(Transcript has been lightly edited for clarity and length)
Aaram A. Kumar: Hi, everyone, welcome to this episode of Science Speaks, an interview series from Sciencera that discusses a variety of topics about science and life in the world of science.
Today, we have with us Dr Nicole Putnam, Ph.D. We’ll be discussing with her some questions many of us have encountered about the COVID-19 pandemic. She is a scientist who has studied infectious disease pathogenesis and immunity at the Johns Hopkins School of Public Health and also Vanderbilt University Medical Center, focusing on measles virus and also invasive staphylococcal infections.
She is currently a clinical microbiology fellow at the National Institutes of Health and as you can see, she has a good deal of public health and microbiology and immunology background. Her personal interests lie in clinical diagnostics and research, education and training of scientists and clinicians. She’s also passionate about public health and science communication.
Before we start, in the spirit of full disclosure, we wanted to convey that the insights and answers provided by Dr. Putnam today reflect her personal views and not of her employer (NIH), or Sciencera.
Welcome! Thank you so much for taking the time to chat with us, really appreciate it!
Before we dive into some of these burning questions that we have, I was wondering if you would share with the audience what clinical microbiologists do?
Nicole Putnam, PhD: Yeah, that’s a good question. So clinical microbiology is a really interesting area to think about: when you go to the hospital or somebody is an inpatient and your physician suspects that you have an infection, they will get a specimen and send it to a clinical microbiology lab, where that specimen is processed and worked out to find that answer.
So, we basically just find the microbes by different methods and then help figure out what treatments might work and communicate that to the physicians.
AK: So, you’re like these medical detectives. Perfect. Thank you for giving that background.
If you don’t mind, we can jump into some of these questions.
So maybe start with one of the hot or controversial topics that we have encountered this week: as you I’m sure you’re aware, there has been a sort of resurgence or a second wind at the advocacy or for from a number of groups who have been asking for Hydroxychloroquine to be added as a treatment. And as far as I’m aware, this is something that the FDA had previously given emergency authorization for. But then given the overwhelming number of randomized clinical trials that showed evidence that hydroxychloroquine may not confer benefit and and if anything, may even cause harm to certain patients, they suspended that authorization. Do you know of any new respected or established clinical trial data coming to light this week that caused, a demand or increased enthusiasm if you will, for hydroxychloroquine?
NP: I haven’t seen anything this week that would cause a resurgence in claims.
And a couple of things that you said are important to touch on – there are randomized controlled trials. So that is something that they did or started doing when there was all of this media hype around having something that could potentially work. A randomized control trial is the best way to get the answer about “Is this drug going to help and do the benefits outweigh the outweigh the risks associated with taking that drug?” A lot of evidence that came out early was anecdotal reports. So, not controlled, not really scientifically approached. But as far as I know, all of the randomized controlled trials have shown that there really is no benefit. And if anything, there may be more harm.
AK: I see. Thank you. I really appreciate you taking the time to talk through that and also giving a little bit of overview as to why randomized controlled trials are important and carries more weight than anecdotal studies or case reports.
I guess the other thing we have frequently been hearing a lot of information on is regarding masks, right? Initially there was guidance about whether or not to wear masks and then it changed. So, what evidence do we currently have on masks reducing COVID-19 transmission?
I have come across some folks saying: “Cloth masks don’t offer any protection, so why wear them” or the other thing I’ve heard is “if your mask works, then why do I need to wear mine as well?”
I’m wondering, what can we say to address that?
And also, if you don’t mind, maybe touch upon a bit about face shields – with masks or without masks – since that’s something that’s really popular these days?
NP: Yeah, that’s a lot of questions. So, I’m going to try to break them down. Remind me if I miss anything.
I would say, I guess just to give some context into this: the guidelines and public health recommendations are going to come from scientists. And in general, we don’t like to say things that we don’t have data from. So early on in the pandemic, there was not a lot of data to support that masks can help. And now we’ve done studies. There are several peer reviewed publications that show that they do help. And one reason why there’s been a lot of change in the guidelines over time is because we’re still doing the studies to learn what is helpful.
