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Academic medicine on the front lines of the coronavirus outbreak

Stacy Weiner , Senior Staff Writer
January 30, 2020

As a deadly virus spreads from China to at least 15 other countries, U.S. experts are mobilizing to decode the disease and protect patients. AAMCNews spoke with a leading virologist at Vanderbilt University about breaking developments and what lies ahead.

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biohazard worker
A health worker checks a woman's temperature before she boards the subway in China to prevent the spread of the novel coronavirus.
Betsy Joles/Getty Images

As a novel and dangerous coronavirus continues to sicken thousands in China and a few dozen others in countries around the world, including the United States, U.S. academic researchers and government experts are working around the clock to understand, treat, and help prevent further spread of this emerging viral threat.

“We are already functioning as if there is a worldwide pandemic,” says James Crowe, Jr., MD, an immunologist at Vanderbilt University School of Medicine and director of the Vanderbilt Vaccine Center.

Although in “24/7 scramble mode,” Crowe recently took time to update AAMCNews on what’s happening behind the scenes in a well-developed nationwide system created to handle such potential disasters. Below are key insights that he shared.

Do you anticipate that we may see many more cases in the United States and worldwide soon?
Because of the amount of travel between the United States and Asia, I think it’s likely there will be more cases in the next few weeks here. Also, even excluding ill persons at the border isn’t going to keep the virus out [because] travelers may board an airplane while infected but without any symptoms. We think that's already happened.

Do you have a sense of whether this is going to be a manageable outbreak or a global crisis?
If you connect the dots of the number of cases being tracked, at present it's not possible to say when that line stops going up. Two weeks ago, people thought it was just smoldering, and this week it’s clear the number of cases has continued to increase dramatically. So it's possible that this will be a major worldwide outbreak, but predicting is very difficult.

How are researchers in medical schools and teaching hospitals responding?
What's going on right now is that academics who have capacity to contribute are contacting government sponsors with whom they already have relationships and are offering their services. It’s very encouraging that the entire community that has capabilities has made themselves available.

Also, the U.S. government has been convening both government and extramural experts almost on an hourly basis. There have been calls with people from all over the country and the world, the CDC [Centers for Disease Control and Prevention], the NIH [National Institutes of Health], the Department of Defense, and experts in major medical research centers in the U.S.

What are you personally working on?
Vanderbilt is a contractor in the federal Pandemic Prevention Platform, and we were already starting a year and a half ago to prepare to rapidly respond to an epidemic by developing antibody treatments. Two weeks ago, the potential targets for these programs were still called Pathogen X. Everyone would say, “When Pathogen X occurs, you will execute your program.” Now, X has been filled in with the word “coronavirus.”

We are also embedded in a greater virology community, so with collaborators at the medical schools of Washington University in St. Louis, the University of North Carolina at Chapel Hill, and other institutions, we immediately started having conversations about sharing cells [and other tools]. Within a day, we had a plan of how to do an antibody discovery program and get it into the clinic.

What we need to do is get blood cells from people who have survived the infection and who are now immune, and we will use their blood cells to make a biological drug. So, we are working on that process now.

Also, we’ve already had some very good conversations with manufacturers and biotechs offering to engage them if we have a lead antibody drug candidate. Our goal would be to have the drug ready for clinical trials within about three months — and that would be the fastest response ever in history.

Are there other potential significant leads on treatments?
Another category is antivirals. Gilead Sciences will be testing whether or not their existing drug for other coronaviruses, remdesivir, works against this virus. If so, that drug could be made available very rapidly. But first, investigators need to test the drug against the virus. So they would need to get the virus, most likely from the CDC. Also, it is possible to make the virus synthetically from DNA, and there are groups that are actively working on that approach. But all of those procedures take days or a couple of weeks.

Those are treatments. What about a vaccine?
At least two companies are working on a vaccine, Moderna and Inovio, and certainly there will be more to follow rapidly. First, there is development of vaccine candidates, and then there is a selection of a final vaccine to be tested. Certainly, they have candidates already. I suspect that they will have a final selection of a possible vaccine within a few weeks, and they might be able to be in clinical trials by early summer. They want to move fast, but they also don't want to hurt people while developing the vaccine.

What else is a high priority for researchers in academic medicine?
We need animal models to test vaccines, antivirals, and antibodies. Academics are much better than industry about developing new models, and that's going on right now at several places, including Washington University and UNC Chapel Hill medical schools, figuring out which small animal will best replicate the virus or mimic human disease.

And then there are some very basic, fundamental questions about how the virus attaches to the human body that are being researched at Harvard, Washington University, and UNC Chapel Hill medical schools, Vanderbilt University Medical Center, and some of the NIH government laboratories as we speak.

What's being done in terms of preventing further transmission of the virus?
There are a lot of things we need to know immediately, and many academics are working on that, such as how many people one person infects. Right now, we think it's between one and a half and two, but if that number were higher, it would be even more concerning.

Then another question is, "How does the virus move from person to person?" That mode of transmission will determine what PPE [personal protective equipment] and facilities are needed. So if it’s spread by contact, providers will need to wear gloves and gowns and masks and face shields. And people will retrain on proper donning and doffing of PPE to be up to speed.

If it turns out that it's spread by small particle aerosol, that will be very challenging because hospitals have negative pressure facilities for these issues, but they don't have an unlimited number of those rooms.

Look at China. They're going to build an entire hospital on the fly because there’s just not sufficient capacity to keep these people in isolation. So in terms of infection control and personnel protection, academics are figuring that out, and the CDC will establish recommendations.

How prepared are hospitals to handle an outbreak?
After some of the events that we've had like bird flu and Ebola, most hospitals in the country have created a plan. At a big hospital like Vanderbilt, we’ve also had war game-like simulations where we used the NFL football stadium to triage patients. We also have rooms in the emergency department with special showers to bring the person in and contain them right at the door, but not every facility would have that.

Then there are even very special containment units for things like Ebola at Emory University, the University of Nebraska Medical Center, the NIH, and elsewhere. They don't have a huge capacity, but no one's talking about that right now. This is probably going to be containable under some sort of rather standard hospital facility.

How would you say this compares to previous global outbreaks such as SARS or Ebola?
That's a good question. I've lived through the response to chikungunya, Ebola, Zika, and bird flu outbreaks — we’ve responded to all of these — and I would say the country is in a much better place now to respond rapidly than it's ever been before.

In some ways, it still seems like a surprise every time it happens even though that’s what we do in my lab, continually prepare to respond to an epidemic. Last week, we were still arguing with ourselves: Should we pull the trigger and go full blown in sprint mode, or should we keep on with our other important work? By yesterday, the answer was "pull the trigger.”

What is your long-term goal in terms of potential outbreaks like this?
Outside of the current episode, what we're doing on a day-to-day basis is trying to make human antibodies for 100 of the known viruses in the world that cause human disease and to have candidate treatments ready prior to an epidemic, a program we have called AHEAD100.

We've been systematically developing antibodies for as many viruses as possible. Once the current event is over, we'll reset and we’ll go back and try to prepare for all the other viruses that are out there. I think that would be preferable to everyone scrambling every 12 months in urgent mode.

For more information, visit the Centers for Disease Control and Prevention coronavirus webpage.

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