Children & COVID-19 — Interview with Dr. Daniel Griffin, MD, PhD

March 23, 2021

Throughout the pandemic, many medical professionals have relied on Dr. Daniel Griffin’s weekly “clinician updates” to better understand key updates that may impact guidance and treatment. Dr. Griffin has contributed extensively to the body of SARS-CoV-2 research and recently sounded the alarm that many dangerous misconceptions exist about children and COVID-19.

Dr. Griffin is a board-certified physician in infectious disease, as well as an Associate Research Scientist and Instructor in Clinical Medicine at Columbia University in New York City. Medcram Co-Founder and Producer, Kyle Allred, interviewed Dr. Griffin about the latest information on the impact of SARS-CoV-2 infection on children, as well as progress on vaccine research for children, safely reopening schools, and advice on keeping kids safe as some social activities start to resume.

In this video, Dr. Griffin shares information on the prevalence of “long COVID” in children, Multisystem Inflammatory Syndrome in children (MIS-C) and, as parents, what symptoms to look out for. He also provides an update on monoclonal antibodies and explains his research on understanding different stages of COVID-19 in treatment timing and trials.

Watch the full interview here, or read through the transcript below.

Are kids less likely to get, transmit, and test positive for COVID-19 than adults?

Dr. Griffin: Well thank you, Kyle, for giving this opportunity to speak about kids and COVID. I think we all care about this important issue, and I will start off by saying that is clearly now a myth that children don’t get COVID, that children can’t spread COVID, and we all suspected this early on.

And this is one of, I’ll say, of the nice perspectives that I can often bring, because I’m on the ground. I’m not just reading, you know, the literature and then digesting it and spitting it back out. I’m actually, you know, working directly with patients in my position where I get to talk to a lot of other clinicians; I get to see what’s going on not just in my experience, but in our experience. And I’ve also worked with a lot of schools and camps and programs, because hey, we all have kids; we all care about kids; maybe some of us once were kids; and I like in this first scenario we saw the initial reports out of China: hey, kids are not getting COVID.

But then you have to look a little deeper, and I like in the analogy like, “hey on a rainy day when I keep my kids inside the house, they don’t get wet.” That’s what we were doing early on in COVID. We were keeping the kids home; we were keeping them in the house. And yes you don’t get COVID if you’re not going to the supermarket, if you’re not going to work, if you’re not going to the schools or these other areas, and I’ll get into the risk factors in those other areas, but no; you put a child in the same proximity to someone with COVID, kids get COVID. Kids spread COVID.

Kyle: Are kids turning up positive on the acute tests for COVID-19 as compared to adults, and if so, why might that be the case?

Dr. Griffin: Yeah, so children definitely can test positive for COVID, but there are a few differences. One of the things that you’ve probably noticed is if you’ve ever seen a child being tested, we tend to be a little gentler with the kids. You know, even early on when we were doing the brain biopsy routinely — these beautiful tests, as they were described — with kids, we often were just sampling the anterior nares, maybe weren’t getting quite as good a sample.

And also there’s a bias to not wanting to test kids, right? If mom and dad both have COVID, they test positive. Johnny’s coughing sneezing, not feeling well, we presume COVID. So a lot of times, you’ll end up with these biases. But no, kids test positive just like adults, if you get a good sample, but there might be a little difference. We’re learning that children may not shed the virus as long, so there may be a shorter period, a shorter window that you can catch them having that positive PCR test.

Kyle: We know that any testing strategy for acute infection is not going to pick up every infection; what do we know at this time about the prevalence of past SARS-CoV-2 infections in the general population and specifically with kids?

Dr. Griffin: Yeah, so one one of the ways that we look back and say, “oh how many people have been infected over time?” is to do these serology, these antibody tests, and I think what we’ve realized is, wow we probably missed half or the majority of the infections. You know, not necessarily missed them so much as the people did not go in, they did not get tested, it did not get confirmed, and more people are testing on these blood tests of having had COVID than we initially identified. We’re seeing that for parents. We’re also seeing that for children.

But one of the things — there’s two two challenges here — one of them is people with mild cases sometimes will have negative blood tests, negative serology tests, and so that’s particularly a challenge for us with children, because it is true that in general children have more asymptomatic, more mild cases than adults.

Some recent data that was just put forth by the CDC it looks like actually maybe ninety percent of the cases in children were missed. When they looked at the numbers reported, less than ten thousand cases reported in children. When they did the blood test, it looks like maybe over a hundred thousand cases in children. And as I mentioned, that’s probably an underestimation as well, because not every child infected with COVID ends up with that positive blood test. So we actually think that in areas where children have been out and about, where parents and adults have been out and about, that we have a much higher number of infections than we initially realized.

What are the numbers of kids who’ve had COVID-19 and/or severe COVID-19 complications?

Kyle: At this point we’ve all heard that severe complications from COVID are less likely in children than adults, but can you put some context on this? Is it like one in a million children that get infected with COVID-19 have a severe complication, or is it more common than that? And are any particular groups of children more at risk for severe complications from COVID-19?

Dr. Griffin: I think it’s really important to put in perspective what we say about COVID in children as far as severity, as far as the risks. So I’m going to break it down into, say, three categories. So the first is, you know, what’s the risk that a child gets exposed, gets infected with COVID, and ends up in the hospital? And I’m going to say that is much less common than we see in adults.

Early on, we’re seeing about 10 to 20 percent of the adults ending up in the hospital, but there’s really a curve here. You know, if you’re in your 80s, okay, maybe 30 percent. You get down to about 65, it starts dropping. You actually get down into children, say 18 and under, here you’re talking about, well, less than one percent. We’re talking about maybe a percent of one percent end up in the hospital. So it is a low likelihood that a child will end up in the hospital.

