How Covid-19 can damage the brain
For Julie Helms, it all started with a handful of patients admitted to her intensive care unit at the Strasbourg University Hospital in north-eastern France at the beginning of March 2020. Within a few days, each ICU patient had Covid -19 - and it wasn't just their breathing difficulties that alarmed her.
"They were extremely agitated and many had neurological problems - mainly confusion and delirium," she says. "We are used to having some ICU patients who are restless and require sedation, but that was completely abnormal. It was very scary, especially because many of the people we treated were very young - many in their 18s and XNUMXs, even at XNUMX. "
Helms and colleagues published a small study in the New England Journal of Medicine documentingneurological symptoms in their Covid-19 patients , ranging from cognitive difficulties to confusion. All are signs of "encephalopathy" (the general term for brain damage) - a trend that Wuhan researchers noticed in patients with coronavirus in February.
Now, more than 300 studies around the world have found a prevalence of neurological abnormalities in Covid-19 patients, including mild symptoms like headache, loss of smell (anosmia) and tingling sensations (arcoparasthesis). ), up to more serious results such as aphasia (inability to speak), beating and seizures. This is in addition to recent discoveries that the virus, which has been widely regarded as a respiratory disease, can also wreak havoc on waist , liver , heart and just about every organ system in the body.
Technicians research Covid-19 in a laboratory in Buenos Aires, Argentina; more than 300 studies have found neurological abnormalities in Covid-19 patients (Credit: Getty Images)
"We don't know yet if encephalopathy is more serious with Covid-19 than with other viruses, but I can tell you that we have seen many," said neurologist Elissa Fory of the Henry Ford Foundation in Detroit . , Michigan. "As the number of cases increases, you will start to see not only the common manifestations, but also the rare manifestations - and we see them all at the same time, which we have never encountered in our life."
Estimates of exact prevalence vary, but it appears that approximately 50% of patients diagnosed with Sars-CoV-2 - the virus responsible for Covid-19 disease - have experienced neurological problems.
The extent and severity of these neurological problems have largely gone under the radar. Most people, including doctors, may not recognize neurological abnormalities for what they are when they appear - a person who has a seizure may simply look dazed, without shaking or shaking. With its beep system, sedative medication and isolation in bed, an intensive care environment can exacerbate and induce delirium, confounding our ability to link any symptom to the virus.
To further complicate matters, many people suffering from the effects of Sars-CoV-2 are never actually tested for the virus, especially if they do not have a cough or fever. This means that if they have neurological symptoms, we may never know if it was related to Sars-CoV-2.
A medical worker takes a sample to test the Covid-19 in New Delhi; many people with the virus are never tested (Credit: Reuters)
"In fact, there is a significant percentage of Covid-19 patients whose only symptom is confusion" - they have no cough or fatigue, says Robert Stevens, associate professor of anesthesiology and intensive care medicine at Johns Hopkins Medicine of Baltimore, Maryland.
"We are facing a secondary pandemic of neurological disease."
A different disease
Since the start of the pandemic, it has become increasingly clear that Sars-CoV-2 is not just a turbo version of the common cold virus: it has a number of bizarre, unusual and sometimes terrifying features.
For example, most viral pandemics (including influenza) have a U-shaped mortality curve, killing the very young and the very old. But Sars-CoV-2 does not cause usually only mild symptoms in children. The new coronavirus also affects men disproportionately: up to 70% of people admitted to intensive care units worldwide are men, although men and women have been infected at equal rates. (Learn more about the how Covid-19 affects men and women differently ).
Sars-CoV-2 has unusual features - including that, unlike other viral pandemics, it usually only causes mild symptoms in children (Credit: Ai Aung Main / AFP via Getty Images)
"Happy hypoxia" is another mystery. Our blood normally has “oxygen saturation” levels of around 98%. Anything below 85% should cause loss of consciousness, coma or even death. But a large number of Covid-19 patients have been found to have oxygen saturation levels below 70% or even below 60%, while remaining fully conscious and functionally cognitive.
