health

‘Health systems should be prepared’: doctors brace for tsunami of long Covid


When his throat first started hurting, John Brown didn’t think much of it.

It was March 2020 and the 48-year-old was onboard the Voyager of the Seas, a cruise travelling through the Pacific Islands.

“There were people on board that had the odd cough and splutter,” says Brown, a retired public servant living in Canberra, in Australia’s capital. He put it down to what regular cruisers refer to as “cabin cough” – the result of travelling for several days in air conditioning and close proximity to thousands of other passengers.

The ship docked in Sydney Harbour on 18 March. Brown was one of 34 passengers disembarking the ship who would go on to be diagnosed with Covid-19.

His symptoms were initially moderate – lethargy, a mild cough – but worsened 10 days after his diagnosis. He was admitted to intensive care with breathing difficulties and put on a ventilator. In hospital, Brown says, he was told by doctors that he was Canberra’s eighth confirmed coronavirus case.

John Brown: ‘I walk over to the kitchen to make a cup of tea and by the time I’m at the kitchen bench I’m gasping for air.’
John Brown: ‘I walk over to the kitchen to make a cup of tea and by the time I’m at the kitchen bench I’m gasping for air.’ Photograph: Mike Bowers/The Guardian

Now, more than a year later, Brown is still affected by persistent health issues as a result of Covid-19.

The extreme shortness of breath he experienced in the acute stage of his infection never went away. “I walk over to the kitchen to make a cup of tea and by the time I’m at the kitchen bench I’m gasping for air,” he says.

A lifelong non-smoker, Brown now uses an inhaler typically prescribed for the treatment of chronic obstructive pulmonary disease. He has also been prescribed a medication to treat high blood pressure, a condition he didn’t have before Covid.

A previously active person, Brown is plagued by constant fatigue, requiring 10 to 11 hours of sleep every night and an extra nap in the afternoon. The week before we speak over the phone, he says he got halfway through washing the car before needing a break.

“I came in and sat down and fell asleep – and that was after I’d only been awake for an hour and half,” he says. “I’m glad now that I’m not trying to hold down a job while I’m in the condition that I’m in.”

According to Brown, his eyesight has been affected too, as has his memory – he frequently loses his train of thought mid-conversation. “Why is this even happening?” he says. “I’m dumbfounded.”

Brown is part of a growing number of people who continue to experience symptoms of Covid-19 months after being infected.

Research suggests one in three people who contract Covid will have symptoms that last longer than two two weeks, while about 10% of people have symptoms that persist for 12 weeks or longer. Online, support groups for Covid-19 “long haulers” have swelled to tens of thousands of members.

Almost every organ affected

Doctors are increasingly referring to the condition as PASC: post-acute sequelae of Covid-19. Colloquially known as long Covid, the syndrome can affect nearly every organ system in the body, with sometimes debilitating effects. No standardised clinical definition exists yet.

“This is a really serious problem,” says Assistant Prof Ziyad Al-Aly, director of clinical epidemiology at the Veterans Affairs St Louis Health Care System in the US.

To better understand how long Covid manifests differently in people, Al-Aly and his colleagues tracked 87,000 Covid-positive US veterans over six months after their initial diagnoses.

They found that among those with long Covid, respiratory signs and symptoms including cough, shortness of breath, and low blood oxygen were the most commonly reported. The findings of the study were published in April, in the journal Nature.

Though respiratory conditions were the most common, the syndrome seemed to affect most bodily systems. “Wherever we looked there were signals of disease,” says Al-Aly. In their patients, long Covid involved organs including the lungs, brain, heart, liver and skin.

An MRI machine at St Vincent's hospital in Sydney
Neurological symptoms, including fatigue, headache and memory problems, are a common feature of long Covid. Photograph: Carly Earl/The Guardian

The disorder had a wide range of effects, including cardiac and lung damage, sleep problems, memory issues, mental health disorders and skin rashes.

“The risk was evident even among those people who were not hospitalised for Covid-19,” Al-Aly says.

People with long Covid also had increased rates of new prescriptions for painkillers, drugs for depression and anxiety, and blood pressure and diabetes medications.

In Australia, researchers at the University of New South Wales’s Kirby Institute in Sydney have been following 99 patients who were diagnosed with Covid-19 in Australia’s first wave in March and April 2020. Results published as a preprint showed that a third of patients still reported persistent symptoms eight months post-diagnosis.

“The symptoms are very much what we would link to a post-viral syndrome, with quite intense fatigue that comes and goes, headaches, brain fog [and] a variety of other generally quite nonspecific symptoms,” says Prof Gail Matthews, one of the lead investigators of the study.

Long Covid bears similarities to other chronic syndromes that affect some people after other viral infections, including Ebola, Chikungunya and hepatitis B.

For many survivors of Sars, to which the Covid-19 virus is closely linked, fatigue symptoms persisted even four years after they were first infected. A 2009 study of more than 200 Sars survivors found that 27% met the clinical criteria for chronic fatigue syndrome.

Chronic fatigue syndrome, also known as myalgic encephalomyelitis or referred to as ME/CFS, can also follow a seasonal flu infection, although it isn’t common.

“Post-influenza, some people also continue to have fatigue and respiratory symptoms,” says Al-Aly.

His team also compared the effects of long Covid on the body to chronic post-flu conditions. They found that people diagnosed with Covid-19 had a far higher risk of developing chronic symptoms than those infected with seasonal influenza.

“The breadth of organ involvement is much, much more extensive with Covid,” he adds.

