Wednesday 29 September 2021


What We Know So Far about How COVID Affects the Nervous System

Neurological symptoms might arise from multiple causes. But does the virus even get into neurons?

Thursday 21 January 2021

The Emerging Links Between Corona Virus And Nerve Damage

 Today's post from (see link below) is an excellent article, based on the story of one patient's experiences of the virus and highlighting both his and the potential consequences for everyone of a corona infection. You have to remember that this is still a new virus and both the medical experts and we as neuropathy patients are learning as we go along. This sort of well-written article greatly adds to our knowledge and understanding of how Covid-19 works.The more we hear, read and see about the current pandemic, the more obvious it becomes that it can have serious consequences for people already living with nerve damage symptoms. It's alarming, bordering on the frightening and yet we're consistently underestimated as a risk group that needs more specific rather than token protection. Yes it's fantastic news that effective vaccines are being developed and rolled out at record speeds but a virus's one and only purpose is to adapt to new conditions and circumstances and cause as much damage as possible. Now, it's becoming evident that that damage can having devastating consequences over the long term, for neuropathy patients yet we've got little option but to try to abide by the rules and wait until science catches up and starts to address the consequences of Covid-19 for specific conditions such as nerve damage. It's going to be a long wait folks! So what can we do to maintain hope and sanity while the virus mutates and finds new ways to spread itself across the population bands. It looks like the vaccines may need to be updated every year in much the same way as the current flu jabs are - a mutating virus is the enemy of all of humanity and worst of all, if you have to anthropomorphize doesn't care!!

 The subject of this article's images have not been reproduced here to avoid potential associations with HIV that are totally unnecessary.


Long after the fire of a Covid-19 infection, mental and neurological effects can still smolder

By Elizabeth Cooney @cooney_liz August 12, 2020

Early on, patients with both mild and severe Covid-19 say they can’t breathe. Now, after recovering from the infection, some of them say they can’t think.

Even people who were never sick enough to go to a hospital, much less lie in an ICU bed with a ventilator, report feeling something as ill-defined as “Covid fog” or as frightening as numbed limbs. They’re unable to carry on with their lives, exhausted by crossing the street, fumbling for words, or laid low by depression, anxiety, or PTSD.

As many as 1 in 3 patients recovering from Covid-19 could experience neurological or psychological after-effects of their infections, experts told STAT, reflecting a growing consensus that the disease can have lasting impact on the brain. Beyond the fatigue felt by “long haulers” as they heal post-Covid, these neuropsychological problems range from headache, dizziness, and lingering loss of smell or taste to mood disorders and deeper cognitive impairment. Dating to early reports from China and Europe, clinicians have seen people suffer from depression and anxiety. Muscle weakness and nerve damage sometimes mean they can’t walk.

It’s not only an acute problem. This is going to be a chronic illness,” said Wes Ely, a pulmonologist and critical care physician at Vanderbilt University Medical Center who studies delirium during intensive care stays. “The problem for these people is not over when they leave the hospital.”

Doctors have concerns that patients may also suffer lasting damage to their heart, kidneys, and liver from the inflammation and blood clotting the disease causes.

No one can yet tell patients with neurological complications when, or if, they’ll get better, as doctors and scientists strive to learn more about this coronavirus with each passing day. Their guideposts are the experience they’ve gained treating other viruses and delirium after ICU stays, sparse results from brain autopsies, and interviews with patients who know something is just not right.

“We would say that perhaps between 30% and 50% of people with an infection that has clinical manifestations are going to have some form of mental health issues,” said Teodor Postolache, professor of psychiatry at the University of Maryland School of Medicine. “That could be anxiety or depression but also nonspecific symptoms that include fatigue, sleep, and waking abnormalities, a general sense of not being at your best, not being fully recovered in terms of the abilities of performing academically, occupationally, potentially physically.”

John Bonfiglio, 64, counts himself among the fortunate ones. He remembers nothing between sitting in Newton-Wellesley Hospital’s emergency department with a fever and waking up 17 days later in the Massachusetts hospital’s ICU. He’d been on a ventilator, lying prone until his failing kidneys meant he needed to be flipped over onto his back for dialysis. Weak and confused from his ordeal after moving to a regular hospital floor, he tried to slip around his bed’s guardrails and slid to the floor. Nurses would routinely ask his name and if he knew where he was. One day he answered “Las Vegas.”

