TWiV 800 COVID-19 Clinical Update #78

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 4 September 2021

pdf of this transcript available (link)

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

[music]

VR: From MicrobeTV, this is TWiV, This Week in Virology, Episode number 800, recorded on September 2nd, 2021. I’m Vincent Racaniello and you’re listening to the podcast all about viruses. Joining me today from New York, Daniel Griffin.

DG: Hello, everyone.

VR: Well, there’s no airplane that’s 800, but that’s a pretty good number for this episode. Daniel, congratulations.

DG: Yes, I like 800. I’m happy with this. I only wish the clinical update had been 80, we should have timed it. It’s clinical update 78, but it’s episode 800.

VR: I don’t know. I think we’re going to be doing this for some time. Don’t you, Daniel?

DG: Yes. I’m going to do the Anthony Fauci thing where I just put my hand on my face and say, “Oh my gosh, it’s two years into this.” You started, I think, what? In the 500s, right? 500s. I would not be surprised if we’re not hitting a thousand and the pandemic is still something we’re talking about and still trying to get through.

VR: I remember your– I’m sorry. Just one more thing, I remember your first clinical reports were from your car in the hospital parking lot, remember?

DG: I remember that. I was trying to do it in the stairwell, but I was worried that there was a crack under the door and the whole ICU had been turned into a theoretical negative pressure. It’s quite a ways, but all right– Let’s jump in. We have a lot to do today. Vincent, you jump in at any point because I’m going to touch on a few controversial things.

VR: All right.

DG: I’m expecting a lot of hate mail, like, to get that.

VR: [laughs] Oh, you must be saying ivermectin, right?

DG: Yes, we’re going to talk about ivermectin. [laughs] Let me return to Winston Churchill. I feel like I’m back in the Winston Churchill mood. “A fanatic is one who can’t change his mind and won’t change the subject.” We’ll figure out who the fanatic is, if it’s me or if it’s people that I try to talk to. I like to keep saying, “A single point does not make a line.” We do keep learning, we do keep moving forward. I think people can take a deep breath. You’re not going to wake up tomorrow and find out that everything we’ve thought to date is completely wrong. I’m going to talk about a number of items right upfront, ivermectin and convalescent plasma.

Ivermectin has been in the news a lot lately and I’ve actually been getting a lot of calls, a lot of questions about it. I think early on, I said that this was going to happen. What did I say was going to happen? We are two years into this pandemic and we still do not have really clear data on the role of ivermectin in COVID-19. We certainly do not know what a correct dose or timing might be if someone wants to use this. I’m going to say this, the way the media portrays us, I’m going to challenge. There are certain individuals that I know who are looking at studies out there and they are, themselves, convinced by the data. I am not convinced by the data for ivermectin nor is the FDA, but what I think we’re all on the same page with is that you should not be using your horses’, your dogs’ animal preparations of ivermectin.

I don’t think there’s any physician that I know or respect who would be advocating that, and even the Front Line COVID-19 Critical Care Alliance, which has been, I’ll say, supportive of ivermectin, they actually came out with a statement on August 27th very clearly stating, this is from them, “We support the FDA’s direction that humans should never take medication formulations meant for animals. We also agree that self-dosing of medications without the guidance of a physician is potentially dangerous and could cause serious harm. Please stop stealing your dogs’, your horses’, or your other animals’ deworming medication.”

It did occur to me, “Do we deworm cats?” Apparently, indoor cats don’t need to be dewormed, but you should deworm your dogs. We currently do not have the data to know if there is a role for ivermectin in the treatment of COVID-19, and this has created a vacuum.

I think that’s what I talked really about two years ago is– ivermectin is one of the most prescribed and used medications for people with COVID. Until we really get clear data, that’s going to continue. Physicians have the ability to use medications off-label. People, as we’re seeing, have the ability to get stuff that they feel that social media is supporting. There are a number of large trials trying to address this question. In the U.S., I’ve talked about this, we have the ACTIV-6 Trial. There’s the COVID-OUT Trial being run by a friend of mine at University of Minnesota.

The UK, they have the PRINCIPLE Trial. There’s a lot of trials. This is the way we move forward in medicine. Science, it’s nothing mysterious, it’s really you, in a nonbiased way, ask a question. Do people do better with or without a certain therapeutic? People are excited about ivermectin, and I actually did, I emailed Paul Marik and Pierre Kory, who I know well, and I said, “Hey, maybe on the front of your website you can actually add ways for patients to connect with clinical trials.” That’s really where I’m going to go with that. Do you have a comment there, Vincent?

VR: What do you tell people, Daniel, who write all the time “Well, I took ivermectin and I got better.”?

DG: This goes back to the three most dangerous words “in my experience.” You can’t string anecdotes. The plural of anecdotes is not data. Most people with COVID get better. Most people that didn’t take ivermectin get better. Most people that took ivermectin get better. The question is if you took ivermectin, did that increase your chance of getting better? There actually is a problem now and I’m going to actually, I think I’m going to bring up the CDC page. There’s a bunch of individuals who have had some really horrible experiences with ivermectin.