We’ve probably all heard about the multi- inflammatory disease that we see in children. We’re talking about thousands of cases in our entire country. So this is, again, this is a low risk. We have seen deaths in children, but a lot less. You know, we’re looking at half a million deaths in adults; we’re looking at thousands of deaths in children. So much smaller just looking at our country.

The one thing I do want to bring up, and I think this is what parents are getting quite upset about now, is children like adults may get COVID and then not be better in just a week or two — the long-COVID that we’ve been hearing more and more about in adults. In adults, we say that’s about 20 percent. Now in children, it may be as high as 10 percent, at least what we’re hearing in the UK where they have really good surveillance.

Here in the US, we’re starting to see this more and more on the ground, as children are trying to return to sports, as children are trying to do their virtual school. Kids are going out to play soccer, and they’re realizing I can’t run up and down a soccer field, what’s going on? I had COVID a couple months ago, and I thought I was fine. Or the teacher calling and saying, “hey your son is not paying attention in school, what’s happening?” And the parent relating that, okay a couple months ago my son had COVID, but it was mild. But this is long-COVID. So, I think that’s really important when we think about children we say oh don’t worry it’s going to be mild they’re not going to die they’re not going to end up in the hospital, but they may have trouble doing sports. They may have trouble in school. So I think that’s one of the components of COVID and children we can’t lose sight of.

What symptoms should parents be looking for?

Kyle: With this long hauler syndrome, or post-acute COVID syndrome, long-COVID, goes by many different names, I know you’ve been a big advocate for these patients during the pandemic and you’ve seen a lot of these patients and spoken with colleagues about them. As a parent with a child that’s watching this, what symptoms should they be looking for? Because, as you’ve mentioned, you know, many children that have had acute covid, they may not have had remarkable symptoms. But it’s we’re finding out now it’s, from my understanding, possible that they could go on to have long-term symptoms from COVID. So yeah, what tips can you give parents to kind of clue them in to what to look for?

Dr. Griffin: Yeah, I mean the first thing is don’t let your child get COVID, right? You can’t develop long-COVID, you can’t have a post-COVID complication if you never had COVID.

There are certain things about the presentation that make it more or less likely, but what I think the most frightening things we have now realized is about a third of our long-COVID patients had an asymptomatic initial infection. And when they started having their symptoms, we did a blood test and realized “oh my gosh you had COVID before” and then we sort of pieced together the exposure. That seems to explain that.

So, you know, it’s hard. If your child is exposed and tests positive, you know, reassuring I could say 90 percent they’re probably going to be okay. But now we’re hearing 10 percent maybe not. So we don’t see long-COVID just when people end up in the hospital. We don’t see long-COVID just in people that have severe disease. We sometimes see long-COVID in adults and children who’ve been infected and maybe even had an asymptomatic first episode.

Kyle: You mentioned the potential symptom of, you know, not returning to sports as well, you know, their sports performance diminishing, maybe cognitive performance diminishing in the classroom. Any other specific symptoms that you’re seeing? I mean, I’m hearing that it can be all different types of symptoms with long-COVID. But are kids experiencing the loss of taste and smell that adults are chronically in some cases?

Dr. Griffin: Yeah, so it really seems to be very similar. I actually do calls on a regular basis with our pediatrician just to get a really big overview of what are we all seeing, right, to get larger numbers, and children end up with the same. It could be headaches — headache’s actually quite common in kids. It could be loss of taste and smell. It could be hair loss.

Actually, I have to say a few of those cases have been really traumatic. You can imagine an adolescent and their hair starts falling out and not growing in. It can be challenges — this brain fog as we see in adults, we see that and kids also, having trouble concentrating in school. But really big stuff is the fatigue, the low energy, you know. I know it’s hard enough to get my teenagers out of the bed every morning, and I can imagine, like, if that was magnified to any degree.

So really, think about what we hear long-COVID in adults; we’re seeing that spectrum in our kids as well. I mean, one of the things that I think is a challenge, more of a challenge for my pediatric colleagues, is that a lot of times COVID presents in a child just as a stuffy nose, just as a sneeze. We usually say, “oh my gosh the only thing COVID doesn’t cause is sneezes.” Well in our adolescents and children, we’re seeing sneezing, congestion, and what we would have thought is not typical COVID symptoms.

Kyle: You mentioned earlier that kids certainly are less likely to get severe COVID as compared to adults. What are the current theories about why that may be the case, and is there anything we can learn from a child’s immune system that we can apply to our own lives as adults?

Dr. Griffin: Yeah, I mean one thing we’ve known for years is that children tend to handle first exposures to respiratory viruses, respiratory infections, better than adults. You know, maybe it’s, they’re sort of getting used to what’s in their world, to use almost an analogy there.

As we get older our immune systems don’t work quite as well. They overreact, and I think what we’re seeing in a lot of the children is actually a reasonable appropriate immune response, and as we get older — and there’s a spectrum to this — the older you are, the more likely it is that you’re going to over-respond. You’re going to have all these cytokines, this whole inflammatory storm. Kids, most kids as I’m saying, you know, they get this, most of the time they clear it. Most of them don’t even have symptoms. And unfortunately there is this small subset, and I think that’s what raises concerns for us. The kids that seem to have something up with their immune system.

What advice can you give to a family whose child wants to return back to activities, like sports, after COVID-19 recovery?

