TWiV 865 COVID-19 Clinical Update #101

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 12 February 2022

pdf of this transcript available (link)

Vincent Racaniello: This Week in Virology, the podcast about viruses, the kind that make you sick. From MicrobeTV, this is TWiV, This Week in Virology, Episode 865, recorded on February 10, 2022. I’m Vincent Racaniello and you’re listening to the podcast all about viruses. Joining me today here at The Incubator, Daniel Griffin.

Daniel Griffin: Hello, Vincent. Hello, everyone.

VR: We have a new arrangement here.

DG: It’s very comfortable. I’ve got my blue jeans on.

VR: This is update number 101.

DG: Yes, it’s been a while.

VR: 101 episodes. What are we up to here in the country?

DG: Things are going in the right direction. Let me start off with my quotation and let’s get right to our update on where we are. “Courage is not having the strength to go on, it is going on when you don’t have the strength,” and that’s Teddy Roosevelt. I know a lot of people are exhausted and we’re going to get into the fruits of that exhaustion, if you call them that, when we talk about masking. But where are we? Case numbers across the U.S. are dropping quickly, deaths look to have peaked. They’re also dropping but let’s put that in perspective. We reached a peak of 3,563 deaths on January 26 and they have dropped all the way down to 2,777 deaths on February 8, so that’s still very high.

We’re still seeing over 2,000 deaths per day and everybody’s ready to be done. Here in New York, just to give the same numbers, the peak in New York, we’re a little bit ahead of the curve on this. January 18, we were at 404 at a single day. On February 8, just a few days ago, down to 2,008. Still over 200 people dying just right here in New York in a single day. The case numbers though, these are really dropping. Test positivity rates are down. Things are actually getting pretty quiet. I have to say, at urgent care, starting to get pretty quiet. In the hospitals, I’m seeing empty beds. Today, I was at one of the hospitals and didn’t take care of any COVID patients at that hospital. I went to another and there were just less than 20 in the entire pretty large hospital.

I’m going to spend a little bit talking about masks today because people want to turn this around. They worry the hospitals are a little too empty. In many parts of the country, mask requirements indoors and then probably next month is schools, it’s going to go away. I will say here in New York, Wednesday, the 10th of February, the mask or vaccine mandate expired, so that is no longer a thing. I took the train in. I am unhappy to say there are a lot of people on that train without masks.

You’re supposed to still be wearing the masks on airplanes, on buses, on trains. Vincent, were people wearing the masks coming in from New Jersey? Are they any better behaved than us New Yorkers?

VR: Last night, this morning, all masks. Today, the mandate expired in New York State. Is that what you’re saying?

DG: In New York State. It used to be that a business had to either check to verify that you were vaccinated or you had to wear a mask or they could pick which one they were going to go with, either the mask or the vaccine. Some institutions and businesses were switching. Like some days it was masks, some days it was vaccine. You had to figure out which one. Now it’s a free for all.

VR: There’s still a federal mandate for some activity.

DG: Transportation.

VR: Transportation, okay.

DG: When you’re on that train, when you’re on that bus, when you’re on that airplane, theoretically supposed to.

VR: Now, Columbia University still has a mask mandate. Who are they marching to?

DG: Well, schools are a little bit different. I think it’s good that you bring that up. In New York– and this is different in each state. In New York, there’s still a mask mandate in effect until at least February 28 and then it’s going to be addressed. We’re thinking in March, a lot of schools are going to be dropping. A lot of parents– and we’ll get to this, the timing issue. Those kids under five. A lot of parents say, “We’ve been keeping them safe for so long. Couldn’t you have given us a little bit more time?” We’ll talk about some dates on that as well.

VR: We’re thinking after spring break, when we come back, probably no masks.

DG: In a lot of states, I think that’s going to be the case.

VR: Could Columbia conceivably make its own decision or do they follow the state recommendations? Do you know?

DG: They could conceivably make some of their own decisions. They could decide, for instance, even though mask mandates are no longer required, if they felt like there was a reason they could potentially go a little bit longer.

VR: I’m teaching right now in person and I would very much like to not wear a mask. Now, I was discussing with the students yesterday, “Do you think we’ll ever not wear a mask?” They think not because they think Columbia wants them to wear a mask but they told me I could not wear one because I’m way at the front of the class. I said, “No, I want to give you moral support. I’ll wear a mask.”

DG: I applaud that. Let’s go right into children, COVID, and mental health because we’re going to get back to masks a lot today and have a little bit more of a dialogue, Vincent. I’m going to put you to work today. As we’ve been saying for quite a while, children are at risk from COVID. The most recent data from the CDC and the American Academy of Pediatrics, we have data up to the 3rd of February. Looking at the week right before that, we are up to a cumulative 828 pediatric deaths from COVID. Say that one more time – 828 children have so far died from COVID. This is 21 additional deaths just in that last week.

