Celebrating Progress, Continuing Prevention: A Q&A With VUMC Infectious Disease Expert Dr. David Aronoff

What do we know now about COVID-19 that we didn’t know back in the spring?

That was the question the Employer Solutions team posed to David Aronoff, MD, Addison B. Scoville Chair in Medicine and Director of the Division of Infectious Diseases at Vanderbilt University Medical Center (VUMC). The Employer Insights blog last checked in with Dr. Aronoff in May as he answered questions to help business get back to work safely. Since that conversation, he has been busy advising Ryman Hospitality Properties, American Airlines and Nashville employers with the Good to Go program on disease prevention, along with his colleague Dr. Thomas Talbot, VUMC Chief Hospital Epidemiologist. Dr. Aronoff regularly educates the Middle Tennessee community on ways to protect themselves from the virus in their lives and at their workplaces.

While he does have reassuring news about VUMC's work and worldwide progress toward COVID-19 treatments and potential vaccines, Dr. Aronoff underscored the need to keep up our guard against the virus and stay the course with proven prevention methods. Here are the highlights from our conversation:

Now we know, unequivocally, that masks help reduce the spread of the virus. What other messages relating to prevention do you wish everyone would take to heart?

After the pandemic peaked here sometime in late July, numbers recently have been improving in Nashville and across the state. By participating in simple, fundamental practices of prevention that by now we know work well, we’ve decreased our number of cases and people hospitalized. Wearing masks in public, maintaining our distance from others, not going out quite as much, paying close attention to hand hygiene and surface disinfection—these are all still important practices to stopping the spread. There are data now to show that that maintaining distance and wearing face coverings has slowed viral spread all over the world.

Even though case activity is slowing down in Tennessee, that’s not because most people in Tennessee have already been infected. In fact, the vast majority of Tennesseans have not been infected. If we look at confirmed cases of COVID-19 in our city, county or state, it's still less than 5% of the populations of those regions. The reason that things are improving is because of fundamental participation in acts that slow the spread of this virus.

People can get fatigued from wearing masks or feeling like they're trapped inside, and it can be frustrating when we just want to give somebody a hug. But we're not out from underneath this pandemic yet. It's still active and there are still a lot of vulnerable populations to consider.

Have we found better and more effective ways to treat those critically ill COVID patients that we didn't have at the beginning of the outbreak?

Treatment has been a quickly moving target. It's so easy for us to forget that this disease didn't exist until essentially the end of 2019. There are literally hundreds of clinical trials for vaccines going on, and we have seen randomized controlled trials already completed that have told us vital information about potential therapies that have changed our practice.

One good example is an antiviral drug remdesivir, an intravenous medication that has been mostly deployed for hospitalized patients. It has been repurposed for use in COVID-19 in large part because of the pioneering work of Mark Denison, MD, VUMC Director of Pediatric Infectious Diseases, and other pediatric infectious disease experts at VUMC. Dr. Denison has been studying coronaviruses for over 30 years, and it was his idea to go to the manufacturer of remdesivir years ago and suggest that it might have some coronavirus activity. That drug has been in clinical trials for COVID-19 and has been shown to accelerate recovery.

The other great advance has been the use of an inexpensive medication called dexamethasone and some of its cousins in the corticosteroid family. These anti-inflammatory drugs have been around for a long time and can reduce the exuberance of an immune response to an infection. One of the ways that people get really sick with COVID-19 is because their own immune response flares, particularly in the lungs. We have learned from randomized control trials that dexamethasone actually improves survival for patients who require oxygen and are hospitalized with COVID-19.

Here at VUMC, we are using both remdesivir and anti-inflammatory corticosteroids like dexamethasone. We're anticipating that new options are going to come online soon. It’s been rewarding to see that the scientific method works and can be used in a way that saves lives.

Why is it essential to test treatments in a structured, controlled way to determine if they’re beneficial?

With COVID-19, most people who are diagnosed with this disease do relatively well. Most patients recover without requiring hospitalization, and the vast majority do not die of the virus. For example, in Tennessee, for every 100 people who get diagnosed with COVID-19, 95 of them will recover. Some will recover with disabilities, but they will recover. However, that can make it challenging for us to understand how to improve outcomes.

A healthcare professional might want to try out a vitamin, nutritional supplement or certain medicine on their COVID-19 patients. And if they treated 100 of their patients with COVID-19 with that medication or intervention, they would see about 95 of those patients avoid hospitalization and death. That might appear promising, but what's not clear is whether those actions are better than not doing them. In other words, we don’t know whether it's acceptable to accept any kind of risk of a potential therapy without knowing that there's a potential benefit.

The beauty of placebo-controlled randomized trials is that we can test to see whether these ideas are truly effective. To do that requires enrolling a lot of patients in large studies in numerous hospitals across the United States and world. These studies must follow strict protocols, provide informed consent to participants and let them know that they may receive an active drug or a placebo. Through this learning process, we've seen how drugs like remdesivir and dexamethasone have become more valuable to us, as well as how drugs like hydroxychloroquine have become less useful.

What do we know about the potential for new treatment, such as convalescent plasma?

People who have survived COVID-19 have donated plasma, which may contain antibodies against the virus. In principle, the idea is that those antibodies could be protective for somebody who's infected with the virus and might reduce their risk of severe disease or death from COVID-19. Because there are a lot of people recovering from COVID-19, it has led to a lot of enthusiasm and immediate use of convalescent plasma to treat COVID-19 patients.