Kyle: For a child that’s had acute COVID-19 and is active and maybe on a sports team, what type of advice would you give them and their family as far as deciding whether to return back to sports safely? Should they get a cardiac evaluation? Should they check in with their, you know, pediatrician? What should be the protocol for getting back to sports?

Dr. Griffin: Yeah, a lot of us actually have put protocols in place and we have protocols here in place in the tri-state area: any children that have actually had symptomatic COVID, particularly any that have had more than a mild case, we’re recommending that they’re evaluated by a cardiologist prior to returning to sports. We don’t necessarily do a stress test, but it might just be an exam, it might be an EKG, and then we kind of go from there.

But just to be on the safe side, we’re trying to make sure that we don’t send these kids back out there while they have inflammation of the heart, which we’ve clearly seen. And then once they get out there doing the sports, then we sort of get a sense of have they had this impact on their ability to perform on the sports field?

Multisystem Inflammatory Syndrome in Children (MIS-C) and symptoms to look for

Kyle: Going back to this multi-inflammatory syndrome, you mentioned in a previous interview, or maybe it’s on This Week In Virology that this potentially seems to have changed a little bit over the last several months and that it may be presenting differently now. Can you talk more about that?

Dr. Griffin: Yeah, so this is something originally we started hearing about communications. Pediatric ER clinicians were seeing this. The first case reports were coming out of the UK,

and these were mostly children who did not have a recognized acute COVID infection and then were coming into the emergency room basically in shock with all this inflammation of their blood vessels, with multi-organ effects, and then on blood testing, maybe even sometimes when you did the PCR test, you could still document that they had the infection. So this is sort of a week three, four, a later complication, something that all our evidence suggests is an immune mediated complication.

Early on it was about 50/50 whether or not these children would end up in the ICU. Over the last couple months, 80 to 90 percent of these children have ended up requiring ICU level care, so something has changed here.

Kyle: And they go to the ICU specifically for just respiratory complications not hypoxemia presumably?

Dr. Griffin: So it could be both. It can be the respiratory complications ,needing the oxygen and the respiratory support. A lot of times these kids can’t even keep their blood pressure up. It’s like they’re in septic shock. Blood pressure’s dropping; they need IV fluids; they need all kinds of medicines to keep that blood pressure up, what we call pressers. These kids can be really ill, and unfortunately we have lost a number of children from the syndrome.

Kyle: And what are the first symptoms that one should look for that could clue them in to this syndrome?

Dr. Griffin: Yeah, I have to say this is tough. I mean a lot of times the child will become listless, low energy, fever is often, the breathing might start to increase. Yeah, I mean I don’t want to alarm all the parents; this is fortunately not horribly common, but we have seen thousands of cases already here clearly documented. And so this is one of the challenges, because you don’t have that acute COVID necessarily warning you that this is something to think about three to four weeks later. It’s just out of the blue. Your son, your daughter is just not feeling well, is kind of listless, and then we realize that this is what’s going on.

As a parent, how is Dr. Griffin handling COVID-19 risk for his children?

Kyle: Well Dr. Griffin, you are a parent yourself, and you’re navigating this situation like the rest of us. As more, more, and more adults get vaccinated and schools are opening up and people are also looking ahead to summer plans and summer camps, any tips? How are you navigating this as far as social time for your kids, activities, back to school? And any practical tips you can give to other parents that are watching this?

Dr. Griffin: Yes, so this is the challenge, you know, now that our teachers, our adults are getting vaccinated. Unfortunately what we’re seeing right here in the New York tri-state area is an increasing number of infections in the kids, and I think it’s — there’s two perceptions here.

One is the reason why a lot of children were kept home from school, were kept indoors, had limited play dates, and other social interactions is we were concerned that the children would get infected and then it would spread to a more vulnerable person. I’m a little concerned now that we’re seeing clear evidence of the long effects of of COVID and children so, you know, I use my son, Barnaby, as an example. He’s 15. He’s in high school. He loves to run, and you know he is probably not going to die of COVID if he gets infected. But what impact might it have on his ability to concentrate? What if he starts developing these chronic headaches? What if he goes out for sports, which as a young boy is really critical to his sense of self and he can no longer run and compete and enjoy that activity with his friends?

So this is a challenge for us, because as the parents, that everyone else gets vaccinated. If we go into the school openings, and we go into the sports with the idea that “oh if the kids get infected, it’s fine,” that’s going to be a problem. We don’t want 10 percent of our children having the long-COVID, even though we count the numbers of children that have died, you know, in the thousands as opposed to the hundreds of thousands. That’s a lot of children that have died, so I’m concerned going into this. But, I will say we have learned over the last year, we can open camps, we can open schools safely. Unfortunately, we’ve also learned that we can do it unsafe as well.

Kyle: Do you think that kids need to wear masks outside if they’re playing soccer or engaged in other sports outside, for example?

Dr. Griffin: Well, one of the things we’ve learned, so I’m going to say they can play soccer without masks. It’s going to get me in trouble, but everything I say about kids does, so that’s okay. You know, we’ve learned that there are different things that you can do, and they increase or decrease your risk accordingly.

So one of the biggest things we’ve learned is that if you are outside, that reduces the risk of transmission about 20-fold. That’s huge; that’s orders of magnitude. We talk about a mask reducing the risk by 80 percent: that’s not orders of magnitude; that’s an 80 drop, but outside. So outdoors is great if the kids, you know, the kids are all hunched together in a ball on the sideline at the soccer field, that’s a little bit different. So masks on when they’re at the side; try to keep them a little bit distanced, but when they’re out there playing a soccer field, those sort of short quick interactions, that seems to me to be a very low risk activity and is reasonable.

