Hoping for a breakthrough, the search for answers on long Covid continues

A new US study is the latest to identify several factors that make some people more susceptible to long Covid than others. Yet with millions around the globe experiencing debilitating symptoms weeks or months after first being infected, the medical establishment does not yet understand why. 

Patients who have been obese at some point prior to infection with Covid-19 are at higher risk of developing long Covid, a new study from the University of Southern California (USC) has found. 

Researchers also found links between specific symptoms experienced during initial infection and the likelihood of developing long Covid, with sore throats, headaches and hair loss more likely to indicate that symptoms would persist months later. 

The World Health Organization (WHO) defines long Covid as the presence of symptoms that last at least two months and cannot be explained by another diagnosis following coronavirus infection. The WHO says common symptoms include fatigue, shortness of breath and cognitive dysfunction, noting that symptoms may also fluctuate or reappear over time.

Since medical professionals first became aware of the long Covid phenomenon back in 2020, scientists and researchers have been perplexed by the varied profiles of susceptible patients and researchers have struggled to provide conclusive answers. 

Studies indicate a laundry list of possible predictors, including repeat Covid infections, high viral load infections, the presence of dormant Epstein-Barr virus, the presence of autoimmune antibodies and a lack of vaccination

Some studies also contradict each other. The USC study did not find links between long Covid and age, race or gender while a June 2022 study funded by Johnson & Johnson found that the likelihood of having long Covid syndrome was “significantly greater” among females. 

“At the beginning in 2020, we knew nothing,” says Rebecca Livingston, a clinical lead physiotherapist in the post-Covid service of London’s University College Hospital.  

“Our thinking and our understanding around long Covid has definitely moved on and research is helping us to put together some of those pieces of the puzzle. But the more we discover, the more we realise that we don’t yet fully know.”  

‘People don’t think they have it’

In the meantime, long Covid is affecting millions around the world.  

A UK study found that an estimated 2 million people were living with long Covid in June 2022. The USC study found that nearly one in four people who had coronavirus infections were still reporting symptoms up to 12 weeks later. In Wuhan, China, a May 2022 study found that among people hospitalised with Covid, half still had at least one symptom two years after infection.  

Numbers are so high, in part, because the Covid-19 virus is highly contagious. In the past two years, more people have caught Covid than the common cold or seasonal flu. 

But these figures are also likely to be underestimates. “People don’t think they have it,” says Ruth Ainley, respiratory physiotherapist and long Covid specialist. “They think they’re just tired all the time because they’re run down from the virus, so they don’t put two and two together.” 

Even when people do believe they are unwell, some people are more likely than others to seek medical help. “The data that we have would tell us that the majority of people that have long Covid are women, they’re middle-aged and they’re white,” Livingston says.

“That data also reflects the people who we see in clinic, and we know that there are significant inequalities in terms of accessing … health care, so it probably isn’t wholly representative of the full picture.”  

News articles have often focused on the shock of long Covid leaving people who are young, healthy and athletic with debilitating symptoms. But those with highly active lifestyles may also be more likely to notice symptoms such as fatigue, and to take those symptoms seriously, than older people.

“Older people are very under-diagnosed,” Ainley says. “It’s written off as they haven’t shaken off Covid, or they’re a bit weary and that’s to be expected at their age.” 

A ‘difficult picture to piece together’

Even among patients known to have long Covid, the complicated nature of the illness makes analysis difficult. There are more than 200 recognised symptoms of long Covid, according to the American Medical Association, which estimates that some 20 to 30% of patients are affected, even after a mild initial illness. 

And there are few recognisable patterns for when symptoms might appear or how long they might last. 

“Our expectation, when we started working with people post-Covid, was that we would assess them systematically and they would fit into categories. But the reality is it’s much more blurry,” Livingston says. “People will have symptoms that affect lots of different systems and some people will have some symptoms and not others. It makes it a very difficult picture to piece together.” 

The impact of long Covid on many patients’ lives is significant. As well as physical symptoms, a 2022 National Institutes of Health study found that a “substantial” number of patients – more than a third – experienced PTSD, anxiety or depression three months after the onset of symptoms.

“You see really heartbreaking cases every day,” says Livingston. “It’s a really difficult condition to live with.” 

Waiting for an ‘aha moment’ 

Looking to the future, there is some hope.  

Ainley compares the struggle to understand the Covid-19 virus, and long Covid especially, to early experiences with HIV, when little was known about how to treat the virus or how it spread. “Now, HIV is not a death sentence like it used to be, but that took 30 to 40 years. The problem with long Covid is, we’re two years into this and we just don’t understand enough of the mechanisms as to how it works.” 

Livingston expects that as more representative data about who has long Covid comes to light, more patterns will emerge to shed new light on who is susceptible.  

“Every bit of research is chipping away and it does help to develop our understanding,” Livingston says. “I’d like to think that there will be an aha moment at some point in the future. You’ve got to hope for that when you’re a clinician or a patient.” 

As cases continue to rise in Europe and the United States, taking steps to prevent Covid infection in the first place is still the best line of defence.  

And for those who already have the illness, research may soon provide much-needed answers. “There’s research to look at why people are susceptible to things, but there’s also research that needs to look to how we treat people and how we help people recover,” Livingston says.  

“Long Covid is something that we’re going to have to think about and treat for a long time. But we do know that people are recovering and that there are rehab approaches that can help people.” 

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