TWiV 820 COVID-19 Clinical Update #85

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 23 October 2021

pdf of this transcript available (link)

Vincent Racaniello: This Week in Virology, the podcast about viruses, the kind that make you sick. From MicrobeTV, this is TWiV, This Week in Virology, Episode 820, recorded on October 21st 2021. I’m Vincent Racaniello and you’re listening to the podcast all about viruses. Joining me today here at The Incubator in New York, Daniel Griffin.

Daniel Griffin: Hello, everyone.

VR: Daniel is right next to me, which is unusual. We’ve never done this before. The updates started after COVID. Now and then, you would come to the Columbia to do a TWiP.

DG: Things were starting, I think, it was at right the end of February. early March. I came to the office, keeping very distant, looking in a different direction. I was already very worried.

VR: That’s right. That was maybe what? February?

DG: We should look back, but that was the first year at the end of February early March. Just when it was.

VR: This is actually not the first time I’ve seen you because we actually searched for this space last year, I guess it was last summer.

DG: I remember coming and taking the train in and looking at some spaces.

VR: Daniel is here today because he’s spending some time at Columbia and we decided to record right here at The Incubator. What do you think of The Incubator, Daniel?

DG: I like it. It’s convenient. I started my morning coming in on the train just like I did when we were looking at spaces, spent the morning up at Columbia on the wards. I feel like I’m back in the scrubs world again being the attending, and then just quick subway ride and I was here. It’s a nice space– looking forward to this.

VR: That’s a very nice space. We’re going to be able to do a lot, but we’re here for COVID-19 clinical update number 85. What’s new, Daniel?

DG: All right. I don’t have my clock that I usually look at, so keep me on schedule, but let me start with my quotation, “Good decisions come from experience. Experience comes from making bad decisions.” That’s Mark Twain. As we’ll get into the show, understand we’ve got decisions, a lot of people here in the United States have some decisions to make.

That’ll be relative to our discussion of boosters, but lots going on. One of the first things I wanted to put out as far as updates is the living guideline from the WHO on drugs for COVID-19 was put out. Do you think it’s important to make that comment? This is on drugs. I’m talking about all the non-pharmaceutical interventions, which still are critical. Masking, distancing, ventilation, all the other things we’ve talked about, but if you go to the WHO website or you can actually go to the British Medical Journal

The BMJ has this article, and they actually have a really nice visual to walk people through this. They break it down into disease severity, but I really feel like there should be more timing, but they go through that early period of time when people are just starting to have maybe fever, cough, headache, feeling crummy, but they’re not requiring oxygen. At that point, really, it’s very limited in what they recommend, and it’s really neutralizing monoclonal antibodies.

There’s a lot of stuff they recommend against; ivermectin except in a clinical trial, recommend really strongly against hydroxychloroquine. The data’s in there. We have about maybe a 10% mortality increase, a strong recommendation against lopinavir-ritonavir, that’s one of our HIV drugs we tried to repurpose here. It’s interesting and I think this is going to be a little bit– The remdesivir, there is a recommendation against in all stages in the mild initial week and also into the next two weeks.

Now the Corticosteroids, they’re going to recommend not giving in that first week. We’ve talked about this maybe a six-fold increase, risk of progression if you give them in that first week, but then they have a recommendation in favor, very strong. During that second week in people with oxygen saturation less than 90%, they’re using 90% as a cutoff, signs of pneumonia, signs of respiratory distress, but then also sepsis septic shock, ARDS.

Another, which I’ll say is a big one in here, is the IL-6 receptor blockade. We’ve talked about Tocilizumab and they’re basically saying in those individuals with an oxygen saturation of less than 90% on room air, and we’ve talked about those that are given steroids but continue to progress, they have a strong recommendation in favor.

We’ve talked about the experience at the Northwell Health System where you really want to get that in early if they start to progress at least in that reported experience if you waited until they were on high-flow nasal cannula, till they’re on BiPAP, you’ve waited too long. It wasn’t clear that we had much benefits. Just nice to get an update. I know people are always wanting to have a recap, something visual, and this is, I think, a great thing that can be posted around the world in a lot of these clinics.