I think we’ve got to start making reasonable, low risk decisions, not looking for that hundred percent safe, because it is not 100 percent safe to keep a kid locked in the basement. We’ve got to start figuring out what are acceptable risks.

Update on vaccine trials with children, herd immunity, and future of COVID-19 vaccines

Kyle: I want to shift gears to vaccines, and all three of the authorized vaccines in the United States at this time have been in the news lately, because they are running trials with children, and can you give us an update on this and where we stand with vaccines and children?

Dr. Griffin: Yeah, so let me link up an update on vaccines and children. I’m going to talk about the three that are currently available in the US. What do we know? So we have Pfizer, which is EUA, down to 16. We have Moderna which is down to 18, and J&J, which is down to 18.

Now the Moderna and the Pfizer are a newer technology. This mRNA technology, which we have never used in children before — actually we never used it in adults before — but now I can say a few months into this, we’ve now given it to millions of adults: pregnant women, women wanting to get pregnant, you know, all sorts of people. Women never wanting to get pregnant, men never wanting to get pregnant.

So we have a growing experience in adults, but we still have not used this in children. From a scientific view ,there’s no reason to think that these vaccines will represent a risk to younger individuals, and they’re being actively studied right now for safety and efficacy. Everyone’s guessing about the timeline, you know, the current is the “under promise, over deliver,” so we say that “oh these will eventually be there” but then we give you a really long time scale.

And then when they show up early, you’re delighted. The J&J, actually, I’m going to talk about this platform, because this platform, this technology actually has been given to kids to children as young as four months of age. Now, not this specific vaccine targeting the SARS-CoV-2 that causes COVID-19, but when we were doing this in West Africa, hundreds of thousands of individuals were vaccinated to end the ebola outbreaks using the same technology. That went to pregnant women; that went to children down to four months of age. So that vaccine platform, we actually have quite a bit of safety data.

We are getting the safety data on this specific vaccine for J&J as well, so all those studies are ongoing. They’re actually, they enrolled pretty quickly. Poor Barnaby again, we tried to put him in a Moderna trial, but, you know, you had to drive to Massachusetts multiple times, which we were maybe willing to do at one point, but no. We’re going to get this data going forward, and there’s every reason to believe that these are going to be safe, effective, and available for our children. It’s just a question of when.

Kyle: So along those lines, do you think the J&J vaccine might be the front runner for authorization among the vaccine candidates for children?

Dr. Griffin: I have to say, when I saw that there was an extra 100 million purchased, right, when we now have 200 million doses of J&J, this vaccine honestly makes the most sense for children. It’s a one and done; it’s a vaccine which has very low reactogenicity. So most people get this vaccine, they don’t have much of a reaction. They don’t have a fever, really kind of an ideal thing to do mass vaccination in schools and other venues like that. A little tougher if you think about it, you know, giving a child one shot, then they have a fever or maybe don’t feel so great, trying to bring them back for that second one. So I have to say from a logistical, from a reactogenicity, from a per patient uptake, the J&J is really an ideal platform for vaccinating our children.

Kyle: Do you think the widespread vaccination of children is a key component of reaching herd immunity, not only in this country, but as a global community as well?

Dr. Griffin: I honestly think it is key. You know, looking globally, yes. Just because you start looking at the numbers, you know, in the United States, we have an older population. The percent of our population under 18 is smaller than some other parts of the world, like Africa, India, even Ireland, I think. But, so you know, if you start looking at the numbers, can we get pretty close in the US without vaccinating kids? Maybe, if everybody else wanted to be vaccinated, but not everyone in our society wants to be vaccinated. So to get to those numbers, I’m probably going to have to have uptake in our children as well. So in the US, I’ll say yes. And the rest of the world, I’ll say definitely yes.

Kyle: I know you can’t predict the future, but what do you think the most likely outcomes are with regard to vaccines in both adults and children? Do you think it’s something we’ll need to get a booster every year for? Do you think SARS-CoV-2 is going to be, you know, endemic in the population, and we’re going to be dealing with it like influenza? How do you see this panning out?

Dr. Griffin: Yeah, no, I mean I think we’re supposed to predict the future, right? It’s the only thing worth predicting. The past is easy to predict, and I think, you know. And I think in our training in infectious disease and global health and public health, we’re supposed to be trying to get an understanding of what is likely to happen in the future. So it’s not looking into a crystal ball; it’s looking into the science.

I mean, there’s a couple things here. The SARS-CoV-2 does not just infect humans; it also infects a lot of other animals on the planet. So this is not an easy virus to think that it’s ever going to go away. The other thing is we don’t live in a society where 100 percent of the population is going to get vaccinated. So again, there’s every reason to think that SARS-CoV-2, that COVID-19 is here to stay. It’s really just a question of “at what level?” So as we go forward, the question of “at what level,” the question of “how durable is the immunity that we get” will really dictate how often we need to get a vaccination for this.

The other thing, I think this is really critical, is, you know, this is sort of ours to lose. This is a race between the vaccines and the virus. If we do a great job and we really spread the wealth, so to speak, and get everyone in the world vaccinated, that puts us in a great spot. The more we give this virus the opportunity to replicate, to reproduce, to make changes to its sequence, the more we give the opportunity for vaccine resistant variants.

And that’s on us. So if we just vaccinate ourselves here in the US, and then we celebrate on July 4th and forget about the rest of the world, it’s just a question of “on which plane flight someone brings a variant back into our country that our vaccines are not effective against.”

