TWiV 870 COVID-19 Clinical Update #103

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 26 February 2022

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 870, recorded on February 24th, 2022. I’m Vincent Racaniello and you’re listening to the podcast all about viruses. Joining me today from Washington DC, Daniel Griffin.

Daniel Griffin: Hello, everyone.

VR: How is the COVID situation in Washington? Any different from New York?

DG: I haven’t looked at the numbers too much, but I’ve been watching behavior because we’re actually going and trying to do some things. We’re staying mostly outdoors. It’s actually been easy to eat out a lot on the outdoor, the alfresco-type dining. People seem to be behaving themselves. We were just in the congressional library, Library of Congress, today, everyone wearing masks, people distancing, not a lot of crowds. So far I feel like it’s a safe, comfortable experience.

VR: Very good. Sounds great.

DG: All right. Well, let’s get going. I have to say, this has been a tough week Vincent. First, I’ll start with our quotation and I think people will understand why this has been tough, “If I am hungry, that is a material problem. If someone else is hungry, that is a spiritual problem.” That’s Paul Farmer. As people may have heard, this week Paul Edward Farmer died. He died a young man in his early 60s. This is tough. This is a tremendous loss.

People not familiar with Paul Farmer might want to read the book Mountains Beyond Mountains by Tracy Kidder, really getting a glimpse into just a tremendous human being. Just really a horrible loss. Unfortunately, Paul, very much to his tradition was down in Rwanda, up in the mountains taking care of people, and unfortunately, died in his sleep from a cardiac event. Really quite a loss.

The other thing listeners might have known or not, I was supposed to be in Kyiv, Ukraine at the moment. My wife’s sister is married to a diplomat, so she and my brother-in-law were in Kyiv. We were going to visit them, but as we know, there’s all those political issues going on. A tough week, but we still have tough issues COVID-related.

Let me start with the update with the mention of the Omicron subvariants again. I will focus a little bit on BA.2 or what is referred to as the stealth variant. It does appear to have some degree of a fitness advantage because we are seeing an increase in prevalence, but I still think it’s very premature to be saying much about the mechanism of this fitness advantage, severity of disease, but this really does continue to be a problem mostly for the unvaccinated.

Don’t worry, there are already some experts claiming to know why it has a fitness advantage or ready to tell you that it’s more virulent. I’m going to be old-fashioned, actually, wait till I have science to help on those issues, but as I learn more, I will make sure that in each section I’ll reference what we know. When we get to our section on monoclonal antibodies, I will discuss the potential impact on Evusheld, on sotrovimab.

As the prevalence in some areas, and we break down the US into these different regions, in the New York, so that’s region two, we’re still down about 4% or 5%. Region one, that’s just north of us Connecticut, Massachusetts, Rhode Island, Maine, New Hampshire, Vermont, they’re up to about 7%. The FDA has already repeated their warning about you can’t use monoclonals when they cease to be effective. We’re going to have to keep our eye on BA.2.

What about case numbers? They are dropping. I just want to keep people connected to what’s going on with Omicron in terms of numbers. February 23rd, what about deaths? 2,440 deaths recorded here in the US. Over 10,000 deaths worldwide. In New York on the 22nd, we had 158 deaths in a single day. I do wonder if there’s any amount of data that will get people to stop using the word mild in reference to Omicron. Once it got in there, it just continues to echo.

I do want to point out the height of deaths during Omicron and the time above 2,000 deaths per day. With Omicron, we’ve been above 2,000 for twice as long. Just a reminder, COVID-19 is killing more people now than during most of the pandemic, and yes, this is Omicron. I think that will influence when I talk about some other topics going forward, particularly when we get into children.

I’m going to expand this section a little bit. I would say children COVID, mental health, I’m also going to say and other vulnerable populations, because I think it’s important to expand this section as we go forward just realizing that we still have large segments of our population at risk unable to enjoy the full benefits of vaccination protection. It’s estimated that we have over 20 million children under five in the US. We have over 50 million individuals over the age of 65, many of them with comorbidities, a large number of our population with medical conditions that put them at higher risk of a bad outcome.