VR: Daniel, how penetrant will that be? Will it reach every little medical center throughout the world?

DG: A lot of times when I’ve practiced in these areas, you’ll actually see something like this stuck up on the wall. This will get translated from the WHO to the various ministries. A lot of the ministries will require health district number three or whatever will have to have this on the wall. I think that can be helpful and some of the things here, the IL-6 receptor blockers, I’m not seeing that in every one of these smaller centers. There’s just a huge cost there. Again monoclonals, there’s going to be certain centers where those are– I think the big impact this will have is what you shouldn’t be doing and, hopefully, this is going to help get that corticosteroid use timed properly given to the patients, not given to the wrong patients.

All right. Holidays on the horizon. We have updated CDC guidance. I don’t know if I was planning on celebrating, looking forward to Halloween, which is a great holiday when it comes to– well, just it’s a great holiday and we’re going to go with that. They’re giving some safer ways to celebrate the holidays here, and they are acknowledging holiday traditions are really important. They’re important to families. They’re really important to children. I should say they’re really important to those of us who are older. This is really important. It’s a mental health thing as well.

This is when multiple generations might gather to celebrate the holidays. What can we do to make this safer? Nothing is 100% safe. Don’t let perfect stand in the way of what can be a good holiday. The one thing right up front, “What is the best way to minimize the COVID-19 risks?” Keep your family, friends safer as per the CDC holiday guidance, get vaccinated if you’re eligible.

Then go into a couple of the other things. What can you do? Again, if you feel like you’re repeating yourself, then you’re probably saying it long enough, protect those not eligible for vaccination such as young children by getting yourself and other eligible people around them vaccinated. Wear well-fitting masks over your nose and mouth, if you are in public indoor settings. They say if you are not fully-vaccinated, but we’ll put that in there– The big thing, and I put this in bold, outdoors is safer than indoor.

This is one of my plugs for why Halloween is such a wonderful holiday. Being out there going door to door, getting those bags filled with candy, outdoors is much safer than indoors. What you really want to be doing, as per the CDC guidance, and I agree with this, is avoiding crowded, poorly-ventilated spaces.

If you’re sick, if you’re not feeling well, don’t host or attend a gathering. And get tested. Get tested if you have symptoms, get tested if you have any concerns, and we’ve always talked about, “Get tested if you’re going to be around a more vulnerable individual.” And we’re starting to see better access to those rapid tests here in the U.S. I’m going to hit on those rapid tests in a story shared with me as we moved forward.

All right. Children are at risk of COVID. Wearing a mask is less traumatic for a child to being hospitalized. There’s a bunch of trackers that I’ve talked to people about, where we can keep track of what’s going on among our younger segment. Let’s talk a little bit about some data we have here on vaccines and adolescents.

We are hearing that there was great effectiveness for the Pfizer-BioNTech in adolescents and in the MMWR, we had the early release, “Effectiveness of Pfizer-BioNTech mRNA vaccination against COVID-19 hospitalization among persons aged 12 to 18 years, United States, June through September 2021.” This study used a test-negative design in which vaccine performance is assessed by comparing the odds of antecedent vaccination among laboratory-confirmed case patients hospitalized with COVID-19 and hospitalized controls without COVID-19. There were 464 patients in the final analysis. This was 179 case-patients, 285 control.

The nice thing here is we’re going to get real-world experience. We saw from our trials this near 100% efficacy, but what are we seeing out there in the real world? The vaccine efficacy against COVID-19 hospitalization. Here’s what I ask, “What is that efficacy?” Vaccine efficacy against COVID-19 hospitalization was 93% during the period when Delta was the predominant variant.

Among the 179 COVID-19 case-patients, only 3% were vaccinated, 97% were unvaccinated. Overall, 43% of the case-patients were admitted to an ICU. Almost half of these, adolescents, were admitted to the ICU. 16% actually required life support during hospitalization. This is mechanical ventilation, this is vasoactive infusions, this is ECMO. Then 7% of these critically ill patients died.

