TWiV 840 COVID-19 Clinical Update #92

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 11 December 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 840, recorded on December 9th, 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: Omicron, omicron.

DG: [chuckles] Yes, we will talk about omicron, however you want to pronounce it. But let’s get right into it. Let’s start with the quotation. We actually have a lot to cover today. Oh my gosh, we’re at clinical update 92, TWiV 840, and still there keeps being a firehose of information every week. “A smooth sea never made a skilled sailor,” and that’s by FDR. There has been no smooth seas over the last two years. This has been quite a challenge, but I’m hoping, I’m optimistic, that we’re getting better, but let’s talk a little bit about omicron.

So far here in the U.S., we’re still seeing trouble with delta. We saw that post-Thanksgiving surge in infections, and then that was followed by a surge in death. We actually had a day here in New York where we had over a hundred deaths in a single day. We are starting to come off that hump here. We’ll see what happens because we have another holiday coming right up, so we’ll see where we are there, but let’s start talking a little bit about omicron. First, I’m going to start with a preprint, and don’t worry, you’re going to get bad news, you’re going to get good news.

I think it’s going to work out in a positive direction in the end, but this first preprint, “Increased risk of SARS-CoV-2 reinfections associated with the emergence of the omicron variant in South Africa.” Now, this got a lot of attention and here the authors are reporting on a retrospective analysis of routine epidemiological surveillance data collected through South Africa’s national notifiable medical condition surveillance system. Basically, what they’re doing is they’re looking at individuals that had a positive test, and then they had a second positive test. It had to be at least 90 days apart. This isn’t just someone who has a string of positive tests.

This is suspected of reinfections based upon that criteria. They looked at 35,670 suspected reinfections. These were identified among 2,796,982 individuals with laboratory-confirmed SARS-CoV-2. I remember, Vincent, it was not that long ago, there was this whole debate about, “Can you get reinfected?” In this one study, we have 35,670 reinfections meeting this criterion. If there was any doubt, you can get reinfected. What they reported was that the recent spread of the omicron variant was associated with a decreased hazard of primary infection and an increase in reinfection hazard.

Of the infections they’re seeing here, they were seeing about a 2.39 increase in the hazard ratio for reinfection. Just as far as what did they conclude? What would you take away from this? I’m going to read, “Population-level evidence suggests that the omicron variant is associated with substantial ability to evade immunity from prior infection and contrast. There was no population-wide epidemiological evidence of immune escape associated with the beta and delta variants.” I think this interesting and concerning, but let’s not just do what we do with vaccines, we make a distinction.

What we want to know is not only can the individuals get reinfected, but we’re also going to be interested in how do they do? Are they just getting reinfected? It’s breaking through that initial line, but are they still protected against moderate to severe disease? I think that that’s going to be coming with data that comes in the future. A couple of the things I thought were interesting is in this dataset– There were actually 332 individuals who had three infections. It was even an individual who was infected for the fourth time during November. Not only do we see reinfections, but we see re-reinfection and re-re-reinfections.

VR: Daniel, if you did this as a careful study elsewhere earlier, maybe you would find the same thing, but we just didn’t do it, right?

DG: I think that’s important. It’s unfortunate that we don’t have the data at this point because we don’t just want to say like, “Okay, you’ve been infected. You’re at such and such risk of reinfection.” We also want to know, “How do you do?” Because at some point, this is a virus that is here to stay and so we need to know these things.

VR: Well, Daniel, the common cold corona, the study of Jeff Shaman, showed that people get multiple infections even within a year. They don’t even know it because they’re so mild, they’re asymptomatic. This is not necessarily a bad thing, right?

DG: Yes, and I think that’s really important. I still remember– and I emailed Jeff early on in the pandemic talking about this. He’s been on, actually, I think he’s been on TWiV. That’s important to know. Let’s think about a future when we are either vaccinating or not vaccinating, and a person either gets infected when they’re really young or gets vaccinated and then gets infected maybe they keep getting infected every year. If it is nothing more than the sniffles, that is a much different world that we’re living in than we’re living in right now.