It’s also estimated that about 3% of the US population or about 10 million people are immunocompromised. The CDC actually has a page devoted to individuals with higher risk medical conditions in the context of COVID, but I just wanted to put this in context, maybe address some of the myths. There’s an article published in 2016, that is not so old that we can disregard it, and it was prevalence of immunosuppression among us adults 2013. This was published in JAMA. There’s a really nice figure in this paper.

One of the things I like about this is that it breaks down the immunosuppressed into different age groups. I think there’s this perception that somehow we know who are immunosuppressed, that this is really pretty much the older folks, but what we can see if we look at that figure, and I do recommend people take the time to look at this, it does not appear to be behind a paywall. If you look at those youngest individuals that they looked at, 18 to 39, between 1% to 2%, it’s actually about 1.6% or about 1 in 60 people in that younger age group are immunosuppressed. If we look at females, the number goes up. Certain ethnic groups, it goes up even a little higher.

Think about this when we’re moving forward, you’re in a movie theater with 100 people, perhaps you’re in a lecture hall with 100 students, on average, 1 to 2 out of the 100 will be immunosuppressed. Ed Yong recently wrote a nice piece for The Atlantic, “The Millions of People Stuck in Pandemic Limbo: What does society owe immunocompromised people?” It’s a really nice article and I recommend people look at this, because as we go forward, this is going to be an issue.

VR: Daniel, this is a whole range of immunosuppression, all different B cells, T cells, everything, innate immunity and so forth, is that correct?

DG: I think it’s good that you bring that up, Vince. I’m glad you did. I want to bring this up in a reassuring. The person who has lupus and is on a low dose of an immunosuppressant, that’s not the same as someone with a kidney transplant. When we hear from the CDC, Dr. Walensky was talking about who it is that are still dying despite vaccination. She really made the point, and it’s tough because it’s political, but the people that are dying despite vaccination, despite our therapeutics, they tend to be almost all of them, so 75% over 75, four or more medical conditions. Every degree of immunosuppression is not the same.

If you have an immunosuppressed condition, don’t feel like you’re being left out in the cold. Talk to your physician, your level of immunosuppression might be different than someone else’s. Also, as we’ll get, there are things we can do, and in coming weeks, we’re going to have better access to therapeutics. I think that’s important. Immunosuppression is not a binary.

VR: Also, Daniel, there are people immunosuppressed because of, say, transplants or HIV/AIDS, but then they’re also with genetically-based immunosuppressant, agammaglobulinemia skin, so forth. Who’s in the majority, do we know?

DG: It’s interesting. It’s evolving over time. We’re doing more organ transplant, that population is growing, but no, that’s not the main population. It’s a lot of individuals, actually, a lot of individuals are, as mentioned, medically immunosuppressed, they’re on therapeutics that are interfering with their responses. As we get better at medicine, better at keeping people alive, the comment an individual made to me in Ghana then, the people with comorbidities, they’re not still alive. We’re doing a really good job of giving these people extra years.

No, but excellent. Thanks for bringing that because I think that this is not binary, this is a complex population. I like to say people living with immunosuppression, you’re not defined necessarily by it. Back to children. How are we doing there? Vince, you got to make Dickson listen to my episodes too because he seemed shocked when I mentioned that children were dying from COVID 19. What I will say- [crosstalk]

VR: He doesn’t even listen to our episodes too.

DG: [laughs] He doesn’t even listen to you and he is on the show. Don’t have Dickson to listen to this, he’ll say we’re not being nice to him. Dickson, if you’re listening. Anyway, so what about pediatric deaths? We are still another 20 pediatric deaths for the week ending 2/17. For the last three weeks that we have data, we’re still averaging about three pediatric deaths a day. This is terrible.