That’s three children dying a day here in the U.S. from COVID. It still kills me because whenever I say that people say, “Well, they have comorbidities. Like they were chubby. Maybe they had asthma.” It kills me. Like the best man at my wedding, he has asthma. I would be really upset if he died. Don’t keep asking me if they have comorbidities. We’ve talked about before a third of all the children who end up hospitalized with COVID have no discernible comorbidities.

VR: Now, if I remember from last week, you said most of the deaths are in fact since August.

DG: Unfortunately of those 828 deaths, the majority of those deaths have been just in the last six months, just since August.

VR: It’s a good number from Omicron.

DG: Well those 21 deaths that we just saw, that’s Omicron. I think again, people really got to watch that word “mild,” 3,400 plus deaths in a single day. We’re still at over 2,000 deaths a day, that’s Omicron. Anyone who’s maybe in a political arena, maybe an elected official who calls this “nature’s attenuated viral vaccine,” it’s wrong. This is not something you want to mess around with.

VR: I don’t think the FDA would approve it as an attenuated vaccine, would they?

DG: With the mortality side effect here, no. This is not the way to get immunity. The way to get immunity is through these well-studied, well-tested vaccines. I had the privilege of attending our ProHealth Pediatric Summit meeting this Monday. Eventually, it’ll be Optum Tri-State undergoing a branding but so far, ProHealth tries to keep all this straight. School safety was a big concern. I want to talk a little bit about the updated CDC science brief. The CDC has a page you can go to, Science Brief: Transmission of SARS-CoV-2 in K-12 Schools and Early Care and Education Programs. They update this periodically. The most recent update, I’m going to actually just read right from the website.

“Although outbreaks in schools can occur, multiple studies have shown that transmission within school settings is typically lower than or at least similar to levels of community transmission when prevention strategies are in place in schools.” This is interesting. I usually don’t step in it and get yelled at much. Well, maybe that’s not true. Whenever I try to say that our schools can really keep our kids safe if they might make the right choices, a lot of parents get very upset but it is true.

The CDC guidance really talks about what are these prevention strategies that keep our kids safe. Let’s go through. Number one, promoting vaccination. Now, evidence from studies primarily before vaccine approval, we’re really seeing staff-to-staff transmission as much more common than transmission from students to staff, from staff to students, or even student to student. Seeing the really high amount of vaccination in our teachers, I think that’s encouraging.

Consistent and correct use of masks– and this is interesting. They say for people who are not fully vaccinated, sort of interesting because we’ve started talking about not thinking about vaccination. As we’ve repeatedly talked about, vaccination does reduce your chance of getting infected. We also think it reduces your chance of spreading it to others if you are vaccinated and correct mask use. I was listening to the most recent TWiV involving the comment about how the peak viral loads actually in the nose. If you’re not covering your nose, what are you doing?

VR: That’s right.

DG: Barnaby and I were driving to school this morning pointing out all the people with their nose just sticking out. When I was in Ghana, they call them nose masks. Really pointing out, it’s got to cover the nose. Physical distancing, screening tests, and improved ventilation, that is huge. This is a respiratory virus. I’m also hoping improved ventilation helps us with some of our other respiratory pathogens. Now they throw in handwashing and that’s something that was really kind of great. What they noticed in Ghana was that a lot of people have really doubled down on the hand washing and you should be washing your hands all the time. It helps with so many other things. They were seeing less parasitic, less gastrointestinal, a lot of less other things, because people actually are washing their hands.

A lot of times we’ve talked about, where did everything go during COVID? Well, washing hands, the American Society of Tropical Medicine– and hygiene. Hygiene is huge. Respiratory etiquette, that’s coughing into your arm, not coughing into someone else’s face. Hopefully, you got that mask on.

This is a big one, stick home when you’re sick. If you’re sick, you don’t really want to go and give that to others. Contact tracing and then again, routine cleaning, let’s keep the schools clean.

VR: Daniel, what’s the proper etiquette if you have to sneeze and you have a mask on? Should you put your mask in your elbow? Should you take it off?

DG: Now we’re stepping slightly outside of evidence-based guidance, but we’re actually using practical things. One of the things is, it’s pretty forceful when you sneeze, and we just talked about, we want that mask to be close fitting to contain respiratory droplets and so if you actually bring up that arm, that’s going to keep that mask tight against your face. I would think it should help but we need some of those cool laser studies where we can see what happens so we can make that evidence-based. Here’s the exciting– and this will be when we talk next time, we’ll get to talk about this. But the FDA is meeting to look at the Pfizer COVID-19 vaccine for children under five years, six months up to four years of age, that’s going to be February 15.