Practical tips for upcoming holidays and family gatherings

Kyle: So we have some holidays approaching, including easter passover and other holidays. You’ve already given some practical tips for parents to help keep their kids safe from COVID-19. What about families that have decided to gather with other families? Any other practical tips that you can give as holidays approach and presumably more gatherings are going to happen?

Dr. Griffin: Yeah, one of the things that, and I think hopefully this is helpful to add to the dialogue, is what about the kids? And a lot of people have basically this perception that “oh the kids will be all right, they don’t end up in the hospital, they don’t die.” But we do want to say that “hey, a percent of the children can get sick and not be well in just two weeks.” They might have this long-COVID in children. We don’t know how long it lasts. We’re learning more and more about it every day. So you don’t want to just write them off. You don’t want to just say “hey you’re under 18, you know, you’ll be fine.” Let’s still make an effort to try to protect them.

And how do we do that? So one of the first things is those people who can be vaccinated, that’s fantastic. Not only does it protect them, but we have growing amounts of evidence suggesting that they’re less likely to transmit COVID to other people. The other is gathering sizes. We’re really headed in the right direction, but we’re not there yet. Right now, in a lot of parts of our country, we still have pretty high prevalences.

So when you get to, you get a gathering, if you get more than a certain number of people together, you really start increasing the risk that someone’s going to be there infected and able to infect your children. So you want to think about those decisions. Can the venue be outdoors? Can people get tested before they come?

I think we’ve got to look at the same way we did at the prior holidays we had. A lot of transmission around the December holidays and New Year’s. And we saw over 300,000 cases that next month, because of that. So these holidays, with the growing number of variants, with the growing complacency, definitely represent a risky time. So make these decisions. Really think it through. I think we were told that “hey July 4th is going to be a fantastic outdoor holiday where we’re going to be having barbecues and the like,” so let’s not sort of miss this opportunity to continue to be safe. Let’s not give that virus a leg up in this next set of holidays.

Pros and cons of PCR and antigen tests for children and asymptomatic patients

Kyle: Would it be better for kids to get a PCR test as opposed to an antigen test, which we believe may not work quite as well in asymptomatic patients?

Dr. Griffin: So, I think it’s a complicated question, but I’m going to give you a straight answer.

One of the things we’ve noticed about these rapid tests is they’re not as sensitive when the level of the virus is low. But, then again, people are not as likely to transmit. So the rapid tests are fantastic for picking up in real time someone with high levels of infectious virus, but there certainly are going to be lots of situations where you want that higher level with the PCR. Not only can the PCR pick up low levels, but because it can pick up low levels, it can pick it up while someone is just starting to have an increase in the virus, so it might pick it up a day early.

So ideal is to get the rapid test, you know, right away if it’s positive. But if it’s negative, then we are recommending doing the PCRs, and one of the great things is, we have a lot of testing capacity. Unfortunately, we’re not having a lot of people doing a lot of tests, which results in another great thing is we’re usually getting results back really quickly.

So I think that if you’re thinking about testing before the holidays, the capacity, the quick turnaround time is there. And I think we even have some new legislation saying “hey, no one should pay for these other than those big insurance companies in the government.” So I think we have access to quick turnaround, free testing. I guess not free; it’ll probably be paid for by our taxes, but that’s okay. Rather pay taxes than a hospital bill.

Kyle: Do you think there’s a role in antibody testing for parents? You know, getting their kids tested and looking at things like play cohorts, other kids that their kids can safely play with, could antibody testing be part of that strategy?

Dr. Griffin: So, I don’t think antibody testing is great. Unfortunately, we have certainly seen re-infections, and we’ve certainly seen people with a positive antibody test go on to have a positive PCR afterwards. So I usually discourage the antibodies, and I say, you know, go ahead, keep your kids safe, do the testing for the virus. The antibody is not as reliable, I think, sometimes gives people a false sense of security.

Kyle: Well, we’ve covered a lot so far. Any other angles to kids in COVID-19 that we haven’t discussed yet that you want to mention?

Considerations for students and teachers when reopening schools

Dr. Griffin: Well, I think the big hot topic now] is schools. Are we going to be really opening schools to full enrollment? And tied in there is this three feet versus six feet, right? Is six feet magical? Is three feet enough magic? And I’ll continue to talk about this, but there’s levels of safety. We know that if you wear a mask, about an eighty percent reduction in your risk. If you get the desks out to about three feet, you’re gonna get another eighty percent reduction. You get to six feet, a little bit more. But most of our schools cannot go back to full class with a six foot distance.

So a lot of our schools are going to be looking at ways of combining different strategies. If you have upgraded ventilation systems, if the kids are wearing masks, sometimes they’re even doing these plexiglass shields, they’re keeping the desks three feet apart, because they have those physical barriers. There are ways that we now know to get our kids safely back to school. Schools have not been areas of high transmission. So this is going to be our next challenge is looking at real world examples and seeing how we can safely get our kids out of the house and back back to their peers, back to their teachers and moving forward with their lives.

Kyle: And along those lines, do you think it’s appropriate at this time for kids to go back to in-person learning?

Dr. Griffin: You know, I’ve worked with a lot of schools, giving them advice, free advice right, so it’s worth whatever I get paid, so my free advice. And some of our schools, actually have to say, one of our school districts on the south shore has had in person in the morning for half the school, in person in the afternoon for the other half. They’ve not had to shut; they’ve not had transmission. I’ve worked with another school in New Jersey.