What about hospitalizations? It was a nice MMWR, hospitalizations of children and adolescents with laboratory confirmed COVID-19. I’ll just go ahead and say in this data. Coinciding with increased circulation of the Omicron variant, COVID-19-associated hospitalization rates among children and adolescents aged 0 to 17 years increased rapidly in late December 2021, especially among children aged 0 to 4 who are not yet eligible for vaccination. Now, the Omicron variant peak was four times that of the Delta variant peak in terms of hospitalization for children, a thousand children a day getting hospitalized.

These are the numbers. These children still we’re hearing that we’re not going to have vaccines until maybe April at the earliest. When we’re moving forward, we still have this high risk population. Yes, children die of COVID. I was over at the Lincoln House. This is actually where Lincoln spent some time. I was in the room today where he wrote the Emancipation Proclamation. The person was talking about, very distracting for Lincoln, they were burying 40 union soldiers a week, I’m like, “You know what? We’re burying 20 children a week from COVID,” so just to give this context.

Transmission testing. I think we’re doing better with testing. Let’s continue with that. This is not the time to stop, if you’re feeling crummy, decide to skip that test and head to a Super Bowl party. Pre-exposure period NPIs. We’re actually expecting guidance on masks from the CDC. We’re expecting some changes. Currently, we’re slated next month to have masking end on airplanes and other situations like that.

As I mentioned, this is why I bring up the immunosuppress. We’ve got the protection of those vaccines, but for many in our society this is going to be tough in the coming weeks. Active vaccination. Never miss an opportunity to vaccinate. There’s a lot happening here. A few changes in the CDC recommendations on COVID vaccination. They updated this web page on February 22nd, that was Tuesday. It was 2/22/22. We should have recorded this at 2:22 in the afternoon, but they added a consideration for an eight week interval between the first and second doses of a primary mRNA vaccine schedule.

We’ve talked a bit about the logic before and the fact that this was perhaps less than ideal an immunization, from an immunology standpoint, the idea that, “We’re in a pandemic, we want to leave these people unprotected for as short a period of time as possible getting that second dose in,” but the thought over time that if you wait for about eight weeks before you get that second dose, maybe we’re going to get a robust response.

Also, and I think this is important as well, there’s a suggestion that this may even decrease the incidence of myocarditis. There’s actually a little bit of a qualification on the CDC recommendation saying an eight-week interval may be optimal for people aged 12 years and older, especially for males aged 12 to 39 years. A little bit more flexibility, but what I want to say here is active vaccination recommendations have gotten rather complicated.

For a lot of us taking care of particularly immunocompromised individuals, we’re going to have to start looking at these tables, as mentioned last time, for the immunocompromised. There’s actually three doses up front for the mRNA vaccines. First dose, three weeks later, second dose, three weeks later, third dose, and then three months later is that fourth or shall I say boost. Getting a little complicated. We’ll have to keep looking this stuff up, making sure we’re staying up to speed, even the CDC, I have to say I’ve gone through their different pages and not all of them are updated.

Another vaccine option might be coming our way. We recently heard that Sanofi and GSK will seek regulatory authorization for their recombinant protein-based vaccine. This is a 10 microgram antigen formulation of the SARS-CoV-2 adjuvanted recombinant protein-based vaccine to be given as a two dose primary and then probably followed by a boost, a similar tried and true tested technology as Novavax or the SHINGRIX shingles vaccine.

We have a press release at this point with some data. What do we know? The final analysis of the global VAT02 booster trial confirms universal ability to boost neutralizing antibodies, so that’s the boost role, but we also have a VAT08 Phase 3 primary serious trial. Two doses of the Sanofi–GSK vaccine in Sierra native populations, what did we get? 100% efficacy against severe COVID-19 disease and hospitalizations, 75% efficacy against moderate or severe COVID-19, 57.9% efficacy against any symptomatic COVID-19 disease.

Just a couple things to throw in here, really encouraging data for a primary two dose series, but as I also mentioned, we have that other trial showing that we can use this as a boost, increasing those neutralizing antibodies 18- to 30-fold, and if we boost after a primary series with the Sanofi-GSK, with the Sanofi-GSK as a boost, they were reporting neutralizing antibodies increased 84 to 153-folds compared to pre-boost levels.