There’s actually a CDC brief that they sent out, an alert, would actually describe cases. There was an adult who drank an injectable ivermectin formulation intended for use in cattle. They presented to the hospitals confusion, drowsiness, hallucinations, tachypnea, tremors, they ended up being hospitalized. There was another individual who ended up with altered mental status after taking ivermectin tablets of unknown strength purchased on the internet. I think that we have to really be clear here. This is not something–

If something works, it might have side effects and so it’s really a balance. Drink your tap water and okay, there’s no side effects there, but there’s also no efficacy. I often get patients who ask me, “Dr. Griffin, would you recommend ivermectin?” Well, no, prior to the pandemic, I was one of the few physicians in the country with my focus in parasitology using ivermectin for strongyloidiasis, for scabies. We even had a case of a gentleman at Yale who got way too much steroids and ended up with the strongyloidiasis hyperinfection.

Ivermectin has a certain role in certain patients. We have yet to have the level of data that I would consider compelling that the FDA would consider compelling that whatever side effects are outweighed by any benefit.

Convalescent plasma, throwing this right here at the same time. We still have people that are very excited about convalescent plasma, and I just really want to say here, the data is in. I don’t want to prove me wrong. I’ve said with ivermectin, we didn’t do the trials. We’re still waiting for a clear guidance. Convalescent plasma, we spent billions of dollars. The data is in, and the ID Society of America, the IDSA really has made it clear in their recommendations based upon this science. Recommendation number eight from the IDSA for COVID treatment among patients hospitalized with COVID-19, the IDSA guideline panel suggests against COVID-19 convalescent plasma.

In the outpatient setting, okay, they still say it’s reasonable to consider clinical trials, but not using it outside. It doesn’t matter to me if you get your local bee-produced artisanal plasma, the data does not support. I understand the passion, people are excited. The data’s in, this does not really have a role in the treatment of COVID-19. All right. Make sure I get those. Where do they mail those, [email protected]?

VR: That’s right.

[laughter]

DG: All right. Children, COVID, mental health. Now, children are at risk if they get COVID. I think that is now really clear. I keep saying, “Wearing a mask is less traumatic for a child than being hospitalized.” I’m going to throw in here not only children, but pregnant women, women who are about to have children– I’ve been asked actually to give an update on pregnancy and COVID-19.

We certainly have much more data now than I was first asked this question live on CNN back in March 2020. When they prepped me I would be talking about the president and testing and then boom, “Dr. Griffin, tell us about pregnant women and COVID.” That seems a little bit different than what we were going to discuss, but anyway, the article “Characteristics”– Oh, I was wearing the same bowtie. Just to bring everyone back to that day, I’ll mess with it. The article “Characteristics and Outcomes of Women With COVID-19 Giving Birth at U.S. Academic Centers During the COVID-19 Pandemic,” was published as a peer-reviewed article in JAMA Network Open. I think it really gives us a solid overview of how devastating COVID-19 can be for pregnant women. For some time, we’ve been encouraging vaccination before, during, after pregnancy.

Here’s a little bit of data. Not only do we know it’s safe, but what is driving this? What can happen if a pregnant person gets infected with COVID? This was a retrospective cohort study. They looked at 869,079 adult women. Within this cohort, 18,715 of the women had COVID-19. What did they find? The pregnant women with COVID-19 were more likely, if they got infected with COVID-19, to have a preterm birth. So the negative impact on the baby; significantly higher rates of ICU admission, significant odds of ending up getting intubated, mechanical ventilation, that was up by about 14-fold, and they were 15 times as likely to die if they ended up in the hospital.

These are vaccine-preventable tragedies for the mothers and the babies. As per the CDC numbers, we are seeing over 1,000 new infections per week in pregnant people. These are vaccine-preventable tragedies. Pregnant women, they should get vaccinated. Don’t wait for any particular trimester. The earlier in the pregnancy, the better chance that they’re going to have the ability to not only protect themselves, the unborn child, but also when that child is born, the ability to pass those antibodies.

We suggest people bookmark on their computer. I have a few things that I bookmark where I keep track of what’s going on. One of the things that I bookmark is the AAP Children and COVID-19: State-Level Data. This is where they keep track of what’s happening in children. We are now seeing thousands of children each week– Thousands of children each week are being hospitalized for COVID-19. If you look at that greater than 100,000 people in the U.S. that are currently in the hospital, depending on which state you look at, that’s 2% to 4% of those hospitalized individuals are children. If not for yourself, get vaccinated and engage in behaviors to protect our children. Remember, wearing a mask is less traumatic for a child than being hospitalized.