This was announced on February 1, this is going to be for children in this age range, getting the three microgram doses. A first one, three weeks later, a second one. While they continue to study that third dose– but I am going to throw this in, this is critical. I’ve seen all these news articles, what’s different? Well, we’ve heard that there will be a science brief that’s going to go to the FDA and this submission is going to be looking at the data on safety, tolerability, immunogenicity, and available efficacy on 8,300 enrolled children. We’re actually going to see data in the coming days, we don’t have it, I want it, I’m sure you want it, Vincent, our listeners probably want it.

We’re going to get that and that’s what this decision is based on. It isn’t just, oh, my gosh, let’s go ahead and do this. The FDA encourages this application so we do expect there to be compelling data here for going ahead while they study that third. A lot of people keep asking, “What if they find out that third dose doesn’t really get us there?” Well, we’re hoping that this data that we see tells us that we’re getting something and that’s reasonable to have that expectation.

VR: The two-to-five year olds, there is an EUA application, correct?

DG: This is an EUA.

VR: And we expect it to be approved relatively quickly after the 15th, did you say?

DG: We expect them to meet on the 15th, we expect on the 21st of February, to be the day that people can start getting vaccinated, there’s already distribution plans in place, there’s a lot of– there must be good data here if we’re already getting ready to distribute it. They already have the particular color caps to the bottles. I’m encouraged and I know a lot of parents– not every parent is going to be rushing out on day one, but a lot of parents are really anxious to have this as an option.

All right, to talk a little bit about our transmission testing. Never miss an opportunity to test. I know people are exhausted with testing, like the pile of tests I just saw before I left my house, and I do encourage people to listen to the most recent TWiV, 863, where there was a big discussion on the safety tolerability and viral kinetic string SARS-CoV-2 viral challenge.

This has come up several times, I’m not going to discuss the ethics of exposing people to a virus which is fairly novel still, which can cause Long COVID, which may have long term side effects, we’re not aware. I’m not going to talk about that but there’s a lot here, there’s a lot of data here and one of my takeaways was this observation that if you look at those lateral flow tests, there’s really a good correlation between the lateral flow test and when people have viable virus. And that’s one of the things I liked about this paper, they’re not just doing PCR, they’re not just looking at lateral flow, they’re viable viral isolation and even just looking at the screenings, if you did lateral flow twice a week, you are going to pick up 70% to 80% of viable virus, people who are contagious.

Again, though, and this is also in that same paper, what we’ve been recommending, if someone’s been sick for a few hours, stay home from school that first day. Still feeling crummy that second day, you’re still home from school or work, that’s the best time to test, you really see that symptoms start, the lateral flow, the other testing really has the best sensitivity a little bit past 24 hours after symptom onset.

This came up a lot in our pediatric discussion. Kid wakes up, he’s not feeling well, they want to come to the pediatrician’s office to get cleared, you really can’t clear them that first day. You really got to say, “Stay home. We want to test you tomorrow.” A little bit of triage there. The nice thing about home tests is it gives us that flexibility for $10, $12 to say, “Let’s get a test tomorrow.” You can always do that test right away but that test tomorrow is going to really be key.

All right. This is going to be the meat of what we’re talking about. We’re talking a lot about masks today, Vincent.

I want to discuss the MMWR report, Effectiveness of Face Masks or Respirator Use in Indoor Public Settings for Prevention of SARS-CoV-2 Infection – California, February – December 2021. There’s an eye-catching graphic, we’re going to talk a little bit about this, where they suggest in this graphic, wearing a mask lowers the odds of testing positive, cloth mask 56%, surgical mask 66%, and a respirator that N95 or KN95 83%. But let’s go through this a little bit. Where did things stand prior to this publication and where are we after this? What is this study really telling us? The use of face masks or respirators, the respirators are those at N95, KN95, has been recommended to reduce transmission of SARS-CoV-2, the virus that causes COVID-19.

Well-fitting face masks and respirators are felt to effectively filter virus-sized particles in laboratory conditions. We’ve mentioned a little bit about those cool laser studies but there aren’t as many studies as a lot of people would like looking at the real-world effectiveness in preventing transmission or acquisition of SARS-CoV-2 infection. In this context, the authors report results of a test-negative design. You’re having people come in, testing positive, testing negative, that’s a case-control study, enrolled randomly-selected California residents who had received a test result for SARS-CoV-2 during this time period, February 18 through December 1, 2021. Face mask or respirator use was assessed among 652 case participants who tested positive and 1,176 match control participants who tested negative, and then what they’re going to do is they’re going to ask them self-reporting.

They’re going to ask self-reporting into our public spaces during the two weeks preceding testing, “What were you doing relative to face masks?” What did they find? The people who reported that they had always used a face mask or respirator in an indoor setting, this was associated with adjusted odds ratio of 0.44. About a 56% reduction in them testing positive. Let me try to break it down. They say, well, “What about those folks who report they’re wearing an N95, or a KN95?” So adjusted odds ratio 0.17, so about an 83% reduction. The surgical mask adjusted odds ratio of 0.34, that’s about 66% reduction. Then they asked folks wearing a cloth mask, adjusted odds ratio 0.44, about a 56% reduction.

