Dr. Amesh Adalja (AA)
Randy Larsen (RL)
June 22, 2020
We are pleased to have with us a scientist and frontline physician, Dr. Amesh Adalja. He is a Senior Scholar at the Johns Hopkins University Center for Health Security, a Fellow of the Infectious Diseases Society of America, the American College of Physicians, and the American College of Emergency Physicians. He practices infectious disease, critical care, and emergency medicine in the Pittsburgh metropolitan area.
Our interview with Dr. Adalja covered a wide-range of topics including: Lessons Learned During First Four Months of the COVID-19 Pandemic, Testing (virus and antibody), Reopening the Economy, Therapeutics, MMR and TB Vaccines, The Age Issue, Schools and Daycare, I Think I May Have Been Exposed–What to Do?, and more.
Lessons Learned During First Four Months of the COVID-19 Pandemic
RL: In addition to your work in healthcare policy, you have been very busy treating COVID-19 patients during the past four months. Tell us about some of your key lessons learned.
AA: I’ve learned a lot about this virus by treating patients. I’ve seen that there is a really, really wide spectrum of illness. There are some people I have treated with very mild symptoms … or no symptoms at all … and then there are others who have life-threatening disease, and some of my patients have died.
It can be very impressive to watch this virus make its way through a person’s body. It is really eye-opening to see that first hand, and be managing it. We’ve learned a lot. When you’re a pandemic preparedness expert, you think that all the plans are ready, but then something, one thing … such as insufficient diagnostic testing can really foul up the response for an entire country .. and put us into crisis.
I can definitely say from my own personal experience in March … in the early days of the pandemic. It was very, very difficult to get a test. We had to make all kinds of decisions about test rationing … who could be tested … who couldn’t be tested … and it was very uncomfortable … and we had no idea who was infected and who wasn’t. We just assumed many of these people were infected, but we just couldn’t do the tests, and we knew that they were contributing to community spread.
I think that really taught me how important it is to think about diagnostic testing … how it has to be a cornerstone of the pandemic response … and how just a little thing like that can magnify and really throw an outbreak out of control.
I think we’re going to learn more and more every day with this virus. Every day, I learn something new about it, or some new aspect of it, I think that’s going to be the case for a long time as we’re stuck with this virus until there’s a vaccine.
RL: Do you have confidence in the tests currently being used to detect the virus? The antibodies?
AA: I do think that the PCR test … done either on a nasal, nasopharyngeal or a saliva sample is very accurate. It’s something that we’re doing to diagnose acute cases, and that’s what we’re talking about when we see these 500,000 tests being done per day. That’s the mainstay of our testing, and I am confident that those are good tests. We’re getting better at doing them. We’re looking for quicker and easier ways to do it, but it’s still the mainstay.
And when it comes to antibody testing, I think it’s kind of a little bit of a mixed picture out there. There are some antibody tests that are very specific, but you have to remember that this coronavirus is the seventh human coronavirus we’ve discovered. Four of them cause about 25% of our common colds. So there is some cross reactivity with some of the some of the tests. So you have to actually know what brand test you’re getting and look up its specificity. When people come to me with antibody test results, I ask what brand, and then I look up the operating characteristics of that test and tell them whether or not that’s a true positive.
The question with the antibody tests is how do we operationalize them? What type of information is it actually giving us? How long might those antibodies last at a level that’s usable?
RL: Yeah, and I guess there’s no technology to really know how long the antibodies are going to last. There’s no quick way to figure that out. Right?
AA: Correct. We just have to actually do the testing. We have to see who has antibodies and follow them and see what happens to them. That’s why it’s called a natural history study. We’ve gotta wait for history to happen. You can do tests with animals, and you can get some ideas in a lab, but it’s not the same thing as having a person recover and see if they get re-infected when they come into contact with the virus again.
RL: Speaking of antibodies … in your practice … are you transfusing antibodies from people who’ve recovered from COVID-19 to other people … as a therapeutic?
