Article summary
Three years after the COVID-19 pandemic, there is a growing awareness of the impact infectious diseases have on the brain and peripheral nervous system, say neurologists. However, more training programs and better infrastructure are desperately needed to address emerging diseases with neurological complications.
After 38 years of breakthrough and innovation at the National Institute of Allergy and Infectious Diseases (NIAID), Anthony Fauci, M.D., who retired last month, left the field with the following message: …highlights the global lack of public health preparedness for an outbreak of this magnitude….” New England Journal of Medicine“There is no reason to believe that the threat of emerging infectious diseases will decrease, as underlying causes are likely to exist and increase.”
Fauci’s message resonates strongly as neurologists struggle to understand and treat the key neurological symptoms of acute sequelae of COVID-19 (PASC), they said. Neurology TodayThe next neuroinfectious disease pandemic may be around the corner, but they’re not as prepared as they should be.
Allison Navis, M.D., Ph.D., an assistant professor in the Department of Neuroinfectious Diseases at the Icahn School of Medicine, said the question wasn’t whether there would be another pandemic that would cause severe neurological disease, but when. However, she said: No one knew what I did before the pandemic. It’s a little better now, but we still don’t have a neuroinfectious society. There is much more to be done. “
Part of the problem, experts say, is that subspecialties are not clearly defined. “Neuro-infectious diseases are not taken seriously for granted,” said Avindra Nath, MD, FAAN, her senior research fellow in the Neurological Infectious Diseases Section of the National Institute of Neurological Disorders and Stroke (NINDS). I’m here. “It clearly doesn’t apply in neurology. It doesn’t directly apply to infections. It falls through the cracks.”
But three years after the COVID-19 pandemic, there is a growing awareness of the impact of infectious diseases on the brain and peripheral nervous system, said NINDS director Walter Koroshetz of FAAN.
“The most obvious improvement is that for years people doubted there was such a thing as a post-infection neurological condition,” he said. I don’t think anyone would question that today.”
NINDS is currently preparing to conduct clinical trials to test treatments for people with persistent cognitive or other neurological effects of COVID-19. Similarly, pathological studies are underway to investigate the mechanisms behind PASC, he said.
“We don’t have all the answers,” Dr. Koroschetz said. “But we are definitely learning a lot about the neurological effects of COVID-19 and other viruses.”
Keith Van Haren, MD, assistant professor of neurology and pediatrics at Stanford University, says there is growing awareness among young doctors of the importance of neurological infections.
“There’s definitely a growing interest among the younger generation of trainees,” said Dr. Van Haren. “But I agree with Dr. Nath that the clinical and scientific community still feels like we’re circumventing the edge of something much bigger than we realized.”
it’s been a long time coming
The pandemic has exposed some systemic shortcomings. Months after the COVID-19 pandemic, Dr. Nath said he was unable to find a facility equipped to safely perform brain dissections. Similarly, nowhere on the NIH campus was there a biosafety He Level 3 lab prepared to safely process samples or conduct research with live viruses.
“What we had was used for storage,” Dr. Nath said. “It took us almost nine months to get it up and running again.”
As a result, it has been impossible for months to obtain brain samples to determine if the SARS-CoV-2 virus is present there, he said.
“Nobody does an autopsy,” he said. “They were afraid of the dust that would fly into the air when they sawed through the skull. You’d need a negative pressure room, a vacuum saw, and PPE.” [personal protective equipment], Stainless steel mesh gloves to avoid cutting fingers. No one was prepared for it. Finally, many places have everything you need. “
COVID-19 is not the first virus that scientists failed to recognize its effects on the nervous system.
“When the AIDS pandemic started, patients had dementia, but people said it was just because they were sick,” Dr. Nath said. “It took years to convince people that HIV actually got into their brains and affected their brains. It was the same with Ebola. When we went to Liberia, we found that almost 50% of the survivors had meningoencephalitis.”