VR: Daniel, what was the gap between the two doses?

DG: I believe it was three to four weeks, but I do not have it mentioned here. Again, that front-loaded short interval.

VR: What would be the reason for boosting with this as opposed to mRNA or adenovector, for example?

DG: We just recently ran into this, the issue with healthcare workers requiring that they be boosted. A number of individuals, they tolerated the first dose then they had an issue with that second dose. Boy, this is another option. Some of the second doses, clear cut, pegs, something like that. Some of the other, let’s say you had myocarditis, something like that, this might be an option for saying, “I want to jump ship, try a different platform.”

What about the science behind vaccination versus just getting infected? An interesting meme I was reading lately about people who want to get infected to protect him against getting infected. It was funny the whole point that, well, then you’re getting infected and all the risks that come with getting infected. The preprint SARS-CoV-2 Omicron triggers cross reactive neutralization and FCE vector functions in previously vaccinated, but not unvaccinated individuals. This is up as a preprint. The researchers used plasma from 20 unvaccinated, and seven vaccinated individuals who were then infected during the Omicron wave in South Africa.

They went ahead, they tested binding antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, so neutralization against VOCs. In unvaccinated individuals, they found that Omicron-triggered neutralization was not extensively cross reactive to other VOCs, variants of concern, with 20 to 43-fold reductions in titer. In contrast, and this is really the important, vaccination followed by Omicron infection improved cross-neutralization of variants of concern with titers exceeding 1:2,900. A couple interpretations by the authors.

This has important implications for the vulnerability of unvaccinated Omicron-infected individuals to reinfection by circulating an emerging variants of concern. Further, while Omicron based immunogens may be adequate boosters, they are unlikely to be superior to existing vaccines for priming SARS-CoV-2 naïve individuals. Interesting speculation in the last sentence, I’m not sure, the science will tell us. Interesting building this story that people who get infected by one variant seem to have some degree of protection against the same variant, but really showing that vaccination prior to infection really triggers a better immune response.

Now, this next paper is one that Amy sent my way. “SARS-CoV-2 Reinfection Prevents Acute Respiratory Disease in Syrian Hamsters, but Not Replication in the Upper Respiratory Tract.” This is available currently as a journal pre-proof accepted for publication in Cell Reports. I really like the introduction, actually, and I encourage our listeners to read this. The authors point out that reinfection with coronavirus is not unprecedented and has been clearly demonstrated for three of the four seasonal human coronaviruses, so NL63, OC43, and 229E, prior to this current COVID-19 pandemic.

They point out that before the COVID-19 pandemic, we already had evidence that immunity gained from primary infection with these seasonal coronaviruses can wane quickly and they reference a number of studies, including one study demonstrating reinfection within six months of primary infection at a rate of respectively 21%, 5.7%, and 4.0% for NL63, OC43, and 229E respectively.

They also describe that some of the first patients in this paper who had that documented reinfection. I still remember the days when there was really– I think a lot of people did not want to believe that you could get re-infected. It’s now clear that reinfection is not uncommon and we now have several examples of people that have had worse outcomes with their second infection compared to their first, including hospital admissions, ICU admissions, and death with a reinfection after surviving the first infection.

In this study, the investigators looked at homologous reinfection, so getting re-infected with the same isolate, and heterologous reinfection, so getting infected a second time with a different isolate. The good and the bad, it did appear that prior infection conferred protection against severe disease in the hamsters for a period of time that they investigated, but it still looked like there could be robust replication in the upper tract with those reinfected, potentially allowing them to participate in onward transmission. That’s the bad. Lots of limitations, as the authors acknowledge, but this is an important topic to investigate, as I know a lot of people are looking at this situation.

A lot of people have been infected then been vaccinated or been vaccinated and then been infected. Still a lot of people that have been infected not yet been vaccinated, just more science there helping us sort that out.

