A comprehensive study of more than 230,000 people by Oxford University researchers has linked neurological disorders, such as stroke and dementia, to Covid-19. By Rick Morton.
Covid-19 and its effects on the brain
The largest study of Covid-19 sufferers and the long-term effects of the virus offers some good news: it doesn’t appear linked to an increased incidence of Parkinson’s disease or Guillain-Barré syndrome. But the novel coronavirus is causing significant neurological symptoms, Oxford University professor of psychiatry Paul Harrison says.
“There is no doubt that the [Covid-19] virus is detectable in the brain,” he tells me from England. “It probably spreads through the olfactory nerve. It gets up your nose, travels along the nerve and gets into your brain.”
Harrison, who also leads Oxford University’s translational neurobiology group, is one of the authors of the groundbreaking study, which examined 236,000 people who’d contracted Covid-19.
At the headline level, the research makes for astounding reading: 34 per cent of people in the sample developed a neurological or psychiatric disorder. Nearly 13 per cent received their diagnosis for the first time. The rest experienced a recurrence of a former illness.
The paper, published in the journal The Lancet Psychiatry, answers a lingering question about the long-term health consequences of Covid-19. The SARS-CoV-2 virus does coincide with an increase in psychiatric conditions and, more alarmingly, it can cause a medley of neurological malfunctions. For the latter category, the more severe the Covid-19 infection, the more likely a condition will develop.
“These are the first real and reliable estimates of how common the neurological syndromes like dementia and stroke really are,” Professor Harrison tells The Saturday Paper. “People had reported that these appear to be common [in Covid-19 patients] but we didn’t really have any good numbers on it.”
The ongoing health problems now linked to SARS-CoV-2 six months after first diagnosis include haemorrhages in the brain, strokes in the brain caused by blood clots, nerve disorders and damage to a bundle of interwoven nerve fibres running from the spinal column, known as a plexus. The Oxford study also noted dementia, disorders in the myoneural junctions, where motor neurones chemically speak to the muscle fibres, and encephalitis.
But remember, this is a good news story.
“In terms of the things that we didn’t find that we might have done, we didn’t really find there was more Parkinson’s disease after Covid,” Harrison says. The findings were similar for Guillain-Barré syndrome, an autoimmune condition that presents with muscle weakness beginning at the extremities.
“So, there were two neurological syndromes people had worried about which we really didn’t find good evidence for being commoner after Covid-19 than the other conditions we looked at,” Harrison says.
To make sure their study results were robust, the Oxford team – led by Dr Maxime Taquet – compared detailed health records for a cohort of Covid-19 patients against two other groups. The first was 105,000 people who’d had a confirmed influenza diagnosis. The other group was made up of a further 236,000 people who had a respiratory tract infection that was not Covid-19.
Although people were diagnosed with Parkinson’s and Guillain-Barré syndrome six months after their illness in all three cohorts, the rate was not appreciably higher among those with Covid-19.
“The worry about Parkinson’s really came from this historical event with the Spanish flu after the First World War when we had this condition called encephalitis lethargica in people who survived the proper influenza epidemic,” Harrison says. “There was this remarkable occurrence, almost an overnight Parkinson’s disease developing in some of those survivors. It was something people worried about for that historical reason.”
For other neurological conditions, though, the Oxford findings don’t bring much good news. The researchers broke down the conditions observed by severity of the Covid-19 illness. Sufferers were grouped into those who did not go to hospital, those who did, those who ended up in intensive care and those who developed delirium or other forms of altered mental states from the infection. The study grouped this final cohort under “encephalopathy”.
Mental illnesses such as depression and anxiety did not become significantly more common with the advancement in severity of Covid-19. In fact, Harrison and his Oxford colleagues found that although almost a quarter of those who had Covid-19 had one or more of these illnesses six months after contracting the infection, this was largely not related to the biological basis of the virus. Instead, it stemmed from the fear of the pandemic itself – fear of dying from this mysterious and new illness, being quarantined and so on.
But more severe and debilitating neurological ailments did become more frequent with the seriousness of the viral illness, which tells researchers the virus itself is, somehow, triggering these secondary diagnoses.
Of the 236,000 people in the main study who had contracted Covid-19, more than 2 per cent had an ischaemic stroke, which occurs when blood clots block circulation in the brain. Slightly less than 0.6 per cent had brain bleeds. For patients with the most severe expression of the virus, however, the incidence for these conditions rose to almost 10 per cent and 3.6 per cent, respectively.
