COVID-19 Insights from Former FDA Commissioner, Scott Gottlieb, MD

The coronavirus has spread beyond the point of containment, and there’s a looming shortage of personal protective equipment. Those are two of the takeaways from the March 13 webinar sponsored by WCG and Accumen. It featured  former FDA Commissioner, Scott Gottlieb, MD and Massachusetts General Hospital’s (MGH) Paul Biddinger, MD. The on-demand recording of the webinar is available here.

We have summarized key points and observations from Dr. Gottlieb below, followed by questions addressed during the Q&A portion.

Insights from Dr. Scott Gottlieb

Dr Gottlieb, was the 23rd FDA commissioner; he now serves on the boards of Pfizer and Illumina. He’s a resident fellow at the American Enterprise Institute and a partner at the venture capital firm New Enterprise Associates. Prior to being the FDA commissioner, Dr. Gottlieb served as FDA’s deputy commissioner for medical and scientific affairs.

We're pleased to share insights from Dr. Gottlieb, gathered during the WCG COVID-19 Webinar held on March 13, 2020.

Testing will uncover many cases

We’re really at the beginning of what is likely to be an epidemic spread of the novel coronavirus here in the United States. As we get very broad diagnostic screening in place, “we’re going to start to turn over the card on a lot of additional cases.” Roche just announced approval of their high-throughput platform that’s going to be able to substantially increase screening. Once that gets into place we’re likely to turn up a lot of new cases. And if you look at the testing that’s been going on in the country, there’s been a very high positivity rate. That’s partly a reflection of the fact that appropriate patients are being tested, but it also reflects that this virus probably has been spreading for some time.

American mobility a unique challenge 

The United States’ population, relative to other countries, is very mobile, and we’ve probably seeded infection in multiple parts of the country. And so, I think what you’re likely to see is multiple outbreaks grow up simultaneously in disparate regions to give you a proxy. If you look at Seattle, the modeling shows that there could be upward of 5,000 cases just from a single cluster.

Seattle Airport has about 44 million domestic passengers coming through it annually. Those are passengers flying through Seattle to other parts of the United States. By comparison, the airport in the Hubei province in China has about 24 million international and domestic passengers coming through the airport--less transit to a much bigger region of China.

Will we be Italy or South Korea? 

The question some of us are grappling with is, will we look like Italy? Or will we look like South Korea? South Korea looks like their epidemic has peaked. They’ve had upward of about 8,000 cases and I think about 65 deaths versus Italy which has probably upward of 15,000 cases now and so far more than 1,000 deaths. They are countries that are relatively similarly sized. Italy;s population is a little more than 60 million, while South Korea’s is about 51 million. So, they are about comparable in size.

So, what did South Korea do right? They put in place strict, aggressive mitigation steps early on to engage in social distancing, trying to get people apart to break off chains of transmission. They also implemented very broad-based diagnostic screening, so they were able to identify their clusters very early and identify people who were infected within those clusters and get them into quarantine. They had an epidemic, they were certainly past the point of containment but they were able to use some of the tools of containment to reduce the scope of the epidemic versus Italy, which was very slow to implement the mitigation steps, thus allowing the virus to spread in the country.

Flatten the curve, protect the health system

The purpose of mitigation steps and social distancing is to keep the peak of the epidemic below the point at which the healthcare system gets exhausted.

What happened in the Hubei province and what’s happening now in Italy is the surge in cases came so fast that the healthcare system became exhausted; taxed beyond the point the system could adequately care for patients. You had a dramatic rise in deaths compared to South Korea where they were able to put in place mitigation steps, closing schools, having workers telework, canceling large events. So that slowed transmission to the point where their healthcare system was able to adequately deal with the people who were presenting who were infected.

When you put in place those mitigation steps, you can actually extend the length of the epidemic. If you think of an epidemic curve as a mountain with a very sharp peak, that’s a normal epidemic. If you do nothing, you get a very sharp rise in cases. And then after enough of the population is infected, you start to see a drop off, in part because the people who are susceptible and were going to be infected have become infected. And in part, once you get a sufficient number of people infected in the population, it creates a natural wall of immunity, it’s hard for new infections to form.

The goal of mitigation is to basically take that peak and push down on it, flatten it out a little bit and extend it out so the total time of the epidemic can actually get longer but the number of cases at the peak is a smaller number of cases.

Systemized approach: 

Right now, you see an ad hoc approach among states and localities, and even among businesses, where some are being very aggressive and some are not. We really need a more systematic approach.

Health system burden: 

We need to take steps to try to reduce burden on the healthcare system. Should hospitals be putting off elective procedures? Think about trying to reduce volumes in the hospital. What can the government do to try to alleviate burdens on hospitals? Should any hospital be undergoing a Joint Commission audit this month? There are probably things administratively that the government, both state and federal, could do to try to reduce some of the burdens on the hospitals and put things off that aren’t going to adversely affect patient care in the near term while the hospitals focus on a much more difficult challenge right now.

Contagious and virulent: 

All the emerging evidence shows that this is a dangerous virus. “This is maybe a once-in-a-generation pathogen that straddles that really terrifying area between being contagious enough that it can spread pretty efficiently but still virulent enough that it could cause a lot of death and disease.”

So, when you look at the data, the case fatality rate looks like it’s going to be about 1%, maybe a little bit less. The transmissibility of it--how many new infections you get for each infection--looks like it may be between two and three. “If this statistic holds, this is a very frightening pathogen.”