I also think it’s important as numbers are decreasing and we as a country appear to be moving away from non-pharmaceutical interventions such as masks, distancing behavior, that we look at the fact that only 65% of Americans are fully vaccinated. It’s a little more encouraging in that the percentage of fully vaccinated is highest in the highest risk group, so the over 65, but then starts to drop in the 18 to 64. By the time we get to the 5 to 11, we’re down to only about 25%.

It is regional, but I know a lot of people are hoping that prior infection are going to help us here, but we’re seeing a falling off of people showing up for those first vaccine doses. We’ve tried carrots, we’ve tried sticks, perhaps we could try a little more science communication.

I wanted to actually, again, keep hammering on the same topic, the concept of reinfection. I’m actually going to bring up a paper that was published a year ago, Direct Observation of Repeated Infections with Endemic Coronavirus, published by Marta Galanti and Jeffrey Shaman who’s been on TWiV. They presented data from proactive sampling carried out in New York City and they noticed no significant differences between the probability of testing positive at least once and the probability of a recurrence for the beta coronaviruses HKU1 and OK43 at 34 weeks after enrollment first infection. They also found no significant association between repeat infections and symptom severity.

It’s just this big thing. Whenever I bring up, “Oh, we’re here with the vaccines,” people like, “Oh, can I just add prior infection on? Are those people going to be just OK?” I think this is the big challenge with all these discussions of herd immunity with prior infection, is that coronaviruses, this is their operandus modi, is they’re associated with reinfections and that reinfection, as we have a recent celebrity person, second infections can be really bad and actually worse than the first.

VR: Daniel, there was no reason to think in the beginning that we wouldn’t get– I remember that very early on, people thought, “Oh, we’re not going to get reinfected,” but that not only ignores what we know about common cold coronaviruses, but most other vaccines against viruses which don’t prevent infection. I’m not clear why we got into this mode, you and I did not, but why did the mass media get into this mode? There are certain pundits who told them this?

DG: Yes. I think that’s what it is. It’s reassuring, people wanted to hear one and done, and then when it turned out it wasn’t true, they still didn’t want it to be true. Passive vaccination, have you shelled? We’re still using that, so just continue to think about that as we mentioned. If you have an individual who cannot develop that robust protective response to vaccine, this is something that is available. At this point it’s every six months, we’ll see how that goes, hard to predict that far out into the future, but a number of patients we’ve been using this in very well tolerate it, so everyone, remember that as an option.

The period of detectable viral replication. Everything has fallen through, the person is now tested positive. I like to say this is the time for monitoring monoclonals antivirals and enrollment in clinical trials, not the time for steroids, or antibiotics, or zinc, or aspirin, or other unproven and potentially harmful potions.

I’m going to emphasize antimicrobial resistance here, and I want people to go. I’m going to plug one of our other shows TWiM 259. This is where there’s really a great discussion. I actually have a paper I was going to discuss, so I will only briefly mention it here, but just published in the Lancet, “Global Burden of Bacterial Antimicrobial Resistance in 2019, a Systematic Analysis.”

As we’ve discussed several times, despite really good data, that there is no benefit to antibiotics to treat a virus during the first week. There’s really no benefit to treating viruses with antibacterial agents, which is what is happening here. Even that doxycycline study we discussed, where there was higher mortality in the antibiotic-treated group, the majority of people with COVID-19 are still getting antibiotics. Ouch.

What that is doing is that is feeding antimicrobial resistance, and the authors in this paper estimated that over a million deaths were attributable to antimicrobial-resistant organisms. These were mainly lower respiratory infections, bloodstream infections, some intra-abdominal infections, urinary tract infections. E. coli came out as number one, followed by staph aureus.

What triggered me, Vincent, was I was looking, I made the mistake of looking at one of the comment sections on one of the TWiV’s. I think it was the last time where I talked about how azithromycin was not helpful, and then someone’s comment was, “I’m over 65, I might just take a Z-Pak to be safe.” It’s not safe. It’s ineffective. It’s potentially harmful. You know what? You might not die in the next few weeks, so you are going to join us going forward into the time when our antibiotics stop working.