Dementia occurred in almost 0.7 per cent of Covid-19 patients but this jumped to 4.7 per cent among those who developed encephalopathy. Nerve disorders were the highest of the total neurological group, with almost 3 per cent of the 236,000 patients developing these conditions after contracting Covid-19. The rate was 4.7 per cent for those who had the most severe cases.
About 0.5 per cent of people developed a myoneural junction disorder but this, too, leapt to well over 3 per cent among those who needed intensive care or who developed delirium as a result of the coronavirus.
These findings have implications for vaccination programs around the world. To varying degrees, the different vaccines that have reached the market to date prevent contraction of the virus but also, according to study data, prevent its most severe forms developing where infection cannot be stopped.
“There is every reason to expect and to hope, if you’ve been vaccinated, not only will you either not get clinical Covid-19 at all or you certainly won’t get it badly, but I would imagine these numbers [of secondary conditions] would go down as well,” Harrison says. “It would be bizarre and bad luck if the vaccine stopped you thinking you had Covid-19 but still left you with strokes.”
In Australia, with the time line for the vaccine rollout now scrapped, it will likely take longer to reach population immunity than it took scientists to develop a vaccine for this entirely new virus.
Professor Harrison and his team have now shown the proof that the burden of disease goes well beyond Covid-19 itself.
“If you take it at face value, there seems no doubt there are going to be more cases of the disorders that we measured than might have happened without Covid-19,” he says.
Although he does note that “because we’ve all not been going to get healthcare properly, we’ve all been stressed” there are going to be increased health issues as we emerge from this crisis.
“How much of the Covid-specific burden is going to contribute to the overall increase in health burden? I don’t know,” he says.
Harrison and the team of Oxford University researchers “tried very hard” to match the Covid-19 group not only against control cohorts who had the flu or other respiratory tract infections but also for the severity in those control groups.
There is something about the make-up of the SARS-CoV-2 virus itself, with its spiky crown of thorns and ability to induce a chaotic nervous system response that attacks the human body, which marks it as a particularly efficient wrecking ball in the human body.
“So, the greater numbers [of neurological and psychiatric conditions] we saw after Covid-19 wasn’t just that the average Covid patient was more ill than the average influenza patient,” he says.
Still, Harrison says, it could have been worse. The world was always going to get another pandemic: “This is exactly what SARS and MERS told us was going to happen. It was a matter of when, not if.”
In a sense, he says, we were lucky – given that Covid-19 “for most people, is relatively mild and for most people is asymptomatic”.
The real concern is that the next pandemic will be more severe. “That would be my rather more cynical view of this. We now have a world that allows viruses to come together and species to come together that were probably never meant to,” Harrison says. “And every time that happens you are throwing the dice of a random recombination event between viruses.
“One of the lessons I think we need to learn from this is what epidemiologists have been telling us for decades: another pandemic is going to come along. So, to what extent can you be prepared for it when you don’t know what bug it will be, what part of the body it will affect. It’s difficult but at least I hope we’ll learn some lessons about working together and sharing information.”
While the world has witnessed the most concerted scientific effort in human history, there are many questions about Covid-19 that remain unanswered.
One mystery Harrison hopes to clear up is the situation of the Covid “long haulers”.
He notes a distinction between the medically recognised conditions of his Lancet study and this “patient-led” condition, also described by many tens of thousands of people who have had the viral infection known as “long Covid”.
“Long Covid doesn’t have an official definition yet,” he says. “It has a wide range of symptoms but at its core is a sort of persistent breathlessness, persistent pain, persistent malaise, fatigue, anxiety, GI [gastrointestinal] symptoms and a range of other slightly more odd ones.
“Now, some of those are diagnoses but many of them are symptoms or complaints. So it’s a bit more difficult to answer the long Covid question using this network [the health records database TriNetX] where mostly what is recorded are established diagnoses.”
That said, Harrison announces that his team are just now finalising a paper on this exact subject looking at six-month outcomes.
“How common is what people are calling ‘long Covid’? How much is there a syndrome of lots of things happening together? We hope those data will also be of interest when the peer review is published.”
Harrison is coy about what the upcoming paper will reveal.
“You do have to ask,” he says, “and I do have to say that people will think it is interesting.”
This article was first published in the print edition of The Saturday Paper on Apr 17, 2021 as "Long blows".
A free press is one you pay for. In the short term, the economic fallout from coronavirus has taken about a third of our revenue. We will survive this crisis, but we need the support of readers. Now is the time to subscribe.