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April 2020

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Dr. Megan Murray Interview: Harvard Epidemiologist on the Forefront of the Fight for COVID-19 Cure

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Image attributed to Dr. Megan Murray

Dr. Megan Murray

Dr. Megan Murray, MD, MPH, ScD, is an epidemiologist and an infectious disease physician with over 25 years of experience in the management of TB programs and TB epidemiology, as well as the transmission dynamics of emerging infectious diseases. She is a Professor of Global Health and Social Medicine at Harvard Medical School, where she leads the Global Health Research Core, a multidisciplinary group of researchers who work with the Global Health Delivery Partnership faculty and staff to develop its mission to link research to the teaching and service activities of the Partnership.

Dr. Murray is also a Professor of Epidemiology at Harvard School of Public Health and the Director of Research at the Brigham and Women’s Hospital Division of Global Health Equity and its sister organization, Partners In Health.  She has conducted field studies in Peru, Rwanda, South Africa, Russia and the US, and has previously worked in Kenya, Niger and Pakistan.

"We’ve speculated – based on data on the impact of BCG on non-TB respiratory infections in several recent clinical trials – that it might be useful in protecting people against COVID-19."

Smashing Interviews Magazine: Dr. Murray, how are you doing these days?

Dr. Megan Murray: (laughs) You know, every day is the same now. There are meetings from morning until night on Zoom interspersed with frantically writing proposals and protocols. It’s crazy. But I think it’s better than the alternative, which would be feeling frustrated and not knowing what to do with oneself at home alone.

Smashing Interviews Magazine: Are you still a practicing infectious disease physician?

Dr. Megan Murray: I gave up actual clinical practice about 10 years ago to do full time research and teaching and run research groups, and most of my research has been in infectious disease until recently. Way back, when I started in this field, my research was on infectious disease dynamics, and we worked on SARS (Severe Acute Respiratory Syndrome) when it emerged in China in 2002. But over the past 10 or 15 years, I’ve mostly worked on tuberculosis. Now of course, I’ve gotten very much involved in this new COVID-19 response.

I also lead a group of epidemiologists and biostatisticians who work on global health related issues. So that could be anything from infectious diseases, which is most of my work, but also a number of things like treatment for noncommunicable diseases, surgical outcomes, and maternal and child mortality in the different countries we work in. We work very closely with a non-governmental organization called Partners in Health which has health related programs in 10 different countries, and we support the operational research that they do. So half my life is spent organizing and supporting that team of researchers, and then the other half is my own tuberculosis research and teaching both doctoral students and post-doctoral fellows.

Smashing Interviews Magazine: Are you currently doing research on COVID-19?

Dr. Megan Murray: Yes. We’re working on a number of things all over the map. We’ve been working on modeling the predicted trajectories of the epidemic and the needs for intensive care unit beds and staff. A lot of groups are doing that in the US. We wrote a paper a while back on the needs in the US, but we’re also very interested in looking at helping low to middle income countries where the number of beds available is much, much lower and where there’s a whole spectrum of issues that might make things very different from what we have seen in China, Europe and the US. So that’s one part of what we’re doing.

My main focus, at the moment, is on trying to get a clinical trial going to look at the impact of BCG on Covid-19. BCG is a vaccine has been used for more than a century for tuberculosis – it’s actually the most common vaccine used throughout the world. It’s usually given to people at birth, and it’s known to protect kids from disseminated forms of TB. But weirdly, it has also been documented to protect kids from death even when it was clear that TB itself wasn’t killing enough people to account for that effect.  So, for almost a century, people have known that BCG has this unexpected effect on other outcomes and infections. It’s also been used as an immune modulator in different cancer therapies, so it seems to activate the immune system to fight off a sort of a range of infections, some of which are unrelated to TB, and also some kinds of cancer.

We’ve speculated – based on data on the impact of BCG on non-TB respiratory infections in several recent clinical trials – that it might be useful in protecting people against COVID-19. So you might ask why in countries like China, where people get BCG at birth, do people get sick with Covid-19 despite BCG vaccination?  It is possible, even likely, that the non-specific effect of BCG – its effect on infections other than TB – wanes over time, so by the time people are adults, it may not be having an impact. We’re trying to set up a clinical trial in health care workers in the US and Peru and in a group of elderly people in Taiwan. Those just happen to be places we have the ability to do research because we have worked there before or have links to research teams in those places. But setting up a clinical trial is a major undertaking – it’s just a ton of work. So that’s where most of my efforts have been.

Smashing Interviews Magazine: President Trump has urged Americans to take the anti-malaria drug hydroxychloroquine for the coronavirus, and Dr. Fauci has disagreed.