Children. Children are at risk from COVID. I think this is right up there with reinfection. We now know this happens. Children get infected, children, actually, unfortunately, some of them can end up in the hospital, and some of them can end up dying from COVID. There was an expansion of the EUA for the Eli Lilly monoclonal cocktail all the way down to newborn, so let me just go through this.

The U.S. FDA revised the EUA for the Eli Lilly cocktail, bamlanivimab and etesevimab, to additionally authorize the administration for the treatment of mild to moderate COVID-19 in all younger pediatric patients, including newborns, who have a positive COVID-19 test and are at high-risk for progression to severe COVID-19, including hospitalization and death. We’ve talked about this before; congenital heart disease, immunodeficiencies, the requirement to be on immunosuppressive medication. It used to be that there was a certain age and a certain weight cutoff, but now at least for Eli Lilly, we can actually extend access to this therapy all the way down to newborn, so I think that’s a bit exciting and there is even more exciting monoclonal updates to come.

Pre-exposure transmission testing. I like to say, “Never miss an opportunity to test.” I’m going to go a little off-script here. There was a White House press conference. I saw that, I wasn’t watching it live, but I saw afterwards. Someone was asking about testing and Jen Psaki responded, “What? Are we supposed to mail out tests to everyone?” Well, the quick response on the Internet was “yes.” I do think there is a hunger in the United States. There is an appreciation that testing is a really important way to keep people safe, especially with the upcoming holidays. Vaccination reduces your chance of becoming infected, but you still can get infected, you still can transmit. Testing really adds another layer, so yes, we do need rapid tests out there. Let’s flood the U.S. with rapid tests, as opposed to what we’re currently seeing is the U.S. being flooded with COVID.

Back to serology tests, and I want to reference the recent TWiV. Actually, I just enjoyed that this afternoon. I carved out a little time as I was driving from hospital to hospital. I listened to it on 2X, Vincent. When you and I talk, it’s funny because my kids are like, “Why does Vincent talk so slowly?” Because even they’re used to hearing you at 2X.

VR: [chuckles] Oh my gosh. Can you understand it at 2X?

DG: There’s a moment I have to shift over, but I hope I understand it.

VR: Wow.

DG: [chuckles] What I thought was really important on that episode and this is something that we really are going to want– As I go forward, you’re going to understand why we’re going to want more of this. Right now, everyone and their uncle make a serology test for COVID. I get patients, “Oh, I got this test and it was negative. I got this test and it was greater than 250 and this other test–” We should be able to reach a point where we have serology tests neutralization assays that we can use as clinicians to get at least some sets, something we can use clinically to decide at what risk an individual is. We have all these serology tests where a person was infected and then they got one vaccine, maybe they got a second vaccine, they’re trying to decide, “Am I supposed to get boosted? Do I need to get a third vaccine?” We have individuals that got one shot, a second shot, they’re trying to make decisions about that third shot. Maybe they had difficulty with that second shot. At some point, maybe people are going to be talking about fourth shots.

It would be nice for certain individuals to actually have access to a reliable test that does correlate. This is my– Everyone listening, we need those tests. I think, as clinicians, a lot of clinicians are out there using what’s currently available. It’s all over the place. We don’t really have a tight correlate with immunity. There certainly are research essays and studies suggesting that this is something that can be done. We could use those tests that would really help us. I think it would also help address this question.

We don’t necessarily want to know on a population level, but if someone was infected and they had one or two shots, it would be great to be able to help guide them. Do they need a third shot? Do they even need a second shot after that first one? Vincent, I don’t know if you had any thoughts. I got to hear all your thoughts and I’ll recommend everyone listen to that TWiV.

VR: No, I agree. I think we need a standardized test and that can be used by everyone. I don’t know that will happen quickly, Daniel. It takes time.

DG: Yes, it will take time, but I think it’s a priority. I think there’s a lot of individuals out there, unfortunately, who’ve been infected, who are trying to decide about vaccination; How many doses? What do they need to do? I think omicron is a big push to go ahead and get at least one or two of those vaccine doses. Do they need a third? We’ll have to see, but maybe they don’t. I think that’ll be important to say.

