TWiV 675 Forget what you’ve herd about immunity

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 25 October 2020

Vincent Racaniello: This Week in Virology, the podcast about viruses, the kind that makes you sick.

[music]

VR: From MicrobeTV, this is TWIV, This Week in Virology, Episode 675, recorded on October 23rd, 2020. I’m Vincent Racaniello and you are listening to the podcast all about viruses. Joining me today from New York, Daniel Griffin.

Daniel Griffin: Hello, everybody.

VR: Hello again, Daniel. Another week has gone by.

DG: It has. It has.

VR: COVID-19 is still with us apparently. [chuckles]

DG: Oh, things are getting worse, Vincent.

VR: They are.

DG: [chuckles] I have a lot to say today, so probably jump right in on it. Shall I start with my quotations?

VR: Always, absolutely.

DG: Okay. I have two quotations today. “The best thing about the future is it comes one day at a time.” And that was Abraham Lincoln. The second, “If we open a quarrel between past and present, we shall find that we have lost the future.” And that is my favorite Winston Churchill quote. As we go forward, people can try to figure out the relevance of those quotations and what we talk about today.

All right. I’ll just start by a thank you and then I’ll get into this, but thank you for everyone that has been going to Parasites Without Borders to help us during the MicrobeTV fundraiser. This is going very well and I’m actually now getting the paper donations. The crowd that supports MicrobeTV, I’m actually getting snail mail with nice cards and nice letters there. So thank you. Everyone continue going to parasiteswithoutborders.com and donate to help us get this information out there. We have, as Vincent keeps saying, we have no other source of income, right. [chuckles] This is where it all comes from. All right.

Patient updates. I feel a little bad, I’ve been talking about how long it’s been since I had a patient die. There’s a number of us that are doing, we’ll call it pro bono remote guidance for people in other parts of the world. There’s actually a nephrologist, a kidney doctor, Dr. Kurapati. He and I talk quite a bit and we’ve been emailing, phone, texting, different ways of reaching out to people throughout the world, India in particular. A tragic story. First, one family member got sick and then this doctor’s mom and dad got sick. Mom was sicker than dad.

The mom was having a tough time and then the dad about week three had a sudden heart attack and died. It’s just a tough reminder that this is an unpredictable disease. You thought he was through that tough part and this reminds me of those early days when the coagulation issues arise at week three. The process probably starts during week two, it probably starts when the whole early inflammatory process starts, but just tragic.

In New York, we’re having increasing numbers, almost 1,000 people being hospitalized per day, new hospitalizations per day. Speaking to my colleagues in the urgent care centers, I don’t know if I shared this before, but the call that we have a lot of people that are sick enough to go to the hospital, but not smart enough. The actual number of people that are hypoxic that are having severe COVID is higher than those numbers that we’re seeing.

News. Again, I try to be positive so take a deep breath. We’re starting to hear about vaccines, how they’re going to be distributed. But I just, just hot off the press, today as we’re recording this, Moderna just announced that they have fully-enrolled their vaccine study. They’ve also announced that they have given people the first and the second vaccine. Over 25,000 people, actually over 26,000 people have already been fully-vaccinated. This is exciting news. We are actually getting people vaccinated and now we get to wait to see what happens, and we’ll talk a little bit about the alternative approach to waiting and seeing what happens.

Each state has been asked now to create a distribution plan and I did talk on Wednesday morning for UnitedHealth Group about vaccines and I touched on this a little bit, but each state has been asked to announce a phased rollout plan for vaccines. We are hoping that by April, we’re actually starting to vaccinate in huge numbers. How do we do this? This is going to require a lot of cooperation, a lot of coordination getting that vaccine from production to everyone’s arm.

Phase one, this is New York State announced its five-phase plan, phase one is going to be healthcare workers, in-patient care settings, long-term care facility workers, and some long-term care residents are going to be the first to receive the vaccine. Phase two is going to move to first responders, school staff, other public-facing frontline workers, and people whose health conditions put them at extreme risk.

