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Drs. Anthony Fauci and Walter Koroshetz on the Turning Point for COVID-19 and the Work That Remains

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Anthony Fauci, MD, and Walter Koroshetz, MD, discuss the COVID-19 pandemic, the vaccine, new targeted therapies in the pipeline, health disparities in rates of infection and death, and the work that remains.

In their virtual keynote address for the 2021 virtual AAN Annual Meeting, Anthony Fauci, MD, and Walter Koroshetz, MD, said they see a turning point coming in the battle against COVID-19, but emphasized that much work remains to be done.

“I believe as more and more people get vaccinated—we're averaging two to three million per day [in the United States]—you will see a rather strong turning to much more normal than what you and I are living through right now,” said Dr. Fauci, director of the National Institute of Allergy and Infectious Diseases and chief medical advisor to President Joe Biden.

Medical technologies developed to fight the pandemic might even help neurologists diagnose and treat virus-mediated disorders, said Dr. Koroshetz, director of the National Institute of Neurological Disorders and Stroke.

“I'm very hopeful that when the pandemic is done, the companies developing innovative technology will help us make rapid diagnoses of some of these rare viruses,” Dr. Koroshetz said. “With the mRNA technology for vaccines, which seems to be so much easier and more precise than older approaches, would we be able to have a vaccine for Epstein Barr virus? A lot of us think if we could wipe that out that, perhaps there wouldn't be any MS. And eastern equine encephalitis virus, could you wipe that out, or West Nile virus? We have lots of viral illnesses we haven't been able to attack. I'm hoping we can scale some of these technologies.”

Rather than present formal speeches, the two keynoters answered questions posed by Natalia S. Rost, MD, FAAN, chair of AAN's Science Committee and chief of the stroke division in the department of neurology at Harvard Medical School, and by Paul George, MD, PhD, FAAN, vice chair of the Science Committee and assistant professor of neurology and neurological sciences at Stanford School of Medicine. Their questions and answers are edited and excerpted below.

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“I believe as more and more people get vaccinated—were averaging two to three million per day [in the United States]—you will see a rather strong turning to much more normal than what you and I are living through right now.”—DR. ANTHONY FAUCI

What is our understanding to date of the varied response to the virus? Why do some never get infected, others remain asymptomatic, and children rarely get infected?

Dr. Fauci: I could have a common answer to all those questions in that we don't fully understand why, and we must be modest and humble about that. You can make some surmises. Is it the density of people's ACE2 receptors in the nasopharynx? Is it that some people have previously been sick with a coronavirus, had a common cold from it? We don't really know.

‘As a person who's been dealing with infectious diseases my entire professional life, I've never seen anything with these kinds of disparities. You have younger people who either have no symptoms or very mild symptoms. The same viral pathogen can be without symptoms in one person and cause enough death and destruction in others that you have over 540,000 deaths in the United States thus far: That is really a pathogenic mystery about how that can happen. Obviously, elderly individuals have a greater propensity to severe outcomes. ...Individuals with underlying disease, regardless of what age they are, have a higher degree of risk.

Beyond those typical kinds of variations, why is that people who are obese are among the very, very much at risk, as much or more than people with other conditions? Is it the fact that the mechanics of their breathing, their diaphragmatic movement, is not as normal? We're really playing a lot of guessing games. Most diseases that have the potential to kill as many people as COVID-19 does make at least most of the people sick to varying degrees. Thirty-five to 40 percent 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.

Does the SARS-CoV-2 virus have a predilection for infecting the nervous system and causing neurologic disease?

Dr. Fauci: The nasal mucosa is part of the neural system. It sends nerves into the brain, the olfactory nerves. But from what we see, it doesn't infect the neurons themselves. There are questions from Germany as to whether the virus moves through the olfactory nerves into the brain. That's still a bit of a controversy. Dr. Avindra Nath at NINDS has been looking everywhere for virus in the brain and hasn't been able to find it. Some of the German researchers have been able to find it. Whether it's real, a contaminant, some unusual cases—we don't know yet.