I will say, “Why confidence intervals when we get to those cloth masks?” But one of the issues, I got a lot of issues, I’m going to bring it in on this Vincent. This is not a randomized, prospective, controlled trial, you’re really just asking people, “What are you doing?” And a person who’s wearing a KN95 is probably a little bit different than someone who’s not wearing a mask at all, it might be a difference in their interest in vaccination, it might be their interest in going to these higher risk indoor settings.

There’s a big athletic event coming up this Sunday. I think the person who’s wearing a KN95 might not be enjoying that experience in the same fashion as someone who has not been wearing a mask, so it’s really tough. The numbers in my mind don’t quite add up because this is really a study looking at what– I’m going to use the term and introduce this term if you aren’t familiar– but “one-way masking”. We’re not asking you, “Are you in a setting or a school or a business where everyone wears a mask?” We’re just asking about your behavior. If you look at these numbers, the suggestion is if you wear a surgical mask, you have reduced your risk by 56%. If you’ve worn a cloth mask, which we were told don’t work at all, which we’re going to get into, you’ve reduced your risk by 56%. I don’t think that really fits with all the data we have to date. What we’ve gotten is maybe there’s about a 20% reduction, if you’re doing it.

The main benefit is to others when you are wearing it to contain those respiratory secretions. There is a little bit of an interesting issue here at the cloth versus surgical, the disposable mask versus something that you can wash and reuse. I am a little bit concerned about this idea of all this trash. I’m also a little bit upset because I like the fashion. There were people who enjoyed wearing masks because they could match with their dress or in my case, their bow tie and socks. I’m sure Greta’s not happy of us filling the oceans and landfills with all these disposable masks, but this concept that you don’t have to care what other people are doing, because you can just wear a mask and you’re going to get this tremendous amount of protection. The message, “don’t you worry about mask mandates going away because you can get vaccinated, you can mask. It doesn’t matter whether the people are doing it.”

VR: The difference between the surgical and cloth really is nothing because there’s a huge confidence interval, 56, 66, but they overlap.

DG: Huge overlap there.

VR: I think they’re the same. Given the limitations of this study, which you’ve pointed out, I’m sure the respirators are better and that’s supported by these, but it’s not surprising. The problem here also, there’s no people with no masks.

DG: This is the relative risk compared to the people–

VR: Compared to no mask. What else were these people doing? What environments were they in? Were they people sitting at home alone or people in classrooms? How about vaccination status? That must play into it to some extent.

DG: These are all the confounders that they didn’t address.

VR: The right way to do this is the way the Bangladesh study was done, which was a control trial where some people wore masks and some people did not. Even with the limitations, those data are far more reliable.

DG: It’s actually a researcher that I was flying back from. I was flying back from Africa pre-pandemic and they do a lot of these studies where they roll out interventions into one community and then the next community, and then you can see over time this community where it didn’t get rolled out. Here you did it, you compare like Bangladesh, introduce an intervention versus don’t introduce an intervention, compare. I’m not as reassured as the study would like me to be. I’m sure a lot of people will put up that MMWR graphic where your mask is this much. I’m not sure this really jives with all the data we have to date.

VR: This is a very easy study to do if you just ask people, whereas the Bangladesh is hard. It’s to do that.

DG: It’s hard, it’s expensive.

Active vaccination, I’d like to say we need to stop scaring the wrong people. We have a couple updates here. One is an update on waiting to vaccinate after getting monoclonals. For a while we’ve been saying, if you get those monoclonals, you got to wait 90 days. Never made a lot of sense to me mechanistically. This is not a vaccine that is dependent upon a replication-competent vector. The CDC has basically gone away with that. The CDC has removed any waiting period after getting monoclonals to get vaccinated. There’s really no waiting period. If you get infected, if you test positive for SARS‑CoV‑2, if you’ve got COVID-19, as soon as you’re no longer isolating for being infectious, so you’re past those 10 days, you’re feeling matter, you get monoclonal, doesn’t matter, you go right ahead, you get vaccinated.

As we’ve seen repeatedly, even if you’ve been infected, getting vaccinated still offers you decreased risk of infection, decreased risk of hospitalization, decreased risk of death. I know a lot of people, oh my gosh, “I recently had this– like if I get vaccine horrible reaction.” It’s not true. Millions and millions of people are tolerating those vaccines after infection, so continue to make that recommendation. What about, “should we wait for those Omicron-specific boosters?” There was a nice preprint, mRNA-1273 or mRNA-Omicron boost in vaccinated macaques [those are our non-human primates] elicits comparable B cell expansion, neutralizing antibodies and protection against Omicron, posted as a preprint.