I know when I was going through these I wondered about the first responders and school staff. I feel like as a healthcare provider, we have better access to PPE. I might’ve done phase one and phase two a little bit different. I might’ve looked at first responders and school staff as sort of a higher priority, but just that’s me. We’ll see if Andrew Cuomo gives me a call. I don’t know if he listens to TWiV, but phase three people over 65. Phase four, you move to all remaining essential workers, and in phase five you roll out to basically everyone else.

Now, I also have some other, I’m going to say that in my opinion, very positive news. What about these vaccines? Who’s going to get them? How much is it going to cost? The federal government is procuring hundreds of millions of doses of what they call safe and effective vaccines. We’ll see. I think by the time they’re released, they will be, but they’ve contracted with McKesson for vaccine distribution, and this is the part that I think is great, no American will be charged for either the COVID-19 vaccine or its distribution. The objective is to ensure that no one desiring vaccination will face an economic barrier to receiving one. I think that’s fantastic.

Then we move on to some vaccine news, which is a little more gray. It was announced this week that British scientists plan to infect healthy volunteers with Coronavirus in a vaccine-challenged trial. The British experiment is scheduled to begin in January, volunteers will have a purified laboratory-grown strain of – They use the word live, I thought that would also upset you if I said of live – [laughs] I’ll say active virus blown into their noses, while they are being quarantined in a biosecurity unit at the Royal Free Hospital in London, where they’re going to undergo tests over two to three weeks after this exposure.

Now, what’s the argument? Why are they doing this? Christopher Chin, he’s an Imperial College immunologist who will be one of the lead investigators, is saying that doing it this way, they will be able to tell within 10 weeks how effective a coronavirus vaccine is. He compares to says, by contrast, studies that rely on chance exposure rather than deliberate infection can take months and tens of thousands of inoculations to prove efficacy.

VR: Yes, but we’re almost done with those aren’t we?

[laughter]

DG: Speed up. I’m hoping we have information before this has to even happen.

VR: Daniel, they’re using young people. That is the only people you would be able to give these vaccines to, right?

DG: Well, that is the problem with a study like this. You say, “Oh, well, we’re only going to give this – We’re only going to do this in young healthy people because then we feel like that’s something we can do.” Then you’ve got to ask the question, “Does your vaccine work outside of that demographic?” There’s multiple issues with the whole idea of vaccine challenge studies, which I think that we’ve touched on.

VR: We have. Of course, even though they’re young and healthy, these people still die as you’ve said before.

DG: Yes, and we’re going to get to that actually because that is a little bit of the myth that I want to make sure we talk about today. The other thing I want to talk about, and this directly ties into this, is when do we start getting that efficacy data? When do we start finding out if the vaccines work? There is what we talk about as interim analysis, triggered interim analysis.

The different vaccines have already decided when they set up their trials, at which point the boards would go ahead and look and see what is going on. We’ll do Moderna first and then we’ll do Pfizer second but in all reality, Pfizer may be coming out with interim analysis first, but that’s okay. Moderna has said as soon as 53 infections are seen in their large study group, 30,000 people fully-enrolled, they’re going to do an interim analysis. They’ll do another in 106.

Pfizer has actually slated four interim analyses, so 32, 62, 92, and 120. What you do is you basically stop, you say, and we’ll use Pfizer’s example, you have 32 infections and then they break it down and say, “What number of those infections were in vaccinated people, what were in non-vaccinated people?” Because you’re really looking early, you need to have greater than 76% occurring in the non-vaccinated for you to be able to extrapolate that you’re above that 50%. You don’t stop the trial, but you’re starting to get preliminary efficacy data.

AstraZeneca has an interim analysis at 75%, and actually, J&J has a very complicated four-part requirement for interim analysis. I won’t go into that, but basically, each different vaccine trail is going to be coming out with interim analyses. We’re predicting that we’ll be getting the first of these interim analyses in November. In next month actually, coming up pretty soon.