Who is the most at risk for an antimicrobial-resistant organism? The person who has recently taken antibiotics and selected that. This is not helpful, it is harmful. Those of us that took some kind of an oath, keep in mind, do not contribute to this, please be good stewards of antibiotics.

Ivermectin. Vince, I’m going to talk about ivermectin, but which studies shall I talk about? Well, this was, ivermectin does not protect against SARS-CoV-2 infection in the Syrian hamster model. These investigators found that ivermectin did not reduce lung viral load, and even significantly worsened the SARS-CoV-2-induced lung pathology. They even looked at combining with molnupiravir, and you know what? That wasn’t helpful either.

I want to keep pointing out here, if you’re excited about ivermectin, look at enrolling in a clinical trial. We do not have any reliable studies that were done that were not plagiarized, that were not fraudulent, that really are compelling for the use of ivermectin at this point.

VR: Danny, we do have some ongoing trials currently, is that right?

DG: Yes, we have two really big trials. There was one that was recently published that was not supportive. They’re still waiting for the COVID-OUT trial fully enrolled, so we’re really waiting to see the data from that. We still have the ACTIV-6 trial. We’re going to get more data soon. You know what? We have yet we’re two years into this and I have yet to see any compelling placebo, randomized control, properly-done studies that show ivermectin work.

There’s a lot of stuff out there that now we realize trials that were never done, people who forged the data for whatever agenda. Ivermectin at this point does not have a role in the treatment of COVID-19, and you can quote me on that. [laughs] What does have a role? Because we do have options here, Paxlovid We are headed towards better access to the highly effective outpatient therapeutics for acute COVID-19 and we have a couple things working for us here.

One, is the number of acute cases is dropping, so the demand is going down. So far, more than half a million courses of Paxlovid had been distributed to the states. This means that we’re having better access. It’s still not great across the whole country. We’re not quite there, we’re almost there. I expect next month to be when we really are at that point where when we want to get Paxlovid we can.

I’m also hoping it’s at that point where it’s just a matter of clicking it on your electronic medical record, a lot of us do e-prescribing on our phones, at this point it’s still picking up the phone, it’s still knowing where to call, talking with the pharmacist knowing, one, is my patient high risk and is this warranted? Two, what’s the kidney function? Three, are they on any other medications?

Funny enough, last time I was with my parents, I ran through their kidney function, their medicines, just making sure we were good to go should they get an infection and to give people follow up, our 75-year-old was CLL, we talked about last time got started on Paxlovid same day and so far, so good. All right, if Paxlovid 88% to 89% reduction in progression is not available or cannot be used, then we move to monoclonal therapy.

Here’s our bit about keeping track of variants. More investigations have questioned the efficacy of various monoclonal, such as sotrovimab and Evusheld should you have the BA2 variant circulating. The article “SARS COVID 2, Omicron BA2 Variant Evades Neutralization by Therapeutic Monoclonal Antibodies” was posted as a preprint.

This is out of Nathaniel Landau’s lab over at NYU. We now have concerns raised by investigators at Columbia, David Ho’s lab, NYU. Now, these investigators use the same pseudo for antiviral assay, and in their hands found that the BA2 evaded neutralization by all the currently available monoclonals, including sotrovimab and Evusheld. We’re going to need to keep track of that. That’s the one thing about BA2 that we are starting to have some well-based concerns.

Still, on the sotrovimab, on the sotrovimab have submitted GSK and Vir have submitted EUA application to the FDA for intramuscular administration. Think about it now, you’ve got to go somewhere, they’ve got to establish a main and maintain an IV, but here, phase III randomized open-label non-inferiority tail trial demonstrating that 500 milligrams IM administration of sotrovimab was non-inferior and offered similar efficacy to 500 milligram IV administration. There was a 250 milligram, 500 milligram arm. The 500 milligram dosing is what they’re going, but this would really be a great addition. Paxlovid as your first choice, sotrovimab, IM, a lot easier to get into patients than having to deal with IV.