I’m going to throw this in in this section, and it was where they were looking about long COVID in children. I was a little shocked, I guess. Confused by the BBC News interpretation of this. Let me go through the preprint that the BBC News was talking about. This was the preprint “Long COVID, the physical and mental health of children and non-hospitalized young people 3 months after SARS-CoV-2 infection.” A national-matched cohort study, the CLoCk Study. This is a preprint under review. This was a cohort study of test-positive compared to age, sex, and geographically-matched test-negative children.

What they did here is these children completed detailed questionnaires three months post this positive test or post not having a positive test. This is a challenging paper, I’ll be honest. You can imagine if you have an adolescent child and you start asking them how they feel. There’s a lot of background here. It’s really a challenge sorting out what might be going on relative to background.

There’s also the challenge here that there’s no universally agreed upon definition of long COVID. I like to say long COVID is really a subset of post-acute sequela of COVID. It’s a chronic syndrome where PASC includes things like new diagnosis of diabetes, new diagnosis of stroke, other things in there. It really was one of the tables that I wanted to go through.

If you go through this study, and I’m going to encourage people to go ahead and spend some time. Hopefully, we’ll post this, but they have a really nice table, Table 3. Here you can look at the different issues. I did not find this reassuring. They asked a number of questions. One of the big things we see in long COVID in all ages is this just incredible amount of fatigue. In the negative, that was 3.3%. Three months out, it was still 22.7% of the children reporting that. Shortness of breath, 1.5% up to 11.6%. 20% of them still couldn’t smell. That was rare. There’s only about 1.5% in the negative group.

Headaches, 4.8% background. This was 26.3% at three months after acute COVID in these children. Unusually strong muscle pains, a lot of people have these muscle pains, that was about 1% background. It was 11% in these children at three months. I was not reassured when the BBC said, “Oh, it’s much lower than that 80% we were fearing.” I was quite concerned when I’m seeing such high prevalence three months out of symptoms in these children. Just to repeat, COVID is a problem in children. They may not die of COVID, they may be at lower risk of ending up in the hospital than adults, maybe in the 1% or 2% of them, but boy, this is a large chunk of kids three months out still suffering.

Transmission, testing, never miss an opportunity to test. Here, there’s a bunch of things I feel like I’m saying over and over again. There was a preprint here. Actually, it wasn’t a preprint. It was published in the MMWR. As much as people criticize the CDC, you’ll find out I discuss a lot of MMWR papers. Kudos to the people at the CDC who keep getting this information out there.

This, I thought, was very interesting. It’s one of several publications along this line that I saw this last week and this was “Outbreak Associated with SARS-CoV-2 B.1.617.2, the Delta Variant, in Elementary School, Marin County, California.” One of the things I really liked about this was they showed a seeding map. This is where we have an unvaccinated symptomatic infected teacher who does what I see all the time. When someone wants to talk, when they want to generate all those droplets and aerosols, they pull off the mask, she wants to read to the children. She was unmasked, reading aloud to the class, the majority of the kids got infected. Everyone in the front row, most of the kids in the second row. You really wanted to be in the back. Really tough when we talk about masking and vaccination in these settings.

All right. Well, what about testing? I feel like I go through this talk every time and I do it every week. Every week on Wednesdays, I do a COVID clinical update for all our urgent care centers in the Tri-State Area. About 250, 300 providers tune in to these. It’s still shocking to me that this far into the pandemic, there’s still so much misinformation about testing. Now, I will say that New York, Riverside, CareMount, ProHealth Connecticut, all these parts of Optum Tri-State have really invested heavily in creating access to COVID-19 tests. Each week, a chunk of my week is spent addressing questions.

One of the biggest challenges is understanding what’s the best test and whether or not there’s certain situations when you may do more than one test. The research letter “Validation of an At-Home Direct Antigen Rapid Test for COVID-19” was published in JAMA Network Open. I know it’s been quite a while since we first looked at this idea of people having the ability to test themselves at home with rapid tests.

This study, I think, really builds on things that we keep talking about. This idea that we talked about last week that the peak of contagiousness, and perhaps the majority of all transmission from infected individual, occurs in the two days prior and the three days following the onset of symptoms. During that period of time when there’s a very high level of viral RNA load, when there’s a very high level of antigen.

Here, the investigators followed 257 individuals self-collecting nasal swab specimens twice weekly at home during a six-month period. The investigators were studying a real-world implementation of this high-frequency testing using an inexpensive at-home self-administered direct antigen rapid test, so the DART. D-A-R-T, direct antigen rapid test. They were then using RT-PCR as a comparison.

Now, remember, these are individuals. These are not medical experts. These are just people taking swabs and sticking them up their noses. The individuals self-collected these during the six-month period, the DART sensitivity for that zero to three days was 96.3%. I know a lot of people keep talking about antigens being low sensitivity tests. If you are looking for someone who is infectious, who is capable of transmission, 96.3% is not low sensitivity in my book. Even if you really stretch this out to zero to 12 days after symptom onset, when we’re really starting to get past the point, they still were 78.9% sensitive. Want to even challenge this concept that antigen tests have an issue with sensitivity? They actually have great sensitivity if the question is, “Is this person acutely infected and potentially contagious?” This does feed into that experience that don’t think the portal of anecdotes is data because you will, when a person comes in. If you do this test, you’re going to pick up, most people are contagious right away within 15 minutes, you’re going to be able to pull them out of circulation before transmission.