VR: Well there’s certainly enough cases now to power these trials, right, Daniel?

DG: Yes. That’s the silver lining of every mushroom cloud, is that as the case counts go up, as the infections go up, that means we’re going to get our data. This has been an issue with some trials where they, by the time you have everything ramped up, the numbers are on the way down. That happened in China in a few situations. We’re not going to have that problem in the United States where we’re ramping up, if anything.

Case numbers testing schools, the MMWR put out an early release, “Race, Ethnicity, and Age Trends in Persons Who Died from COVID-19.” They looked from May through August 2020 and there were a few interesting things here. I think people should take some time and take a look at this. A lot of it has to do in how you interpret the data. The data’s the data, but how do you interpret it?

One of the things you could say is that the majority of the deaths are in people over the age of 65, but 20% of the deaths, one in five people who have died of COVID who’s under the age of 65. The other that I always worry about is a lot of – We live in America where it’s a Caucasian predominant ethnic group society and there’s been a lot of press about how this has been hitting the African-American population and the Latinx and other non-Caucasian populations, and sometimes I worry that creates a sense of, “Oh, well, it’s not our problem from the dominant ethnic group.”

The majority of the people that have died, they are Caucasians. It is disproportionately affecting the minority populations. Just to sort of let you know, this isn’t that, “Oh, I’m white, I don’t have to worry about it. This is someone else’s problem.” The data basically points out that this is affecting everyone. I want people to get that message here. Just because you’re young, just because you’re Caucasian, just because you’re female, COVID-19 can still potentially kill you.

The other, and this is a research letter that came in about excess deaths from COVID-19 and other causes where they basically were looking at causes of death during this, well, it’s a period of time, March to July. They were pointing out, there’s going to be two articles I want to talk about here because again it’s an interpretation of the data. Based upon the article, they suggest that of the excess deaths, 67% of these deaths were due to COVID. What they’re suggesting is that maybe we’re not counting all the COVID deaths.

The MMWR had another excess death article and it was looking at January 26th to August 3rd, it was a slightly broader, basically estimating that there were close to 300,000 excess deaths that were occurring during this period of time. Also, hit right about the same number 66% versus 67% were attributed to COVID-19, but the largest increase in deaths was in the age from 25 to 44. I think that’s again sort of raising a couple of questions here. Why are they dying? Are they dying from COVID-19? Are they dying from other reasons? Are they neglecting care?

Do I think 25 to 44-year-olds are dying because they didn’t see the doctor routinely? Are the lockdowns so bad that everyone’s committing suicide? I’ve seen that in the press. I don’t think that is actually consistent with the data. Just really sends the message that we have lost 300,000 more Americans than we normally would have lost in just this nine-month period.

VR: We have 100,000 confirmed deaths from COVID. Some of these are probably COVID that weren’t diagnosed and others are somehow related. Is that the idea?

DG: We think it’s a mix. Like 2/3 are confirmed COVID-related, as in COVID was why you died. The other are the, occurred during this period of time we don’t know specifically that it was due to COVID, it’s probably a mix and we don’t know what percent of those were due to COVID. The other is actually something that’s going to become more relevant, I think we’ll probably be returning to this but it is the question of indoor dining and the upcoming holidays.

The EPA has a webpage actually, Indoor Air and Coronavirus [COVID-19], and they have links to lots of resources and some guidance. There’s been a little bit of press about this lately. The CDC has updated some of its guidance, make sure we touch on that. Just to reinforce what we know relative to this issue, the principal mode by which people are infected with SARS-CoV-2, the virus that causes COVID-19, is through exposure to respiratory droplets carrying infectious virus.

What about the term ‘airborne transmission”? It’s a hot wedge issue. COVID-19 and how this applies to indoor environments. The CDC recently updated its website to clarify this point, and I’m going to go through and point out several things. The terms ‘airborne transmission,’ as some of our listeners know, but not necessarily all of them, has a specialized meaning in public health practice, and the CDC points this out.