John Mascola is in there among 60 authors. If people enjoy John being on that time, so it’s a pretty impressive author list here. Basically, these over 60 authors put this pre-print out there. They looked in non-human primates who received either the Moderna booster, so the mRNA-1273, or they were given an Omicron-specific booster. If you go through all the data, there’s a lot. Really, it was not clear that the Omicron boost provided any greater immunity than just getting boosted with that third Moderna shot.

VR: They’re challenging them with Omicron.

DG: Basically it’s time for your boost, the macaques, it’s time for the macaques.

VR: The macaques were previously immunized.

DG: Previously immunized, two doses of the standard mRNA, 100 micrograms, three weeks later, 100 micrograms. Here we are six months out, and so there was a choice. We’re either going to give you a standard 50 microgram Moderna boost or a standard 50 microgram Omicron boost. Looking all across, it looked like equivalent.

VR: They’re looking at disease or infection or both?

DG: You’re looking at immune marker.

VR: They don’t get serious disease, the macaques, right?

DG: You’re really looking at immune markers. You’re looking at CD4, you’re looking at CD8, you’re looking at neutralizing antibodies, a lot of data actually. It’s hard to do, that what we really want to do is, what about disease? There are all those correlates.

Now a lot of people are excited, still in the realm of vaccines. When can I get my nasal spray? There’s a lot of people out there who don’t like shots. The paper published in Cell, Respiratory mucosal delivery of next-generation COVID-19 vaccine provides robust protection against both ancestral and variant strains of SARS-CoV-2. This is a Cell paper, so as you can imagine, it’s incredibly dense. Some people don’t like needles, some people are excited about this.

Excited maybe about the immunology as well as anything else, this focus on understanding mucosal immunology, but what did the authors do here? The authors tested adenoviral vector vaccines, so human and chimpanzee origin. These were AD-vectored trivalent COVID-19 vaccines. They’re expressing spike, nucleocapsid, and the RNA-dependent, RNA polymerase. They’re testing these in mice, to point that out. We’re not even in human testing yet. They reported that single-dose intranasal immunization was very effective at generating, they say, tripartite protective immunity consisting of what are those tripartite local and systemic antibody responses. We got our antibody response, mucosal tissue resin memory T cells and this lasts, pretty interesting, mucosal trade, innate immunity. We don’t really think of innate immunity as adapting and responding, but they were basically encouraging data. This is encouraging, it’s still in mice. This data suggested that they were providing protection against ancestral as well as some of the variants. Encouraging, but still in early states.

VR: This was given as a boost, or as the sole vaccine?

DG: Sole vaccine in these.

VR: This would have to go through trials obviously. Are we able to do a clinical trial on a new vaccine at this point? It’s going to be a while before they’re able to do it in people.

DG: It’s interesting, would this be something you’d look at as a boost? From a research point of view, there’s still a whole cadre of people out there who’ve never gotten SARS‑CoV‑2, who are not vaccinated.

VR: Maybe for them, a nasal spray would be appealing.

DG: This may be a population saying I am not interested in that injectable vaccine, but I would be willing to participate, generate this knowledge because some people maybe would be more comfortable with this approach.

VR: I would look forward to the results. I would just say that the FLUMIST never does so well. That’s influenza, so it’s a different virus.

DG: Passive vaccination. We’re still starting to get EVUSHELD out there. It should be you have your shield, but now more places are making that accessible. This is getting passive antibodies for those people who for some reason are unable to generate their own. It’s not an alternative to vaccination. It’s really a supplement for certain people.

The period of detectable viral replication. This is the time for monitoring monoclonals, antivirals, enrollment in clinical trials. Listening to one of the TWiVs a couple back, I won’t mention which participant prompted me to do some reminders here. Just a reminder, timing is so critical here. If a person is at high risk, you can’t wait to see if they start to decompensate. Once they get to day six or seven, once they start to enter that second week, once they start to get hypoxic, require oxygen, you’ve missed your therapeutic window for a lot of these efficiencies. I know actually, when there was discussion about the trial, well if someone starts to do poorly, we could just jump in. It’s too late once they start to do poorly. That’s one of the issues with that.

VR: The challenge trial, you mean?

DG: With the challenge trial. Once they’re doing poorly and become hypoxic–

VR: It’s too late.

DG: We don’t have a lot of great therapeutics. Our great therapeutics are really in that first five days. So, PAXLOVID is– These are in the hierarchy from the NIH, as far as recommendations. PAXLOVID is suggested to be the first one to consider. It’s about 88, 89% reduction. If given in that first three-to-five days twice a day, you need to do their kidney function. You need to know what other medicines they’re on.