AA: Some of the hospitals that I work at have been doing that. I haven’t actually been involved personally in one of those. I practice primarily in Pittsburgh, and we’ve had a lull in the cases right now. It’s been some time since I’ve actually seen a fresh COVID case here. We’ve done pretty well with managing the cases, but there are hospitals now … including in the Pittsburgh area … that have the ability to do convalescent plasma, and it’s something we’re trying to see whether or not it works.
There’s been some mixed data out of China, but it is a solution that may help decrease the mortality rate, and that would actually be very meaningful.
Reopening the Economy
RL: Have we reopened too soon?
AA: I don’t think that that’s the way I would put it.
You have to remember that social distancing enforced by the government was really to protect hospital capacity. That’s what flattening the curve was about. Beginning re-opening wasn’t about saying that everything was going to be risk-free, and the virus was going to be gone once stay-at-home orders were lifted. I think there’s a disconnect there.
So when people start to socially interact … they still need to remember that the virus is going to be with them, and no activity is going to be risk-free … and they have to take precautions that are particular to their individual risks as well as their risk tolerance. I was somebody who thought the blanket economic shutdown for all 50 states was not actually necessary. I think what we wanted to do is a surgical … a more targeted type of social distancing … which focused on activities that were meaningfully protecting hospital capacity. And I think that that’s the way we should have managed our pandemic response. Things were kind of fouled up in January, February, and March, so we left the governors with these very blunt tools of economics shutdowns.
So I don’t necessarily think we opened up to too soon. I think what happened is that people just are not understanding that this virus is the new normal. It’s a risk that we’re going to have to take, and we have to keep an eye on hospital capacity all the time, because that’s really what’s going to be the main gauge of when the cases are getting to a level that’s unmanageable by the healthcare system.
RL: Okay, and one of the things I’ve heard you say on TV several times that made so much sense to me is that governors, county executives and mayors must keep a close eye on hospital capacities and the percentage of positive tests.
AA: Yes, those are the two measures I think are the most important. First, hospital capacity, because that’s where we get into trouble. We see hospital operations being disrupted and the mortality rates of other things going up because hospitals can’t take care of the patients that they’re getting from COVID-19. Second, the rate of positive tests is a really important measure. Lots of places are getting better at testing now and we are uncovering more cases because we’re able to test more … but what we really need to look at is the percentage of positive tests. It tells you so much.
The percentage of your tests that are coming back positive tells you whether or not the increase in cases that you’re getting is because you’re just doing more testing, or because you’ve got chains of transmission that you don’t know about that.
In some states they have had increases in case counts, but the percent positivity is staying pretty low … like California, for example, but in other states like … like Arizona, Alabama, and Florida … you’re seeing percent positivity rise, and I think that’s worrisome. That tells me that they need to really get more aggressive with case contact tracing, and really be looking at hospital capacity because eventually those chains of transmission may spill into the hospital and those hospitals need to be prepared and adequately resourced.
RL: Most people I talk with seem to agree we will have one or more effective therapeutics long before we have a vaccine. When do you think we will have effective therapeutics? Any comments on dexamethasone? Hydroxychloroquine?
AA: We already have an IV therapeutic … Remdesivir … which is available on emergency use authorization. That’s an antiviral. It doesn’t decrease mortality, but it does get you out of the hospital faster, which is important when you’re looking at hospital capacity.
Additionally, there are many different drugs in clinical trials.
We talked about convalescent plasma earlier. That’s in a trial. There are people trying to make what are called monoclonal antibodies. They’re based on antibodies that people form after they are infected. These antibodies then get refined and synthetically produced. We saw them have great success with ebola. Clinical trials with monoclonal antibodies are now underway for COVID-19… and I suspect we’ll see some of those in the future We are also hearing about a steroid that can be used in people with the need for oxygen, and that may decrease mortality. We haven’t seen all the data yet, but it looks promising. Hopefully the data actually bears that out.