Active vaccination, I’m talking about vaccines and now we’re getting right into it. Never miss an opportunity to vaccinate. We’re all starting to hear about the effectiveness of our vaccines against omicron. There is some data starting to become available. The investigation, “SARS-CoV-2 Omicron has extensive but incomplete escape of Pfizer BNT162b2 elicited neutralization and requires ACE2 for infection.” This was sent my way. I think, Vincent, you may have even shared it with me.

VR: I think it was Amy.

DG: Was it Amy who shared it? Okay, excellent and thank you for all the people that keep sharing preprints or even stuff that isn’t even preprint. It’s great to try to be able to keep up on this and it helps when one of my colleagues, so Amy, thank you. Here, the investigators used early passage of isolated and sequence-confirmed omicron variant virus isolated in South Africa. They’re actually using the virus. This is not a pseudotyped assay. They used a human lung cell line clone engineered to express the ACE2 receptor to both isolate the virus and test neutralization.

They were able to demonstrate that the omicron variant virus was still using ACE2 for entry. They tested the ability of the plasma from the BNT162b2. These are the Pfizer-vaccinated study participants to neutralize omicron versus the ancestral, the 614G virus, in a virus neutralization assay. Beautiful figures. If people read this or see Figure 1 shared on social media, I’ve seen it shared on social media. They are using something called an FRNT50. This is a Focus Reduction Neutralization Test. It’s somewhat similar to plaque assays. It’s been suggested that it is easier. It is less labor-intensive. I see Vincent shaking his head. Some people–

VR: Easy way out. Always taking the easy way out, folks.

DG: They went ahead and they tested plasma samples from 12 participants that had all been vaccinated with the Pfizer vaccine. Now, six of them had no prior evidence of SARS-CoV-2 infection. They’re just getting the two shots. The remaining six actually had a record of previous infection. They were infected with the ancestral D614G, and then they got two shots on top of that. What did they find? They found that there was a 41-fold decline compared to the only three-fold decline seen with the beta variant as far as this neutralization with the initial neutralization being so elevated with the three exposure scenario versus the two vaccine.

When you actually look at the drop, you drop to a level that was actually higher than we were seeing with the two doses of vaccine. The escape was incomplete, so even after this drop, there’s this suggestion that three exposures might get us there. I’m going to get into that next. What about three exposures of the vaccine? What if instead of infection and two doses of vaccine, you get two doses of vaccine and then another dose of vaccine?

I haven’t seen the raw data on this, but here we’re talking about a 41-fold drop. We are seeing or we are hearing from Pfizer and again, I haven’t seen the raw data on this, a 25-fold rise with that third shot. Really, getting us up to a level where we anticipate that three doses of the mRNA vaccine are actually going to continue to give us protection. The folks at Pfizer are suggesting that since this is the case, that we should feel a little bit better. Vincent, what are your thoughts on getting a booster after hearing this?

VR: We did a paper on TWiV, which you listened, to where a group in Canada showed that if you spaced dose one into 16 weeks apart, you get a much broader antibody response than if you space them four weeks apart. It seems to me that a third dose would correct for that inappropriate early spacing. It makes sense to me now to get a booster to broaden those antibodies. I think it would include omicron as well, I don’t see why it wouldn’t. Now, I am slowly seeing the data that a booster is probably a good idea for that reason.

DG: I think this is really interesting. I remember John Mascola and I were emailing a bit like when the boosters were first being rolled out, I guess, to the general population. There was this idea that really the mRNA vaccines were turning into a three-dose primary series. Maybe that third dose, really boost isn’t really the right word– It’s really just you’re finishing off your vaccine, you’re getting that breath, you’re getting that high level. It is interesting this discussion, like if we could go back and do all the science again, would we test one dose, wait three months, one dose, wait six months?

The logic was, it still makes sense to me, is as you give the first dose, you give that second dose three to four weeks later, you get up to a high level. You’ve got a degree of protection while you’re waiting for that third dose and that broadening and expansion. It makes a lot of sense in the midst of a pandemic with high transmission. I don’t know if we’ll go back. I think it’ll be much like hepatitis B where the standard is one dose at time-zero, another dose at one month, another dose at six months. That being said, there is now a two-dose hepatitis B vaccine out there. We’ll see with time.

