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On Aug. 17, 2020, Dr. Anthony Fauci, Director of the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institute of Health (NIH), and valued member of the White House Coronavirus Task Force, joined ��������appMicrobe Online for a keynote address in which he discussed not only the extent of knowledge that has been cataloged for the novel coronavirus, to date, but also shared some personal reflections about what he believes it's going to take to get us "back to baseline" as a country.

An opening summary of the epidemiology, basic virology and transmission dynamics of SARS-CoV-2 both reminded listeners where we've come from and openly confronted our current position in this ongoing pandemic.

Asymptomatic Cases May Drive COVID-19 Transmission Events

"This is a respiratory-borne disease, and transmission occurs between people in close contact, through particles that remain in the air, as well as those that drop to the ground," Dr. Fauci explained. "We've learned that the risk of infection varies by type and duration of exposure. Crowded situations, mostly indoors, are hotspots for transmission and what we call 'superspreader' events."

Fauci made multiple references to the "extraordinary" nature of the virus, highlighting the fact that SARS-CoV-2 has been uniquely challenging to track and contain. "I've never seen a viral disease in which you have such a wide breadth of symptoms, ranging from no symptoms at all, in 40-45% of cases, to severe enough to kill you. We've learned that asymptomatic persons are likely key drivers of transmission events, when we thought months ago that they did not play an important role in transmission."

Aberrant Immune Mechanisms Contribute to COVID-19 Pathogenesis

Another extraordinary characteristic of SARS-CoV-2, about which Fauci is uniquely qualified to comment as chief of the NIAID Laboratory of Immunoregulation, is the immunopathogenesis of the virus. During a live Q&A session with former U.S. Food and Drug Administration (FDA) Commissioner, Dr. Margarette Hamburg, he discussed some of the strange ways this virus affects our immune systems.

"Understanding the aberrant immune mechanisms that contribute to pathogenesis, particularly in the advanced state of disease, allows you to get targets for intervention. Which is why we study immunopathogenesis.

"We're still learning an incredible amount about this virus. It's most extraordinary. In some individuals, it triggers an out-of-control, aberrant immune response. We don't know why it does, but it does. The cascade of events that follow make the response to the virus more dangerous to the host than the virus itself.

"We see that in the acute respiratory distress syndrome and therapy. Dexamethasone significantly diminishes the death rate [of COVID-19] because it's the inflammation that's killing people. Then you have a phenomenon in some children who get a multisystem inflammatory syndrome that looks like Kawasaki's, which is an out of control inflammatory response. [We need to figure out] why the virus triggers this and what it does to dysregulate the immune response."

Long-Term Deleterious Effects of COVID-19 Are Troubling

Our understanding of the long-term deleterious effects of COVID-19 is emerging on a daily basis, something that Fauci acknowledged as troubling. "We have seen that even individuals who are young and otherwise healthy, and get symptomatic enough to be in bed for a week or 2 but don't require hospitalization, may have residual symptoms for weeks to months after clearing the virus. We're seeing a substantially high proportion of cardiovascular abnormalities. Evidence of myocarditis. Evidence of emerging cardiomyopathy. Evidence of inflammatory processes in the brain. And these are people who have recovered from the disease."

COVID-19 Therapies and Vaccines Are Showing Promise 

Fauci recognized the grim reality that, "this has been an explosive pandemic, the likes of which we have not seen for the last 102 years, since the infamous pandemic of 1918. And the United States has been hit harder than any other country in the world." Which begs the question, how do we "fix" this? Fauci elaborated on a number of prevention and treatment strategies, highlighting the efficacy data of remdesivir and dexamethasone and listing the broad classes of therapeutics that are under investigation for the treatment of COVID-19, including antivirals, blood-derived products (convalescent plasma and hyperimmune globulin), monoclonal antibodies, immunomodulators (cytokine inhibitors and interferons) and adjunct therapies (anticoagulants).

He also discussed development of COVID-19 vaccines. "We believe we will get an effective vaccine," he said. "The animal studies are pretty crisp in protection, and the phase 1 studies showed that you can induce a robust degree of neutralizing antibodies comparable, if not better than, with natural infection."

But Fauci made it abundantly clear that safety and efficacy are of utmost importance and must be proved before any vaccine is circulated. He once again acknowledged that the immune response to COVID-19 is different from other viruses. "We know that the durability of COVID-19 immunity following infection is really variable. It's measured in several months to a year. Will we be able to do better than that with a vaccine? I hope so. I think we will be able to do at least as good, but it might require a booster. The only thing you need to eliminate measles is a vaccine. That's just not going to be the case with this respiratory virus. It will likely require a combination of good public health practices together with a vaccine."

Vaccine Hesitancy Needs to Be Addressed

In response to questions about vaccine hesitancy, Fauci made a couple of key points. An independent Data and Safety Monitoring Board is in charge of evaluating vaccine trials and is made up completely of people who do not own the company or trials under review.

Still, "We have our work cut out for us," Fauci acknowledged. In order to address vaccine hesitancy, "[we have to] get people involved with good representation, particularly minority communities, who have a couple of reasons not to want to get vaccinated — the history of abuses coupled with standard hesitancies about safety and efficacy. And we must prove that the vaccine is safe and effective by using community engagement and being transparent about the data and benefits of vaccination."

We Must Pull Together to "Get Back to Baseline"

But perhaps the most pivotal moment of the session developed from a more personal question that Hamburg posed to the former principal architect of the President's Emergency Plan for AIDS Relief (PEPFAR).

"When I first started working with you it was in the early days of the HIV/AIDS pandemic," Hamburg recounted. "What lessons, good and bad, do you take from that experience to how you're coping with the good and bad of the current COVID response?"

"They really are very different," Fauci explained. "In the early 80's people wanted to get our attention because what they had to say was absolutely important. They wanted to have input into the design of the trials. What they wanted was right, correct and good, and they attacked not because they hated us or disliked us, or were so different from us that we never could come together. Never for a moment did we feel we were physically in danger. It was less a strong political difference than it was the stigma they were under and the policy they wanted to change.

"Now, we are in such a politically divisive situation that has taken on an air of really strongly attacking the other person, the same way politicians attack. And what's happened is, unfortunately, public health, which should be free of all kinds of interference with politics and severe ideological differences, has now gotten caught in that. I mean just the whole issue of if you wear a mask, you're on one side of this story, and if you don't wear a mask, you're on the other side. So instead of public health being a vehicle to gaining what we want, it's being interpreted by some as an obstacle. It's the obstacle to opening the economy. It isn't! It should be a measured, prudent way to safely open the economy, and it isn't that way. Now it's like I'm, in some respects, to some people, the enemy. Where you get death threats and harassments of your family and harassments of you.

"There's something deep in there that I think is just a reflection of the divisiveness that we need to get through. If we're going to get through this, we've got to all pull together as a country. The same way we did in World War II. The same way we did after 9/11. The only way to get back to baseline is for everybody to pull together. Sharp divisions in the country, make that very difficult."

��������appthanks Dr. Fauci and Dr. Hamburg for joining us for this important, informative and inspiring event.