There will be a certain number of people who you’re catching either prior to becoming contagious or you’re catching after that. I will certainly say when we’re in the hospital, we’re looking for a higher sensitivity test because we’re really asking the question “Did you get infected a week or two ago?” Because we’re usually seeing them when they’re showing up during that early inflammatory phase. One of the things that I say is, “Don’t miss an opportunity to test.” But I guess I’m going to say, “Don’t miss an opportunity to rapidly get an answer and intervene.” If you want to throw a PCR in as a second test, that’s going to make sense in certain situations. Also, a test does not predict the future, so you get exposed on Saturday, you have a negative test on Sunday, I would expect that. You’re not going to really start turning positive until about four days later.

Another preprint just posted today, hot off the preprint press, and this really helps continue along these lines of connecting dots about what happens when a vaccinated person gets infected with SARS-CoV-2. This was “Longitudinal analysis of SARS-CoV-2 vaccine breakthrough infections reveal limited infectious virus shedding and restricted tissue distribution.”

Now, the authors reported on viral dynamics and infectious virus shedding through daily longitudinal sampling in a small cohort of adults infected with SARS-CoV-2 at various stages of vaccination. Not vaccinated one dose. Two doses. This paper’s still binary in terms of being able to culture virus or not, so it doesn’t have that quantification that we would like, but they did report that vaccinated individuals were less likely to test viral culture-positive and that the decay of the viral RNA load was more rapid in vaccinated individuals. They also have nice data again on antigen tests correlating with the ability to culture virus really continuing to support that narrative, that antigen tests are a great way to jump in and pick up those people during that infectious period when they’re capable of transmitting virus. That was in Figure 1(g) of this, which I think is worth reading.

All right. Active vaccination, never miss an opportunity to vaccinate. Yes, vaccination is how this pandemic ends. This is actually, I would say this is a pearl. I get this question every so often and perhaps our listeners do not realize we have a lot of clinicians that listen. Also, maybe we have some people still waiting to get vaccinated or people getting ready to get that third dose. COVID vaccinations don’t necessarily have to go in the deltoid. You can actually, as for the CDC, the anterolateral thigh can be used. They actually have a nice table, a 1.5-inch needle may be used if administering the vaccine in this site, in the anterolateral thigh. Encourage people not to stick needles in the behind. You’ve got nerves, blood vessels. The lateral thigh, that’s the modern place if you don’t want to go into the deltoid. All right.

VR: Why did my pediatrician always give it in my butt?

DG: That was old school, I have to say. Actually, it’s funny, I was in the Dominican Republic when this came up and in certain parts of the world, people have a lower body mass than in the U.S., so you actually see about 1% of the time in some of these populations you’re causing complications. Maybe you had, I don’t know, adequate butt tissue there, let’s say, but yes, we’ve tried to, if you look at the science on this, it’s probably better off to move away from the tail. Okay.

We’ve entered a period that I’m going to call, “The battle of the vaccines.” I see t-shirts on the horizon, the Spikevax and the Comirnaty t-shirts, but people all want to know what is the best vaccine and what team are you on? The first, this peer-reviewed publication that I’ll talk about, “Comparison of SARS-CoV-2 Antibody Response Following Vaccination With BNT162b2 and mRNA-1273.” That’s the Pfizer or the Comirnaty, and the Spikevax or the Moderna. Everyone keeps telling us don’t look at the antibody titers, but what did they do? They looked at the antibody titers and they’re twice as high after the Moderna shot. Of course, we all want get the Moderna shot now. [laughs]

We also had another preprint– I got Spikevax, the Moderna, by the way, just saying—“Comparison of two highly-effective mRNA vaccines for COVID-19 during periods of Alpha and Delta variant prevalence,” and here they’re actually reporting on what they say is effectiveness. Now, what does that mean of the mRNA vaccines?

What they say here, they looked at data from the Mayo Clinic Health System, this period January to July of 2021 we had different variants, Alpha and then Delta variants. First, the reassuring data. Both vaccines continue to be highly-effective during this period against SARS-CoV-2 associated hospitalization. We’re looking at 91.6%. We’re looking at 85%. Even when you go into July, still 81%, still 75%, but then they throw in the new superpower comparison, vaccine effectiveness against infection. Here, they say 76% for the Moderna Spikevax and only 42% for the Comirnaty Pfizer folks. Then they go ahead and, of course, just to make it worse– This is a two-fold risk reduction against ‘breakthrough infection.’ They speculate on mRNA content and, Vincent, do you have any comments about this?

VR: Oh, why do we care about infection? Don’t we care just about disease and in particular serious disease?