Bonfiglio chalks that up to post-ICU disorientation that included his feeling more emotional. Ordinarily “not a crier,” as he put it, he would choke up sometimes. More troubling were the persistent dizziness, muscle weakness, and tremors in his hands that made it impossible to put his contact lenses in his eyes. 

He was discharged to Spaulding Rehabilitation Hospital in nearby Charlestown, Mass., where he spent the balance of his 51-day hospitalization — during which he saw no family members since suggesting to his daughter that she go home from the emergency room that night in April.

From his early days in rehab, when sitting up in bed was exhausting, to learning how to walk again with a walker, to finally going home to Waltham, Mass., Bonfiglio lost 40 pounds — “all muscle.” He’s regained some of his strength, and weight, now. His dizziness and tremors are gone. And his mind is clear.

He’s back driving part-time for a food-delivery service, and he jokes that being in a drug-induced coma meant he missed the pandemic’s surge in Massachusetts. When he visited the Newton-Wellesley ICU after a checkup, he couldn’t remember any of the staff there. He does remember what one nurse said as he was leaving the hospital for Spaulding: “‘You are the first person that is going to rehab and not to hospice,’ she told me. So I feel extremely lucky, you know, just making it through.”

Vanderbilt’s Ely worries about patients who emerge from the ICU with more serious problems than Bonfiglio’s, including delirium caused by high-potency drugs like benzodiazepines and nerve damage from low oxygen levels.

“And then they’re getting isolated. When they’re isolated and away from family, it makes it worse,” Ely said. Later, “they’re having either post-traumatic stress disorder, anxiety disorder, depression, or cognitive impairment, and some combination of all of that. So these people are really in for some neurologic and mental health problems.”

Right now, there is little that researchers can say definitively about how best to prevent and treat neuropsychological manifestations of Covid-19. Nor do they know for certain why the brain is affected.

“It’s sort of like you’re trying to put out the fire and then a little bit later, you go look at  the nervous system as the embers,” said Victoria Pelak, professor of neurology and ophthalmology at the University of Colorado School of Medicine. “Because you are so concerned with the raging fire, you haven’t really been able to pay attention to the nervous system as much as you normally would.”

She and others are piecing the story together. So far the virus appears to cause its damage to the brain and nervous system not as much through direct infection as through the indirect effects of inflammation. Pieces of the virus, not actual viruses multiplying, can trigger an inflammatory response in the brain, said Lena Al-Harthi, chair of the Department of Microbial Pathogens and Immunity at Rush Medical College.

“If you have an uncontrolled level of inflammation, that leads to toxicity and dysregulation,” she said. “What I am concerned about is long-term effects, obviously in the people who have been hospitalized, but I think it’s definitely time to understand long-term sequelae for those individuals who have never been hospitalized. They’re young, too. We’re not talking about [only] older individuals, but people that are 30.”

Fred Pelzman, who practices internal medicine in New York City, fell sick with Covid-19 in March but has yet to recover fully. He doesn’t have his wind back, or his normal sense of taste and smell. His patients who have had Covid-19 are suffering from varying degrees of depression, anxiety, or Covid fog. One can’t do simple math calculations in her head any more. Others don’t feel as mentally sharp, struggling to find the right words to say. His colleagues tell him their patients, too, dread being reinfected with the virus.


“It’s hard to separate the physical from the psychological score, and we know they are intimately related,” he said. “It’s hard to separate the Covid-19 signal from the social justice upheaval and global warming and politics and the pandemic and anxiety of just being, you know, isolated and working at home and economic turmoil and all the rest.”

Neurocognitive testing, psychiatric evaluation, and diagnostic imaging might help determine the cause for these problems, Pelzman said, but not having a baseline for comparison could make that challenging, especially when hospitals are racing to keep patients breathing and prevent blood clots from forming and clogging blood vessels or triggering strokes — common problems caused by Covid-19.