Not just elderly: The virus is taking a disproportionate toll among the elderly, but many in their 30s, 40s and 50s are getting very sick from this virus--even dying. The case fatality rate in people between the ages of 40 and 50 is about .2 to 2.4%. It is dramatically higher than the case fatality rate for flu within that age bandwidth which is around .02% --sometimes even less.

This is a dangerous pathogen. Once you get into the older age ranges, look at 60 to 70, case fatality rate is about 4%, 70 to 80 as high as 10%. And when you get above the age of 80, it’s as high as 14% depending on what data you’re looking at; those are the high end.

That data that came out of China; it would likely be lower here in the United States especially if we can adequately address our healthcare needs. But evidence suggests that even if we’re not seeing the high fatality rates, the people who are 30 to 40, 40 to 50, 50 to 60, they’re still getting very sick. And so, you’re seeing a percentage of patients that, while they’re not succumbing to the virus, they’re getting very sick and consuming enormous healthcare resources.

Possible summer break, back in the fall: We have a difficult couple of months ahead of us right now. Ideally, this will peak sometime in April and will be coming down the epidemic curve into May. July and August provide somewhat of a backstop against continued transmission, the hot sticky months. But it’s something that we could be dealing with again in the fall. By then, we hope to have point-of-care diagnostics; we’ll be able to isolate and screen people better. We’ll have some therapeutics available. “But I don’t think that this is something that is going to come and go. I think it’s something that we’re going to be grappling with for a period of time now.”  

Audience Questions:

Dr. Gottlieb's presentation generated hundreds of questions. Here are a few; questions and the responses have been lightly edited.

Q: Could you talk a little bit more about the current work that’s being done towards both prophylactic vaccines and therapeutics?

Gottlieb: I think of this as a three-pronged strategy.

  1. The first prong of the strategy is to look at antivirals that are already on the shelf and try to repurpose them. Some of them were developed against MERS and SARS; they’re being screened to see if they have activity against coronavirus.

    One is remdesivir by Gilead, which is in two clinical trials in China. It was developed for Ebola, tested in MERS and SARS, and is now being repurposed for this coronavirus. In some ways, it’s not an optimal drug, it must be delivered intravenously. It’s hard to manufacture … and I think it’s given three times a day. But it could be a very important tool as a backstop against really bad outcomes. If remdesivir works, it could be available in the fall.
     
  2. The second prong is antibody-based prophylaxis. This is like the antibody that was developed for the treatment of Ebola by Regeneron where you basically have a monoclonal antibody drug that targets some feature of the virus itself that you can give as a monthly injection as a prophylaxis. And in this case the target would be the spike protein in the coronavirus.

    This would be used for people like frontline healthcare workers who are going to be exposed to coronavirus. You might use it in people in nursing homes or people who are uniquely vulnerable to coronavirus. People who are immunocompromised, maybe going through chemotherapy. “We had a drug like that. And there’s a potential that we could have that drug available as early as August of this year.”

    A drug like that would provide a natural backstop against continued transmission, since a lot of the transmission is in the healthcare setting and could be used by healthcare workers. It would also reduce the overall morbidity and mortality because you’d be basically giving a prophylaxis to the people who are most likely just to come to a bad outcome.
     
  3. The third leg of the strategy is the vaccine strategy. There are multiple efforts underway for different vaccines. I think we have to be realistic and believe that a vaccine is probably about two years away. But unlike with H1N1 in 2009, where we inoculated frontline healthcare workers first, I think in this setting you’d be reluctant to inoculate your frontline healthcare workers because there is some theoretical concern that a vaccine could effectively potentiate your susceptibility to the virus.

 

Q: What is the impact of temperature and climate on coronaviruses?

Gottlieb: Typically, coronaviruses don’t circulate in the summer. This one is probably going to be different because we have no cross immunity. So, people are probably going to remain susceptible to it even in the warm weather. But we should see decreased transfer in July and August, and that’s for a couple of reasons. Number one, there’s a general belief that things that transfer through droplet transmission don’t transfer well in hot, humid air. And there’s some evidence for that. So, the hot humid months--July and August--should provide somewhat of a backstop.

The second reason is that the epidemiology of spread of respiratory diseases changes in the summertime. People are not in close quarters, and that could have a very big impact on the epidemiology of spread.

So, I think that the summer should help. I don’t think it’s going to break off the transmission. If you remember the 2009 H1N1 season that was first diagnosed April 15, 2009, it was a case in California. The second case that was diagnosed in the country, it was about two weeks later. What we didn’t know at the time was that it was already epidemic across the whole country. And it’s pretty warm in Milan right now--60, 70 degrees--and they’re getting pretty good transfer of this.

About the Author

Dr. Lindsay McNair, MD, MPH, MSB | Chief Medical Officer, WCG

Dr. Lindsay McNair has extensive experience in the pharmaceutical industry. Prior to joining WCG, she was a consultant to pharmaceutical and biotechnology companies, providing medical guidance on clinical development strategies and study designs for new drug studies, and medical oversight of all phases of clinical trials. Dr. McNair teaches graduate-level courses on the scientific design of clinical research studies. She has been actively involved in IRB work for 18 years, and has a Master’s of Science in Bioethics with a concentration in research ethics.

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