There are several schools that have successfully kept the kids in class. I think we now have the resources, we now have all this stimulus coming that I think a lot of schools are going to be able to safely be open. But again, I always say it’s also possible to open a school in a manner that is not safe. So a lot of our ability to open the schools and get the kids in person really comes to us getting those resources there, making sure we have those ventilation systems, the spacing and all the other mitigation strategies. But yeah we are at a point where I think we’re gonna get, we’re gonna get schools open very soon. If they’re not opening in the next few months, I think we can all look at September of next year as having our schools fully open and in person, not hybrid models.

Kyle: Any other practical tips for teachers that are going back to in-person learning to help keep themselves safe?

Dr. Griffin: I mean, the best thing a teacher can do is get vaccinated. That really has turned out to be a really tremendous, effective approach. But the other, you know, continue with these mitigation strategies that we’ve talked about. You don’t really want to have a mild case. So, you know, wearing the mask is reasonable; keeping your distance is reasonable, also keeps you invested in the ventilation and everything else.

So I think we’ve learned that teachers can safely do this. What are the high risk activities for teachers? Not so much teaching the classes, hanging out with your colleagues in that break room, taking off that mask to have a cup of coffee or something to eat. So you know, think about your decisions and we want to keep our teachers, as well as our kids, safe and healthy. So make smart decisions, and I think we’ve learned there are ways to do this safely, but there’s also ways to make mistakes.

What are the different stages of and treatment options for SARS-CoV-2 infection?

Kyle: For several months now, you’ve highlighted the different stages of a COVID-19 infection that I found really helpful, and I believe you had a publication about it as well. Can you describe that for listeners that are new to your work?

Dr. Griffin: That took a lot of work. I’m very proud of that work, but we did. I got together with, it was about 35 of us from around the world. It was, you know, clinicians at the bedside, researchers, people looking through what were their personal experience, what were we learning, and we really really realized with COVID-19, timing matters.

This is not a monolithic disease; there’s a first week after someone has been infected, what we call the “viral replication phase.” This is when they’re out; this is when some of our therapies like the monoclonal antibodies are really critical, really make a big difference, but it’s not when they end up in the hospital. It’s not until week two, and they enter into this early inflammatory phase that we start seeing them end up in the hospital. And at this point when we throw our antivirals, we throw our monoclonals, in a sense we’ve missed our window. This is when our focus is on, how do we modulate this dysfunctional immune response? And then unfortunately, some people continue to progress. They end up in the ICU; they’re there week three, there week four, and we start realizing this is when we’re starting to see the clotting complications. This is when you’re starting to see the secondary infections. This is where those kids who were fine initially come in with this late multi-system inflammatory process. And then, even after you’ve made it through, then there’s a post-infection risk of clotting.

This post-infection hypercoagulable phase. And then for some individuals, as we discussed today, it doesn’t even end there. There’s a tail for months continued; fevers for months continued; fatigue and impacts on their life. There’s a stage when the hair starts falling out, other things like that. So you know, that was a bunch of us getting together, “what are we seeing? Let’s come up with common terminology, because if you try a therapy at the wrong time, it’s not going to work.” That doesn’t mean the therapy doesn’t work; it just means your timing was off. So until I think we really laid this out and really understood the stage of the disease, it was really hard to design our trials, also hard to know when you should give which therapy.

Kyle: And have you seen those stages that you and your team identified, have they been adopted internationally pretty well?

Dr. Griffin: They seem to be. You know, if you look at the treatment recs, they’re sort of falling right into these categories, right? You know, the monoclonals we talk about, they want to be in the first seven to ten days. Once you see signs of that early inflammatory phase, require for oxygen, then you’re moving into the dexamethasone stage. That’s when you’re moving into the anticoagulants and the hospital admission. So I think this framework has been adopted and is really being used in a lot of the trial designs now.

Dr. Griffin’s current COVID-19 research projects

Kyle: Is there any current research that you’re working on?

Dr. Griffin: So actually the big thing now, I guess I’m shifting into the long-COVID, but I’m also working, continuing to work a lot, on the monoclonals. So I mentioned earlier today I was on a call. We’re shifting over to “cocktails” in a lot of our sites, actually all our sites across the country, as we’re seeing changes in the virus sequence. And we’re trying to look at a couple, I think, interesting questions. One is not only how well do people do with the monoclonals, but does it prevent long-COVID? So maybe this isn’t just a therapy to keep people out of the hospital; maybe this is a therapy to protect people from that disability.

So large, large study ongoing looking at that, but then we’re also following, we got funding to follow up to 10,000 people who’ve had COVID to see how they do over time. We want to see, you know, what percent of them continue to have symptoms. We want to see what happens with those antibodies after natural infection as well as vaccination. We also want to see this sort of exciting new development: what’s the impact of vaccination on long-COVID? We started seeing some interesting observations that maybe 30-40 percent of people with long-COVID get a vaccine and get better. So we’re studying, trying to get a real solid number on that, and also trying to understand, are there particular vaccines that have that impact? And then what’s the mechanism? What’s going on there? So hopefully a lot of more exciting information to be coming in the future?

Long-COVID symptoms resolving post-vaccination for some patients

Kyle: I gotta ask you more about the patients with long-COVID getting a vaccine and then having a resolution of their symptoms. What kind of theories are floating around out there about how that could work?

Dr. Griffin: So I have to say that was a very pleasant shock. You know, a lot of my patients with long-COVID were quite hesitant to get the vaccine. You know, “Dr. Griffin, I’m starting to finally feel a little bit better. What if I get the vaccine and I just lose all this ground?” And so I scheduled to see my patients couple weeks after that vaccine, and lo and behold, a chunk of them said “Dr. Griffin, I don’t understand what happened, but my brain fog is gone. My fevers have resolved. I can smell again. My fatigue…” I mean, it was really tremendous to see.