Dr. Megan Murray: I think what Dr. Fauci was saying is that the data are not clear yet, and that we need to wait until the completion of some clinical trials to really understand if this drug works. There was an initial study that came out of France that looked encouraging, but the study had some major flaws and so it’s hard to interpret. There are a couple of other studies that don’t look as promising, and we really just need to see what a very well conducted trial will show. I think it’s interesting.

I mean, I certainly wouldn’t recommend the use of a drug until we know if it works or not because all these drugs can have serious side effects. Then there are two issues here. One is, does it improve disease outcomes in people who are sick? And the other question is, does it prevent infection in people who are taking it before they’ve been exposed? I know there is a clinical trial that’s already been started at Baylor in Houston, randomizing health care workers to get hydroxychloroquine or a placebo and then seeing if the drug prevents them from getting Covid-19 disease. I would say this for any drug, that it’s a good idea to trial it, and it’s a good idea to look at the data before one makes a recommendation on how the drug should be used. Most drugs have the potential for both good and harm, so you really want to know if it works before you use it.

Smashing Interviews Magazine: More and more doctors, nurses, healthcare workers are contracting the virus. Is that because of a shortage of protective gear or just from being constantly exposed?

Dr. Megan Murray: We’re short on protective equipment everywhere in the country. People are working hard to bring in masks and other kinds of protective gear. But, yeah, there’s some data from China that once protective gear was available to people and they really started using it in very rigorous ways, the rate of infection of healthcare workers started to fall. But in general, this is a very transmissible infection, especially through the respiratory route. So, when one is taking care of a patient in these kinds of extreme circumstances, in intensive care units where the medical staff are involved in intubating people – meaning putting breathing tubes into their airways –  or doing bronchoscopies, procedures in which  a tube is inserted through the airway right into  the lung so that samples can be obtained for testing – those are high risk procedures that generate cough and aerosols that put the people doing them at high risk. So even if they’re wearing protective gear, they’re still at some risk.

The other group at risk is people who are in less extreme health care settings – for example, healthcare workers who are just taking care of people with routine medical issues who don’t think they have COVID-19, people coming into primary care clinics for their regular appointments or coming in with a broken leg. A lot of younger people who have COVID-19 infection don’t have any symptoms but are still infectious, and so any circumstance in which people are interacting with a lot of different people in the kind of physically close way that it takes to put a cast on a broken leg, those circumstances are going to put the health care workers at risk.

We’ve tended to think of these ICU workers and emergency room workers as being at the highest risk, and I expect they are, but really all healthcare workers who are coming into close proximity with the general public are at risk. And that is really horrifying. Not only are the people who are doing the hardest work putting themselves at the greatest personal risk, but they are also the people we need the most to try to deal with this crisis. We really need to be doing all we can to protect them.

Smashing Interviews Magazine: A lot has been said about higher risk factors such as heart disease, diabetes, being older than 65, lung disease, being treated for cancer. A French epidemiologist said that obesity is a major COVID-19 risk factor also. Have there been some studies done on the people who have contracted it and the percentage of underlying health factors they had at the time of infection?

Dr. Megan Murray: Yes. That’s coming out of China and these results have been validated in other places. Studies in Italy and Europe on risk factors for poor outcomes are a little further along than we are here in the US. The strongest risk factor for severe disease and death is older age. We think that lots of young people could be infected and don’t even get sick, or their sickness is so mild that they’re not recognized as having COVID. But the death rate goes from around one percent for people under twenty years of age to about 5% in people over 60, but then up to about 15% in people over 80. So really age is a huge issue, as has been shown initially in China and also in Italy and Spain.

Beyond age, it seems that heart disease is one of the main risk factors for bad outcomes. The thing about diabetes, obesity, heart disease and hypertension, is that the same people tend have more than one of these conditions. In other words, if they have diabetes, chances are they’re also obese. If they’re obese and have diabetes, they probably also have hypertension, so it’s hard to know which of those things is actually driving the risk. We do know that people that have these multiple comorbidities are at much higher risk of serious outcomes and death.

Smashing Interviews Magazine: President Trump has said that there are two million test kits out there, so tests are not available for everyone?

Dr. Megan Murray: No. I don’t think we are anywhere close to tests being available for everyone. I have also heard that they’ve done two million tests, but I think their goal was to have done 30 million by now. So, we are way under that goal. It’s a really complicated story about how we got to this situation in the first place. There was a test the World Health Organization was using. It wasn’t perfect but it was reasonable. The CDC wanted to make their own tests. It has a long history of making excellent tests, so they started to do that. But in this case, one of the components of the test was a faulty reagent. So when they sent the initial batch of tests out back in February, not all of them were working. They recalled them, and they tried to fix the problem. They eventually did, but in the meantime, there was a regulatory issue that prevented the initiation of other kinds of testing that might have happened earlier.