“Strokes are larger, potentially more damaging with this disorder. Once inflammation or blood vessel problems occur within the nervous system itself, those people will have a lot longer road to recovery or may die from those illnesses,” Colorado’s Pelak said.

Doctors are also watching for  a syndrome called demyelination, in which the protective coating of nerve cells is attacked by the immune system when there is inflammation in the brain. As in the autoimmune disease multiple sclerosis, this can cause weakness, numbness, and tingling. It can also disrupt how people think, in some cases spurring psychosis and hallucinations. “We’re just not sure if this virus causes it more commonly than other viruses,” Pelak said.

In Italy, three Covid-19 patients with no previous history of neurologic or autoimmune disorders developed myasthenia gravis, a disease that weakens the arm and leg muscles, causes double vision, and leads to difficulties speaking and chewing. While such symptoms could follow the viral infection of nerve cells, it’s also possible that an autoimmune mechanism — the body attacking healthy cells — is at work, the group reporting these cases said.

Recovery from Covid-19 often begins in rehab. Ross Zafonte, chief medical officer at Spaulding, said he is seeing some patients’ cognitive and brain-related issues last for much longer than expected. That includes depression, memory disorders, and PTSD, as well as muscle and peripheral nerve damage that makes mobility difficult. For some patients, their mental awareness has been slow to recover. 

“We’re trying to follow people long term and do a longitudinal study to see what are the comorbid factors,” he said. “What are the characteristics of people who don’t get back to normal? How can early intervention try to deal with that? Are there some biomarkers of risk? Can we try to define better targets for early intervention?”

Maryland’s Postolache thinks Covid-19 infection might act as a “priming event” for problems to resurface in the future. Psychological stress could reactivate behavioral and emotional problems that were initially triggered by the immune system responding to the virus. “What we call psychological versus biological may actually be quite biological,” he said. “We don’t really say this is permanent … but considering all complexities of human life, it’s unavoidable.

Ely of Vanderbilt suggests three things to do now.

We can open the hospitals back up to the families. That’s important,” he said. “We can be aware of these problems and tell the families about them so that the families will know that this is coming. [And] we can do counseling and psychological help on the back end.”

Elizabeth Cooney

General Assignment Reporter

Liz is a general assignment reporter.

Friday 18 December 2020

Facing The Mysterious Long-Term Complications Of Covid-19 - Knowledge Is Understanding

 Today's post from (see link below) follows on from yesterday's post and goes into much more detail about the potential long-term neurological effects of Covid-10 and is therefore extremely useful for patients who may be confused about what they're experiencing. If any group of patients understand what it is to be confused by their symptoms, it's neuropathy patients but most people won't realise that this virus can attack the nervous system as a whole, or in part. If you don't already suffer from nerve damage then this will come as a frightening surprise after the elation of supposedly surviving the virus itself and if you're already used to the symptoms of nerve damage, long Covid will be yet another slap in the face with a wet fish!! The problem is...existing neuropathy patients may end up suffering much more than patients who's nervous system is not already compromised. It's vitally important that if you are suffering extended problems from the virus that you set up lines of communication with your doctors as quickly as possible. They need to realise that the neurological problems associated with Covid will be exacerbated by an existing condition. Do your own research and talk to your doctors - as you know...knowledge is power!


Brain Deficits, Nerve Pain Can Torment Covid Patients for Months


Scientists are starting studies on mysterious long term ailments 

Initially mild symptoms worsen later in thousands of Americans

Eli Musser

Eli Musser Photographer: Mark Kauzlarich/Bloomberg

A growing contingent of Covid-19 patients whose symptoms were initially mild are now facing mysterious long-term neurological problems, including memory and sleep disturbances, dizziness, nerve pain and what survivors refer to as “brain fog.”

The phenomenon, involving thousands of patients with symptoms lasting months at a time, complicates the Trump administration’s argument that most illness is mild so the U.S. can quickly reopen the economy. These frightening long-term cases aren’t captured in official statistics that show that the vast majority of younger adults survive the virus.