DG: That’s an interesting question and I’m going to– The one thing I will say, and I think in general, this is a new thing we’re asking vaccines to do. We’re asking about– and we’re going to get to a study where we look at, “What if you’re vaccinated and you get an infection? You don’t end up in the hospital. What about your risk of long COVID? Do people who are vaccinated get long COVID?” That, I’m going to hold onto that thought because I’m going to talk a little bit about– because that is going to potentially raise an issue because that is disease. Long COVID is disease and are the vaccines protecting against that?

All right, so passive vaccination. We have a developing story here. Passive vaccination is ideally getting something, a monoclonal and antibody as prophylaxis. We got the PROVENT Phase III prophylaxis trial results. They met their primary endpoint. The data was announced. This was a trial that included 5,197 participants in a 2:1 randomization to receive this AZD7442, two-monoclonal cocktail, or placebo. This is still at the press release stage. They do report that most of these individuals had comorbidities, so putting them at higher risk, and then they report that this combination reduced the risk of developing symptomatic COVID-19 by 77% compared to placebo. No cases of severe COVID-19 or COVID-19 related deaths in those treated. In the placebo arm, there were three cases of severe COVID-19, there were two deaths. I keep pushing on, and I’ve actually seen a number of emails, number of alerts from the Catholic Health system, which I really applaud.

If my buddies over there are listening, it’s been already added as an order set. We send folks over– You’re a high-risk individual. You’ve had an exposure. We get these individuals monoclonals prophylactically. Regeneron actually has EUA expansion for this. Unfortunately, only about a third of eligible patients are getting this highly-effective therapy. If someone is vaccinated, it doesn’t matter. If someone is pregnant, actually, as I think we’ve discussed, that puts them in a high-risk category and they would be eligible for this as well. Okay.

Now, the period of viral replication. What I like to say, “The time for monitoring and monoclonals, not the time for antibiotics.” I’ve talked previously and I hit on this early on, the ACTIV-6 trial, which is a COVID-19 study of repurposed drugs. David Fajgenbaum was on TWiV 766 talking a little bit about this whole concept of trying to find stuff on the shelf that might be potentially helpful. This trial is going to investigate ivermectin, inhaled fluticasone, and fluvoxamine.

What is fluvoxamine? We’ve all heard about ivermectin. A lot about ivermectin. We’ve all heard about steroids like dexamethasone, here as an inhaled formulation, but what is fluvoxamine? Now fluvoxamine is a– I’m going to say a Prozac-like drug. It’s an SSRI, a Selective Serotonin Reuptake Inhibitor. We recently had a preprint. This is the “Effect of early treatment with fluvoxamine on risk of emergency care and hospitalization among patients with COVID-19” – the TOGETHER randomized platform clinical trial. We’ve been waiting for this for a while. This was a placebo or controlled randomized adaptive platform trial conducted among symptomatic Brazilian adults confirmed positive for SARS-CoV-2. These were patients with a known risk factor for progression to severe disease. The patients were randomly assigned to either fluvoxamine, 100 milligrams twice daily for 10 days, or a placebo.

The primary endpoint was a composite outcome of an emergency room visit for greater than six hours of observation or ending up in the hospital in the 28 days post-randomization, this was an intent to treat analysis. Now, a total of 3,238 patients were allocated. We ended up with 739 getting fluvoxamine, we ended up with 733 in the placebo group. There actually were other treatments and it was an end of 1,766 for those.

What did they find? The proportion of patients with this composite endpoint of observation in the ER for greater than six hours or admission to the hospital was lower relative risk 0.71, so about a 29% reduction. Most of these outcomes, 88% of them, were hospitalizations. They also looked at viral clearance, they didn’t see a difference there. They looked at other outcomes; mortality, time to death, number of days ventilated, etc. They didn’t find anything there. It really was just this really mainly an outcome on the impact of hospitalizations.

This is an interesting study, but this is what ACTIV-6 and other trials are going to address. I really don’t want people to rush out. This is not two years ago where everyone starts rushing out and putting someone on a drug just because there’s one study. This is helpful, this supports, including this in ACTIV-6. So if you find this exciting, Google, go to clinicaltrials.org, get your patients connected for ACTIV-6.

VR: Daniel, out of all of the things they looked at, mortality, time to death, days hospitalized, days ventilated, no change except the time you spend in the emergency room. What does that mean?

DG: [chuckles] Let’s look at remdesivir, so remdesivir is $3,000 a course. All we have is maybe less people spend less time in the hospital. Here is that medication, we’re not seeing a mortality benefit. There’s no crime against humanity here. We don’t have to rush to get this to market. Maybe less people end up in the hospital. It is a psychiatric drug, so maybe they feel a little bit better. They don’t feel like they need to go to the hospital. Made me think of digoxin, which apparently if you give people digoxin, they’re less likely to go to the hospital. Okay. All right.