I’m going to quote the title of a piece by the journalist Roxanne Khamsi, she’s a WIRED contributor, “They Say Coronavirus Isn’t Airborne – but It’s Definitely Borne By Air.” What is this confusion and controversy and how did this become such an emotional hot wedge issue? It really goes back to this specialized meaning that the CDC is trying to explain.

The CDC webpage points out that diseases such as tuberculosis, measles, and chickenpox are efficiently spread by smaller droplets and particles that can remain suspended in the air over long distances, usually greater than six feet, and time, typically hours. Now I’m going to actually quote the CDC, “The epidemiology of SARS-CoV-2 indicates that most infections are spread through close contact, not airborne transmission.” Now that they’ve mentioned airborne transmission there was all these people very excited, but just to point this out, they are saying that this is not the dominant spread.

“Pathogens that are mainly transmitted through close contact can sometimes also be spread via airborne transmission under special circumstances.” Then they go on to point out that there are several well-documented examples where this looks like it may have happened, but they then say these transmissions appear uncommon and typically involve the presence of an infectious person producing respiratory droplets for an extended period of time in an enclosed space.

That leads us to indoor for the holidays. Because what are they actually talking about doing? Well, they go on to say enclosed spaces within which an infectious person either exposes susceptible people at the same time or to which susceptible people are exposed shortly after the infectious person has left the room. They talked about prolonged exposure to respiratory particles and they talk about inadequate ventilation or air handling.

Where are these indoor dining opportunities available? One is in our homes. Most of us do not have advanced ventilatory systems. Most of us, perhaps Vincent has a large palatial dwelling, most of us do not have a huge space. We actually, when we come indoors to dine together, we’re actually in pretty close contact for a prolonged period of time performing respiratory particle producing activities such as speaking. We don’t sing in my home. Actually, I have some teenage daughters, they do actually break out in song without being provoked.

There is the concern, and actually, epidemiologically, what we’re seeing is most of the transmission that’s occurring right now is actually in the indoor home setting. A lot of restaurants, because they’re trying to do the outdoor dining, have created these closed bubbles with no ventilation systems. And I’d like to point out that you have just created an indoor space. Just the fact that those walls are made out of plastic, that is not great. Usually, those enclosed areas do not have great ventilation and air handling.

What are the current recommendations? A lot of physicians are being asked these questions so I’m going to give nine recommendations. One, if possible, stay outdoors. We estimate that this is 20 times safer than indoors. Distance, stay six feet apart, much easier to do this outdoors. Time, and this was actually something that was added to the CDC. We say, if you’re within six feet for 15 minutes or longer, it doesn’t have to be continuous. You can’t walk away for a minute and then come back for another 14. It’s not like you set your clock, if you’re there for 14 and you leave and you come back for two, you’re now at 16. Exposure is cumulative and that was updated. It actually made it to front page, I think of The Times. [chuckles]

Masks, masks catch your respiratory droplets, the large ones, the small ones. I do want to point out, you have three holes in your face through which you breathe. Unless you’re a strict mouth breather, you’ve got to cover your nostrils. If your mask is too small, go get yourself a big boy mask. Not sure why this is such a male thing, but it tends to be the men that are walking around with their nostrils sticking out. If you’re exhaling through your nostrils, you got to cover them otherwise, the mask isn’t doing much.

Ventilation, open the doors. This is like the Jimmy Carter days, remember when he told you to just put on a sweater? Open the windows, put on a sweater, let’s try to improve the ventilation. I remember my cross country running coach back in high school, Twiggs Myers. He used to say, “Daniel when I want to enjoy the outdoors, I crack a window and when I’m done, I shut it.” Keep the windows cracked.