If you can’t do that, the recommendation is then to look to get this person sotrovimab. That’s the monoclonal therapy that still works. If for some reason you can’t get access or there’s a delay, remdesivir. IV outpatient remdesivir based on that New England Journal of Medicine article. If you get this within the first five days, this is a 200 milligram right upfront IV, and then 100 the next day, 100 on day three.

Actually, there are a number of places where this has been set up. I actually have to say on Long Island, the Catholic hospitals have set this up. When someone shows up in the ER, maybe there’s a reason why they can’t get the sotrovimab. They’ll go ahead, get the first dose of remdesivir right then, and then set them up for the two days following. Then molnupiravir is that fourth line. If you have no other great choices, it’s only about a 30% reduction in progression, but no issues with kidney function, no issues with drug interactions. But the big take-home here is you can’t wait, you’ve got a look at the high risk, and you’ve got go ahead and treat them during your window.

VR: In the challenge trial, none of those people were at high risk, and so–

DG: They wouldn’t really qualify for this anyway, but then if they get in trouble–

VR: It’s too late.

DG: It’s too late.

VR: Because they said they had remdesivir and monoclonals, but you would say it’s too late if they’re really–

DG: Once they start to decompensate and become hypoxic, yes.

VR: Do you think they told them that before they enrolled? Who knows?

DG: Yes.

VR: One would hope so.

DG: I hope so. It is tough. I will say there’s a minimal benefit to someone getting monoclonals in the last seven to 10 days if they have not mounted their own antibody response.

All right. Let’s go to the tail phase. Long COVID. This is a tricky paper and I want to make sure I go through this in the proper way. There was a paper, Long term cardiovascular outcomes of COVID-19 published in nature medicine. There really is a lot in this paper. Let’s talk about what they actually did.

In this study, the authors looked at U.S. Department of Veterans Affairs national healthcare databases to build a cohort of 153,760 U.S. veterans who survived the first 30 days of COVID-19, and then they’re going to compare these two control groups.

So, a contemporary cohort consisting of over five million users with no evidence of SARS-CoV-2 infection and then a historical cohort predating the pandemic with another, almost six million non-COVID-19 infected veteran health affair users back from 2017. These cohorts were followed longitudinally to estimate the risks and the 12-month burdens of cardiovascular outcomes in these overall cohorts. They looked at acute infection status. Were they hospitalized, not hospitalized? Were they admitted to the ICU? There’s really a lot in here and this is open access. Our listeners can go to this– figure three is where I’m really going to tell people if you want to just look at the figures to get a sense of what was going on. Here they were looking at any cardiovascular outcome as well as breaking down specific ones and just to really cut to the chase.

These are individuals who got infected got COVID-19. They were reporting about one in every 200 individuals had some cardiovascular outcome. It could have been a rhythm disturbance. It could have been an inflammatory or an ischemic issue. It could have been clotting. Just putting that in context, when people are concerned about myocarditis and other risks with the vaccine, we’re talking maybe about one in 5,000 in the highest risk age group. But then again, this is something that usually resolves within about 24 hours here.

You’re looking at people to 12 months later, one in 200 having some cardiovascular issue. Now as my wife pointed out to me, the data she wants is, she wants to look at people that get COVID post-vaccine to see if the vaccine really reduces these cardiovascular risks because that’s what we’re hoping for. We’re encouraging people to get vaccinated. They avoid death, hospitalization, but we’re also hoping it avoids all these negative cardiovascular outcomes as well.

VR: The incidents are largely in men of a certain age, correct?

DG: There’s this teenage male, one in maybe 5,000 incidents 90%+ of the time. It’s one day of inflammation of the heart.

VR: In COVID-associated cardiovascular, do you see the same young man bias as well?

DG: Not necessarily, no. Which is interesting, right? You would’ve thought there would be that sort of matchup. I’m not sure I understand the full mechanism. It may be, and this is true that older men are getting the most significant disease, the more severe your disease, the more likely the negative outcomes. These young men usually have pretty mild syndromes. As we talked about previously, those athlete studies, COVID really likes to– I’m going to anthropomorphize this horrible virus. It is often associated with cardiac issues in young athletes, so much safer to get the vaccine. My wife points out, we would like to really see this data showing that here’s vaccinated, here’s unvaccinated cardiovascular outcomes.

All right. Now, no one is safe until everyone is safe. I’m going to finish here with an article from PLOS Neglected Tropical Diseases, Perceived COVID-19 vaccine effectiveness, acceptance, and drivers of vaccination decision-making among the general adult population: A global survey of 20 countries. I mentioned when we recorded the last two sessions that physicians in Ghana were reporting that there were some issues with social media misinformation about vaccines. They’re starting to see hesitancy. Even some of the medical students were starting to have questions because of stuff they had seen on social media. I talked a little bit about how it might be nice not to give so much air to those individuals with their misinformation agendas. But the purpose of the study was to determine the characteristics that might influence perceptions of COVID-19 vaccine efficacy, acceptance, hesitancy, and decision making to take the vaccine among general adult populations in a variety of socioeconomic and cultural contexts.