We’re going to jump to tail. The tail phase, long COVID, post-COVID. We had the article “1-year outcomes in hospital survivors with COVID-19: A longitudinal cohort study.” This was published in The Lancet. This was an ambidirectional study, meaning it’s both retrospective and prospective phases of the study. COVID-19 survivors who are discharged from this particular hospital in Wuhan, China between January 7th and May 29th of 2020. We have a six-month and 12-month follow-up visit questionnaires looking at symptoms, health-related quality of life questions. These individuals also had a physical examination, a six-minute walking test, and laboratory tests as well. What they reported, that the proportion of patients with at least one sequelae symptom was 68% at six months and 49% at 12 months, fatigue, muscle weakness were the most common symptoms. Maybe this is why they said in kids it’s better than this, so by comparison, maybe that’s what they were after. I have to say, long COVID is continuing to be a tragedy.

We do a lot of, let’s say, consulting with companies who are trying to figure out employees that developed acute COVID, who now cannot end up back at their pre-COVID employment. It’s about 10% or 12% of these large companies that use UAC as their insurance. This is tough, right? Even if you could cut that in half, you’d still be 5% or 6% severely affected enough that they can’t return to work. One of the things they did comment, and I think this is consistent with what we’ve seen before– What’s predictive of people who end up with long COVID, which I suggest is a subset of PASC, higher risk for women, higher risk for people who received steroids or had more severe disease? Those two may be a little bit intertwined. If you have more severe disease, you may meet criteria for steroids.

Now, we have, I’m going to say, this is positive news, but then you can tell me if it’s positive news because this gets back to this issue of, “Do we need to, in fact, do we need to prevent more than hospitalizations and deaths? Do we care about infection?” This was the paper “Risk factors and disease profile of post-vaccination SARS-CoV-2 infection in UK users of the COVID Symptom Study app: A prospective, community-based, nested, case-control study.” Actually just COVID, not COVID-19. I think we’re starting to drop COVID-19. It’s the only COVID out there. This was a prospective, community-based, nested case-control study, so they’ve got a big cohort and they’re looking within that. This was self-reported data from this UK-based database cohort. Everyone was an adult, so greater than or equal to 18 years of age. This is a mobile phone app that they’re using, so really clever here. Then they’re going to look at cases that received a first or a second dose, they’re going to look at people that tested positive.

What’s the takeaway from this? In addition to all the other benefits of vaccination, which is reinforced in this study, they found that the odds of having symptoms for 28 days or more, so long COVID, after post-vaccination infection was approximately halved by having two vaccine doses. This result suggests that the risk of long COVID is reduced in individuals who have received double vaccination. This is a little bit of an issue, and I think gets back to that original– I was saying that from our large cohorts, maybe 10% or 12% of individuals have such severe long COVID they can’t return to work. It’s going to be really interesting to tease out how severe is this long COVID because half of 10% or 12%, half of those large numbers if we still have 5% or 6% of people who get COVID, with long COVID preventing them from going to work. If you take some of those other numbers that we talked about, 68% having a symptom at six months, you drop that to 34%, these are still big numbers.

This does raise the question of considering long COVID as disease. Maybe that gets at my like, “Do we want to protect them against infection completely?” I think that what I’m really trying to say here is, I think, long COVID falls under the disease and one of the things we want to prevent.

VR: The problem, Daniel, is that this is different from every other vaccine because there’s no long measles, there’s no long polio, right? If this is true, and I think we need to know more about what variants were circulating and so forth, that could be an issue, I agree.

DG: Yes, no, excellent point. Excellent point. All right. I always like to touch on the world situation. No one is safe until everyone is safe. I think on an upcoming episode I’m going to probably spend a little time talking about the global vaccine initiative, discussing Gavi and COVAX. Also, potentially give our listeners a little bit of insight into how they might contribute and be part of that effort, but along those lines, reminders to all our listeners throughout the months of August, September, October, donations made to PWB are going to support Floating Doctors. Let me share an email I just recently got from Jolie LaBrot at Floating Doctors just letting folks know what’s going on down there.

“The team in Panama is faring well and is accepting volunteers to begin seeing more patients for primary care. Thankfully, cases in Panama, including Bocas, are on the decline. Though, as in the U.S., misinformation spreads as quickly as the virus itself. Right now, Bocas is getting doses in waves, vaccine doses. Through the 5th, they will be offering the vaccine in Bocas town and on three neighboring islands, the more remote communities have yet to receive the vaccine though some of the communities on the mainland closer to cities have been able to access them. Floating Doctors is currently working hard to educate people about the vaccine and are coordinating with the local ministries of health to assist in distribution when they become available. Go to parasiteswithoutborders.com, donate so we can help support this effort.”

VR: Daniel, let me go back very briefly to the long COVID. Is it possible that since we don’t really know how long long COVID is, maybe people who are vaccinated, even though 50% may still get it, maybe it’s shorter than non-vaccinated long COVID?