Wash your hands, not just for employees. Get tested, particularly if you’re thinking about getting together with vulnerable people during the holidays. Not just one test, try to get a couple of tests because each test has a certain miss, a certain sensitivity. If you can get a couple of tests right before the holidays, this is going to help. Nothing is foolproof. Number nine, consider a Zoom holiday party. We actually did this with some of the past holidays where older friends and families, they’re having a tough time with all the social isolation. We actually set up the computer and they had set up an iPad and I think by now everyone’s getting a little savvier, but it allowed them to be part of the conversation and to participate. Those are my comments on indoor dining.

VR: Can I make a comment on the CDC description that you gave us? I find this terribly confusing. Here’s how I look at it. Most SARS-CoV-2 is through the air, it’s either droplets, which are close within six feet, or aerosols, which can go a long distance. This close contact implies contact, but what they really mean is within six feet, right? [chuckles]

DG: Yes. That is it exactly. We’ve got to like just scrap the English language and come up with something that’s – [chuckles]

VR: It’s all airborne.

DG: We use the same words for too many different things. Yes, it is transmitted through the air and dominantly within that six-foot zone. Stop spraying all your groceries with bleach, it’s the coughing, the sneezing, the breathing, all that stuff. Some treatment drug updates. Unfortunately, this is lots of negative data here so I’m just going to march through this.

We now have the results of the WHO Solidarity Trial, which was the repurposed antiviral drugs for COVID-19. They looked at over 400 hospitals, 30 countries, or 11,000 adults. They looked at a whole bunch of stuff. I’m just going to cut to the chase, remdesivir, hydroxychloroquine, lopinavir, and the interferon regimens appear to have a little or no effect on COVID-19 as far as mortality, ending up on a ventilator, duration of hospital stay. The mortality findings are not very exciting.

I do want to say something positive right after that. [chuckles] Just a reminder that prone positioning does appear to be beneficial, and back in June, there was the article, “Prone Positioning in Severe Acute Respiratory Distress Syndrome,” published in The New England Journal of Medicine. This actually was encouraging. I just want to bring up that you have to be careful when you do something.

This study back from The New England Journal showed that the 90-day mortality was 23.6% in the prone group, versus 41% in the supine group. That was a hazard ratio of 0.44, that was encouraging. You have to be careful when you prone position patients. There was just a paper, “Improving Prone Positioning for Severe ARDS During the COVID-19 Pandemic,” an Implementation Mapping approach basically outlining how do you do this successfully?

Basically, you got to educate people. It’s ideal to have a proning team, and I just want to bring this up because we had a patient that was recently seen by one of my neurology colleagues who was proned improperly at a, we call it an OSH, an outside hospital. He actually ended up with a brachial plexus injury. Somehow. when they took this large gentleman and turned him over to be proned, they actually, they ended up ripping the brachial plexus out. It came right out at the roots and now the person can’t feel or move that arm. Proning is important to do, but you have to make sure you do it right. Organize a team, think it through.

Next thing I want to hit on, and this is actually really important. I don’t know if it seems important to people when they think about it, but the issue of unnecessary antibiotics being used in COVID-19. Only 10% or less of patients with COVID-19 have a bacterial infection at initial presentation yet the majority end up receiving antibiotics. There was a nice article, “Confronting antimicrobial resistance beyond the COVID-19 pandemic and the 2020 US election,” interesting tale to that title. It was in The Lancet, which I’m not sure why the Brits are so concerned about our election.

It was outlining this issue with inappropriate antibiotic prescribing during the pandemic, and actually raising concern that we’re going to follow this pandemic with an antimicrobial resistance pandemic. Where we’re no longer able to treat common bacterial infections, a simple cut, someone going for surgery because we’ll have bred such degrees of antimicrobial resistance. We risk returning to the dark times before antibiotics.

A lot of this is directed at ER physicians, not everyone with COVID needs that first dose of antibiotics, just to be safe. Urgent care doctors, let’s stop giving out all that Augmentin and Zithromax. Primary care doctors, you’re going to want those antibiotics or other things after COVID-19. Patients too, when your doctor offers you an antibiotic to treat a virus, think it through, have a dialogue, sometimes they think they’re going to improve patient satisfaction. This is a viral disease. Let’s stop using those antibiotics.