The authors looked at these issues in 20 countries: Australia, Austria, Bangladesh, Denmark, Egypt, Germany, India, Indonesia, Iraq, Ireland, Malaysia, Myanmar, New Zealand, Nigeria, the Philippines, Scotland– Is that really a country? –Sri Lanka, Thailand, Turkey, and Vietnam. They reported that marital status, age, rural versus urban, socioeconomic status, education, and being in certain countries were associated with different degrees of vaccine uptake and hesitancy. They did report that most participants felt that a healthcare provider’s advice was critical in decision-making. Convenience was important. The cost was also important as well.

I thought it was interesting and sort of surprising, people who have been married are more likely to get vaccinated than people who’ve never been married. I thought that was just interesting and some of the interesting stuff about age, rural versus urban. Rural, less interested, urban, more interested. I think that one of the things that was a takeaway from this is they did find that most adults throughout the world believe that vaccination would effectively control and prevent COVID-19. Most people said they would accept vaccination if they had access, if it was available.

I think, again, this is this call to arms. Based on some of the discussions I had with physicians in West Africa, it’s a little bit more than just shipping vaccines to places. You need to think about cold storage. You need to think about delivering those vaccines. You need to think about the staff. You need to think about supplies, and education is critical. So, really a lot here that we need to do. Again, we’re talking about giving people fourth doses when people haven’t even had their first or second.

VR: In the United States, is there any issue in distributing vaccines anywhere?

DG: A little bit actually, right? I think this has come up on a few TWiVs. If you’re in a very small rural community, they want a certain amount of vaccines before they’re gonna deliver them out there. They’re not going to just send a vile of 10 for one person. You might have to get in that car. You might have to get on a bus. They have to organize as a community and make it happen. Even here in this country, there is some challenges.

All right. Well, before we get to emails I want to say the MicrobeTV fundraiser went incredibly well. Thank you so much. Everyone who sent in $1,000 or more who want one of these virology textbooks, shoot us an email. Let us know, we’ll check, verify that, and then we need your address. If it’s going to be international, we need your telephone number as well. Let us know so we can get those books sent out to you.

VR: Some of you have emailed and said, “Where is my book?” We’re getting to it, but if you haven’t, daniel@microbe.tv, and give us the information that Daniel just asked for. In the next few weeks, we’ll get your books out for you.

DG: All right. Let me say, we’re now entering a new fundraising phase. During the months of February, March, and April, donations made to Parasites Without Borders will be matched and doubled up to a total contribution of $40,000 to American Society of Tropical Medicine and Hygiene, minimum donation of $20,000. Where does this money go? This is going to go to support annual meeting travel awards. These are individuals, particularly I’m going to say people from low income, low to middle-income parts of the world so that they can come. We’re going to preferentially support women. We’re going to be a little sexist here. Really want to try to do what we can to help with inequity throughout the world. Help us support American Society of Tropical Medicine and Hygiene.

VR: It’s time for some email questions for Daniel. You can send yours to daniel@microbe.tv. Sandy writes, “I can’t understand why the hospital rates and deaths are so high if we now have PAXLOVID to help fight COVID. Do you prescribe this to your patients? How many does it help? Are people refusing? It seems like if we now have this available to everyone unvaccinated or vaccinated, it would help.”

DG: Now, so this is an excellent question. My wife who was– interesting, she now goes on Twitter. Twitter was new to me before the pandemic. I was introduced to it, right as the pandemic began and a physician was talking about this. They were suggesting it was actually difficult for them to get PAXLOVID and I’ll say we’ve been prescribing PAXLOVID, but it is still in short supply. There’s only so many thousand doses per week available in an entire state. This is ramping up. We’re not going to have PAXLOVID-a-plenty, probably until March into April. This as of right now, it’s not that easy to get to. There’s only a few pharmacies or hospitals or other locations in each region where you can pick up the phone and call and get it set up.

Again, it’s not an easy lift. They come into your center, they see a provider. That provider has to know that this is the way to go. We have to stop giving everyone Z-Pak and steroids shutting down their immune system when this is the time to let that vaccine protect you. Because that’s number one. The clinicians need to know this is available. They’ve got to get on the phone. They’ve got to talk to that pharmacist. They’ve got to run through what’s the kidney function, what are the drug interactions? This is not a-plenty. We’re seeing thousands of people. The other is the timing, you really got to be on this. This is the public as well as providers. This is a medicine that has its efficacy. If given in those first five days, if you wait until someone’s having problems and start to get hypoxic, you’re really missing your window of efficacy.