DG: Yes, there’s several things that this study doesn’t tell us and I think it’s great that we’re bouncing back to this. This is people using a phone app, right? There’s going to be a little bit of selection bias. If you’re done with COVID and moving on with your life, there may be a reporting bias you’re more likely to jump on so that the number may be different, the severity may be different. Also, this is really a short follow-up, right? This is 28 days, you’re barely there in my mind. I always say that 28 days is sort of the early people who are vaccinated, what if we go to two months, three months? I’m still optimistic. The biology, the science suggests to me that we should see protection against this type of disease as well.

VR: Okay, yes, I agree. All right, time for some questions for Daniel. You can send yours to [email protected]. Jeff from California, “My wife and I are both scientists and we are having a serious scientific disagreement. By studying the literature, she has decided that one can be infectious without the tests detecting the infection. She’s not talking about normal false negative rate, but rather there is a couple of day period before the symptom onset where some patients can be infectious, but not shedding enough virus to be detected by the standard tests below the detection threshold of the test. I think that regardless of her reading around, this is impossible. I suppose this might be slightly possible if somehow the virus is in your lungs, but not your nose, where the test is done, but this seems unlikely to me and would happen in a vanishingly small number of cases. Can you help distinguish between her reading around and my logic? Thanks.”

DG: Yes, I’m going to get in trouble here, right? Your wife is always right, but some of the things she’s thinking perhaps need to evolve a little bit. Our tests are incredibly sensitive. I think I’ve talked several times about this large testing program we have for the movie industry. The test actually, particularly the PCR, turns positive prior to a person becoming infectious. Yes, the period when the person is mostly contagious, mostly transmitting is two days before symptom onset, three days afterwards, but there’s a little bit of a tail there to the right. Your PCR turns positive prior till you spray. If this wasn’t true, our whole screening program would have been a disaster. All the content you’re enjoying on Amazon Prime and Netflix wouldn’t be there at Lionsgate, etc.

No, the tests pick a person up before they become infectious. Actually, with the PCR, it continues to pick you up even after you’ve passed through that period of time. The antigen tests tend to correlate more with that period of contagiousness, high levels of the viral antigen. I will state the one thing that maybe your wife is right about, and maybe she was thinking this, none of our tests are 100% sensitive. You’re going to miss stuff, but you’re just missing stuff because of failure of the test not because of the biology.

VR: Zinta from New York writes, “Our daughter was born during the pandemic and due to lockdown, had limited contact to other children and adults. As a result, she’s never been sick with colds or other illnesses. She’s now 15 months. We would like to enroll her in daycare for socialization and learning. However, the increasing rates of COVID and hospitalization in young children is alarming as you highlight in 797. I worry that by sending my one-year-old to daycare, I may be dooming her to COVID-19 with unknown consequences. To minimize risks, would you keep infants and toddlers out of daycare as long as possible and try to wait for a vaccine? Or can risks of infection be minimized by going to daycare two or three days a week? Or by dropping out if prevalence increases above a certain threshold in the community? Or is hospitalization still so rare in toddlers and infants that we really should not worry about COVID and focus on the benefits of socialization at this young age?”

DG: Okay, there’s a lot in there to unpack, but I’m going to focus on– I think the main overriding thing is that we’ve been talking about for a while. We have presented several studies on this, is that you can safely get children in schools? You can safely, actually, get children under the age of six in these child care settings. There are certain recommended mitigation strategies to make that safe. I think there was actually a recent study where children in school had one-third the rate of infection as opposed to the community, right? If you look at some of these mitigation strategies, vaccinating the staff, that’s huge. That’s going to reduce their chance of getting infected and I think we have a growing body of evidence their chance of spreading it to the others. Regular testing programs, good ventilation. Kids at this age, they’re not wearing masks. I think that’s just reasonable. There are ways to do this safely, and I’m going to say there’s ways to do it safely that outweigh, that would err on the side of you’re potentially better off having your child in this setting with all the advantages of the social interaction. This can be done safely.

VR: Jamie writes, “I’m an emergency physician and mom of two, ages one and two years old, working in Albuquerque, New Mexico. You mentioned in the last update that the overall risk of hospitalization is 2% for children. I was wondering if we have more information about that? Specifically, what’s the breakdown by age group? I would imagine under one year old is most likely to require hospitalization but beyond that, what’s the median length of stay for these children? What interventions are being heeded and what is the rate of children requiring intubation? What comorbidities or other factors contribute to risk of hospitalization? Lastly, what is the rate of MIS-C or do we even know?”

DG: Okay, this is fantastic, right? This is the kind of questions and knowledge that you want your physician to seek. I talked early on in the children COVID section that the AAP Children and COVID-19: State-Level Data page not only does it have an overview, but you can go to the very bottom and you can actually download this extensive pdf with answers to a lot of the questions that you’re asking about. Yes, as you can imagine, I’ve looked through this and there really is a gradation, right? The closer you get to being an adult, the closer your risks are to those of an adult. The younger you get, the lower those get. I talked a little bit about depending on where you look in different states, it might be as low as 1.6 of the hospitalizations are children, other states it’s 3.6, but they break this down into all these different variables, age, state, etc.