VR: Daniel, could be that two doses, 16 weeks apart, is as good as three doses when the first two were too close?

DG: Yes.

VR: I wish they’d do a larger trial, especially in 5 to 12-year-olds who are just starting getting their four weeks based, and maybe they shouldn’t be.

DG: It is interesting, I think if we circled back to having a really reliable correlative immunity like serology test, the T cell, you don’t need huge numbers to redo that. It does help. We’re still in a pandemic. It would be nice to know– Also, would be nice to know as we come out of this if this becomes a routine childhood vaccine. Do we just do two shots, but “properly spaced”? That science would be helpful.

Passive vaccination. This is exciting. This is big. We now have monoclonals for pre-exposure prophylaxis. This is hot off the press Wednesday, December 8th, the FDA announced EUA for AstraZeneca’s and they named it, EVUSHELD. I think it should have been evushield or something. You can call me, I’ll help with the names. This is a combination long-acting antibody cocktail, tixagevimab co-packaged with cilgavimab. Okay, rolls off the tongue. This is for pre-exposure prophylaxis for COVID-19 in certain adults and pediatric individuals. This is going to stop there right at age 12 and a weight of 40 kilograms or 88 pounds. Now, the product is only authorized for individuals who are not infected, not currently infected with SARS-CoV-2. Not right after a recent exposure. This is upfront. You plan this ahead of time. This is for individuals who either have moderately to severe compromised immune systems due to a medical condition or due to taking immunosuppressive medications or they have a history of a severe adverse reaction to a COVID-19 vaccine. This could, in certain individuals, let’s say, they get that first dose and they develop a vasculitis or some other really significant adverse, we’re not just talking about a rash or something that we could get through.

This can be used in both of those contexts. There’s a list of who are these individuals that are moderately or severely immunocompromised, so active chemo treatment, active treatment for a solid tumor or a hematological, that’d be a blood cancer, the person who’s actually received a solid organ transplant. I think there was a discussion of the West Nile transmission in transplant patients, individual who’s on immunosuppressive therapy, and the list goes on to include a lot of other immunosuppressive conditions. There is a huge need for this, and I think we’ve talked about this before.

There are individuals who cannot get protection from the vaccine or cannot get the level of protection we would like to see. Those individuals have been basically living frightened. A lot of them afraid to reenter society because they have been vaccinated, but they don’t have B cell function, they have other issues. This is huge. This is really big. Still remember, this is our pre-exposure prophylaxis. It’s going to be a twice-a-year injection. We also still have our post-exposure and we have our early treatment with the other antibodies out there.

VR: Daniel, are these two monoclonals able to neutralize omicron?

DG: Maybe our listeners can help us with this. The company has not released data yet. They’re working on it. They’re testing this. One of the things I do not know is I don’t know exactly where the spike protein these two antibodies bind. Actually, I have the maps for all the other antibodies, and I could not find this information. If anyone has it, it would be nice to know up front where it’s targeting. Is it outside of this rather variable receptor binding motif? Like the Vir or GSK’s sotrovimab, which looks to still be effective. I think that’s going to be really important if omicron moves into our region. How much protection will these individuals have against that variant? Excellent question. Yes, if any of our listeners know a little bit more, I would love to know.

The period detectable viral replication. Now, an individual has tested positive. I’m still saying this is the time for monitoring and monoclonals. We’re still waiting on those oral therapies that might enter into this region, but now we’ve entered what I call “the battle of the monoclonals.” Which is best? Which is the best monoclonal?

We had the, “Real-world Assessment of 2,879 COVID-19 Patients Treated with Monoclonal Antibody Therapy: A Propensity Score-Matched Cohort Study.” This was published in Open Forum Infectious Diseases. The authors reported on 4,328 SARS-CoV-2 positive patients who were treated with monoclonal therapy. I’m just going to cut right to the chase. Among the infused cohort, all of them did significantly better than the control, the matched controls, but those who received the Regeneron cocktail had the best outcomes.