Moving next, Paxlovid monoclonal, the next remdesivir. Remember, three-day outpatient IV therapy, 85% reduction in progression if given early. Don’t leave our patients without an option because the next is molnupiravir. Almost two million courses of molnupiravir have been distributed to the states. As I mentioned, we’re not quite there yet as far as having as much as we need, but this is that last option in our acute therapeutics, with about a 30% reduction in progressions, hospitalizations, and death, but remember, do not wait to see how the patient does.

This is a numbers game. If your patient is high-risk, go ahead. If you wait till they start feeling bad, till they start getting hypoxic, you have missed your window. Unfortunately, that appears to be a continued issue. If you missed your window, you end up in that early inflammatory phase where our therapies are rather limited. Remember, steroids anticoagulation, if they end up in the hospital, pulmonary support.

Moving to the tail phase. Again, I feel like I’m going to keep plugging other this week in podcasts. I really enjoy TWiV 869: Epstein-Barr virus and MS, a perfect storm, and as we discussed on a prior episode, one of the predictors of long COVID was EBV reactivation in the acute period. We still have millions of people suffering from long COVID and other post-acute sequelae of infectious diseases. Properly funded and conducted research is how we will end up with ways to help these people. Millions of people are continuing to suffer without a lot of great options.

VR: Daniel, it will be interesting if one of the antibodies against EBV, like in MS, it’s against a nerve protein, maybe a different protein that leads to cross-reactive antibodies in long COVID, right, that could be looked at very, very easily?

DG: Yes. I know they’re actually looking at that up at Yale, which is interesting, and a number of other labs. That’s one of the ideas, you’ve triggered– and it probably is a number of mechanisms, but one of the mechanisms very well may be an antibody with an off-target impact like that. Yes, but we need the research to sort this out, and millions of people are waiting for those answers. No one is safe until everyone is safe. I wish I had more good news here, I wish I could say, “Oh, we’re vaccinating the world at a rapid pace,” but we’re not, we still have a lot of work to do.

I will remind everyone to please go to Parasites Without Borders, click donate. During the months of February, March, and April donations made to Parasites Without Borders will be matched and doubled up to a potential donation of $40,000 to the American Society of Tropical Medicine and Hygiene, including scholarships for their annual meeting travel awards to attend the 2022 meeting in Seattle, Washington. Priority for the scholarships will be placed on females from low-income countries who might not otherwise be able to attend.

VR: All right. It’s time for some questions, your questions for Daniel. You can send them to daniel@microbe.tv. Philip writes, “I currently take atorvastatin, which I understand is not compatible with Paxlovid. I would think about suspending it if I got COVID and say, “To hell with the lipids for a week or two.” I have an appointment with my doctor in April. I may discuss switching to another statin. What are your thoughts on this? To TWiV land.

DG: Yes, so this is perfect. Vincent, this may sound an esoteric question to you, but this is my bread and butter. I’ve been actually going through, because what they say now is, “Oh, it’s binary, if they’re on this, you don’t want to use the Paxlovid,” look at those medicines. Start using medicines that don’t have cytochrome P450 interactions because COVID is here to stay. At this point, Paxlovid is the most effective therapy.

It’s very simple to say, “You know what? Let’s switch from that Lipitor, that atorvastatin, to Crestor.” That’s one of the alternatives that doesn’t have interactions, and then you’re good to go. Because that’s what you want to do, you want to be good to go, you want to have a plan because COVID is here to stay.

VR: Madeline writes, “COVID has finally found my family, and of course, the experience brings up some questions. My husband and I are both 32 and triple-vaxxed. We have a seven-month-old son who obviously is not. Due to a negative rapid test about 24 hours post-symptom onset, we thought it wasn’t COVID, and by the time we had a rapid come positive the next day, my son and I were clearly improving. This was really the best case scenario without having the stress of worrying about COVID while it was in the acute phase. I now know that my son has some active immunity and didn’t have to suffer much for it, but then I was thinking about how hospitalizations aren’t really due to the acute infection so much as the inflammatory phase of the disease and I wondered are we necessarily in the clear yet? For example, if class COVID is weak viral and a weak inflammatory, would you expect that a two-day viral course would also have a two-day inflammatory phase, or does SARS-COV-2 only get the immune system really revved up when it’s a lot of virus, or is it a lot of virus for a long time that matters? For us, it feels like it will be another day or two of feeling crummy, so I’m not worried. Just curious.”

