How genetics could determine why some people get Long Covid and others don't

One of the biggest battles of the pandemic has been the scramble for information.

Knowledge is power and the more we know and understand about Covid, the better equipped we are to prevent it and treat it.

But two years in, there is still so much we don’t know. Particularly when it comes to those people who caught Covid and just never recovered.

Why do some people get Long Covid and others don’t? It doesn’t seem to be related to the severity of your initial illness, or your overall health, age or the presence of underlying conditions.

For the many thousands who have been suffering with debilitating symptoms since early 2020, they still don’t have an answer to the question – why them?

Scientists now think our genes could play a part.

Just like how our genetic makeup could mean we are at higher risk of developing Alzheimer’s, or certain kinds of cancer, scientists are now looking in to whether the same could be true of Long Covid.

Are some people genetically predetermined to have a much higher risk of developing lingering Covid symptoms? Dr Patrick Short, co-founder of health tech start-up Sano Genetics, believes a link is highly likely.

‘When the pandemic started, there was a lot of research that immediately kicked in to look at whether there were genetic markers that could predict whether someone was more likely to get a severe reaction from getting Covid,’ Dr Short tells Metro.co.uk.

‘Everyone at the time was very focused, and rightly so given what we knew, on hospitalised cases, people who had a severe reaction and end up on oxygen or ventilator.

‘But what we saw relatively early on, is that there was this group of people who were making it to hospital, not going on a ventilator, leaving the hospital, but then having weeks, months, now years of lingering symptoms. And there was a whole other group of people who were never going to the hospital at all and still having these significant symptoms.’

This is the group Patrick and his team are targeting with their extensive study into the possible genetic causes of Long Covid.

The research, supported by government funding body Innovate UK, aims to aid development of treatments and identification of vulnerable groups, and they are looking for more participants to share their DNA data using free at-home testing kits.

‘Understanding how our genetics influence our response to Covid is key to better protecting vulnerable people, developing effective treatments, and helping the world safely open back up,’ says Dr Short.

‘There has also historically been a huge bias in genetics studies toward analysing data primarily from people of white European backgrounds, meaning new discoveries do not always apply to everyone, and we want to make sure this study does not make the same mistakes.’

Shockingly, around 80% of participants in genetic research are of European descent. This study hopes to achieve age, gender and ethnic diversity to better reflect the population.

So, what have the scientists found?

Emerging data shows that Covid vaccines appear to reduce the risk of developing Long Covid by around 50% – for people who are double vaccinated. This is reassuring, but as Long Covid hasn’t disappeared, Dr Short and his team say the challenge of decoding the condition is ongoing. 

Experts have described Long Covid as ‘unchartered territory’ and, although similar in some ways to other post-viral conditions, it has defied many scientists’ expectations.

This new study aims to enroll 3,000 participants in order to get the full range of data required to make solid conclusions about a genetic link to Long Covid, but Dr Short says the results so far are pointing in that direction.

Speculating about the possible future findings, Dr Short says: ‘The studies that have been done on people who very severe reactions requiring hospitalisation have found a number of very robust genetic associations.

‘I’m very optimistic that we’ll find the same in Long Covid.’

Anyone who has had Covid related symptoms for longer than three weeks can sign up online and receive an at-home DNA testing kit. A positive Covid test or a hospital stay are not required in order to participate.

Anonymised genetic data will then be securely shared within the research consortium so the scientific community can work together on Covid treatments.

In terms of the specifics of what they might find, Dr Short says there are a number of different hypotheses being developed.

‘One of the most compelling ones is that for some people Long Covid is a sort of autoimmune reaction,’ he says. ‘So, for some reason, the virus triggers an autoimmune response where the body starts to attack itself. This is supported by the fact that people with Long Covid have been found to have high levels of what are called autoantibodies – these are antibodies that the body shouldn’t really be producing.’

How likely is it that genetics could be the only factor that determines whether or not a person will get Long Covid?

‘The hard answer to that is we often don’t know with genetic studies how important genetics are until we run the studies,’ says Dr Short. ‘But for most common and complex diseases, genetics plays a role, but it’s not the definitive role. Although with with many rare diseases, it is the definitive role.’

Dr Short and has team are not the only experts looking into whether Long Covid can be predicted.

Researchers at University Hospital Zurich recently found an ‘antibody signature’ that could help to identify people most at risk of developing Long Covid. 

The research team, who published their findings in Nature Communications,  analysed blood from Covid patients and found that low levels of certain immunoglobulin antibodies were more common in people who developed Long Covid than in those who recovered quickly.

This information, along with other factors, enabled researchers to predict whether people had a moderate, high or very high risk of developing Long Covid using a blood test.

What does it mean for treating Long Covid?

If the hypothesis of Long Covid being an autoimmune reaction turns out to be correct, Dr Short says this could be incredibly significant for patients and have hugely positive implications for possible treatments.

‘There are many autoimmune diseases that are already known to us – like lupus, multiple sclerosis, inflammatory bowel disease, and many others,’ says Dr Short.

‘So, if there is at least a subset of Long Covid that fits that pattern, it may be possible to repurpose some of the treatments that already exist for other autoimmune diseases to help this group of people.’

This is crucially important because developing brand new drugs can take many years and many millions of pounds in funding.

‘If we’re able to take existing drugs that have actually already been proven to work in something like lupus, for example, and repurpose that to treat people with Long Covid, that process can be much, much quicker.’

Something that quickly became clear to Dr Short and the research team is that Long Covid is not the same for everybody, and as such, there is likely to be a variety of determining factors.

‘We will also be looking at whether there are differences in people who have significant issues with their brain, cognition and fatigue, versus people whose issues may be more on the respiratory side,’ he explains.

‘Long Covid is a very, very heterogeneous disease where every person presents a little differently.’

Long Covid – what you need to know

Most infections with Covid resolve within the first four weeks. Long Covid is a term commonly used to describe symptoms that continue or develop after you’ve had the initial virus.

An estimated 1.5 million people in the UK (2.1% of the population) have reported experiencing Long Covid symptoms.

The recovery time is different for everyone. The length of your recovery is not necessarily related to the severity of your initial illness, or whether you were in hospital.

According to the latest reports, Long Covid is most common in people aged 35-69 years, women, people living in more deprived areas, those working in health care, social care, or teaching and education, and those with another activity-limiting health condition or disability.

Common Long Covid symptoms include:

  • Extreme tiredness (fatigue)
  • Shortness of breath
  • Chest pain or tightness
  • Problems with memory and concentration (“brain fog”)
  • Difficulty sleeping (insomnia)
  • Heart palpitations
  • Dizziness
  • Pins and needles
  • Joint pain
  • Depression and anxiety

If new or ongoing symptoms do occur and they are causing you concern, you should always seek medical advice and support.

For more information and support you can apply to join the Long Covid Support Group on Facebook, which currently has more than 50,000 members.

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