As the coronavirus continues its retreat across Canada, another public health threat is coming into sharper view, one that some experts have described as a “looming catastrophe”: Long COVID.
Since the pandemic’s first wave, “long haulers” have pleaded for more resources to help patients who survive their infection but continue to suffer from lingering effects.
Their symptoms can be debilitating, hobbling their ability to work, read or climb a set of stairs. Some long COVID patients have suffered for a year or more and fear they will never resume their pre-pandemic lives, even as vaccinations restore normalcy for everyone around them.
The burden of long COVID, experts warned in a recent New England Journal of Medicine editorial, may be the “next public health disaster in the making.”
“Some people have been talking about long COVID as the post-pandemic pandemic,” said co-author Dr. Angela Cheung, an internal medicine specialist at University Health Network and co-lead of CANCOV, a Canadian research consortium studying long COVID.
“In Canada, we’ve had 1.4 million people with COVID. And if you estimate 10 per cent (have long COVID), that is still a significant number — and I think 10 per cent is actually conservative.”
Research into long COVID is finally gaining momentum. On Thursday, the Lancet published a study of more than 70,000 hospitalized patients in the United Kingdom and found that half developed complications that
could have longer-term effects — including younger, previously healthy people, who might be “proportionally more likely to survive and live with complications.”
Last month, the Public Health Agency of Canada released its first scientific review of the medical literature on long COVID, estimating that 56 per cent of COVID patients still experience symptoms after three months. This “living systematic review” — which analyzed 36 studies published before Jan. 15 and will be periodically updated — is a pre-print, meaning it has not been published by a peerreviewed journal.
But the emerging data still raises more questions than answers. The Star takes a look at what we know — and don’t know — about the long tail of COVID-19.
What is long COVID?
On Facebook pages and online support groups, they call themselves “long haulers.” In the scientific literature, the illness has been described as “chronic COVID syndrome,” a “post COVID-19 condition” or “postacute COVID-19.” In the United States, the government’s medical research agency has dubbed it PASC — “post-acute sequelae of SARS-CoV-2 infection.”
A first step in tackling a problem is to define it. But when it comes to long COVID, scientists have yet to even agree on a name — or how to diagnose it.
“There’s an awful lot we don’t know about it and one of the active things we’re doing is trying to develop a case definition,” said Dr. John Marshall, a professor of surgery with the University of Toronto, who is part of a World Health Organization working group tackling this problem. “We’re trying to understand the predominant symptoms that patients experience, and how do we even adequately describe it.”
One reason long COVID is so tricky to define is that it seemingly affects multiple systems and organs, and has a huge constellation of potential symptoms, Marshall said.
In the recent PHAC review, study authors identified more than 100 symptoms. A patientled study in EClinicalMedicine, an open-access journal published by the Lancet, identified 203 symptoms reported by more than 3,700 long haulers who filled out an online survey.
The most commonly reported are symptoms like fatigue, “brain fog,” memory loss, shortness of breath, anxiety, depression and persistent loss of taste and smell. But in the EClinicalMedicine paper, patients also reported everything from hair loss and tinnitus to “an inability to yawn.”
Another sticking point: timelines. What constitutes long COVID — someone who still hasn’t recovered after three months? Six months? A year?
“Those sorts of things are being discussed and debated,” Cheung said. “Personally, I think 12 weeks is a good mark, because (with) other viral illnesses, you expect that someone will have gotten over it” by then.
Coming up with standard definitions is critical from a research perspective, because it allows scientists to measure prevalence, identify risk factors and, importantly, home in on possible treatments, said Dr. Curtis Cooper, a professor of medicine with the University of Ottawa.
Cooper is another co-author on the PHAC review, which he said is one effort that will help researchers develop a checklist for what constitutes long COVID.
But he stressed that from a clinical perspective, it’s important not to be overly restrictive when diagnosing long COVID — especially since so many sufferers are desperate for help and struggling to be heard.
“If someone is in front of you saying, ‘I have this collection of symptoms’ and you know they had COVID, I’m not going to deny they’re a long hauler,” he said. “We can’t send them away and say they don’t have long COVID.”
How common is long COVID?
The phenomenon of long COVID has historical precedent. After the “Russian influenza” pandemic that began in 1889, there were widespread reports of patients with lingering “nerve exhaustion,” “inertia” and “post-grippal numbness,” the Lancet reported in October.
“The official end of the pandemic … did not mean the end of illness,” the article said, “but was merely the prelude to a longue dure of baffling sequelae.”
Many viruses, from mono to Zika, are known to cause persistent symptoms in certain patients. But is SARS-CoV-2 more likely to do so?
Some studies suggest this could be the case. This week’s Lancet paper on hospitalized COVID patients found that the rate of complications was “the same or higher” when compared to influenza.
A Norwegian study published by Nature last month also found that 61 per cent of 312 patients had persistent symptoms at six months. More than half of people between 16 and 30 — none of whom required hospitalization — still had symptoms, including loss of taste or smell, fatigue and memory problems.
“The high prevalence of persistent fatigue in patients with COVID-19 is striking and appears higher than observed after common infections, such as influenza, Epstein-Barr virus, mononucleosis and dengue,” the authors wrote.
But because long COVID is so inconsistently defined across the various studies, it’s hard to nail down a true prevalence. Estimates have ranged from 10 per cent to half of all COVID cases.