VR: Thomas writes, “My mother suffers from a few autoimmune diseases, lupus, Sjögren’s syndrome, antiphospholipid syndrome. She hasn’t been vaccinated yet out of fear of thrombosis. Her doctor could say only that she, on the one hand, recommends getting vaccinated, but on the other hand, does not recommend it. One problem is that depending on which doctor she goes regarding her disease in general, some recommend getting anticoagulants, others tell her she can live without them. She doesn’t take anything against thrombosis as exercise might be enough and is the more comfortable option. Since I doubt that her immunity is around the corner anytime soon, my question is, ‘Do I want to get infected with or without vaccine protection? What’s the best way to go from here for my mother?’”

DG: Okay, there’s a lot in there and there was that one question about a person with lupus, “Do they benefit being on anticoagulation or not?” There are certain features I’m going to defer to the rheumatologist who can sort that out and make that, but what about COVID, right? We’re saying at this point your choice is between getting exposed to COVID, having a natural infection with all the risks and benefits, or the vaccine. I am going to recommend in a situation like this, I would recommend vaccination because the risks of clotting complications with COVID are significant. An individual like this who gets COVID, I would be quite concerned. 20%-30% chance of a venous or arterial clotting complication.

We probably would recommend an mRNA vaccine in an individual like this. The other, I want to use this opportunity, there was a recent study and I was going to put it in, but this is even better just to bring it up. There are a bunch of people say, “I’ve had lots and lots of allergies. I’ve had issues with other vaccines. I want a letter from my allergist or doctor saying I don’t have to get this vaccine.” They looked at these individuals and individuals even with a report of multiple allergies, all kinds of other issues, 99% of these individuals tolerate these vaccines. The few, like the 1% or so, tend to have mild issues. If you’ve had an issue with this vaccine or a component in this vaccine, that’s one thing. But if you have autoimmune diseases, if you have allergies, if you have the other things, we are still routinely recommending vaccination across the board, much safer than getting COVID.

VR: All right, and because this is Episode 800, one extra email. This is a statement that I think we need to make, it’s not really a question, from Lena who says, “I know I’m probably preaching to the choir since most of your listeners are like-minded, but I wanted to send this in.” She posted it on her Facebook page in hopes it would give anti-vaxxers an idea of what life is like for those who are scared. Her child is seven years old. He has made it to age seven only through the help of many doctors, medicines, and the alert and aware adults in his life. “He’s medically fragile. He doesn’t look it, but he’s one of millions with an invisible illness. He’s been in the hospital multiple times, takes multiple medications every day. He’s at high risk. He’s why we’re continuing to stay home, mask up, get vaccinated, and only allow vaccinated individuals to visit. If you think a vaccine is traumatic, imagine watching your child struggle to breathe, gray-skinned and blue-lipped. If you think wearing a mask is too much, imagine watching doctors and nurses pump your child full of medicines to help him breathe.

If you think staying home is hard, imagine a doctor telling you that they’re going to try one more thing, but if it doesn’t work they’re going to have to intubate your child to give him a break from working so hard to breathe. If you think a cold is no big deal, imagine lying behind your child in a hospital bed, watching the number on the oxygen monitor, praying it stays above 90 so it doesn’t beep, and summon the nurse again, so you can get five minutes of sleep. Imagine that, then imagine it again and again.

That’s only a fraction of what we’ve endured as a family. These things are traumatic. They’re too much. They’re hard. They’re a big deal. Those things are why we keep him safe. He’s not disposable, he’s not a burden. He’s very much loved by everyone. He brings joy to our lives, he deserves to be protected. Protect him and the millions of people who suffer from invisible illnesses. Happy birthday, JJ. Thank you for teaching us so much.”

DG: Wow. It’s a very powerful email. I was talking to my wife today. The polls have gotten to the point where it’s down to only about 20% people are saying they would refuse to get vaccinated. We think half those people may have already been vaccinated, they just don’t want to lose membership in the tribe. This vaccine has an anti-vax popu– It’s really shrinking. They’re very loud, they’re very vocal, but I think a lot of people realize that a lot of people are coming– This isn’t just about you. We live in a community. This is like having a protest advocating for drunk driving or something.

If you get COVID and you transmit it, you could kill someone else, and you could end up– We’re seeing thousands of kids end up in the hospital each week. The majority of those children were infected by someone who’s unvaccinated. That’s on the unvaccinated, don’t just think about yourself. I think our listeners are onboard with this.

VR: I also think it’s a good response to people say, “Oh, it’s traumatic for kids to wear face masks in school.” As you have said, Daniel, far more traumatic to be in the hospital.

DG: Yes, yes.

VR: That’s COVID-19 Clinical Update number 78 with Dr. Daniel Griffin. Thank you, Daniel.

DG: Thank you. Everyone, and Vincent, be safe.

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