So one thing that I actually wanted to show, I feel like this is a really good display of information, so this is another clinical microbiologist on Twitter and he took a few different pictures on bacterial growth plates – from sneezing, singing, talking and coughing – either with a mask or without a mask. You can see that significantly more bacteria can grow on the plate if you don’t have a mask.
I mean, that’s not super surprising because we have oral flora in our respiratory tract and it’s a visualization of something else, but is a proxy of the respiratory droplets that are released during these common activities.
What I like to think of masks are as a barrier; any barrier is going to prevent the spread of droplets from one person to another, including cloth masks.
And I think one of your other questions was what can you say to other individuals? That’s something that I find is a touchy topic these days. Just there’s a lot happening in the world, so I would say that my biggest piece of advice is just Generalize, Don’t personalize. If they feel like you’re attacking them for whatever reason, people aren’t going to listen to whatever it is you have to say. They also become defensive very quickly.
I think facts sometimes can turn people off as well. One way that I have used in the past, that makes it a little bit more approachable instead of just yelling facts at people is to bring it up like a question or like an interesting fact. Like, “did you know that people who don’t show symptoms because they’re asymptomatic or pre-symptomatic can still test positive for SARS-COV-2?” That means that anyone that isn’t showing symptoms could still be spreading it and they have no idea they could feel fine, and that’s what makes this more dangerous than, say, the diseases that have more severe manifestations like the previous
SARS epidemic or MERS. It would be nice if you tested positive when you had symptoms and they went away, then you can at least contain that accordingly as these people are showing symptoms.
AK: So, if I’m showing symptoms, I can quarantine myself. But in the other case, I might be infected already and still walking around and potentially can infect others.
NP: I don’t know the exact numbers, but it seems like a pretty high proportion can be asymptomatic. So that could be a serious factor leading to spread.
AK: Absolutely, and I guess that that sort of emphasizes why it’s not just people showing outright symptoms, but also everyone wearing masks would be useful.
And one picture is worth a thousand words. From what we saw in that petri plate picture, certain activities like singing, for instance, generates a lot more droplets. It shows why choirs or things like that in close settings might be potentially risky.
And of course, the difference with wearing a mask, like you said, that’s very telling. So, thank you for that.
You said the masks sort of prevent those large droplets from getting into the air and that’s infecting others. Recently there has also been a focus on aerosol transmission of COVID-19. Does this change any public health recommendations we have?
If it’s transmitted via aerosol, can you get it via air conditioning units?
NP: That’s a good question. I haven’t seen a ton of studies looking at aerosolization and how that can lead to spread. So this might seem like a nuanced point and it kind of is: but there are some pathogens that cause infections that are spread via droplets, like SARS-COV-2. And then there are other things that are spread via aerosol. So, depending on infection control practices in a hospital, you will have different levels of precautions set up for rooms. For droplet precautions, masks seem to work fine, but aerosols can be transmitted. They’re much smaller. So, you need to have increased protection. That would mean that things like tested respirators so that there’s no gaps around your face and negative pressure rooms, like you said, so that it can’t get into a system or a building in other areas as far as I know. I think that respiratory precautions seem to be covering our bases right now.
Another thing I just thought of is to go back to your previous question, thinking about how people are dealing in hospitals. You asked about face shields. It’s another thing that I haven’t typically seen in a lot of respiratory cases, but it’s becoming more commonplace. I think for health care workers or for other people who are at risk of… or can’t socially distance, or are going to be close to somebody who is potentially infected and could get coughed or sneezed on, it is important to have a barrier like that because it’s plastic, a virus, it can’t go through that. The wearing the mask underneath is still important because droplets and aerosols, they can hang out in the air for a period of time.
AK: So, you talked about people who show symptoms. Then there are people who are asymptomatic altogether or people who haven’t started showing symptoms, even though they may be infected for a number of days and start showing symptoms at the later stage.
