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Feature Covid

How “long covid” is shedding light on postviral syndromes

BMJ 2022; 378 doi: (Published 21 September 2022) Cite this as: BMJ 2022;378:o2188
  1. Brian Owens, freelance journalist
  1. St Stephen, NB, Canada
  1. brian.lawrence.owens{at}

The global burden of long covid has put a spotlight on the long neglected mystery of postviral syndromes. Brian Owens asks what’s changing

Long covid really shouldn’t have been a surprise, says Vett Lloyd, a biologist at Mount Allison University in Sackville, Canada. “When the pandemic started, the general assumption was that there were two possible outcomes to an infection—you’d either get better or die,” she says.

But there’s a possible third outcome. It’s long been known that a number of disease causing pathogens—some viral and some bacterial—are associated with ongoing post-infection symptoms in a significant minority of patients.

“There was no real reason to think SARS-CoV-2 should be any different than the original SARS, which also caused post-infection syndromes,” says Lloyd. She is one of many researchers who hope that the attention and funding directed towards long covid will help to shed light on how and why other infections can lead to persistent and sometimes debilitating symptoms.

Common symptoms

The list of infectious diseases linked to long term symptoms includes Ebola, West Nile virus, polio, and Lyme disease. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is also thought to be a postviral syndrome.

While these diseases all have different acute symptoms, the symptoms associated with their post-infection syndromes tend to be remarkably similar: fatigue, neurological impairments, muscle and joint pain, sleep disturbances, and irritability are all common, says Andrew Lloyd, an infectious disease physician at the University of New South Wales in Sydney, Australia (and no relation to Vett Lloyd)—although each acute infection tends to add its own “flavour” or specific symptom.

Andrew Lloyd led the 2006 “Dubbo” study,1 which found that around 12% of people infected with infectious mononucleosis (glandular fever), Ross River virus, or Q fever in the rural Australian township of Dubbo were still experiencing symptoms after six months. He says that symptoms after glandular fever often include a sore throat, while in Ross River virus joint pain is dominant and Q fever leads to ongoing sweats and headache. “The post-infection phenomenon seems to involve a common denominator, with variations on the theme,” he says.

And post-infection syndromes are often not taken seriously by doctors, at least at first—something Vett Lloyd is familiar with. Her main area of study is Lyme disease, and post-treatment Lyme disease syndrome (or chronic Lyme) is still a controversial subject in many medical circles. The same was true of long covid, but that soon changed.

“There was a tremendous response from the medical community,” she says. “It went from ‘this is all in your head,’ to ‘this is real,’ to dedicated clinics, the fastest I’ve seen for any post-infection syndrome.”

That was due at least partly to the huge numbers of people affected, with some studies suggesting that as many as half of all covid-19 infections can lead to lingering symptoms.23 Andrew Lloyd expects the actual prevalence of long covid to be more like 10-15%.

Unanswered questions

Finding a common cause of the various syndromes would be a breakthrough in postviral syndrome research.

Several hypotheses have been put forward, including persistent but undetected infections, autoimmune responses, dysregulation of the microbiome, and tissue damage.4 But Andrew Lloyd of the University of New South Wales mostly dismisses those ideas. “The lessons we’ve learned from other post-infection syndromes is that it is not a persistent infection, not immunological, not a simple psychological disorder,” he says.

Among researchers who study these illnesses, including long covid, the smart money is now on some kind of disorder of the central nervous system,5 he explains. And since there’s no clear evidence of any major structural problems in the brain, this suggests that the disorder lies at the cellular and protein level.

“There is some circumstantial evidence to support that,” he says. “But nothing concrete yet.”


Alba Azola, co-director of the Post-Acute Covid-19 Team at Johns Hopkins University School of Medicine in Baltimore, USA, has been treating patients with lingering covid-19 symptoms since April 2020.

At first, the patients with long covid seemed to have a lot in common with people with postural orthostatic tachycardia syndrome (POTS), a blood circulation disorder characterised by elevated heart rate and other symptoms brought on by standing up, as fatigue and brain fog are also common symptoms of that condition. So Azola, a physical and rehabilitation physician, along with a team of physiotherapists, started treating these patients using the same protocols as for POTS, focusing on things such as diet and exercise.

But after about three months it was clear that this exercise focused treatment regimen was not working. The team realised that long covid was more like ME/CFS, says Azola, and began drawing on ideas from that area instead. This meant focusing on managing and conserving energy levels and understanding which triggers can bring on fatigue, to get off what she calls the “corona-coaster,” where patients start to feel better, become more active, and then crash.

She says that, in the absence of a reliable treatment or cure, patients need to learn to live with the condition by being selective with their energy and what they invest it in, which can be as simple as using a chair in the shower to avoid unnecessary exertion. “I learned all of this from the ME/CFS community,” she says.

Long covid sparks investment—at last

Because post-acute conditions have been neglected for years the medical field is lagging far behind when it comes to finding effective treatments, but Azola is hopeful that the focus on long covid will help to shed light on other related illnesses.

In some places this is already starting to happen. The Canadian province of Quebec recently announced that it was providing C$20.5m (£13.5m; €15.6m; US$15.6m) to open 15 clinics focused on both long covid and Lyme disease. The clinics, which are slated to open in autumn 2022, will bring together different specialists to help coordinate treatments for these complicated conditions, in the kind of multidisciplinary teams Azola is advocating for. The American Academy of Physical Medicine and Rehabilitation has also launched a multidisciplinary team to develop clinical guidelines and educational resources for physicians.

Vett Lloyd also sees the Quebec clinics as an important step in getting to the bottom of the whole suite of post-infection syndromes. “It’s horrible that it’s taken the suffering of so many people with long covid to make it happen, but integrated clinics like these will help people with many post-infection syndromes,” she says.

Andrew Lloyd agrees. “Billions of dollars have been thrown at long covid research,” he says. “With a bit of luck we will find something relevant not only to long covid but to other post-infection syndromes too.”


  • Competing interests: I have read and understood BMJ policy on declaration of interests and have no relevant interests to declare.

  • Provenance and peer review: Commissioned; externally peer reviewed.

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