While lingering lung issues might be expected given the nature of the virus, some of the most common and surprising problems involve the nervous system. For Americans with these symptoms, there are few answers available on why they surface, how long they’ll last and what permanent problems they may cause. Neurologists are only just starting to study the trend.

“A very large number of the symptoms fall within the brain and nervous system,” according to Natalie Lambert, an Indiana University School of Medicine researcher who surveyed more than 1,567 members of an online support group for people with longer-term symptoms in a push to map out their effects.

Adrian Owen, a neuroscientist at Western University in Canada, has been “completely inundated” with emails from people who have found themselves with cognitive problems months after their initial infection, he said in an interview.

“It is becoming completely obvious that many of them are suffering from neurological deficits,” Owen said. “Even if this only affects 10% of people, that can be a massive societal and economic burden a year from now.”

For Eli Musser, a 42-year-old copywriter in Astoria, Queens, the first weeks of Covid-19 were nowhere near as bad as what came later. In late March, Musser came down with a low fever and fatigue for a few days followed by a recurring cough that lasted several weeks.

“And then I got walloped,” he said in an interview.

For months, Musser was so debilitated doing more than sitting on the couch and resting was too much. He’s had tremors and shaking in his arms, dizziness, muscle weakness so severe he sometimes had trouble dressing, panic attacks and depression. One terrifying day in May, he couldn’t move his legs. In June, he experienced intermittent fits of seizure-like sweating and shaking.

Now, five months after his initial symptoms, he’s still on medical leave and only recently received a diagnosis for his neurological symptoms. Meanwhile, Musser’s fiancée, who also fell ill in March but recovered in about 10 days, spends hours each day caring for him.

“A good guess is it won’t last forever, it’ll get better with time,” Musser said. “But also, how much time? How much better? What can I reasonably expect?”

To get a handle on questions like this, the neuroscientist Owen is working with University of Toronto researchers to survey 50,000 coronavirus patients with lingering neurological symptoms to determine who might be most at risk and what the long-term effects are.

They’re using a series of self-reported questionnaires and brain games done online. Other studies, looking at symptoms more broadly in fewer people and with more detail, are just beginning elsewhere as well.

Survivor Corps

Many patients have been sharing their experiences in a Facebook group called “Survivor Corps” that today counts more than 96,000 members.

Diana Berrent founded the group after contracting Covid-19 in March. Since then, she’s partnered with Lambert to survey its members. The symptom list they gathered was pages long, including difficulty concentrating or focusing, anxiety, memory problems, heart palpitations, blurry vision and neuropathy in feet and hands.

With researchers just starting to study Covid-19’s long-term consequences, reliable numbers are hard to come by. A recent federal study found that about 35% of people who tested positive for Covid-19 were still experiencing symptoms two to three weeks later, including many young adults.

While patients 50 and older had the highest risk of long-lasting problems, more than a quarter of those under age 35 had continuing symptoms, including many who had no previous health problems.

Italian Study

Meanwhile, a survey of 143 patients who had been hospitalized for Covid-19 in Italy found that two months later only 12.6% were completely symptom-free, and more than half said they still had 3 or more ongoing symptoms.

There’s no doubt that coronavirus infection can cause nerve complications. One early study from Wuhan, China found that 36% of patients had neurologic symptoms ranging from headache to impaired consciousness.

Since then, researchers have reported a variety of strange neurologic syndromes, ranging from Miller Fisher syndrome, a nerve disease that can paralyze eye muscles, to acute disseminated encephalomyelitis, a nerve-lining inflammation that can resemble multiple sclerosis flareups, to autoimmune encephalitis, and inflammation of the brain’s temporal lobes, which can cause confusion and hallucinations.

But with case reports just emerging, it’s been hard to prove cause and effect.

Even when people clear the virus and test negative, they “can feel out of sorts for weeks and weeks,” almost similar to chronic fatigue syndrome, said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, during a Facebook live interview on July 16th. But it may take a year or more to understand whether the virus produces truly long-lasting complications, he said.