A study that was available as a preapproved is accepted to Gastroenterology, is negative stuff about famotidine. The title says it all, “Famotidine Use Is Not Associated With 30-day mortality.” A coarsened exact match study in 7,158 hospitalized COVID-19 patients from a large healthcare system. Basically, the post-match 30-day mortality was 15.1% in people that got famotidine in and 9.5 in non-famotidine users. The biggest impact was people came in, they had never seen famotidine before you gave it to them, or not giving it to them did not improve outcomes. I think people can look at those numbers and say it looks like it may have done the opposite.

We did learn a little bit more, and this is something I know for months now, my colleagues and I have been really just struggling to understand, patients early on with COVID-19, early on from the ICU perspective, have their lungs start to fill with this thick jelly-like liquid. It’s almost like they’re drowning, and we didn’t really know what is this stuff? In the Journal of Biological Chemistry, there was an article where they actually identified this substance as hyaluronan in the lung alveoli in severe COVID-19.

Now, what is this stuff? Hyaluronan is an important component of all the extracellular matrixes. Its levels tend to go up in response to inflammation and injury. It’s an odd molecule. It basically absorbs water incredibly well, so fancy word for that I’m not going to use. Okay, hygroscopic. It can actually absorb up to a thousand times its molecular weight in water. Basically, people’s lungs are filling with this highly viscous material. Now that there’s been this identification, there’s actually a hope that this might open some treatment options so that’s encouraging. We talked about vaccines, and encouraging stuff there, and now we’re getting to the tail, we’re almost done. Here at the tail I’m going to discuss the tale of COVID-19. There was a recent theme to review for The National Institute for Health Research, suggested that we use the term ongoing-COVID, but then they kept calling it long-COVID after they suggested that as a term. [chuckles] I found that a little bit interesting.

It’s becoming more and more appreciated that people don’t necessarily just get over COVID. Please stop telling your patients to just get over COVID because some people are suffering. Just to put this in human terms, just this week, Melania Trump, the current President’s wife decided, I don’t know if that’s current President or current wife, but both, decided not to attend a rally because she actually was saying that she’s still not fully recovered from COVID, she’s having body aches, cough, headaches, feeling extreme fatigue.

Right now, the media attention was focused on the upcoming election but here’s a mom, a wife, or husband who gets sick, goes to the hospital and she gets diagnosed, her son finds out he’s infected. I think it just reinforces that there’s a lot of people that don’t just get over COVID and continue to have suffering for weeks, and as we now know, months in some cases. Thank you so much. I’ll turn it back to you, Vincent.

VR: I wondered what you thought of this paper published in Nature Medicine where a group at Mount Sinai looked at cytokines in COVID patients and they decide that IL-6 and TNF-α should be considered in the management and treatment of patients. What do you think?

DG: Do they want to give the IL-6? [laughs]

VR: No, those are elevated in hospitalized patients.

DG: Yes, it is interesting. Maybe we’ll get to this, and actually, we’ll probably discuss this in the next one, I’ve been working with about 30 co-authors from around the world to try to put together a phases of COVID consensus, and I’m actually almost there actually. I’m just dreading trying to submit it and enter in the 30 authors. I tried to get one of the other co-authors to do the data entry on all the authors that you have to do.

There is this period, this early inflammatory period, which is when people have the pulmonary decompensation when we now realize that the coagulation process starts. It doesn’t become clinically apparent until week three, but it looks like it starts during that week. We see increases in IL-6 and other inflammatory markers, which got coined as the cytokine storm.

I think a lot of, and actually, the thought behind this consensus is that the different therapies need to be timed appropriately. You time your antivirals during that, really probably start it during that incubation phase, if possible if you can identify. You definitely want to start it as soon as you can when you get the detectable virus. Then during that second week when the virus is on the way down and IL-6 and the other cytokines and inflammatory markers are going up, that’s when I think it makes a lot of sense to start looking at therapies then.