They had a significantly decreased rate of admission relative to the other groups. That was an adjusted risk ratio of 0.51, so pretty impressive. Another preprint, and I think this is going to be exciting too, a lot of exciting stuff here in the monoclonal area. The preprint, “Association of subcutaneous or intravenous route of administration of casirivimab and imdevimab monoclonal antibodies with clinical outcomes in COVID-19.” One of the things that has stood in our way, operational challenge, with monoclonal is having to put in and maintain an intravenous line.

This was the question, “Can we just give them subcutaneous? Is that going to be as effective?” Here, we get the results of a prospective cohort study of outpatients with mild to moderate COVID-19 symptoms who are eligible for and received monoclonal antibody treatment under the EUA. They either receive the subcutaneous or the intravenous administration of the Regeneron cocktail. That’s the casirivimab and the imdevimab, and they found that both routes of administration were very effective with no compelling differences in effectiveness.

I think that’s exciting. There’s, in people’s mind, “Oh, if it’s intravenous, it’s going to be that much better.” It looks like subcutaneous can be very effective. There doesn’t tend to be a big downside and the long-acting antibodies, those might be given intramuscular. We’re starting to see more flexibility, more operational flexibility with getting monoclonal subcutaneous intramuscular. A little bit of an update in this zone. People may share this. One of the things I’ve been doing through the IDSA is helping out with clinical care in Bangladesh, in the Rohingya refugee camps. It’s really pretty exciting.

I get on a call, there’s maybe 20 or 30 clinicians. We use ‘Teams,’ technologically allowing us to connect. We discuss challenging cases in their management. One of the things that came up recently was what about convalescent plasma? Should we try to mobilize and get that in these refugee camps for the early treatment? Just an update, the WHO COVID treatment guidelines were recently updated and they now have a strong recommendation against using convalescent plasma outside of a clinical trial. They go on to say, “Evidence has not shown the costly time-consuming transfusions to be effective.”

The guidance against the use of convalescent plasma was published in the British Medical Journal and was based on the review of the results from 16 trials involving more than 16,000 patients. There’s a lot of excitement here. They’re all these ideas that you would get artisanal convalescent plasma right from people in the local area with the right variant. Really, some passionate people. We’ve spent billions of dollars looking at this. It just does not look like it’s making that difference that we hoped it would. Really think of monoclonal antibodies as the evolution of this idea into something that really does make a difference.

The early inflammatory phase. This is often when an individual might get hospitalized. We’ve got this outline, hopefully, in people’s head where during that first week, the viral symptom phase, this is when you start seeing that early inflammatory phase. This is when you start to see, in some individuals, that oxygen level drop below 94%. Now, this is typically the second week, but remember, this is a crude model. Everyone’s a little bit different. Particularly in older individuals with comorbidities, we might see that drop right around day seven. It might be right the last day or two of that first week.

Lower risk younger individuals, when we see them decompensate, dropping their oxygen, it might be closer to day 13 or 14. You want to be putting it all together. When was symptom onset? That’s the history. I like to say the most important, but least reliable. What is that oxygen level? Putting the pieces together. This is when we start thinking about adding dexamethasone, that’s 6 milligrams a day for 10 days in individuals with oxygen saturations less than 94%. Sometimes we can keep them out of the hospital with that.

Often here in the U.S., we’re using remdesivir. Maybe not as much as we were early on, not as much excitement, and the data is not getting us excited. This is also when we think about anticoagulation. Today, let’s talk about that. There was a recent review. This is this question of, now that we’re doing a lot of things to these patients, including giving them steroids and immune modulators, does that impact that clotting risk? This was the review article, Review in patients hospitalized with COVID-19. The effect of adding immunomodulatory agents to usual care on thromboembolic events was assessed.