So, my question is, why do people respond differently to COVID-19 infection? Some people are not developing serious symptoms, worse than some others. Also we hear these cases of individuals who are seemingly healthy and young and still suddenly have critical or even fatal complications?
NP: That’s a good question. That probably will be an extremely complicated answer for us to work out.
I think that we know a few things: There are a few factors that are associated with worse outcomes, more severe disease or death. Those things are age and gender. Like you said, young, healthy individuals may have better outcomes, but everyone kind of responds differently, so you don’t know how it’s going to turn out, which is kind of scary. But also these are things we can study.
There are lots of things that are different between a man and a woman. That is not the factor leading to differences. So, there must be other things that are associated, and we still need to tease those apart. But in general, I think it’s going to come down to maybe the rate of transmission for you.
One theory that I’ve heard is infectious dose, or if you are in an indoor environment as you are exposed?
So, if you were indoors with somebody who is infected for a long period of time and you guys are really close versus maybe you got on to an elevator after somebody that was infected got off and it was like a really quick interaction. So one theory is that how much virus you take in could cause differences.
Also, it has to do with your overall state of health. So, if you have underlying health conditions, those will likely be exacerbated with COVID-19 infection, but also vice versa. So, if you have underlying conditions, that could be exacerbated as well.
AK: OK, that makes sense. And I’m sure even people who look healthy and are young potentially might have invisible underlying conditions as well.
NP: I mean, somebody can be healthy but have an undiagnosed condition and you might not know about it until something like this happens.
And I think even though there are studies underway to tease the differences apart and whatnot, this probably gives a reason that anybody could be affected by it and so we potentially should try to take the precautions that we can.
AK: Yes, that really helps, thank you. The other thing I heard is, in the U.K., for instance, the government was talking about issuing people COVID passports. It’s basically like if somebody got an infection and they recovered, they are considered OK, and they can go back to work etc. So my question is, the people who get infected and recover, are they immune to future infections? Is it OK for them to not take further precautions against getting infected again?
Because from what I understand, for example, chicken pox, I got a vaccine a while ago. And the understanding is you won’t need another one probably for your life; versus the flu, where I probably got the flu like a couple of years ago, but there’s no guarantee that I’m not going to get it again.
Also, from what data I have seen of COVID, the people who have had a confirmed case and recovered, only a fraction of them had antibodies. So, what do we gather from this?
NP: Yeah, those are all very interesting questions. The answers can be kind of complicated. So I’ll try to break down some different points that you said there. I think that it is too early to say that antibodies are definitely a correlative for protection. That is a guiding principle in immunology that we would love to be able to follow here. Kind of the basis of how we measure vaccines oftentimes is whether antibodies produced and then you can do other tests to see if they’re neutralizing or if they can prevent further infection. But not every infection is going to lead to a lasting memory response – for example, like you said, the flu.
So there’s a couple of different things at play there. Some things like the common cold, you can get every year. I guess similar with flu because their antigens can change so quickly, and they are different so proteins that we’ve made antibodies against aren’t effective anymore. Another thing, however, is just not making an immune response that stays around. So that’s common in some infections where for whatever reason, there’s not a memory response that lasts, in which case you may make antibodies for a short period of time, but those will wane over time, in which case you would then be susceptible again even if those were protective. With COVID, I don’t think we know enough yet. And I’ve seen a couple of different anecdotal case study type reports that kind of go both ways. So there are some people who have virus that sticks around for a long time so they can test positive repeatedly over months, but then maybe they have a couple of negative tests in between, and so it kinda looks like you had a recurring or new infection.
But a lot of people are reporting two distinct periods of them having symptoms and positive tests all time, so maybe they didn’t make antibodies and they truly did get two infections. Or maybe this is a case of prolonged viral shedding and they just have cold symptoms. I don’t know. It’s extremely complicated.
AK: I guess adding another layer to that, the memory response may not always be It’s not solely driven by antibodies either. So, there is there is a lot to unpack there. And we don’t have enough data yet to say one way or the other. And so you probably be confident in thinking that “I got COVID once, so now I’m good.”