What triggers long Covid?

There are several theories as to what causes long Covid. One is that remnants of the Sars-CoV-2 virus linger in the body, in reservoirs such as the gut, and aren’t able to be fully cleared by the immune system, which results in a chronic inflammatory response.

Another is that Covid-19 triggers an atypical immune reaction that lasts beyond the virus’s presence in the body.

The common neurological symptoms of long Covid – fatigue, headache and memory problems – may be a result of immune mediators that build up in the brain, says Prof Frank Heppner, chair of the Department of Neuropathology at the Charité – Universitätsmedizin hospital in Berlin.

Heppner’s work has shown that in the acute phase of Covid, the Sars-CoV-2 virus enters the brain via cells lining the nasal cavity, which helps to explain loss of smell as a common symptom, as well as neurological symptoms including fatigue and headache.

A nurse attending to a patient while they are scanned with an MRI machine
Women are disproportionately likely to develop long Covid. Photograph: Carly Earl/The Guardian

But after a Covid infection, the amount of virus in the brain and nose decreases over time. In long Covid, Heppner suggests, the culprit may be small proteins such as cytokines, which the immune system produces as chemical messengers.

Heppner cites the hepatitis B virus as a telling example. Although the virus itself isn’t able to enter the brain, the post-viral syndrome it results in also involves neurological symptoms.

Why long Covid occurs in some people but not others is likely down to a complex combination of factors, including hormones, immune status, genetic background and nutrition, says Heppner.

Research into long Covid patients has found that the condition occurs more frequently in people who are older and have a higher BMI, as well as those whose initial Covid infections were more severe.

Women, too, are disproportionately likely to develop long Covid, even though men with acute Covid have three times the odds of needing ICU treatment than women.

“Women do tend to suffer more from autoimmune diseases and autoimmune phenomena than men do,” says Matthews, which may point to a link between long Covid and autoimmunity.

No definitive treatments

In the absence of a definitive cure, doctors are falling back on well-established treatment options. “We know how to treat depression, we know how to treat new-onset diabetes, we know how to treat pain,” Al-Aly says.

Research suggests that early rehabilitation may be beneficial, particularly for Covid patients with serious lung damage. Light exercise and a gradual increase in activity may also be beneficial.

A treatment room sign at St Vincent's hospital
Australia now has no specific treatments for long Covid beyond addressing a person’s individual symptoms. Photograph: Carly Earl/The Guardian

This has been the experience of Dr Anna Poletti, an Australian academic who probably contracted Covid-19 in March 2020 in the Netherlands, although she was unable to get a test at the time.

Poletti, who is based in Utrecht, wrote about her persistent Covid symptoms for the Guardian last July. She has since undergone seven months of structured rehabilitation with a lung physiotherapist who specialises in chronic obstructive pulmonary disease, asthma and other respiratory issues.

“I couldn’t walk and talk at the same when I started rehab,” says Poletti. “My entire chest cavity and my lungs would just ache, and I would get so tired that I had to sleep.”

A persistent itchy, inflamed sensation in her chest has subsided over time but she still experiences flare-ups of chest pain every few weeks.

“Rest, relaxation, meditation and pacing are the cornerstones of a post-viral condition like long Covid,” says Dr Raymond Perrin, a UK neuroscientist who has been working with ME/CFS patients for several years.

Perrin is about to commence a trial with 100 long Covid patients in collaboration with Manchester University and the Salford Royal hospital to evaluate whether self-massage techniques may help to improve long Covid symptoms.

There is some evidence, mostly anecdotal, to suggest that Covid vaccination might also help to reduce long-term symptoms.

In a small study of 44 people, published in preprint form, those with long Covid reported a “small overall improvement” in symptoms after vaccination. These findings however, are difficult to verify without a randomised controlled trial.

In future, further studies of how Covid-19 specifically affects the immune system may lead to targeted treatments.

Heppner and his colleagues are using genomic sequencing at the level of single cells to figure out how they respond to Covid-19. Ideally, they are trying to determine what immune mediators increase in response to the virus.

“Once we know that, we can specifically target them and then basically level them down … and even pre-emptively try to treat those acute-state patients to not even allow long Covid to occur,” Heppner says.

Left without answers

In the meantime, people with long Covid are living with uncertainty about how long their symptoms will last.

Al-Aly estimates that in the US alone, long Covid will affect approximately 3 million people. Given the sheer scale of Covid-19 infections worldwide, a rise in the numbers of long Covid cases seems inevitable. “Health systems should be prepared for this,” says Al-Aly.

Long Covid sufferer John Brown at his home in Canberra
Long Covid sufferer John Brown at his home in Canberra. Photograph: Mike Bowers/The Guardian

Part of the frustration for her patients, says Matthews, stems from the unpredictable nature of the condition. “Symptoms can be improving and they can feel they’re on the mend, and then they might have some worse days down the track,” she says.

Matthews says: “Although we do see a lot of these symptoms persisting, for a lot of our patients there is a sense of a gradual recovery. It’s just difficult to know when that will be.”

At the eight-month review, 54% of Matthews’ long Covid patients felt they had fully recovered.

Poletti says that despite the occasional chest pain, she is now back to pre-Covid fitness levels. But throughout her rehabilitation the thought that she might never work again was at the forefront of her mind.

“It’s really important that people in the lives of someone with long Covid also have the patience and the compassion to accept that that person is in fact not in full health,” Poletti says. “The fact that people were understanding and compassionate made a huge difference.”

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