everything we know about long covid, from strange phantom smells to chronic fatigue

at first, there was no sense of smell, “zero, zilch, nothing,” for weeks on end.and then manali mukherjee suddenly could smell smoke. she’d find herself in a panic: is something burning? is there a short circuit in the house? some days it was like being inside a smokers’ lounge, the heavy cigarette smell lasting seven or eight hours and causing crippling cluster headaches.except there was no smoke at all.phantosmia causes people to smell phantom odours, to essentially hallucinate smells, while with parosmia, a known smell is no longer the same. once-pleasing food can smell unusually unpleasant, like rotting meat.mukherjee was diagnosed with covid-19 in january. in addition to serious olfactory dysfunction, the assistant professor in mcmaster university’s department of medicine still has trouble with staggering fatigue, sudden plummeting blood pressure and difficulty focusing. “there were good weeks, and then bad weeks. i just kept thinking, ‘i’m a trained immunologist, i know what might be happening to me, and i’m getting this anxious. what’s happening to other people who don’t know about it?’”what happened to mukherjee was long covid, the same syndrome she’s been granted $500,000 in federal funding to study. it’s a vague, poorly defined condition without a prognosis or proven treatments and that an unclear number of canadians may have had or may still be living with.people describe lungs that feel packed in flour, brain fog that feels more like dementia and fatigue unlike anything they’ve ever experienced.mukherjee believes the answer to these symptoms is rooted somewhere in the immune system, and a hyper-stimulated one: once the virus is cleared, the body’s immune activation goes rogue, unleashing auto-antibodies that turn on its own tissues and proteins. somehow the immune system has become confused and rowdy, “and what you’re left with is the collateral damage,” mukherjee said.with 271 million confirmed infections worldwide, some researchers have warned long covid is the next “looming catastrophe,” with prevalence estimates all over the map, from as low as two per cent of the covid “recovered” to as high as 89 per cent.since early summer of 2020, “long haulers” have described a constellation of symptoms affecting nearly every organ system in the body, and while there are a number of plausible hypotheses to explain them, none have so far been proven. even the definition of what, exactly, defines long covid “is still very much in evolution,” steven phillips, vice-president of science and strategy at the covid collaboration, said in an interview with the new england journal of medicine. while the symptoms are very real, “and really seriously afflict people,” the problem is frustratingly complex, difficult to diagnose and unpredictable, phillips said. no one knows who is truly at risk or how long symptoms might persist, though scientists like mcmaster’s mukherjee are trying their best to solve the post covid “conundrum.”some have called for greater nuance and a more cautious approach to thinking about long covid, worried that, without clear, diagnostic tests, some symptoms are being misattributed to sars-cov-2. one psychiatry intern at mukherjee’s own university once characterized long covid as “largely an invention of vocal patient activist groups,” helped along by uncritical media coverage. some studies have found that people who report symptoms don’t always have evidence of antibodies against sars-cov-2. “the long covid thing,” sir john bell, a canadian immunologist and regius professor of medicine at the university of oxford, told times radio, “has been slightly overblown, and as soon as you do proper epidemiological studies you find the incidence is much, much lower.”but mukherjee and other researchers calculate that even by the most conservative estimate — according to the world health organization, one in 10 people infected with covid will experience symptoms lasting beyond 12 weeks — for canada, that would be on the order of 200,000 people. “staggering numbers,” said dr. fahad razak, an internist and epidemiologist at st. michael’s hospital in toronto. “anyone can be impacted by this, young and old alike, and even if you were asymptomatic during initial infection.”the pathophysiology, the underlying biological causes, are not at all clear. is it an immune response gone chaotic? fragments of virus lurking inside the body? super infections? micro-clots in the blood?various terms have been used to describe it, further complicating things, from chronic covid and long covid to the most recent “post-acute sequelae of sars-cov-2” or pasc. and while post-covid symptoms are being seen in children, “the data is even skinnier when it comes to the under 18,” mukherjee said.according to the public health agency of canada, post-covid conditions are defined as one or more symptoms persisting or recurring 12 weeks or longer after a covid diagnosis that are not attributable to any other diseases. symptoms are wide ranging, from the most frequently reported — fatigue, headache and brain fog — to the more rarely reported, such as paranoia.those who experience severe, or life-threatening infections may be at slightly higher risk. anyone who spends time in an intensive care unit, whether for covid or sepsis, can acquire life-transforming complications, according to research by the university of toronto’s margaret herridge, co-leader of a study looking at one-year outcomes in people infected with covid.herridge’s research into post-intensive care syndrome has found that people who spend a week or longer in an icu, immobilized and heavily sedated on a ventilator can experience fatigue, nerve and muscle injury that can last months after they’re sent home, as well as cognitive dysfunction that messes with memory, attention and problem solving. anxiety, depression and ptsd occurs in 25 to 35 per cent of icu survivors.“with millions of individuals contracting covid-19 worldwide, an unprecedented number of intensive care unit (icu) survivors are now in recovery,” herridge and colleagues wrote in the lancet.but people can develop long covid even after what was initially a mild, or even symptomless infection.other viruses, including other coronaviruses, can affect some people for years. “this has been seen post influenza, it’s been seen after sars,” razak, of st. mike’s, said. studies on survivors of the sars outbreak in 2004 showed lung abnormalities, one year out. others were left with severe, disabling fatigue that lasted four years. “we have to be really cautious about not under-appreciating how chronic and persisting these symptoms can be,” razak said. the fatigue and cognitive effects can affect basic activities of daily life, he said. getting out of bed. bathing. caring for children.yet there is “absolutely” still skepticism among the medical and scientific community “because we’re dealing with a condition that is new,” said razak, first author of an ontario science advisory table brief on long covid. people have described doctors waving off their symptoms as being unrelated to covid, and employers questioning sick time. razak was skeptical himself going into writing the science table brief. after reading the available literature he became convinced that “we are dealing with a real entity here.”risk factors might include having a higher body mass index, being female, being older and having a “higher acuity” of sars-cov-2 infection, according to the science table brief. vaccination reduces the probability of developing it, by greatly reducing the chance of becoming infected in the first place.emerging evidence also hints that vaccination reduces the risk of long covid in breakthrough infections. some people report symptoms improved after their second dose, which might buoy the notion that the problem could be due to reservoirs or fragments of virus, imperial college london researchers wrote in the lancet.as for the long-term prognosis, a study published in the lancet, the longest follow-up study to date involving covid hospital survivors infected in wuhan’s first wave found that, at 12-months follow-up, most had returned to their original work and original lives, and that those with “persisting, severely impaired health status are rare.” however, 24 per cent of people who were employed before covid didn’t return to their pre-covid level of work, and 12 per cent hadn’t returned to work at all. “our data suggest that a full recovery after 1 year is not possible for some patients, for whom it will take longer to attain their baseline health state before covid-19,” the researchers reported.the chinese team found evidence of persistent abnormalities in lung structure and function. razak believes much of the pathophysiology likely isn’t related to the original infection and damage to the organs. “it has to do with things that happen after,” he said, like an immune-related phenomenon — an excess and runaway immune response to the virus — or increased clotting.some researchers have provocatively suggested other elements might be at play.a controversial french study involving nearly 27,000 people whose blood was screened for antibodies to sars-cov-2 found that people who believed they had been infected, but whose infection couldn’t be confirmed by the antibody test, were more likely to report symptoms of long covid.“beliefs regarding the causes of these symptoms may influence their perception and promote maladaptive health behaviors,” the french scientists wrote, the implication being that some people who have symptoms attributed to long covid perhaps never had covid.but serology tests that screen for antibodies can miss previous infections, and antibody levels wane over time — it’s the very reason health leaders are pushing vaccine booster doses. the authors’ conclusion “reiterates a damaging narrative, implying that long covid is a psychological disease and that by taking steps to avoid symptom exacerbation, patients are effectively making themselves sick,” dr. jeremy rossman, honorary senior lecturer in virology at the university of kent said in an expert reaction.multiple studies show people infected with sars-cov-2 can have physiological symptoms that just aren’t present in the uninfected, rossman said.