Also see: Covid malaise poses economic drag long after virus abates

There are logical reasons why people who were hospitalized could have residual neurologic effects lasting for months. These patients may have been so sick that organ failure limited oxygen flow to the brain, said Igor Koralnik, who is chief of neuro-infectious disease at Northwestern Medicine and leads its neurology-focused Covid clinic. Blood clots in the brain or widespread inflammation could also impact brain function, he said.

But the neurological symptoms now being seen in people who had milder cases of Covid-19 are more mysterious. Even the loss of smell that’s been a high-profile symptom of Covid-19 is considered neurologic, likely caused by dysfunction of olfactory nerves or nerve support cells, Koralnik said.

It’s possible, for instance, that small amounts of the virus still remain in outer reaches of the body, hiding out and continuing to wreak havoc. There’s precedent for continuing symptoms with other viruses, including the coronaviruses SARS and Middle East Respiratory Syndrome. Lingering virus has also been posed as an explanation in those settings.

So far, though, there’s not strong evidence that Covid-19 infects the brain.

A more likely scenario is that the body’s immune system continues to fire, even after the virus has been dispatched, according to Dipa Jayaseelan, a consulting neurologist at University College London Hospitals, who has studied neurological complications of Covid-19. In that case, she said, numerous antibodies and immune cells activated by the virus could go awry in subtle ways.

‘Into Overdrive’

“It isn’t the virus itself, but it’s the body’s reaction to the virus,” Jayaseelan said. “The body goes into overdrive” in fighting Covid-19 and may continue to overreact even after the virus is upended.

Allison Navis, a specialist in neuro-infectious diseases at the Icahn School of Medicine at Mount Sinai in New York, has seen about 50 long-haulers in the last month. She believes there isn’t one common cause, but rather a variety of different explanations. “It’s a big mystery,” she said. “Everyone’s commenting that they’re starting to see this.”

An immune reaction may have caused Musser’s dizziness and vertigo.

After a video consultation this month, Northwestern’s Koralnik diagnosed him with Covid-related inflammation of his inner ear nerves and prescribed a motion sickness drug along with specialized physical therapy. It was “truly relieving” to find out that he had something treatable, Musser said in an email.

Covid-19 patients who continue to grapple with symptoms aren’t alone. Some survivors of SARS and Middle East Respiratory Syndrome reported symptoms like fatigue and depression for years afterward.

Ebola, Zika

Ebola survivors often suffer from everything from headaches to joint pain to eye problems long after they recovered from the disease, studies have found. And Zika virus outbreaks have been linked to an higher incidence of Guillain-Barre syndrome, a rare autoimmune disorder where antibodies attack the nerves, sometimes leading to paralysis.

And while long-term brain and lung damage are key concerns with Covid-19, there is also a growing realization that the virus may cause subtle damage to other organs, including heart inflammation.

Tracking the cause of the neurological issues could take a while, given the difficulty of linking far-ranging immune effects to the virus. During the AIDS epidemic, a surge of patients coming in with dementia kick-started the field’s focus on infectious disease. But it took years after HIV was discovered for the concept of HIV-related dementia to become firmly established in the medical community.

At the National Institute of Neurological Disorders and Stroke, neurologist Avindra Nath said he’s received about 200 emails from patients reporting long-lasting neurological complications, including “brain fog,” burning sensations in the hands and feet, headaches and sleeping problems.

Two Small Studies

He’s starting two small studies to look at the neurological complications in detail, and plans to bring in dozens patients for batteries of tests to figure out what might be going on. He suspects some of the burning sensations reported in patients could be an atypical form of Guillain-Barre syndrome or a peripheral neuropathy.

One study will focus on Covid-19 patients whose symptoms are similar to a disease called myalgic encephalomyelitis, a mysterious virus-linked illness better known as chronic fatigue syndrome.

“The effects on the brain are under-recognized at the moment,” Nath said. Finding out what is going on “is all we are thinking about right now. This is the number one top priority.”

For some long-haul patients, exhaustive testing has turned up specific abnormalities. Rachelle McCready, a 57-year-old critical care nurse educator in London, Ontario, was hospitalized for eight days in mid-April after coming down with the coronavirus.

‘Hit by a Truck’

She never needed a ventilator or other extraordinary measures. Still, for weeks after she got out of the hospital, she was so exhausted and out of breath she spent most of the day in bed, too tired to do much more than make coffee or do the laundry.