Similarly, when the COVID-19 pandemic started, “everyone looked at the effects on the lungs,” says Dr. Nath. “It took a long time to understand the effects on the brain.
Despite a slow start, research into the neurological impact of COVID-19 gets a big boost in September 2021 when the NIH provides nearly $470 million in funding to build a national study of PASC. received. The NIH REsearch COVID to Enhance Recovery (RECOVER) initiative will involve over 100 researchers at 30 universities. The goal is to identify why some people develop PASC and its most common symptoms, most of which are neurological: pain, headache, fatigue, brain fog, anxiety, depression, Sleeping disorder.
“I don’t think we really know what’s causing it,” said Dr. Navis, who worked as a primary neurologist at Mount Sinai Health System’s COVID-19 clinic for more than a year. “I’m sure it has many causes. It’s not the same for any two of her, and there are no effective treatment options.”
But other research programs are starting to pay off. Dr Koroshetz pointed to his UK Biobanks study published early last year. Nature, described changes in brain volume after COVID-19. This study confirmed that overall brain size was contracted after infection and gray matter thickness was reduced in regions connected to the primary olfactory cortex compared to controls.
Dr. Koroshetz said: Smell due to trauma or infection.
in March 2021 Journal of Experimental Medicine, using both human tissues and mouse models, demonstrated that the SARS-CoV-2 virus can infect the brain. However, “the role of active infections in the brain itself remains controversial,” says Dr. Koroschetz. But even now, the definition of what constitutes a long COVID is relatively vague, Dr. Nath said.
“The problem is that long COVID is a term coined by patients, not doctors,” he said. There are all sorts of people with symptoms, brain fog, etc.”
Advance
Expanding research opportunities is at the top of Dr. Navis’ wish list for enhancing neuroinfectious disease research and treatment.
“Research is what we need most in infectious diseases in general and neurological infections in particular,” said Dr. Navis. “We don’t have enough treatments and specialists.”
Neurorehabilitation programs are also in short supply, she said. I can’t imagine what it would be like.”
Dr. Nath said he believes every state in the country should have at least one autopsy facility with safe access to the brain in response to the neuroinfection outbreak.
“We have to look at the whole way we do autopsies in a completely different way,” he said. “For example, let’s say there’s an outbreak in North Dakota. They should be in a position to do a high-risk autopsy. If you put it in, you can use it, you can use a lot of things, it should become a daily habit.”
Dr. Koroshetz said more antiviral drugs are also needed to better respond to neurological infections.
“The problem is that the infection happens very quickly,” he said. “It’s almost like acute stroke. is.”
Several major pharmaceutical companies are working on antiviral drugs, but few test whether the drugs cross the blood-brain barrier (BBB), Dr. Nath said.
“From a neurological point of view, it’s very important to know that antivirals can cross the BBB,” he said. “Now they can get approval from the FDA to treat systemic infections. It is not a requirement for them to be tested to pass the BBB.”
Despite the challenges, Dr. Nath is working on a number of studies on the neurological impact of COVID-19.
“We’ve been screening people for cognitive impairment after infection,” he said. We are looking for immune abnormalities and evidence of viral products, proteins, or RNA.”
Dr. Nath is leading a randomized trial comparing intravenous immunoglobulin to placebo in people with PASC-related immune and cognitive impairments.
“We are gearing up to do a clinical trial and have a master protocol in place to test treatments in people with cognitive impairment and exercise intolerance,” Dr. Koroschetz said. There’s a lot going on in that space, and we welcome submissions from outside the NIH, so anyone who has a good idea of how to solve this problem would be very interested. ”
Perhaps the main lesson of COVID-19 for neurologists and other physicians is Dr. Fauci’s New England Journal of Medicine: “It is clear that emerging infectious diseases are indeed a perennial challenge,” he wrote.
“One of my favorite critics, Yogi Berra, once said, ‘It’s not over until it’s over.’ Clearly, we can now extend that axiom: When it comes to emerging infectious diseases, there is no end.”
