can be at greater risk of infection.

“In general with respiratory viruses, the outcome of infection — whether you get severely ill or only get a mild cold — can sometimes be determined by how much virus actually got into your body and started the infection off. It’s all about the size of the armies on each side of the battle, a very large virus army is difficult for our immune systems army to fight off.

“So standing further away from someone when they breathe or cough out virus likely means fewer virus particles reach you and then you get infected with a lower dose and get less ill. Doctors who have to get very close to patients to take samples from them or to intubate them are at higher risk so need to wear masks.”

Genetic differences between those infected

Scientists are currently preparing to scour Covid-19 patients’ genomes for DNA variations that might indicate why some people are more at risk than others.

The findings could then be used to identify groups most at risk of serious illness and those who might be protected, and this knowledge could then inform the hunt for effective treatments.

A huge effort to pool DNA research from patients around the world is now on, with the ultimate goal being to build a body of evidence from people with no underlying health issues, but who have reacted differently to infection by the virus.

One promising strand of research into why some people are more susceptible to the coronavirus is on the gene variation for the cell surface protein angiotensin-converting enzyme 2 (ACE2), found on the outer membranes of cells, and which the coronavirus uses to enter cells in the lungs and airways.

Variations in production of ACE2 could make it easier or more difficult for the virus to enter and infect cells.

“We see huge differences in clinical outcomes and across countries. How much of that is explained by genetic susceptibility is a very open question,” geneticist Andrea Ganna, of the University of Helsinki’s Institute for Molecular Medicine Finland, told Science Magazine.


Another fascinating line of inquiry is whether different blood types could lead to differing levels of susceptibility to the disease.

A Chinese research team reported in a non-peer-reviewed article that people with type O blood may be protected from the virus, and those with type A blood could be at greater risk.

“We’re trying to figure out if those findings are robust,” Stanford University human geneticist Manuel Rivas told Science Magazine.

The first results from the investigations into genetic differences and susceptibility are expected in less than two months’ time.

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