“It feels like you have been hit by a truck, the truck then reversed and hit you again, and you are recovering from that,” says McCready. “I never would have thought it would still be impacting my life here at month five.”

Even after she recovered enough to return to work on a part-time basis in June, she noticed subtle neurological symptoms including trouble finding words and learning new procedures. After an echocardiogram, a heart nuclear medicine scan, a chest x-ray, and other tests came back negative, doctors finally ordered a lung CT scan in early July.

It found subtle damage to the airway walls in her lungs, a condition linked to lung infections and often found in cystic fibrosis patients. Doctors connected it with the coronavirus and, since then, her doctors prescribed oral steroids and asthma inhalers that have reduced her symptoms significantly, she said.

 “People need to know this really isn’t quick for some people,” she says. “I think we are going to be seeing the effects of this for years.” 

Don''t Underestimate The Long-Term Effects Of Covid,

 Today's video from Good Morning Britain (see link below) was broadcast back in June of this year and yet scientists, patients and the media are still struggling to recognise that this is no ordinary virus and can attack various functions and organs in the human body over a long period of time. Long term consequences of viruses are traditionally difficult to predict but in the case of Covid-19, they need to be recognised and allowed for in the ongoing treatment of many patients because they can shock and take people by surprise and therefore extend their suffering. A salient discussion that may lead you to doing more research of your own, especially if you feel either you or someone close to you may be experiencing what they now call, 'long Covid'.


 The After-Effects of COVID-19 Can Last for Months | Good Morning Britain
24 Jun 2020

  Broadcast on 24/06/2020

 Scientists want to ascertain whether "post-Covid syndrome" should be recognised as an illness in its own right as Covid-19 sufferers are reporting debilitating symptoms for weeks or months after recovery. A recent study has revealed that one in ten people are struggling to shake off Covid-19, many are experiencing crushing fatigue, breathlessness and brain fog longer than expected – in some cases leaving them bed-bound or unable to work full time.

  Like, follow and subscribe to Good Morning Britain! The Good Morning Britain YouTube channel delivers you the news that you’re waking up to in the morning. From exclusive interviews with some of the biggest names in politics and showbiz to heartwarming human interest stories and unmissable watch again moments. Join Susanna Reid, Piers Morgan, Ben Shephard, Kate Garraway, Charlotte Hawkins and Sean Fletcher every weekday on ITV from 6am until 9 every weekday! ITV Hub: Website: YouTube: Facebook: Twitter: #GMB #PiersMorgan #SusannaReid

Thursday 29 October 2020

Corona! I Barely Know Her! Learning To Live With A Treacherous Partner

Today's post from (see link below) is an important one for people already living with neuropathy and other neurological disorders and then being confronted with Covid-19. It shows us that far from being at the end, or even in the middle of a new viral pandemic, we're actually at the very beginning of what may be a long learning curve with as yet unknown physical problems as the virus attacks our immune systems. As understanding of the virus increases, we're already learning that there are several different forms of Covid-19 and they seem to affect people randomly across the age groups. You may have heard about 'long' covid for instance, where recovered patients may need to live the rest of their lives with debilitating side effects but that may be just the tip of the iceberg. The medical world doesn't understand yet why it happens!

This article reveals the virus' potential for damaging the brain (and thus our nervous systems) but yet again, the disease is so young, there's a mountain of information yet to be learned and understood and in that respect, only time will tell how damaging the virus will be. One thing is sure; as new, daily evidence emerges, neuropathy patients may end up being in the front line of side effects sufferers as our immune systems adapt to attacks from covid-19. People living with autonomic neuropathy already know how wide ranging nerve damage can be in disrupting our bodily functions. Covid may be about to bring a whole new range of neurological problems into the spotlight. Be alert and keep your doctor informed. He or she may not yet be aware of covid's affects on the nervous system, so it's up to us to do our research and provide evidence from that research, so that our physicians are at least aware of potential neurological problems and can work through our recovery together.