This was published in the Journal of Clinical Medicine, looking at articles that address this concern. They ultimately analyzed data from 8,499 patients, where 4,638 were treated with an immunomodulatory agent, 3,861 without an immunomodulatory agent. Lots of obvious issues with these two groups. Why was one treated? Why was one not treated? Who was their doctor? These are not going to be perfectly matched. What did they find? They found that among the patients prescribed immunomodulatory agents, there was a rate of 1.77 VTEs per 100 patient months compared to 2.30 among those treated with usual care. There was an odds ratio of 0.84, so it does look like a little bit of a reduction, but why 95% confidence interval? This did not reach statistical significance. You see that, we’ll talk about a trend, but a trend that does not reach statistical significance is something that did not reach statistical significance. Basically, I’m going to just conclude with as they say, “They did not identify a statistically significant effect of immunomodulation on thromboembolic events in COVID-19.”

In many ways, this can be helpful because there’s been a lot of trials looking at anticoagulation and the setting of COVID and a lot of concerns that now that the standard of care has changed so much. Can we still use those data? Have the baseline risks really shifted in a measurable manner? This is, I’ll say, reassuring that if anything, things look like they might be going in the right direction, but not in such a huge variation that we have to repeat all those trials now.

I am going to go right to the tail phase, long-COVID, post-COVID. As I think, it has become really clear. Even when I talk to patients that are not comfortable and excited about vaccination, people appreciate long-COVID. This is something that I think we all agree on at this point. Meh, maybe not us all. Most clinicians and a lot of the public are aware or know people who had COVID who did not get better after just two weeks. The preprint, “Reduced Incidence of Long-COVID Symptoms Related to Administration of COVID-19 Vaccines Both Before COVID-19 Diagnosis and Up to 12 Weeks After,” was posted as a preprint.

This was a retrospective analysis of the medical history of 240,648 COVID-19 infected persons that were identified with factors influencing the development of progression of long-COVID. This analysis revealed, I think this is actually pretty exciting if this pans out, at the end of peer review that patients who received at least one dose of any of the three COVID vaccines prior to their diagnosis were seven to 10 times less likely to report two or more long-COVID symptoms compared to unvaccinated patients. This tends to reflect what we’re seeing.

I’ve brought this up several times that we are not seeing a lot of individuals who were vaccinated and then got COVID end up in our COVID Recovery Center. This is, I’ll say, a little bit more dated to support that observation. Now, furthermore, and this is where I think it gets really exciting, unvaccinated patients who received their COVID-19 vaccination within four weeks of that initial infection were four to six times less likely to report multiple long-COVID symptoms, and those who received their first dose four the eight weeks were three times less likely than those people that continue to remain unvaccinated.

We’re starting to get robust– It’s a data set of 240,648 patients analyzed. We are seeing that vaccination before was associated with a decreased risk, vaccination within four weeks really dropped that risk. Getting vaccinated within two months still dropped that risk. What we’ve seen from other studies where if you really wait months out, you may only drop that two-fold, but there’s a couple of challenging and interesting things in this paper. One is the issue of defining long-COVID. I like the fact that they looked at a constellation.

You needed to have two or three or more long-COVID symptoms because if you just start looking at single isolated things, “Are you anxious? Are you depressed?” These things have such a high prevalence in the community that it’s hard to tease those out. I did look over another preprint that was reporting that vaccination does not protect against all diagnoses identified under the PASC umbrella. Just to put this in context with the paper we discussed, they looked at 45 different diagnostic codes and reported that only a little more than half of them were significantly reduced by being vaccinated prior to infection.

I guess I would report it the other– I’d say more than half of these individual codes were decreased. There was some challenge in this, but I think it’s really important and a challenge when we look at post-acute sequelae of COVID to really understand that it is a challenge to identify this cluster of symptoms that identifies these individuals. I will say vaccines are helpful, but as you’re seeing here, it was a risk reduction. The vaccines are not 100% at preventing long-COVID and getting vaccinated after you develop long-COVID is not 100% at getting rid of that.

We still need a lot more research to help these individuals. No one is safe until everyone is safe – looking at the global picture. I am hoping that at minimum, omicron is a wake-up call to the priority of vaccinating the world. We’re now all talking about how we need to get that third vaccine to protect us against omicron– a country of 350, almost 400 million here in the U.S. What if we had just gotten everyone in South Africa vaccinated? That’s less than 350, 400 million folks. We really need a global plan.