NP: Yeah. I guess a couple of other interesting points. So when we think about coronaviruses, at least in the news, it seems like they’re all that, but they usually infect humans, all types of animals, and it’s not necessarily something that always is associated with symptoms. But this virus is particularly scary in my opinion. But there are four normally circulating coronaviruses that have seasonal effects and cause common cold like symptoms. So that’s something that you can get repeatedly infected with and you’re not going to maybe mount an immune response. The symptoms and outcomes are way less drastic, though.
So that’s one thing to consider. But then on the other end just not every pathogen we can make an immune response for. If we could, we would have vaccines against all of the common things causing infections and we would be able to prevent them before they even happen. So clearly, there’s a lot that we still haven’t figured out yet.
AK: So I’m glad you brought up vaccines and our immune response. I was wondering if you could talk a bit about the leading vaccine candidates that are currently in trials. So I’ve heard of the candidate from the company Moderna and then another one in trials run by Oxford University.
NP: Yeah, I’m glad you said leading candidates, because those are really about the only ones I know more about. There’s a lot that are going through the pipeline right now. It’s better to have more options just because it can be a long process. And so both of those – so there’s the Pfizer (which obviously is a large pharmaceutical company) vaccine; and then Moderna, which is based out of Cambridge, which is partnering with the National Institute of Allergy and Infectious Diseases. So both vaccine candidates are mRNA vaccines. They’re both going into phase three clinical trials, which means they’ve gone through phase one, which is basically just safety. They are going to test different doses, look at if you’re able to mount an immune response and measured toxicity and adverse effects to make sure that they can give a safe dose. In phase two, they’ll expand the number of people that they test and also the populations, but still focusing on healthy individuals. And phase three is much more expansive. Pfizer is looking globally open it up to individuals who have like natural disease just to make sure that it’s not going to have adverse effects in people who are not otherwise healthy. I think that in these trials, there’s like thirty thousand individuals that are going to be enrolled. That’s per FDA guidelines. They are a huge entity, So they already have a lot of resources and collaborations, which is one thing that I think probably helped them in this situation.
And I don’t know much about the clinical trial design for the analysis. But that’s something that’s important for clinical trial researchers to develop and have written down before they actually get any of the data: just to avoid any bias, whether they know that they’re doing it or not, and they already have the plan of how to analyze. If you’re picking the wrong population or looking at the wrong people, then that can lead to a lot of problems.
So, both of these studies are going to test the experimental vaccine versus placebo. I think both of them get two doses and then they’ll just look at immune response, toxicity, adverse events in this larger population to see if it’s effective. I think they both target the spike protein, I don’t know that for sure, but that would interrupt the virus from infecting the cells.
AK: Spike protein is the outside protein of the virus that it uses to bind or get into our cells, is that right?
NP: Right. And I thought that the Pfizer one – it’s the receptor binding domain that they are targeting; that’s what the antibody is specific for, or if that’s what they’re hoping the antibody would bind. So, it would eventually try to block the virus from getting into the cells and causing disease.
AK: And you brought up a very important point about testing it in a larger population, and especially given the variability of disease and how much it varies from individual to individual and across the countries, perhaps, having resources or connections in various countries and institutions that run these trials and get data not just from one group of individuals or one country, but multiple areas probably would also help with that.
NP: Definitely.
AK: OK, so you gave us a lot of really great information today that has been very helpful. What are your go-to places for resources to get accurate and reliable info about the novel coronavirus and COVID-19?
Because I know there are all these websites and videos, and if you just Googled them, many of them are not accurate and could even be mis- or disinformation. So where do you go to find accurate and reliable information?
NP: Yeah, there truly are just so many resources out there. I would say that for general questions or maybe guidance on public health guidelines, the CDC, the National Institutes of Health and Mayo Clinic – they all have phenomenal websites. They’re updated regularly, which is helpful.