How COVID-19 can damage the brain

Some people who become ill with the coronavirus develop neurological symptoms. Scientists are struggling to understand why.
View through the bottom of a laboratory dish being held by a scientist containing brain organoids seen as small white dots

Some evidence that SARS-CoV-2 can infect the brain comes from ‘organoids’ — clumps of neurons created in a dish. Credit: Erik Jepsen/UC San Diego

The woman had seen lions and monkeys in her house. She was becoming disoriented and aggressive towards others, and was convinced that her husband was an impostor. She was in her mid-50s — decades older than the age at which psychosis typically develops — and had no psychiatric history. What she did have, however, was COVID-19. Hers was one of the first known cases of someone developing psychosis after contracting the disease1.

In the early months of the COVID-19 pandemic, doctors struggled to keep patients breathing, and focused mainly on treating damage to the lungs and circulatory system. But even then, evidence for neurological effects was accumulating. Some people hospitalized with COVID-19 were experiencing delirium: they were confused, disorientated and agitated2. In April, a group in Japan published3 the first report of someone with COVID-19 who had swelling and inflammation in brain tissues. Another report4 described a patient with deterioration of myelin, a fatty coating that protects neurons and is irreversibly damaged in neurodegenerative diseases such as multiple sclerosis.

“The neurological symptoms are only becoming more and more scary,” says Alysson Muotri, a neuroscientist at the University of California, San Diego, in La Jolla.

The list now includes stroke, brain haemorrhage and memory loss. It is not unheard of for serious diseases to cause such effects, but the scale of the COVID-19 pandemic means that thousands or even tens of thousands of people could already have these symptoms, and some might be facing lifelong problems as a result.

Yet researchers are struggling to answer key questions — including basic ones, such as how many people have these conditions, and who is at risk. Most importantly, they want to know why these particular symptoms are showing up.

Although viruses can invade and infect the brain, it is not clear whether SARS-CoV-2 does so to a significant extent. The neurological symptoms might instead be a result of overstimulation of the immune system. It is crucial to find out, because these two scenarios require entirely different treatments. “That’s why the disease mechanisms are so important,” says Benedict Michael, a neurologist at the University of Liverpool, UK.

Affected brains

As the pandemic ramped up, Michael and his colleagues were among many scientists who began compiling case reports of neurological complications linked to COVID-19.

In a June paper5, he and his team analysed clinical details for 125 people in the United Kingdom with COVID-19 who had neurological or psychiatric effects. Of these, 62% had experienced damage to the brain’s blood supply, such as strokes and haemorrhages, and 31% had altered mental states, such as confusion or prolonged unconsciousness — sometimes accompanied by encephalitis, the swelling of brain tissue. Ten people who had altered mental states developed psychosis.

Not all people with neurological symptoms have been seriously ill in intensive-care units, either. “We’ve seen this group of younger people without conventional risk factors who are having strokes, and patients having acute changes in mental status that are not otherwise explained,” says Michael.

A physiotherapist wearing protective clothing assists a patient suffering from Covid-19 in a hospital in France

Neurological symptoms accompanying COVID-19 include delirium, psychosis and stroke.Credit: Stephane Mahe/Reuters

A similar study1 published in July compiled detailed case reports of 43 people with neurological complications from COVID-19. Some patterns are becoming clear, says Michael Zandi, a neurologist at University College London and a lead author on the study. The most common neurological effects are stroke and encephalitis. The latter can escalate to a severe form called acute disseminated encephalomyelitis, in which both the brain and spinal cord become inflamed and neurons lose their myelin coatings — leading to symptoms resembling those of multiple sclerosis. Some of the worst-affected patients had only mild respiratory symptoms. “This was the brain being hit as their main disease,” says Zandi.

Less common complications include peripheral nerve damage, typical of Guillain–Barré syndrome, and what Zandi calls “a hodgepodge of things”, such as anxiety and post-traumatic stress disorder. Similar symptoms have been seen in outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), also caused by coronaviruses. But fewer people were infected in those outbreaks, so less data are available.

How many people?