We’ve also seen people trying to repurpose other drugs, and there’s many, many drugs that are in clinical trials in the pipeline. I do think we will see a therapeutic.
So what we really need is a game-changing therapeutic … something like an equivalence of Tamiflu … something that keeps people out of the hospital with flu and makes them less contagious.
Vaccines will still be the gold standard, but if you had an effective therapeutic … people will be much more confident about getting involved in their activities if they know that there was something to prevent them from being hospitalized, and made less contagious. But we’re not there yet with this virus.
RL: But do you think that’s something we can see in the next two or three months? Is that a realistic goal?
AA: I think we’ll have some therapeutics, but they’re mostly going to be focused on people who are in the hospital already to decrease mortality. I don’t see a therapeutic in the near-term that is equivalent of Tamiflu. There are few things out there, but nothing looks really exciting to me in the two to three month timeline that will keep people out of the hospital.
They are trying to take the Remdesivir drug that I talked about earlier, and make it an into an inhalant … so people could take that at home, and prevent the need for hospitalization. That might be something to look at, but I don’t see anything that’s kind of a Tamiflu equivalent here.
RL: Okay … hydroxychloroquine, is that completely off the table?
AA: Yes, I do think it is mostly off the table. This is the drug that had a lot of interest from a lot of people early on because it’s an immune modulating drug that has some antiviral activity. It was already approved for some other conditions. So people could use it off-label, but what we’ve been seeing in randomized control trial data, as well as anecdotal data, is that it doesn’t really seem to have any kind of benefit on patients with COVID-19 … not in treatment and not in what we call post-exposure prophylaxis … somebody who has been exposed. We don’t see any benefit, and it does have some side effects that outweigh any benefit. This has really become something that’s fallen out of favor, and likely is not going to be part of the solution to this virus.
MMR and TB vaccines
RL: I have read a few articles about younger people, born after the mid-1980s, may have some immunity to COVID-19 from MMR and TB vaccines. What is your opinion?
AA: There is a hypothesis that there is some kind of cross immunity or some immune stimulant activity by certain vaccines and one of them has been the tuberculosis vaccine … BCG … which is not used in the United States. That’s largely been questioned whether or not there is strong evidence for that. But there’s also some evidence now that maybe MMR vaccination causes a cross reactive immunity to this virus. I think it’s something we need to investigate. We still don’t quite understand why children are spared, and that might be part of the puzzle. It may be the fact that they get infected with so many strains of the ordinary coronavirus.
Children getting more colds might have something to do with it, or it may have to do with their immune system. I think it’s an important hypothesis to think about. I haven’t seen any strong data that’s supporting it, but it is something that we will probably hear more about over the next couple of months.
The Age Issue
RL: There was a recent editorial in the Wall Street Journal that said 80% of Americans who died of COVID-19 were older than 65. Does this sound right to you?
AA: Yeah, definitely … there was a time in Pennsylvania when over two-thirds of deaths were in nursing homes. So it definitely is something where the severe disease is very clustered in the elderly population. So like I said earlier … when you get to the age of 60, you see an uptick in hospitalizations and deaths, and I think that’s mostly what we’ve been seeing. The youngest patient I have treated was in their late 40s and had multiple comorbidities … so severe illness is not something that I’ve seen much in young people … not that it can’t happen, but the clusters are primarily in those over 60.
It’s going to be really important to protect vulnerable populations … especially nursing homes, assisted living centers and personal care homes. They must be really fortified against this virus, because if you can keep it out of those places, you will really take a burden off of hospitals. If a nursing home gets infected … and there was a nursing home in the Pittsburgh area where 300 people got infected … that can really put your hospitals into dire straits.
RL: I understand the elderly are at the greatest risk for severe illness, but there have been many press reports in the past several days about more young people being infected.