It’s not as simple as just sending a whole bunch of boxes of vaccines. You should need a plan to get those vaccines into arms. I’m going to steal a tweet that I saw by Roxanne Khamsi. I don’t know if she originated this or someone else. We need to get the nation out of vaccination. We need to make this a global effort and this could be working with everyone. This is going to be working with those large pharmaceutical companies. They’re our friends right now. Governments, maybe they’re your friends right now. Grassroots organizations, we all like them.

Indeed, people have relationships because, as we saw even in South Africa, the vaccines were arriving, but you need education, you need communication, you need trusted people there on the ground talking with people. Let me get to the last– and our fundraiser, let me remind everyone to go to parasiteswithoutborders.com, click on that donate money, on that donate button, so you can send money to us. Thank you, actually, for all the people who have helped us continue to do what we do. Through the months of December and January, we will continue to match those donations up to a total of $40,000 to send to MicrobeTV.

We may even give a little bit more to them because we have such a great relationship. If you send more than $1,000, send an email to vincent@microbe.tv, let us know, and he’s going to get a book out to you, and Parasites Without Borders is going to cover those shipping costs. If you’re here in the U.S., just your mailing address, but if it’s overseas, throw in that phone number as well. Thank you so much for all your continuous support.

VR: Thank you, Daniel. It’s time for some email questions for Daniel. You can send yours to daniel@microbe.tv. First, from Jack, “I was taking an immunosuppressant drug, Enbrel, at the time I received my COVID vaccines. My booster was in August. I stopped taking the drug in November. Does this mean that my immunity protection from COVID should be at the same general level now as a person who was not immunosuppressed?”

DG: This is interesting. When you get vaccinated relative to when you’re on immunosuppressives, if you’re on immunosuppressive when you get vaccinated, the concern is that you’re not going to develop as robust a response to the vaccine. Then if you, let’s say, you stop and you’ve been off for a while, it isn’t as though suddenly that immune response ramps up. There’s two issues. This one is the potential impact on when you were vaccinated, the other is whatever recovery from being off the therapy.

Enbrel is something that probably, after about a month, it’s really losing its impact on the immune system. By now, you’re pretty far out from that. Boy, isn’t this a great situation? We’d love to be able to go get a test to see where you are, a reliable test that correlated with protection to determine whether or not you needed another shot to get up to that higher level.

VR: Daniel, that test would also be helpful for people who have been infected and recovered to say, “Hey, I have the approved level of immunity.”

DG: I think that would be huge for breaking down the division. There’s a lot of people and they’re frustrated. They talk about why are you not recognizing– The only downside to recognizing that level of protection would be those people who might go out and go to an infection party to somehow get out of a mandate. Don’t do that. I do think a larger group of people are responsible and they’ve been infected and they’re really just trying to decide what is the best thing for their health.

VR: Our next question is from Amanda. “I’m fully-vaccinated, received Moderna in January and February 2021. With my second shot, I had a mild reaction 20 minutes after administration, pretty intense itching around my mouth, inside my mouth, tingling on my tongue, no swelling, rash, or hives. Went away after two hours. I also experienced some heart palpitations, tachycardia for a couple of months after this. Having tried to do my own research, I failed at finding articles about reactions only after the second Moderna. They all concentrated on after the first. My primary care physician has advised me not to get a booster saying my risks outweigh the benefits. I’m curious if your advice would be the same?”

DG: The immediate reaction around the vaccine that you described, that’s something where, usually, I would have someone see one of our allergists, actually, David Wertheim is an allergist here at ProHEALTH. He and I, boy, we have a relationship now. We barely communicated before, but now a lot of times, the allergist can help and they’ll do per-vaccine medications to help control some of those responses. I’m a little bit more interested in the late manifestations when you talk about what might be cardiac manifested. That’s something where I would probably want a little more information.

You really want to make sure that you’re not going to have an issue there. Again, we’re back to, “It would be great to get a sense of where you are because the alternative here is potentially doing something like the AstraZeneca.” If there really is valid concerns that second dose may have caused some cardiac issues and we’re concerned that a third dose would trigger that again, then it wouldn’t be do nothing. It would be, “Look at getting you that protection because if this is somehow related to an immune response off-target from the spike, boy, letting you actually get infected with SARS-CoV-2, that may be a bit of a disaster.”