Cheung believes the truth is somewhere closer to the middle, maybe around 30 per cent. In Canada, that would translate to more than 420,000 people.
She noted that many long COVID sufferers do see their symptoms resolving with time. But the wider societal impact is substantial, even in the short term; in the EClinicalMedicine paper, 45 per cent of respondents with long COVID were working at reduced hours compared to before they got sick, and 22 per cent unable to work at all.
“We know from post-ICU studies that this is a group of patients who have a disproportionate use of health-care resources, and they continue to — it doesn’t go away.”
DR. MARGARET HERRIDGE PROFESSOR OF MEDICINE, CRITICAL CARE AND PULMONARY MEDICINE AT UNIVERSITY HEALTH NETWORK
Who’s at risk?
A critical question for preventing long COVID is understanding which patients are most at risk.
But for Marshall, his sense is there are probably many different syndromes being lumped together under the umbrella term of “long COVID” — so risk factors are likely different for patients in each group.
A COVID patient who languished in ICU and one who
never even developed the sniffles can both experience lingering, debilitating symptoms — but their risk factors, and the pathophysiology of their long COVID, is likely different.
In the critical care world, experts have long understood that seriously ill patients who spend long stretches in ICU can emerge with long-lasting or even permanent issues.
There are potential consequences to spending long periods of time in the ICU, with or without COVID, said Dr. Margaret Herridge, a professor of medicine, critical care and pulmonary medicine at UHN, who co-leads CANCOV with Cheung — not just physical disability, but brain disorders, PTSD or cognitive dysfunction.
And many of these people will require ongoing care, she said. “Those of us who do this already knew that” before COVID, Herridge said. “It’s just that there hasn’t been a critical mass of these folks.”
Herridge has seen many COVID patients leave the ICU with functional disabilities, including younger adults — they might struggle to walk, or climb in the tub. Not all will get better with rehab, she said.
Time and research will tell whether COVID survivors experience more post-ICU problems compared to other patient populations, she said. But anecdotally, Herridge can already see some differences; before, she never saw patients who needed home oxygen after their ICU stay, she said.
“I think the scope is huge,” Herridge said. “We know from post-ICU studies that this is a group of patients who have a disproportionate use of healthcare resources, and they continue to — it doesn’t go away.”
Long COVID patients who never set foot inside a hospital are, in some ways, far more puzzling. Their risk doesn’t seem to be related to the initial severity of symptoms, Marshall said.
“If anything, it’s almost an inverse relationship, in that it’s people who had relatively mild symptoms and never even sought medical attention for COVID-19 finding that they have these long-standing, disabling symptoms,” he said. “It’s a bit surprising.”
People of all age groups have had long COVID, though its prevalence in children is particularly unclear; of the 121 research projects investigating long haulers, only six involve children, according to a group tracking COVID-19 research globally.
One intriguing pattern: women seem to be more affected, based on data so far. This is a pattern that Cheung has also observed among CANCOV participants who were never hospitalized.
And because COVID has disproportionately affected racialized and low-income communities, many experts worry these populations also face a heightened risk of long COVID — and will struggle even more to find help, especially since they face barriers to health care and are often under-represented in medical studies.
“If the past is any guide, (long COVID patients) will be disbelieved, marginalized, and shunned by many members of the medical community,” stated a recent op-ed in NEJM. “Our medical system has a long history of minimizing women’s symptoms and dismissing or misdiagnosing their conditions as psychological. Women of color with long COVID, in particular, have been disbelieved and denied tests that their white counterparts have received.”
Can vaccines help?
The COVID-19 vaccine has delivered many gifts. But one that few people expected was that it could become a potential treatment for long haulers.
Since vaccination rollouts began in earnest, there have been a growing number of anecdotal reports from patients who say their long COVID symptoms finally disappeared post-vaccination. There is very little data to support this and researchers are now investigating whether this is a real effect — and possible explanations.
Cheung said she hasn’t seen vaccines helping patients in her own study cohort yet; out of roughly 200 vaccinated patients, six said their symptoms improved. (Around five said they worsened.) Most reported no change.
But in a recent online survey of 900 long haulers — most of whom still had symptoms after nine months — 57 per cent of people saw symptoms improve after a first dose, whereas 19 per cent saw symptoms deteriorate. The survey, headed by an advocacy group working with two academic researchers, has limitations, and the authors recommended further study.
Writing on the website Elemental, Akiko Iwasaki, a professor and immunologist with the Yale School of Medicine, recently outlined three hypotheses for why vaccines might alleviate long COVID symptoms.
One theory is that long haulers are still harbouring a viral infection, for example in their gastrointestinal tract, and the vaccine triggers an immune response that kills the infected cells.
Another is that the vaccine could be triggering an immune reaction that finally sweeps away remnants of the SARSCoV-2 virus, which are no longer causing infection but provoking an inflammatory response.
And finally, perhaps long COVID is caused by an autoimmune response, so the vaccine, which triggers a transient immune reaction, manages to redirect the immune system.
But as with all things long COVID, much more data is needed, Cooper said.
“It really is too early to say whether immunization has any impact,” said Cooper, who is involved in an Ottawa-based study now looking into whether vaccines can alleviate longhauler symptoms.
“There are lots of good reasons to get vaccinated, but I’m not telling my patients get vaccinated because it’s going to improve your long-hauler symptoms. I’d say, you might find an improvement in your symptoms — and I hope so — but I can’t say that for sure today.”