DG: Yes, no, this is great. Particularly, in people who are vaccinated, I’ll say quite often in younger, healthy individuals, that initial viral phase can actually be pretty mild. Chunk of people have asymptomatic. We’re starting to realize not as many people, if we really watch closely, are asymptomatic. There was actually a NICE recent study in healthcare workers, where they observe them and realized that, “Yes, actually, completely asymptomatic is not out as common as people once thought, but a lot of people never even have a noticeable early inflammatory phase. They feel crummy for a few days and then that’s it. It’s the people who feel crummy maybe start to feel better. I remember Ian, “First I had a virus, but then I got COVID.” That’s the experience that some people get. They feel like they have a virus and then boom, they feel you like that early inflammatory phase. Hopefully, you will not even experience the early inflammatory phase, so fingers crossed.

VR: Fiona writes, “Hi, Daniel, or rather, Kia Ora, as I’m writing from New Zealand, and Te Reo Māori is an official language here. Here in New Zealand, Aotearoa, vaccination rates for adults are getting and high. Third dose rates are climbing, too. However, children between 5 and 12 are still only on their first dose of the vaccine as New Zealand is doing an eight-week gap between doses.” Good for them.

We’re just going into our worst wave of COVID. We were able to pretty much hold off SARS-CoV-2 until very recently and get vaccination rates up as much as possible before Omicron started spreading. How will our children fare against Omicron, which is the partial dose? It’s possible second doses will open up sooner than eight weeks, but if not, our 11 year old is two weeks away from being eligible for his second vaccine, then there’d be a bit of time needed for that to work effectively, I think. That’s potentially a month without good protection against Omicron. What would your recommendations be?

DG: This is a very timely email. I only sent you my notes about 15 minutes ago, Vincent, so I know you didn’t have time to plug this, but this is great. Why did we do three to four weeks? Why are we now talking about eight weeks in younger individuals? From an immunological standpoint, waiting the eight weeks seems to give better response, more robust response. The three to four weeks was a height of pandemic response.

Also, we’re seeing some evidence, a recent study out of Canada, that you’re really going to be reducing those myocarditis risks by way waiting eight weeks instead of doing it right in the first three to four. I actually think this is a reasonable approach. I’m going to just encourage you, be careful, continue to protect your children during these several weeks. Remember, this is a marathon. SARS-CoV-2 is a virus. It’s here to stay. It’s in animals. We’re always going to have the unvaccinated. We’re always going to have people coming from unvaccinated populations. I actually think the science really supports this strategy, and just like Vincent, kudos to this approach.

VR: Fiona writes, “Thank you, Nga Mihi.” Finally Mary writes, “Given the CDC report from 122 showing decreased COVID vaccine effectiveness for EDUC visits and hospitalizations four months post booster. Would it be advisable for pregnant women whose delivery date is four months past her booster to get another shot, so a fourth shot, would age be a factor in this decision?

DG: Yes. We talked a little bit about this last time. Being pregnant is a dangerous time to get COVID, both for the pregnant woman and for the unborn child. Increased hospitalization rates for the pregnant woman increase loss of the child during pregnancy, but we also talked about how being vaccinated during pregnancy can potentially transfer protection to the unborn child. We’re still waiting for a little bit of details here, does it make sense to get that booster in that last trimester? Let’s say, three or four weeks before the scheduled birth to augment that. The science is building to support that kind of a scenario.

VR: That’s COVID-19 Clinical Update, Number 103 with Dr. Daniel Griffin. Thank you, Daniel.

DG: Oh, Thank you, Vincent, and thank you, everyone. Remember, be safe out there.

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