VR: Marshall from Austin, “My son, 10-years-old, no preexisting continuous conditions of concern, he’s back in school in-person. We made the decision to have our son, age 10, vaccinated with a full-dose, 30 microgram times two BioNTech vaccine in May. I know, shame, shame, shame. Indeed, he had nasty flu-like symptoms, but we have no regrets. Obviously, our son does not have correct official records of vaccination since we provided an incorrect age. He’s now eligible for pediatric vaccine and we wonder whether at some point we will need to proceed with this to at least have official record of his vaccination. I’ve spoken briefly with our pediatrician who has a significant number of other parents in the same position. What do you think is the best way to proceed? What will you advise patients, parents in this position? I contemplate possibly having him proceed with two official doses, but spreading them out over several months.”

DG: There is an answer to this and it’s a good answer. If you go to that trusted clinician with whom you have a relationship and you admit that you lied, there is an ability to enter that documentation that then gets uploaded to the state. Here in New York, an individual comes in, they tell me, let’s say, for instance, they say, “Hey, I’m moving back to New York. I’ve been doing school down in Alabama.” We can enter those vaccines into the system. There needs to be a decision by the clinician. Do they trust you? Sounds like you’re telling the truth here. A lot of parents did what you did.

You enter that in and then you enter in when the proper second dose was done and then you move forward. You don’t have to just start giving lots of vaccines to your child to check some boxes. If your clinician’s not aware how to do this, then shoot us an email, but most electronic medical record systems allow you to go in, put in the information, upload it, and then if you come to New York and you use your Excelsior Pass, you’re putting in where the information was uploaded from not necessarily where the vaccine was given.

VR: This is happening because of the ridiculous position the Governor of Texas is putting parents in. It’s crazy. All right, our last one is from Kristen, “I have a booster question for you. I’m a healthy 48-year-old U.S. citizen with mild asthma at work in South America. I’m fully-vaccinated with Sinovac back in April, May. My husband and I traveled to the U.S. in August. I guess you could say we jumped the gun on the booster advice and went ahead and got a Pfizer jab, no side effects.

While we were in the U.S., we wanted to go to events and our Sinovac vaccines were not recognized. We got a second jab of Pfizer to be considered fully-vaccinated. Now, we have four jabs in and feeling healthy. Fortunately, the country we live in recognized our U.S. vaccine. Here’s my question, over the next six months, I will have to travel internationally at least three to four times. I also work in an elementary school this January, which will be the six-month mark since my second Pfizer shot and fourth jab.

Is there any reason I need a fifth jab? If I do have to get another to keep my vaccinated status in my current country, does it matter what kind I get? Where I live, you typically don’t have a choice like you do in the U.S., you take what you get. I want to be responsible, but is a fifth jab over the top?”

DG: All right, so this is excellent and it really gets at a couple of things. One is, what do we think that third vaccine dose does? Because there’s this issue here and one of the things that we think it does is that for a period of time, it raises those antibody levels so that they’re circulating at a higher level. You’re getting a temporary, let’s say, three to four-month, that’s what we’re anticipating vaccine efficacy against infection. A lot of the third dose, that’s been the focus.

Recently, there’s this suggestion that you may also get a broadening of protection. We don’t know if there’s protection against moderate to severe disease, so that’s one side. It’s been six months. Your antibodies may be starting to drop. Where’s that assay? This keeps coming up. We were great to be able to see that because there might be a medical reason to go ahead and get that third jab because it’s been six months to get that vaccine efficacy against infection for another three or four months. The other side, is it safe?

This scenario you are describing is not uncommon. A lot of individuals have gotten vaccines in other countries are in the same situation you’re in. These repeated jabs do not appear to be a problem, it doesn’t appear to be a safety issue. I’ll throw all that at you.

VR: That’s COVID-19 clinical update number 92 with Dr. Daniel Griffin. Thank you, Daniel.

DG: Thank you and everyone, be safe.

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