There’s a couple ideas. I was actually reading an article by Akiko [Iwasaki] up at Yale, and I was waiting to see my name, because everything she wrote was exactly what I think, and it were the competing ideas. One is this idea that a lot of people with long-COVID never really clear the virus, that there’s some sort of low-level viral persistence, particularly in the gut. You know, this is a virus of the gut; this is a diarrhea virus in bats.

So that’s one idea, and the idea is you get the virus and you finally clear that. Finally that anagenic, that stimuli, that persistent virus is cleared. So that’s one idea. The other is there’s something wrong with the immune system. The immune system has never really had a proper response.

Now with the vaccine, you get a nice robust proper response, and when you come down from that, you actually have a proper sort of post-inflammatory calming of this immune dysfunction. Those are really the big, really the big competing theories. Is it the virus, or is it the immune system?

Increasing use of monoclonal antibodies for COVID-19 treatment and how to advocate for it as a patient

Kyle: So interesting. And I also wanted to ask you about the monoclonals, since you’ve done a lot of research around that. Are you starting to see more uptake from hospitals with monoclonals? I know for a while there, they were available; they were sitting on shelves; they weren’t getting used. Has the utilization, kind of, rates gone up?

Dr. Griffin: Yeah, so the utilization rates of monoclonals really shot up recently, and I think a lot of people were waiting for the big phase three trials. And this last week, we saw a couple of phase three trials come out. We saw data from Eli Lilly with their cocktail showing 87 percent reduction of people progressing to end up in the hospital or require any medical care.

We also saw an absolute mortality reduction. Those people in the placebo group that did go on to end up in the hospital, a quarter of them died. Nobody in the monoclonal therapy group died. Vir-GSK, that’s a collaboration, they came out with their data also showing 85 percent protection, reduction in people progressing. So I think when these big phase three trials came out, people got really excited.

Early on, I think the timing was off. In early April, Steve Catani, of United Health Group, and I had a conversation with the folks at Regeneron, and we said “what are you doing testing your antibodies in week three of illness?” We already had an idea at that point that there were different phases and timing would matter, and those trials did basically show if you wait you give this too late, it’s useless. But now we’re seeing really compelling data; you get this in in that first week, and it’s actually pretty miraculous, the benefit.

Kyle: If a patient ends up in the hospital with COVID-19, or a loved one ends up in the hospital, and they ask for monoclonals and they say something like “sorry, we don’t have any here; we don’t do that here,” what should the patient do? What can they do to advocate for themselves?

Dr. Griffin: Yeah, so the key thing with monoclonals is this is a first seven- to ten-day therapy.

This is not something you get once you’ve already been in the hospital requiring oxygen. At that point, you’re not doing anything helpful, may even be harmful. But during that first seven to ten days, you can get monoclonals in a lot of different places, and one of the biggest things the internet, right, has opened up to the world.

So if you type in “got COVID,” that’ll actually bring you — I’m going to thank Survivor Corps for this. They set up a really nice website, which allows you to click a few times. You can either find out a local fit care facility, like an acute care hospital, for the products. You can go to United in Research, where we’ll actually, within 24 hours, deliver you monoclonals in your own home throughout the entire US. Or if you don’t qualify to the current guidelines, there’s actually a bunch of ongoing research trials that people can take a look at. So yeah there’s nowhere in this country that you should not be able to get monoclonals within 24 hours. You might have to drive a little bit; a lot of times you don’t have to drive at all. You can stay home, and we can actually get them delivered to you in the home.

Kyle: And anything —

Dr. Griffin: And should I mention, it’s for free.

Kyle: Right, it’s amazing.

Dr. Griffin: Your tax dollars at work, because, you know what, to be honest not only is it a great thing, but it makes sense. It is much cheaper as a country to treat someone, to cure them, to keep them at home, than to let them go on to develop COVID to end up in the hospital.

Kyle: Absolutely. And any side effects or complications that you’re seeing from monoclonal treatment?

Dr. Griffin: Yeah, so we’ve now given this to thousands of people. It’s actually generally well tolerated. A few individuals, we have seen that they’ll get a fast heart rate; they might feel a little bit faint, but incredibly well tolerated. Incredibly safe therapies.

More about Dr. Griffin’s work and Parasites Without Borders nonprofit organization

Kyle: Well, I want to ask you a little bit about the work that you do, Dr. Griffin. You are an instructor at Columbia University. You are a regular contributor to This Week In Virology and give those excellent clinical updates. You’re also very involved with Parasites Without Borders.

Can you tell us more about what that organization does?

Dr. Griffin: Yeah, I have to say it was really fortunate that Parasites Without Borders existed going into this pandemic, because we’re a non-profit. We’re completely supported by donations, so we don’t have to answer to anyone. So in our collaboration with MicrobeTV, it really allowed us to give unbiased, solid scientific guidance during this pandemic.

So we really had a commitment to “what is the science telling us?” Let’s get that science out there. I didn’t have to answer to any political figures. I had a great team going through the literature, sort of keeping me updated on why I couldn’t sleep, but what I needed to read instead. And through this platform we’ve been able to, every week, we put out the articles that you should be reading. Not just the headline, but the whole article.

We come out every week on This Week In Virology with our clinical updates, where I try to take what I’m seeing on the ground and what we’re hearing from the scientists looking at this, put it together into something that makes sense. It’s been great in creating a forum for a lot of physicians and scientists to communicate. Really allowed us to take clinical observations and translate these into studies that really give us solid data on what treatments work, what mitigation strategies work, so it’s been tremendous that that was in place to allow us to give this information to everyone.