VR: Joy writes, “I’ve crossed the 24-month mark and belong to many large, long-haul COVID groups. I’ve noticed the majority of people who continue to be severely impacted by LHC are mostly on the same initial infection, Alpha timeline. I’ve seen very few who had Delta or Omicron as their initial infection. I’m not including those who were reinfected later in 2021. I would love to know if you’ve seen any differences between the variants and their long-term impact.”

DG: I would love to see a study on this Vincent because I still have a cohort of patients who got infected early on, so March, April and still continuing to suffer. I certainly have seen people who, with some of the newer variants, have actually developed Long COVID after them as well, but I don’t have any really good hard numbers. This may actually– it goes with this perception. I don’t know if those people are less hesitant to come to me because they’re not vaccinated and they’re a little bit– but there certainly are unvaccinated people who got some of these newer variants who are suffering from Long COVID, particularly prominent individual who treated themselves with PEPCID now has Long COVID. I don’t know the exact numbers relative to Long COVID, but I think this is actually important stuff to have. I would love to know, even better, different variants, unvaccinated, different variants, first, second vaccination status and the rest.

VR: We do know that vaccination and being infected, the Long COVID rate is much less than unvaccinated. Correct?

DG: Not only is your risk of low, Long COVID reduced, not gone. It was significantly reduced, but even the severity and the duration seems to be impacted positively by vaccination. Even if we’re seeing Long COVID afterwards, the cases tend to be not as severe, and we’re also seeing quicker resolution.

VR: Is any Long COVID associated with just vaccination?

DG: There is, and I don’t know if I would call it Long COVID, but there are people who have gotten vaccinated. When you vaccinate hundreds of millions of people, there are certain people who, after that vaccination, are having problems – sort of almost like a chronic fatigue, inflammatory issues, almost a syndrome in and onto itself. But yes, in some ways resembling. Incredibly uncommon, but we definitely see it when you’re a specialist like myself.

VR: Molly writes, “I’m curious what the positive controls are for COVID PCR and antigen tests. What antigens or nuclear nucleic acid targets are suitable for constitutive detection? I’ve been unable to find a clear answer,” and Molly is a PhD candidate at Harvard. Maybe that’s where this is coming from.

DG: Yes. These are good questions, and I think we’ve brought up the issue before that if you don’t do these tests properly, you could end up with false positives. That’s really where this is. What’s the negative control here? That individual who maybe they’re drinking orange juice or soda, and then sticking that Q-tip in the back of their throat instead, and it’s turning positive the tests, both of those ones, particularly over the counter, they don’t have a really good negative control to make sure you’re not doing something that just messes with it. If anything, there’s a control so that you see that the test worked, but there isn’t much of a negative control.

VR: All right. For both PCR and antigen, the antigens that you do in an at home, there’s a built-in.

DG: There’s a built-in positive control. Control line comes up, but there isn’t a negative that says, “Hey, you messed up and did something you shouldn’t, a nonspecific.” PCR, usually they have multiple targets. That’s part of the quality control, but not like a real negative.

VR: If I remember the lateral flow, the positive is just an antibody control. It’s not actually antigen in there just to show that the assay is working.

Our last one is from John, who is an MD and it is just praise, and I thought you would like some, so you don’t have to answer a question.

DG: Praise is good.

VR: “Having just listened to clinical update number 100, I want to thank you for your devotion to providing such great, well-prepared clinical information. Your ability to cover such an incredible amount of literature and combine it with your clinical perspective is amazing. When SARS-CoV-2 pandemic struck, I felt discomfort at being a retired ophthalmologist, sitting on the sidelines during what promised to be a hundred-year storm in medicine.

I was able to relieve some of that unease by joining the Virginia Medical Reserve Corp, working on projects at our district health department office, and becoming a vaccinator. Having your updates as well as many of the other MicrobeTV podcasts was a great source of information, as well as being a good antidote to the misinformation from online and media sources. I’ve recommended your updates to many other physicians and friends, one of whom is a retired NASA engineer who follows you religiously. Thank you. Thank you. Thank you. John.”

DG: Thank you, John. Actually, John, thank you for getting out there, coming out of retirement helping with the vaccine efforts. Thanks for the praise, but there’s a lot of praise. A lot of people’s true colors have come out over the last two years. A lot of people, not so great, but a lot of people have really stepped up and made just a tremendous difference, a lot of sacrifices. Thank you for, and all the people that support us, allowing us to do this. We couldn’t do this without the support of our listeners.

VR: This lovely wall of viruses from your contributions.

DG: I couldn’t do this without Vince’s support, so thank you, Vincent.

VR: Sure. Thank you. That’s COVID-19 clinical update number 101 with Dr. Daniel Griffin. Thank you, Daniel.

DG: Oh, thank you, Vincent, and thank you everyone, and be safe.

[00:49:25] [END OF AUDIO]