Clinicians don’t know how common these neurological effects are. Another study6 published in July estimated their prevalence using data from other coronaviruses. Symptoms affecting the central nervous system occurred in at least 0.04% of people with SARS and in 0.2% of those with MERS. Given that there are now 28.2 million confirmed cases of COVID-19 worldwide, this could imply that between 10,000 and 50,000 people have experienced neurological complications.

But a major problem in quantifying cases is that clinical studies have typically focused on people with COVID-19 who were hospitalized, often those who required intensive care. The prevalence of neurological symptoms in this group could be “more than 50%”, says neurobiologist Fernanda De Felice at the Federal University of Rio de Janeiro in Brazil. But there is much less information about those who had mild illness or no respiratory symptoms.

That scarcity of data means it is difficult to work out why some people have neurological symptoms and others do not. It is also unclear whether the effects will linger: COVID-19 can have other health impacts that last for months, and different coronaviruses have left some people with symptoms for years.

Infection or inflammation?

The most pressing question for many neuroscientists, however, is why the brain is affected at all. Although the pattern of disorders is fairly consistent, the underlying mechanisms are not yet clear, says De Felice.

Finding an answer will help clinicians to choose the right treatments. “If this is direct viral infection of the central nervous system, these are the patients we should be targeting for remdesivir or another antiviral,” says Michael. “Whereas if the virus is not in the central nervous system, maybe the virus is clear of the body, then we need to treat with anti-inflammatory therapies.”

Getting it wrong would be harmful. “It’s pointless giving the antivirals to someone if the virus is gone, and it’s risky giving anti-inflammatories to someone who’s got a virus in their brain,” says Michael.

There is clear evidence that SARS-CoV-2 can infect neurons. Muotri’s team specializes in building ‘organoids’ — miniaturized clumps of brain tissue, made by coaxing human pluripotent stem cells to differentiate into neurons.

In a May preprint7, the team showed that SARS-CoV-2 could infect neurons in these organoids, killing some and reducing the formation of synapses between them. Work by immunologist Akiko Iwasaki and her colleagues at Yale University School of Medicine in New Haven, Connecticut, seems to confirm this using human organoids, mouse brains and some post-mortem examinations, according to a preprint published on 8 September8. But questions remain over how the virus might reach people’s brains.

Because loss of smell is a common symptom, neurologists wondered whether the olfactory nerve might provide a route of entry. “Everyone was concerned that this was a possibility,” says Michael. But the evidence points against it.

A team led by Mary Fowkes, a pathologist at the Icahn School of Medicine at Mount Sinai in New York City, posted a preprint in late May9 describing post mortems in 67 people who had died of COVID-19. “We have seen the virus in the brain itself,” says Fowkes: electron microscopes revealed its presence. But virus levels were low and were not consistently detectable. Furthermore, if the virus was invading through the olfactory nerve, the associated brain region should be the first to be affected. “We’re simply not seeing the virus involved in the olfactory bulb,” says Fowkes. Rather, she says, infections in the brain are small and tend to cluster around blood vessels.

Michael agrees that the virus is hard to find in the brain, compared with other organs. Tests using the polymerase chain reaction (PCR) often do not detect it there, despite their high sensitivity, and several studies have failed to find any virus particles in the cerebrospinal fluid that surrounds the brain and spinal cord (see, for example, ref. 10)10. One reason might be that the ACE2 receptor, a protein on human cells that the virus uses to gain entry, is not expressed much in brain cells10.

“It seems to be incredibly rare that you get viral central nervous system infection,” Michael says. That means many of the problems clinicians are seeing are probably a result of the body’s immune system fighting the virus.

Still, this might not be true in all cases, which means that researchers will need to identify biomarkers that can reliably distinguish between a viral brain infection and immune activity. That, for now, means more clinical research, post mortems and physiological studies.

De Felice says that she and her colleagues are planning to follow patients who have recovered after intensive care, and create a biobank of samples including cerebrospinal fluid. Zandi says that similar studies are beginning at University College London. Researchers will no doubt be sorting through such samples for years. Although the questions they’re addressing have come up during nearly every disease outbreak, COVID-19 presents new challenges and opportunities, says Michael. “What we haven’t had since 1918 is a pandemic on this scale.”

Nature 585, 342-343 (2020)


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