And then I would say for data purposes, there is a couple of websites that I look at regularly. So Johns Hopkins, is the JHU COVID-19 global map or dashboard. And then there’s another website called one point three acres, it’s https://coronavirus.1point3acres.com/ But they have a phenomenal repository of data, so and they show you all of the different ways it can be visualized, which I think is incredibly helpful. So they have cases, tests, tests per population. You can look at each state, you can look at globally, different countries. It’s really interactive and user friendly too so there’s that.
And so you said for, say, somebody who is just interested in looking up useful information… if you’re a data nerd, one other source that I use and could recommend would be The New York Times coronavirus briefings. So New York Times is generally something you want to you have to pay for a subscription or you can only see so many free articles a month, but they are making all of their coronavirus articles accessible for free without a limit. Yeah, you can put in your email address and they’ll actually come right to your email. So that’s something that I find helpful too because then I don’t have to go searching through the news, It can come to me, and that’s great.
AK: Another question I had was, schools are slated to open in the US in a few weeks. So, I’m curious as to what kind of data we have, or how does it affect kids.
NP: Yeah, that is also a little bit complicated, like most things coronavirus-related. So in general, and this is like a blanket statement, I have heard that kids are generally going to exhibit more mild symptoms so they may still have a fever, maybe vomiting and diarrhea. I’ve also heard there’s a difference in maybe the ability to transmit. So, if you’re younger, you might be less able to transmit. But then kids over 10 have the same rate of transmission as adults. One big caveat with children is there is a rare consequence, but it’s called multisite inflammatory syndrome in children (MIS-C). And this is basically just generalized inflammation. I think it’s localized to endothelial cells – so, the cells that line your blood vessels, but that can affect various parts of the body, your heart, your brain, organs, skin, and that can have really severe side effects.
AK: I see. So, it’s not all generally mild symptoms. There can be some pretty bad outcomes still.
It’s very interesting that you mentioned the transmission rates are different, but it’s not necessarily across all school children, right. You said for kids under-10, it’s lower, which I guess it’s probably important that we, you know, we’re opening schools and things like that. So it’s good if children are exhibiting milder symptoms in general, so to speak; but I guess it would also be important to know if they still transmit the disease to the adults that are around them, in which case that potentially could be dangerous. OK, thank you.
So, we talked about schools opening – something that is part of daily life for many families. So, I was hoping to ask you about how you would categorize the infection risk for some of the other daily or routine activities like going to the gym, going to the park, going to the dentist, or taking a road trip. Can you weigh in on that?
NP: Yeah. So I think for every person, for these for every activity that you’re considering doing outside of the house, you just have to weigh the personal benefit and your needs with the risks to you or risks to people who are inside your social bubble. There are obviously some things that are riskier than others.
We know that transmission occurs at a higher rate indoors than outdoors. So personally, if I can avoid being indoors anywhere, I do. I can work out in my home without other people or outside, which has a lower risk of transmission; so I don’t go to the gym right now.
And the dentist, I think I could go either way. It’s still indoors, but preventative medicine is important.
If you’re just going for a cleaning, maybe you can put it off a couple of months. But if you need something more major done, I think it would probably be worth it to see a dentist. They’re going to have health precautions in place already, but I’m sure they’re taking up another level with face shields and everything just due to the nature of their work.
And I would say outside is, I think, relatively safe depending on the environment. So maybe you’re going for a hike and you bring a mask just in case if you’re passing people or if you can’t socially distance. I think that your outcomes are going to be better in that case. And just have a plan for if things get crowded, I guess.
AK: OK, that’s great. And so the one thing we have been doing in our household is that, you know, when we get groceries, we currently wipe them down – like the bags and stuff. So, is it safe to stop doing that? What’s your opinion on it?
NP: Oh, I am probably going to hold off giving direct advice. I can tell you that I personally don’t do
that, but I can see maybe taking extra precautions like that if you have someone who’s immunocompromised in your household that may be more susceptible to getting infections. I wash my hands a lot, though. So that’s something you can do before and after you get groceries, when you get home, before you sit at your desk, like make sure you’re cleaning your phone, all of those things. So, there are some things that I will do, but that is not one of them.