Dr. Koroshetz: What we do know is the virus affects systems of the body that are essential to the brain, particularly the vascular system, so these ACE2 receptors that Dr. Fauci mentioned are very common along with the epithelial cells in the brain, and encephalopathy is very common, even in people 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 breakdown. The big question is what the long-term consequences are.

What is post-acute sequelae of COVID-19, or PASC, and how is it different from other post-viral syndromes like chronic fatigue syndrome?

Dr. Koroshetz: We know very little about the biological underpinnings of what people are suffering with. But we do know, unfortunately, it's not a minor problem. The percentage of people could be below 10 percent, but given the fact that so many have been infected, that's still going to be a lot of people. We also know now that the hope that this might be something like infectious mononucleosis, that it might take six months and then you'll be fine—there's certainly evidence now that for some people that's not happening, that some still have problems past six months.

The most prominent symptom of the PASC is fatigue, along with memory and attention problems. Other symptoms include dysautonomia, postural orthostatic tachycardia, pain syndromes, abnormal sensations, and sleep disturbances.

Neurologists must play a really important role in getting to the bottom of this problem. Dr. Fauci and I have been asked by [NIH Director] Dr. Francis Collins to really push on chronic fatigue syndrome [CFS]. There are incredible parallels between the cluster of symptoms seen in those two conditions, and we've never been able to figure that one out. The CFS is a real mystery. But in that case, we never knew what the virus was. A lot of people said they had a viral illness, and then they had this trouble. Now, with PASC, we know what virus they had and when they had it. We can try to trace the biology, hopefully, get some clues to help us understand and treat patients with post-acute COVID-19, and potentially even for the tens of thousands with CFS.

Dr. Fauci: We've been chasing myalgic encephalomyelitis without knowing what the etiologic agent was. Now, we have an absolutely identified etiologic agent. That should be very helpful now in being able to help us understand it. I hope we do. It's been mysterious to us for years. Maybe this will give us a chance at a breakthrough.

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“Im very hopeful that when the pandemic is done, the companies developing innovative technology will help us make rapid diagnoses of some of these rare viruses.”—DR. WALTER KOROSHETZ

What is known about whether people will still be able to become infected and transmit the SARS-CoV-2 virus to others even after being fully vaccinated?

Dr. Fauci: Right now, we have the almost paradoxical situation where you get vaccinated, but you still have to wear a mask. People raise their eyebrows when you say that. Conceivably, you could be infected and, because you're vaccinated, have no symptoms and therefore be carrying virus in your nasopharynx. We are going to know that for sure because we're starting a study literally in the next couple of days on a college campus to see if they've been vaccinated, can they still be infected and transmit it or not. If the answer is they don't, then we don't have to worry about people who are vaccinated having to wear masks.

What are some of the new targeted treatments in the pipeline?

Dr. Fauci: The real endgame is to do targeted antiviral therapy like what we did with HIV, to give [the antiviral] early when they present with symptoms. Just as you treat hepatitis and cure it, or treat HIV, to give a seven- to ten-day treatment, and you don't have to worry about advanced disease.

Please address the health disparities that have been seen with COVID-19 in the rates of infection, hospitalization, and mortalities in vulnerable communities and now in lagging rates of vaccination.

Dr. Fauci: This pandemic has cast a bright light on the very disturbing health disparities in our country. What we are doing right now is focusing resources specifically on making sure that access to health care, and importantly access to vaccination, is not another example of disparity. President Biden has made it clear that equity in this disease is critical, as critical as the distribution of interventions. What he's doing, and what the administration is doing, is setting up community vaccine centers, setting up community federally qualified health care centers in areas populated demographically by minority populations, stocking vaccines in pharmacies, and organizing mobile units. What we're hoping is that when this is all over, we will pay greater attention to the social determinants of health. That's not something you will fix in a month or a year. You have to have decades of commitment.

When do you predict AAN annual meetings can finally be held in person again?

Dr. Fauci: That's going to be a direct relation and effect of getting people vaccinated. We're living through the worst crisis in public health that we've had in a century. The good news is we have highly efficacious vaccines. If we can get most of the population vaccinated, I believe you can have your neurology meeting the same way as you had in the past. I think we can start to think about that by the fall and winter.

Dr. Koroshetz: But we don't make those decisions, the virus makes those decisions.