VR: I asked because TNF-α, I haven’t heard much. I’ve heard IL-6 elevated in COVID, but this week on Immune we did a paper, which suggests that in patients with serious COVID, the germinal centres of lymph nodes and spleens are trashed and that’s why you don’t make good antibodies. They think it’s associated with TNF-α and even suggest that blockade might be beneficial.

DG: We have drugs sitting on the shelves. This is a target that we can look at and we can actually start doing those trials.

VR: I have a question from Rich Condit and Grant McFadden, two Pox virologists. Reuter has reported that a participant in the AstraZeneca trial has died of COVID. but that the trial is not being paused. I think they didn’t die of COVID, but they died. The implication is that the death is in the placebo arm. Further, the implication is that someone monitoring the trial knows who is placebo and who is experimental. Seems someone must know the code to decide. How does this work? Is there, in fact, a person that knows the code but is insured to keep the trial otherwise blind?

DG: Yes. There are these data safety monitoring boards. I actually know several people that are on these boards for their vaccine trials. When something like this happens, actually when something like this has happened in trials where I was the PI, this person would then do this investigation and they would find out. Because you do want to know when someone has a bad outcome, “Is this someone who got the vaccine or not?”

If someone had gotten the vaccine and died, that definitely is different implications. They look specifically at just this one person, there’s a certain code that identifies who they are and they can then break the code. This is all recorded. There are data safety monitoring people. Whenever there’s a serious adverse event, they will look at it and try to determine this.

VR: DSMBs, very important. All right. Tom writes about a sad story of a young man in his 20s who had developed flu-like symptoms on October 3rd and died on October 18th. He was not tested for SARS-CoV-2, but the doctors implied that a leukemia-like illness was occurring. The question from Tom is, “Are you aware of SARS-CoV-2 triggering leukemia-like signs – could accelerate leukemia?”

DG: I’m going to say no. I am not familiar with that. I’ll say no to that. I want to be specific that I say no. There are a number of viruses that trigger these atypical reactive lymphocytes, and examples of those would be Epstein-Barr Virus, cytomegalovirus, and several others. We have a differential for things that trigger this leukemia-like crisis. This is not something we have at any significant amount in COVID-19. We’ve seen millions of cases now, a lot of the clinicians I work with have seen hundreds, if not thousands now. This is not a classic COVID-19 manifestation.

VR: Then he asks about funeral preparations, which we have touched on before, Daniel. He says people want to do this because people expect attendance, but it’s a great way to transmit infection. He’s saying you have an audience of clinicians and regular people looking for real information, please provide science-based opinions about how they should behave in terms of a funeral.

DG: Yes. I know this is really tough. I’m going to reach out to the listeners, but also our clinicians as well as non-clinicians, we’ve actually related some stories firsthand here where funerals are a place where the virus seems to be spread. We had that woman and her husband, his sister died right in Boston, the body was brought down for a wake followed by a funeral and people at a situation like this, they’re emotional, they’re touching their face, they’re crying, they’re gathering together. It’s very hard not to comfort a loved one who’s going through this.

They may have the virus, you may have of the virus, someone else may have the virus, you get into these situations. They’re indoors, not a lot of us do their wakes outdoors. These rituals involve basically the potential for significant spreading. Hopefully, people have started to get the sense that early on there was the idea that there were certain individuals who were superspreaders, but usually, it’s a situation that creates the superspreading. You get a lot of people indoors within that six feet, that magical six feet for more than 15 minutes cumulative, and you have potential to turn one horrific loss into multiple horrific losses.

Start trying to think about ways to do this differently. I remember stories from the Ebola outbreak where you really just sort of sat down with people and said, “Let’s talk about ways to modify our rituals so that they accomplish what they need to, but without putting everyone at risk.” This is a situation where let’s take a deep breath and try to prevent these superspreading events.