Dr. Griffin’s path to becoming a clinician and scientist and favorite sources of COVID-19 pandemic information

Kyle: You are an MD PhD, and what has been your path to becoming a clinician and a scientist? You know, what got you inspired to get into medicine, and what got you inspired so much that you wanted to get both your MD and your PhD?

Dr. Griffin: Well, it was it was a long path, you know, and I always blame my parents for like thwarting my dreams of becoming a plumber, which you know I say would have been financially better, but I as a teenager was living in Greenwich Village when the HIV crisis happened, and enough people know this, but there was this young, excited, energetic infectious disease doctor and my mother was the community member on the task force with this young Anthony Fauci.

And that was actually some of my first exposures seeing what was going on, volunteering at St. Vincent’s hospital and then later I ended up in medical school, trained there in New York City at NYU, and then the crisis was continuing. And then after my early training I actually spent 10 years in rural Colorado as a primary care doc, and it was after that experience that I went back, did my PhD, and got into this MD PhD arena.

So, you know, doing a mix of mainly clinical, mainly seeing patients, but still doing research, still publishing, still trying to contribute to the literature. So you know, I blame my parents getting me getting me down this road. But, no, I think I’ve been really fortunate to be in this position. Hopefully having the, well, my PhD immunology, which really helped a lot. My advanced training in infectious disease and then all the other global health public health training that I’ve had over the years to really, really — because you needed the training before the pandemic started. So I was glad to have gotten it.

Kyle: What does a typical day look like for you now with all these different hats that you wear and clinical duties?

Dr. Griffin: Yeah, it usually starts with me waking early and reading all the papers, and then heading off to the hospital. Usually mornings I’m at the hospital. I’m doing consults on the complicated patients. So my role is often, a physician will call and say, “you know, Dr. Griffin, this is complicated. Can you jump in and help us out?” Going, seeing the patients, talking to them, helping come up with a treatment plan. Some afternoons, iIm then in the office, seeing outpatients and then through the day lots of phone calls, lots of communications with other physicians in our urgent care centers and all our primary care sites.

And then speckled through the week are my connections with the United Health Group and all our research projects. So and then at the end of the day, I think last night it was about 10 40, time to put Barnaby to bed, and then a couple more hours of reading before going to sleep.

Kyle: Very full days. What are some of your favorite sources for getting information about the pandemic?

Dr. Griffin: You know, it has really changed. So, you know, my greatest strength I think is all my friends and colleagues who help guide me towards which papers I should be paying attention to. So people like Vincent [Racaniello] and Dickson [Despommier] and Chuck Knirsch and Peter Hotez and all these people who send stuff my way and say “hey, you should take a look at this.” So that has really been great.

We used to look at basically major journals, but we’ve now shifted towards the pre-prints, right? And before the pandemic, I had never ever put a preprint up there. I also, I would ignore the preprints, that you needed to see it peer reviewed. So now a lot of the preprint servers, the first time I see things, but then once they come out in different journals, and I’m seeing them as well. So it’s really broad. You know, it used to be, you watch the New England Journal, you watch the Clinical Infectious Disease, Open Forum Infectious Disease, The Lancet. Now it’s amazing, the number of different sources where we have to look to get all the most up-to-date data.

Lessons learned and how to move forward amidst the pandemic

Kyle: As we look back on this pandemic and we’ve been dealing with it for over a year now, what are some major lessons that you hope that we can learn as a society and as a medical community as we move forward, hopefully to a much better place with this pandemic and as we look ahead to other potential pandemics?

Dr. Griffin: I think one of the biggest things we learned is that it’s really important that our public health and our scientific institutions are separated from politics. I think, we even continue — I hate to say — to this day, there’s politics in the response, and we have to be careful about that. We want our society to get the truth, to get the science. We don’t need to dumb it down. I actually think we have a bright population who would rather be educated up than spoken down to.

And I think a lot of the different communications that have been put in place, we’re going to have to preserve these. We really, on the fly, had to build up our, you know, COVID update through Parasites Without Borders. We really had to ramp up our MicrobeTV communications. I think it’s going to be critical going forward that the CDC maintains its autonomy, the FDA keeps their autonomy, and the communication is really separated from the politics. So I think, you know, this pandemic was predicted. You know, people say “who could have seen this coming?” Well, actually a lot of us have been predicting it for a while. We’re also concerned that there’s a next pandemic on the horizon, if we don’t change.

So hopefully we have learned these lessons. I know we’d like to just forget this year ever happen and move forward, but let’s not forget this year ever happened. Let’s learn these lessons, so we can never have to experience this again.

Kyle: Any other items that you want to share before we sign off?

Dr. Griffin: Well, I know a lot of people have been worried about the variants lately. You know, and they say it’s a race, the variants against the vaccines. I like to think we’re winning. We are cranking out those vaccines. We are doing millions a day. We are going to blow right past that 100 million people vaccinated in the first hundred days. And I really think there’s every reason to believe that, you know, come this summer we’re going to be in good shape. But let’s just keep an eye on the kids. The kids won’t be vaccinated come July 4th, so just because we’re safe, we still have a responsibility to keep our kids safe. And realize that yeah, being at low risk does not mean being at no risk for our children.

Kyle: Well, Dr. Griffin, really enjoyed chatting with you today. Thanks so much for your research, for your clinical updates on This Week In Virology, and your leadership during this pandemic. Really appreciate it.

Dr. Griffin: No, thank you, Kyle. It’s great to have this opportunity. I know a lot of people care about kids in COVID, so hopefully this will be helpful.