A lot of hospital-based labs have a capacity to do these type of PCR tests themselves, without kits. These are referred to as laboratory-developed tests or LDTs, which are designed and used within a single laboratory. They use their own reagents and protocols, but in this case, at least initially, LDTs were not allowed by the FDA. So hospital-based labs could not move ahead with testing but had to wait for the CDC kit to be fixed and redistributed. That lost a significant amount of time, and then with the need to rapidly scale up production of these tests when they were ready to go out, and there was significant circulation of virus, they just couldn’t keep up with those demands.

At the moment, the CDC is recommending an algorithm for who gets tested because there’s just not enough tests to test everybody. The top priority they list is to test very sick people, then any healthcare workers who have any symptoms – because of course, you don’t want healthcare workers infecting people. And it goes down the list. I think the next category is first responders who have symptoms. But if you’re just a normal, everyday person that isn’t very sick or if you got sick at home and don’t require hospitalization, a test isn’t really available to you in most places. I’ve had numerous friends who believe they have had COVID-19 over the last two weeks, and it’s clear from the clinical presentations that this is highly likely, but none of them have been tested because they’re not sick enough to be hospitalized. So they are recovering at home and not going out so they don’t infect other people. In this case, people know that they probably have it but a test isn’t going to change anything for them in terms of treatment options. The downside is that they are potentially in contact with their family or household when they don’t know if they’re putting those people at risk or not. So there needs to be lot of physical distancing that happens within households, even when people are not sure if they are infectious.

Smashing Interviews Magazine: Is it reasonable to expect a second wave of the coronavirus after April 30, 2020?

Dr. Megan Murray: (laughs) Yeah. We’re guessing that may be the case, right. So what this is about is when there’s an epidemic of a viral disease, in most but not all types of viral infection, people gain some immunity after they’ve been infected. The epidemic curve has a peak, and then it falls off. The reason it falls off is because there’s enough immune people in the population to generate a “herd immunity” that blocks the spread of the disease. What that means, if you are uninfected and go out and meet five people, and if the people you meet are already immune, then they’re not going to infect you. If they’re not immune, some of them could be infectious, and they could infect you. This is what we mean by herd immunity. For different infections, you need different levels of immunity in the population before you’re going to see this decline. It all depends on that. In the absence of having a vaccine, it all depends on how many people actually develop immunity. At the moment, we really have no idea what proportion of the population is immune.

We know that a lot of people who are infected with the virus that causes Covid-19 do not have detectable disease. They have had mild symptoms, which they didn’t differentiate from a cold or allergies, or they may have had no symptoms at all. So we just can’t say. Is 10% of the population immune? Is 20% of the population immune? Is it 50%? When it gets close to 60-70%, I think we can feel like the population, as a whole, is protected even though there will still be some susceptible people in the population.

Without wide use of the antibody test – which detects whether people have been infected – and without knowing what portion of the population has been infected and is now immune, you really are kind of guessing. If there’s a lot of transmission of asymptomatic COVID, and all these people are immune, then the good news is that we’re probably much closer to that level of herd immunity than we thought. If that didn’t happen, and most people are still susceptible, then we’re still at risk as a population. To the extent that the population is still susceptible, it’s almost certainly the case that there will be further resurgences of this coronavirus. Once this initial wave has been suppressed, it may take a while to take off again, but as long as there are people in the population who are infectious, and there’s not enough people who are immune, then we can expect to see another wave. Of course, if we have an effective vaccine, we can also achieve herd immunity by vaccinating a sufficient proportion of the population and that is what we are hoping for.

Smashing Interviews Magazine: So you have to have a certain percentage of the population to be immune before America can actually reopen, unless there'a a vaccine?

Dr. Megan Murray: Yeah. Or you can reopen it recognizing that there will be another wave and put social distancing back in place at some threshold. You could say, “Okay, we need to get the economy started, so we’re going to relax social distancing. But if a case count gets too above some number, we will resume social distancing.” That’s an alternative strategy, which may allow some economic activity to take place. People aren’t thrilled about the idea of doing this again (laughs). I don’t know which is worse, prolonging this one or saying, “Well, let’s let up, but we’ll have to do it again later.”

Smashing Interviews Magazine: Even if people were told that it was safe to get back out there, it seems they would still be frightened of contracting the disease.

Dr. Megan Murray: Yes, but I think the problem is for people who don’t have any cushion here. If they’re not getting paid, and they don’t have health insurance, they can’t go on this way for very long. For people who can stay home, then social distancing is a great idea. I think where it becomes really a problem is if you lose your house or apartment or can’t buy food.

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