Two of the nation's top NIH experts -- Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, and Walter Koroshetz, MD, director of the National Institute of Neurological Disorders and Stroke (NINDS) -- joined American Academy of Neurology (AAN) science committee leaders in special session about COVID-19 at the AAN annual meeting.
Of particular interest to neurologists were questions about COVID vaccines, nervous system involvement during acute infection, and symptoms like brain fog and fatigue that linger for months. Fauci and Koroshetz touched upon those and other topics. Here are a few highlights of their discussion.
Vaccines and Acute Infection
"The question of vaccines and different neurological conditions has been studied over the years," Koroshetz said. "We don't have any real concerns about the COVID vaccine being any different."
"The only thing that we've seen, looking back, is people who had Guillain-Barré that occurred after a vaccine; there was some concern. That was a very small population of people," he continued. "People who had Guillain-Barré where it wasn't associated with vaccines are thought to be completely safe to be vaccinated. That's mostly data from influenza vaccine."
Overall, COVID-19 is "like nothing we've experienced in well over 100 years," Fauci noted. "We're going to look back at this and say we've lived through history, but we're not through with it yet; that's for sure."
Most diseases with the potential to kill as many people as COVID-19 does make at least some people sick to varying degrees, Fauci continued. "About 35% to 40% who get infected with SARS-CoV-2 have no symptoms. That's a big, big mystery. I just can't get my arms around that. So many people with no symptoms, and yet so many people who go on to die from it."
While the virus has a predilection for nasal mucosa and appears to knock out olfactory support cells, studies suggest SARS-CoV-2 does not affect neurons themselves, Koroshetz pointed out. "They seem to be intact," he said. "There's a question from Germany about whether the virus moves through the olfactory nerves into the brain; that's still a little bit of a controversy."
In the U.S., researchers such as Avindra Nath, MD, the clinical director at NINDS, have been "looking everywhere for the virus in the brain" and haven't been able to find it, Koroshetz said.
"What we do know is that the virus affects systems in the body that are essential to the brain, particularly the vascular system," he continued. "Encephalopathy is very common, even in people who are not getting sedating drugs in the ICU. Clearly, the nervous system takes a hit here. In Dr. Nath's studies, he sees multifocal areas of blood-brain barrier breakdown. And of course, there have been the kind of para-infectious conditions that we see with viral infections of different types, such as Guillain-Barré, acute necrotizing encephalopathy, transverse myelitis, things like that. So clearly, it is affecting the nervous system in the acute stages. The big question is, what are the long-term consequences?"
Post-Acute COVID
With post-acute or "long" COVID, recently named by NIH as post-acute sequelae of SARS-CoV-2 infection (PASC), "we know very little, particularly about the biological underpinnings of what people are suffering with," Koroshetz said.
"We do know, unfortunately, that it's not a minor problem," he added. "We also know now that the hope that this might be something like infectious mononucleosis where it might take you six months to recover and then you're going to be fine -- there's certainly evidence now that for some people that's not happening; that people still are having trouble out past six months. So this is a real challenge to us."
The most prominent symptom of post-acute COVID is fatigue; with that comes trouble with memory and attention, Koroshetz noted. "Neurologists have to play a really important role in trying to get at the bottom of this problem, because it really is in many instances, a neurological problem," along with dysautonomia, pain syndromes, abnormal sensations, and "big sleep troubles" that linger for months after COVID is first diagnosed.
In December, Congress provided $1.15 billion over four years to support studies about long-term health consequences of SARS-CoV-2 infection. Research can help identify how people recover from COVID and why some people recover faster and others slower, Koroshetz said. For example, "with Ebola, sometimes you actually see there's still virus there, hidden in the body," he said. "We need to know if that's the case, or is it some change in the immune system, or has there been damage to the autonomic nervous system. There are lots of things to try and understand."
More knowledge about post-acute COVID also may foster a better understanding of conditions like myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), Koroshetz and Fauci observed. ME/CFS may be triggered by infection and, like long COVID, has symptoms that include fatigue and problems with concentration and short-term memory.
"Dr. Fauci and I've been asked by Dr. [Francis] Collins [NIH director] to really push on that," Koroshetz said. "We have over the last couple of years. There are incredible parallels between the clusters of symptoms seen in those two conditions, and we've never been able to figure that one out."
"Chronic fatigue syndrome is a real mystery but, in that case, you never knew what the virus was," he added. "A lot of people said they had a viral illness and then they had this trouble." With COVID-19, "we know when they had it, what it is, and we can actually try to trace the biology, and hopefully, get some clues that will help us understand and treat patients with post-acute COVID" and potentially, people with chronic fatigue syndrome.
"We've been chasing myalgic encephalomyelitis and chronic fatigue syndrome without ever knowing what the etiologic agent was," Fauci said. "Now we have an absolutely well-identified etiologic agent that should be very helpful now in getting us to be able to understand it. I hope we do; it's been mysterious to us for years. Maybe this will give us a chance at a breakthrough."