AK: It does make sense to weigh the benefits versus overall risks of these different activities, so, great feedback on that.
So, we’ve talked about a lot of things and this has been a great discussion. You have provided a lot of really great information and pointed out resources for people to go to. So, in the pandemic, a lot of medical and public health professionals have been doing that, like you guys are working overtime and constantly trying to keep up with the data, keep up with new information, at the same time health care workers are also caring for patients. And you guys are doing testing; so, there’s a lot happening there.
I’ve heard lot of firsthand feedback from my friends, and my wife who is a physician. I have also read that a lot of the medical and public health professionals feeling burned out and frustrated, especially on topics where they have given advice based on scientific data. And the public, or at least some of them, are reluctant to heed that advice. And a lot of this advice is politicized, as we talked about, regarding masks or the use of hydroxychloroquine. So, I wanted to ask you, how are you doing?
NP: I’m doing good. This has been really an incredible learning experience. I am thankful that I have the laboratory perspective on this. And this is something that in our lifetime, most of my colleagues haven’t really seen anything like it. But I mean there’s a lot of correlates here, right? So we think about this is like, “oh, we haven’t seen this since the 1918 flu”. There are so many comparisons to that.
But another important emerging virus that severely impacted clinical microbiology labs was HIV. And that happened in the last few decades. It makes people susceptible to a lot of infections.
So, I am impressed with the amount of information we’ve been able to gain as a science to the community in such a short period of time. I do worry about health care professionals and hospitals continuing to be overwhelmed because as you said many people aren’t taking all the advice that they get.
I guess the one thing that’s like my hope and dream about this is just like public health is something that impacts everyone every right. And people don’t even realize it because it’s built into our society. So if you think about water treatment, foods that are supplemented with different vitamins, salt with iodine, and different screening procedures that you go through with your physicians, there’s just so many things that are done in the nature of public health that are preventing risks. But this is just one that we hadn’t had before. So people are resistant to implementing these new things. And I just think if we had a broader discussion about public health and what the outcomes are and if people were more aware of these things, they may have a little bit more trust in these individuals who really, really know how the outcomes can play out. Because as we see right now in the US, this is something that we need a unified force at, because if you have half the population or even seventy five percent of the population that are strictly wearing masks and washing their hands and being socially distant and you have the other twenty five percent not doing that, then it doesn’t matter because there’s still going to be uncontrolled spread, there’s still going to be asymptomatic spread.
AK: Right, we’re not existing in a vacuum and are always interacting with each other. So yeah, good to know you’re doing good. And I guess that’s a great point that you brought about public health, because a lot of the major achievements basically are unnoticed because that’s the way we know it is working. It sort of reminds me of what Dr. Fauci was saying in the beginning stages of the pandemic. He said, a few months later, when we look back and are able to say, “Oh, man, did we really need to do these lockdowns? It seems all these measures were so strict.” because we haven’t had really bad outcomes would be how we can gauge that it was a success. Unfortunately, that hasn’t been the case. But we
have a second chance where we can learn from our previous mistakes and things that have been recommended by public health professionals.
NP: That’s so true, it is never too late to start any of these things; they are actually pretty simple.
AK: Hopefully, more people start listening and more people follow guidelines and we would get this pandemic under control. I really appreciate you taking the time today and sharing with us your insights and providing us all this information. Thank you very much, we really appreciate it.
Hi there! I’m Aaram, the founder of Sciencera. I grew up in the beautiful city of Thiruvananthapuram in the Southern part of India, famous for its pristine beaches. Now, I am a scientific writer based in Indianapolis. When I am not busy procrastinating on my writing, poring through research articles, or coming up with grand ideas to save the planet, I love playing soccer and chess. I read a bit and write sporadically when caffeinated to the right amount. I am passionate about scientific research, writing, and outreach activities.