Then there is the fact that a huge percentage of people with the virus have no symptoms. Estimates vary, but a mass test report in Iceland found that 50% of the population with the virus expressed no symptoms.
Perhaps most troubling: while about 80% of people who develop Covid-19 get rid of the virus easily, a small percentage worsens quickly and dies within a few days of respiratory weakness and multisystem failure. Many of these patients are elderly or have specific underlying health conditions , but not all .
We have now learned that the disease affects many different organ systems: patients can die not only from pulmonary insufficiency, but also from renal insufficiency, blood clots, liver abnormalities and neurological manifestations - Robert Stevens
"If we have learned anything in the past two months, it is that this disease, Covid-19, is extremely heterogeneous in its presentation," says Stevens. "We have now learned that the disease affects many different organ systems: patients can die not only from lung failure, but also from kidney failure, blood clots, liver abnormalities and neurological manifestations.
“I had patients in intensive care in two to three days. I have others who have been in the hospital for months. "
Medical workers care for a Covid-19 patient in Porto Alegre, Brazil; some patients recover in two days, while others take months (Credit: Reuters)
There are other quirks that Stevens has noticed but cannot explain. "The Covid-19 patients seem to have a lack of sensitivity to the drugs we normally use - we had to use five to 10 times the amount of sedation drugs we would normally use," he says.
Virologists will spend years trying to understand the biomechanics of this invader. And although researchers have examined the virus and its victims for six months, publishing scientific studies at a rate never seen before with a disease, we still have more questions than answers. The last novelty to add is: can the virus infect the brain?
Most researchers believe that the neurological effect of the virus is an indirect result of either oxygen deprivation in the brain ("happy hypoxia" manifested by many patients) or the byproduct of the body's inflammatory response (the famous "cytokine storm"). Fory and Helms believe that the neurological effects are "mediated by cytokines".
Others are not so certain: evidence is starting to accumulate showing that the virus can actually invade the brain itself.
If you had asked me a month ago if there was any published evidence that Sars-CoV-2 could cross the blood brain barrier, I would have answered no. But there are now many reports showing that it is absolutely possible - Stevens
"If you had asked me a month ago if there was any published evidence that Sars-CoV-2 could cross the blood brain barrier, I would have said no - but there are now many reports showing that it 'is absolutely possible,' says Stevens. .
In Japan, researchers reported the case of 24-year-old man found unconscious on the ground in a vomiting pond. He experienced generalized seizures during his transport to the hospital. An MRI of his brain revealed acute signs of viral meningitis (inflammation of the brain), and a lumbar puncture detected Sars-CoV-2 in his cerebrospinal fluid. Chinese researchers also found traces of the virus in cerebrospinal fluid un 56 year old patient with severe encephalitis. And in a post-mortem examination of a Covid-19 patient in Italy, the researchers detected viral particlesin the endothelial cells lining the blood vessels of the brain itself. In some countries like France, autopsies of Covid-19 patients are very limited (or outright prohibited), which makes the Italian discovery all the more important - and worrying.
In fact, some scientists now suspect that the virus causes respiratory failure and death not through damage to the lungs but through damage to the brainstem, the control center that ensures that we continue to breathe even without consciousness.
Radiology staff assist a patient during scanning to produce an MRI scan of his brain (Credit: Science Photo Library)
The brain is normally protected from infectious diseases by what is known as the “blood-brain barrier” - a lining of specialized cells inside the capillaries that pass through the brain and spinal cord. These prevent microbes and other toxic agents from infecting the brain.
If Sars-CoV-2 can cross this barrier, it suggests that not only can the virus enter the central nervous system, but also that it can stay there, with the potential to return years later.
Although rare, this behavior similar to that of Lazarus is not unknown to viruses: the chickenpox virus, herpes zoster, for example, commonly infects nerve cells in the spine, reappearing later in life adult in the form of shingles - about 30% of people who have had chickenpox in childhood develop shingles at some point in their lives.