under who’s definition of long covid, there’s no need for proof of a lab-confirmed infection. it includes a history of probable infection, acknowledging that many people didn’t have access to testing early in the pandemic.still, colleagues have asked razak, of st. mike’s, how is it possible that one condition could cause such a dizzying array of symptoms? more than 100 have been ascribed to it, though the “one most reported, and most debilitating, is terrible cognitive problems, terrible brain fog,” said toronto psychiatrist dr. roger mcintyre. “people say they have absolutely no energy and absolutely no motivation.”“there’s a whole neuroscientific literature now to show that when the immune system is activated it does have a very localized effect on your brain,” said mcintyre, who is now testing the antidepressant vortioxentine for post-covid syndrome. in people with depression, the drug has been shown to improve cognitive function — it makes thinking sharper and clearer — and boost energy and motivation. mcintrye said he’s not implying that post-covid means people necessarily have depression. “there’s no implication this is depression. there is no indication that this is mental illness. we just happen to be repurposing this medication for this very, very difficult to understand condition.”it’s not known whether the hyper mutated and fast-spreading omicron variant, which preliminary data out of south africa suggests causes milder disease than delta, will make things any different. would it mean less long covid if people are less sick to begin with, or several-fold more cases, as more people ultimately become infected?for her study, mukherjee has recruited people who are up to 15 months post covid diagnosis. on lung function tests, physiologically they look fine. but even a simple, six-minute walk test, “and the shortness of breath comes back, the chest pain comes back, the heart rate increases crazily.”“we need to find out what exactly is happening,” mukherjee said. “we need to do studies in bigger numbers, in collaborations, over time. and the people who are fighting this, who are going through this, need to come and get themselves enrolled in studies, and stick to the study, so that we can understand this disease.“because unless we understand it and see it and report it and be honest about what we are seeing, we’ll not be able to get to the bottom of this.”• email: skirkey@postmedia.com | twitter: sharon_kirkey

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