Unfortunately, we aren't at the point where we know if that approach is beneficial. We have a lot of questions: Should we be using convalescent plasma early in the course of disease? Should we be reserving it for people who are critically ill? Is it okay to use it for patients who are not hospitalized? Is it best to use it only for people who require oxygen? Should we measure antibody levels in the plasma before we use it? And if so, what are the best levels of antibody that are therapeutic right now? We don't have great answers to those questions. There are some hints that giving it earlier is better and that higher antibody levels are better than lower levels based on experience to date from uncontrolled clinical studies.

Right now, Vanderbilt is leading a nationwide study on convalescent plasma to see if it’s beneficial and if so, who is most likely to benefit. (Read more about the study here.) If convalescent plasma was not such a precious resource, it may be more likely that it would be given outside of a clinical trial. But we need to make sure we're using it wisely and that it works.

Back in April, you answered questions about antibodies. What do we know now about how long antibodies last and offer protection for people?

Now that we've had so many millions of people around the world infected with COVID-19, we continue to build evidence that not many people come back with symptoms from a re-infection from the virus. That strongly suggests that once people recover from COVID-19, their immune system protects them against a symptomatic re-infection. Recently, there was a report of an individual who appears to have gotten reinfected with a true new infection of the virus. It's interesting that this re-infection was picked up on asymptomatic screening relating to travel, but he wasn’t symptomatic.

That again suggests that it’s similar to when people are immunized for influenza: They can get infected with influenza but tend to be less sick with it and maybe even asymptomatic. It also suggests that even though people have recovered from COVID-19, they might be able to be re-infected and still transmit the virus to other people.

We're also learning that the presence or absence of antibodies against the virus in our blood doesn't always correlate with our past history of infection. So some people with COVID-19 infection are losing detectable antibodies from their blood several weeks to months following infection. That does not mean that they're not protected against reinfection. Our immune system is much more complex than simply antibodies circulating in our bloodstream. This is a virus that infects our airways, so we have lots of immune cells in our airwaves, nose, throat and lungs that protect us at the source of infection.

Our understanding is getting more refined about antibodies and COVID-19, but there’s much we still don’t know. We're still not using antibodies to tell people that they're protected from re-infection or they can't be part of a chain of transmission. We're still not using antibodies to help people return to work. We're not even using antibodies to rule out that somebody had COVID-19 in the past, because they could have had COVID-19 in April and by now their antibody levels are gone. I always need to remind myself we're only eight months into this illness. It’s hard to use the term longterm in terms of anything with this virus, when we haven't even gotten a year under our belt.

Did previous research into the SARS CoV-1 virus help prepare scientists for SAR CoV-2? Has some of the previous research helped in the quest for a vaccine?

The SARS CoV-1 virus, the cause of the Severe Acute Respiratory Syndrome (SARS) and the Middle Eastern Respiratory Syndrome (MERS), helped us understand the potential for animal coronaviruses to hop into people and deposit disease. That led to increased efforts to monitor animal populations and prepare for a pandemic. Other non-coronaviruses like Ebola or Zika have also helped us understand the global threat of viral infections in general. And the funding of basic science research has led to the capacity to do rapid genome sequencing of viruses and the ability to share that information in real time. It helps tell us if a new virus is genetically a new virus, and whether it is changing over time.

Right now, there's not great evidence of different strains of the SARS COV-2 virus associated with different illnesses in people, though that may turn out to be the case over time. This all speaks to why investing in basic science research, informatics and data sciences continues to be important: You never know when all of those elements will need to come together quickly to improve human health and save lives.

What do we know about the timeline for a vaccine that we might not have known in the spring? How do you feel about predictions that it could arrive soon?

I don’t frequently make predictions by looking at a calendar and saying, we're going to have a treatment or a vaccine by this particular date. That’s because as a physician scientist, I understand how uncertain our future is when it comes to finding something that's safe and effective and that will be available to all. We’re seeing a lot of resources being deployed to making a vaccine. In fact, the coronavirus vaccine tracker from The New York Times shows more than 100 preclinical vaccines, with nine in phase three studies.

Right now Vanderbilt is participating in one major vaccine trial. (Read more about the trial here.) It will take time to see results, then that data has to be examined carefully by data safety monitoring boards. So, optimistically, I think we will be into 2021 before we can decide if the vaccines now in phase three studies are ready for prime time. If those trials are successful, the next stage is FDA approval. Then there has to be a clear path to manufacturing them at scale, a way to identify who should get the vaccines first and a plan for how they will be distributed. There's a lot that needs to be worked out, so I'm reluctant to say we'll have a vaccine by January 1st, or one by this time next year. But I'm not reluctant to say that I'm very enthusiastic that we will have a vaccine, and I'm excited to see all the candidates coming down the pipeline.

Why do you think so many vaccines are in the pipeline? Is it normal to have that many possible vaccines for a virus or is that unique to COVID-19?

Yes, it is unprecedented to have so many vaccine candidates working their way through pipeline, but that’s what happens when you have a global pandemic and money and resources are being poured into curing it. There's motivation around not only helping people, but also motivation to do something high impact like save the planet! Normally vaccine development takes a long time in part because you have to search for investors and raise capital between each phase. Those bottlenecks don't exist right now. Yes, there are over 100 ideas in the works, but most of them are early in preclinical trials. But that we’ve gotten this close in just eight months is remarkable.

Until we have new treatments or new vaccines, people need to continue to do the fundamental things that keep us all safe and understand that every individual person's sacrifices make a huge difference. And that's the most protective weapon we have right now.