AA: Yes, severe cases and mortality will remain primarily in those over age of 60, but what’s happening now is testing has gotten so much better in the United States. Now, we’re doing over half a million tests per day. So, many are mild cases that we wouldn’t test in the past … and those mild cases tend to cluster in younger individuals who are now getting tested. That’s bringing down the average age of the cases, and it’s also true that
that as social distancing regulations are relaxed … the people who are most likely to start socially interacting are younger people, and then they’re going to get infected because the virus is out there.
So that’s skewing the data. Like I said before, in the first few months, when there was a lack of testing, we were only testing severe cases. In many areas, we are seeing a rise in cases, but not seeing hospital capacity being compromised … except in places like Arizona and parts of Texas. Many of the people who are getting infected … that are accounting for these new cases … are younger and not requiring hospitalization.
Schools and Daycare
RL: What does this tell us about whether we should reopen schools this fall? K-12…universities.
AA: So I think there’s also an important debate about schools and even when schools closed … there were many of us … including my colleagues … who were really not in favor of closing schools because school closure is something that can’t be a knee-jerk reaction.
First of all, we know for influenza, children magnify the infection. But do we know that for COVID-19? There hasn’t really been much data that children are driving this epidemic … it’s not something that’s being spread or magnified by the children. We also know that your children are likely spared from most of the severe disease.
We do know that there are negative consequences to closing schools. What about child care? What about feeding the children? What about the psychosocial social development? And we know that home learning has not worked very well in most places.
There are big differences between school districts. For example, inner-city schools may have students who don’t have computers … who don’t have high speed internet, and they are kind of disadvantaged over someone who has all of that … and I think that that was really something that needed to be calculated.
And then there were some places that schools did not close, and they didn’t see much worse happen, and we’ve even had daycare centers open during this pandemic for essential workers, and we haven’t heard about those daycare centers driving up cases.
And then the last thing is that some schools have opened in states like Montana and Idaho already … and they seem to be doing okay. So I think that we will see schools open. I don’t think that it was the best decision to close them … although I can understand why people did close them.
I do think that there’s a lot yet to learn to understand the role of children in spreading the disease, but right now I think if you can keep the teachers and the people that are that are vulnerable populations protected at a school … I think you can open schools and daycares in a safe manner. I think it’s important, especially if you want to get the economy going. For many parents, school is daycare.
I Think I May Have Been Exposed
RL: One question I frequently hear … “If I think I might have been exposed, is there anything I can do other than getting a test?”
AA: Well, it depends on what your exposure might have been. You have to remember that when you’re doing a case contact investigation, the CDC considers a significant exposure to be someone who was in someone’s presence for 10 to 15 minutes within six feet. That’s a significant exposure. It’s not passing someone in the hallway or outside on the sidewalk.
So if your exposure was significant, you might be contacted by a health department case worker, but they would not likely recommend a test. You would likely need to self-quarantine for 14 days. That’s what you do for the significant exposures. There are people who can be tested during that period, but that test is only for a moment In time. The incubation period can be as long as 14 days. Although most people get sick within six or so days. And remember … lots of people … maybe half of people who are infected don’t even get symptoms at all. So it may be the case that you’re still going to self-isolate even if you have a test. I think I would defer to your health department.
Although there are certain exposures … like the protests … where there was a blanket recommendation that if you attended a protest, you should quarantine yourself for 14 days.
RL: Dr Adalja. Thank you so much for taking time out of your busy schedule. Is there anything else you would like to mention?
AA: I think we covered a lot of what I wanted to say. We do need to understand … this virus is with us … it is the new normal … it is not going anywhere, and we’re not going to be back to what we were until there’s a vaccine.
But that doesn’t mean that we need to have an economic shutdown until there’s a vaccine. We just have to find a way to get rid of these false alternatives … on one hand, letting the virus rip through our society, and on the other, having a Wuhan-style lockdown forever.
People are going to have to look at their individual needs and determine what’s important to them … to understand their individual risk factors for severe disease, and their own risk tolerance to try and find a path forward with this virus. It’s going to be different for everybody.
Dr Adalja’s detailed biography.