The herpes zoster virus, which causes chickenpox, reactivates later as shingles in almost a third of people (Credit: Science Photo Library)
Other viruses have had far more devastating long-term effects. One of the most notorious was the influenza virus responsible for the 1918 pandemic, which caused permanent and far-reaching damage to dopaminergic neurons in the brain and central nervous system. (Although it has long been assumed that the flu cannot cross the blood-brain barrier, some scientists now think it can ). It is estimated that five million people worldwide have been hindered by a form of extreme exhaustion known as "sleeping sickness" or "lethargic encephalitis".
Among those who survived, many remained in a state of suspended animation. “They neither transmitted nor felt the feeling of life; they were as insignificant as ghosts and as passive as zombies, "wrote Oliver Sacks in his 1973 memoirs, Awakenings. He described patients who remained in this stupor for decades until they were revived by the drug L-DOPA, restoring the levels of the neurotransmitter dopamine. (Learn more about raisons for which the 1918 flu was so deadly).
David Nutt, professor of neuropsychopharmacology at Imperial College London, says that he himself has treated many patients in the 1970s and 1980s who had suffered from severe clinical depression since the 1957 influenza pandemic in the United Kingdom.
"Their depression was lasting and it was solid - it was if their emotional circuits were all cut," he said, warning that we could see the same thing happen again, but on a much larger scale. "People who come out of intensive care with Covid-19 should be routinely monitored for the long term for signs of neurological damage - then receive interventional therapy if necessary."
Doctors treat a flu patient in New Orleans in 1918; some five million pandemic survivors have experienced extreme long-term exhaustion (Credit: Getty Images)
Patients with symptoms should be transferred to interventional trials, such as antidepressants, selective serotonin reuptake inhibitors (SSRIs) or beta interferons (natural proteins often used as drugs for conditions such as multiple sclerosis) in order to mitigate the damage and further prevent long-term effects. But it just doesn't happen, he says, "What really bothers me is that every health trust in the UK looks at Covid's symptoms - but no one is looking at the neurological mechanisms, such as the amount of serotonin in the brain. "
Nutt plans to enroll 20 Covid-19 patients who have developed depression or other neuropsychiatric conditions in a study that will use Imperial's advanced PET scanners to check for signs of brain inflammation or abnormal neurotransmitter levels .
In Baltimore, Stevens is also planning a long-term study of Covid-19 patients who have been discharged from intensive care, which will also perform brain tests as well as detailed cognitive tests on functions such as memory capacity.
And in Pittsburgh, as part of the Covid-19 Global Consortium on Neurological Dysfunction study, Sherry Chou, neurologist at the University of Pittsburgh, coordinated scientists from 17 countries to surveiller collectively the neurological symptoms of the pandemic, including through brain scanners.
The impact of the virus on the nervous system could be much greater and more devastating than its impact on the lungs
While the impact of the virus on the lungs is the most immediate and terrifying threat, the lasting impact on the nervous system will be far greater and far more devastating, says Chou.
"Although neurological symptoms are less common in Covid-19 than lung problems, recovery from neurological damage is often incomplete and can take much longer compared to other organ systems (eg, lungs) , and therefore lead to much greater overall disability, and possibly more deaths, ”she said.
Neurological symptoms are less common in Covid-19 patients than lung problems, but recovery from these symptoms may take longer (Credit: Reuters / Remo Casilli)
In France, Helms knows better than anyone the intensity of the neurological impacts. We had to delay her interview with the BBC after one of her Covid-19 patients - who left the hospital two months ago but still suffers from viral fatigue and severe depression - required urgent consultation for a suicide risk. And this patient is not unique - she has seen many people in similar states of distress.
"She's confused, she can't walk and she just wants to die, it's really horrible," says Helms. "She's only 60, but she said 'Covid killed me' - which means it killed her brain. She just doesn't want anything in life anymore.
“It was particularly difficult because we don't know how to prevent this damage in the first place. We simply have no treatment that will prevent brain damage. "
Patients with pulmonary insufficiency can be put on a ventilator and the kidneys can be rescued with a dialysis machine - and, hopefully, the two organs will rebound. But there is no dialysis machine for the brain.
This article appeared first on: https://www.bbc.com/future/article/20200622-the-long-term-effects-of-covid-19-infection