VR: Tom says I understand Dr. Griffin has written “The Stages of COVID-19” summary, maybe this should be mailed to every doctor treating patients as a public service?

DG: It’s going to very soon. It’s going to be hopefully in the next couple of days. We’re going to get everyone to sign off on the consensus and we’ll get it submitted.

VR: Great. It’ll be a preprint put up that we can share. Is that right?

DG: Yes. I’m accepting the whole preprint world.[chuckles]

VR: All right. One more email from Mona, “I have a question for Dr. Griffin. You say there’s a growing problem with school reopenings and more new infections. How do you think this can square with the upsetting data from the American Academy of Pediatrics and Children’s Hospital Association that show the COVID cases in children have been rising steadily since April, without a jump in August or September? Gatherings such as birthday parties, which have resulted in cases you’ve told us about, aren’t necessarily related to school reopenings.

Mona provides links to several of these reports from these academies and also CDC. She concludes, “We need our children to be able to go to school, so the increase is alarming. Over 300% more cases in children since April.” Perhaps it has more to do with testing, but according to the Pediatrics’ article, “CDC data from public and commercial labs show that shareable test administered ages 0- 17 has remained at 5% to 7% since late April.” What do you think, Daniel?

DG: Mona, I appreciate you writing this email because I always want to try to be clear with the school openings. It was a number of months back I was giving advice to a Montessori school about potential ways to open safely. At one point they offered, “Oh, what is your hourly rate, Dr. Griffin?” and I said, “Well, you can’t pay me because it’s a conflict of interest.” They said, “What are you talking about?” I said, “I really think it’s important that we shoot for students getting back to school in person as a goal, and if I’m getting paid to make that happen, then I’m going to feel like there’s a certain conflict of interest.” They seemed very confused.

My goal, and I think the goal that was stated by the American Academy of Pediatrics, is that the goal is to get K through 12 kids, particularly in school, in-person. This has to be done, I think, safely. What I do want to point out, I think this is really positive, is that what we have not seen is large spreading in most of our public schools. It does not appear to be spread occurring within the walls.

The other thing that I want to say, and I think this is what we’re seeing here in the data is, we are seeing that spread occur outside the walls of the schools. We’re seeing it occur at gatherings such as birthday parties and the rest, and this has been gradually rising. As you point out, you want to be blaming of the schools. It’s not like when kids went back to school suddenly the birthday party incidences increased dramatically, but they have continued to increase. What we’ve observed in the area here is we’re seeing larger birthday parties now instead of just the close friends, it’s the entire school class.

As we’re seeing the numbers rise in our local area, as we’re observing who the positive cases are in this population, the schools I think are doing a really good job with masking, with distancing, with ventilation. Actually, I have a good friend, Scott Bersin, who’s down at the South Shore and is a principal at one of the, I think, the Baldwin schools. They have not closed at all. They’ve done a really good job of, half the school goes in the morning, half the school goes in the afternoon, reducing the numbers so they can accomplish all the spacing, and distancing, and everything they need.

The numbers are gradually going up. It would be ideal if there was testing, some other ways to sort of help this population, but we are seeing the numbers go up. As we pointed out, this is a population though, at low risk, they’re not at no risk.

VR: Here in New York City, they’ve done pretty well. Minimal numbers of cases detected, but the point is, and you’ve mentioned this, you have to space out the students. You have to take measures. You just can’t send them back the old way to school.

DG: Yes. We have to do it differently, but I really am still a believer that it can be done safely if you have the will and you’re willing to spend the time, effort, and money to make it happen.

VR: All right. That’s our weekly COVID-19 report with, Dr. Daniel Griffin. Thank you, Daniel, again.

DG: Thank you so much, and everyone, be safe. Again, thank you so much for everyone who’s gone to parasiteswithoutborders.com to help up with our fundraising drive to support MicrobeTV.

[00:43:47] [END OF AUDIO]

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