A point I want to make, all of the case patients admitted to the ICU, all critically ill case-patients, and all deaths occurred in the unvaccinated patients. Even though we talk about hospitalization, the hospital experience can be quite different. The average length of stay was five days for the unvaccinated, but the vaccinated patients were in and out in three days, with as you saw, not ending up in the ICU, not ending up ventilated, not seeing death in that group.

I think this becomes important because there’s always been a lot of conversation about why are we vaccinating children? Are we doing this just to protect their parents? Just to protect more vulnerable adults? There is an argument there. I think we’ve heard how many, like over 100,000 children have now lost their primary caregiver, so that is a problem if a child transmits and they lose their caregiver. But we’re also seeing evidence here that vaccinating adolescents can really protect them.

We’ve also heard that the White House has a plan, and is getting ready for extension of the EUA for the Pfizer-BioNTech down to children 5 through 11. I really have to say, I like their plan. Once authorized, the White House has vowed it will quickly distribute shots across the country, and where are these shots going to go? They’re going to go to 25,000 pediatrician offices, primary care sites, as well as hospitals, pharmacies, and community health clinics.

For a lot of parents, they really don’t want to just go to one of these mass vaccination sites with the military present. They may want to go to someone that they trust, someone they can have a conversation with. Because for a lot of parents this is a big decision, and they want to trust a person to have that conversation with.

All right, testing. Never miss an opportunity to test. Just a little reminder on the issue of overdiagnosis with PCR, and just how great the rapid tests are for picking up people who are infectious. I think it took us a long time to get here. I’m going to quote an email from a colleague of mine, “I saw an uptick in COVID over the past week. We had four negative rapids, followed by a positive PCR. Thankfully, we do not clear to go back to school until the PCR.”

My response was, “Remember the negative rapids probably mean non-infectious. I say that with 98% confidence. If you could get CT values on those PCRs, I suspect they’ll be greater than 30, and those kids not infectious. I would love to stop picking up kids with just low-level viral RNA with PCR and do a test-to-stay with only rapids. Even more appropriate to think about this as we get more kids vaccinated.” Just my take on that.

This is what we’re seeing– I say this is the rule in my school district, and I think I talked about it before, individuals who didn’t feel well could have done a rapid and I would have felt comfortable. We have some studies, several studies, showing that if that rapid is negative and that child goes to school, we are not seeing transmission. Having to wait for those PCRs, at some point, we’re going to have to have a tide change here because a lot of children are missing educational opportunities, and those rapids, as we’ve seen, are really excellent. Over 98% sensitive at picking up folks that are contagious.

Active vaccination, never miss an opportunity to vaccinate and vaccination is how this pandemic ends. Vaccine, the jabs that keep you from getting sick. We start off here with a public service announcement, “Please get your flu shots.” We’re always already starting to see cases of flu. Remember, schools are open, many places the masks are off, so that little reprieve we had last year when schools were closed in many areas when everyone was wearing masks, not everyone was really doing that.

The flu vaccines significantly reduce the risk for hospitalization and death from flu. I feel like we disparage the flu shots a little, but it may be as high as 90% of flu deaths occurring in the unvaccinated. This is certainly described for influenza-associated pediatric deaths. Think about this, not just for you. Maybe you’re very strong and you’re not going to get that sick from the flu, but you can be part of that transmission. If you can get vaccinated, you’re doing something for yourself, and I’m going to suggest it’s a patriotic thing to do for our country and for our fellow citizens.

Lots new on the booster front. First the article, “Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine.” That’s the Pfizer-BioNTech. This was published in Cell, so it’s hard to read a Cell article. These are deaths, but this article builds on the idea that maybe getting a second dose of an mRNA vaccine three to four weeks after the first dose was perhaps a bit rushed.

We did that because we we’re in a pandemic, and we wanted to get up to that level, but perhaps we would get an even better response if we waited. This actually feeds into that narrative that I’ve been hearing that this dose we’re talking about now is really that third dose is really a better timed second dose.

In this study extension of the interval between doses, it was introduced in the UK to accelerate population coverage. The authors here are reporting in a sub-study of 589 individuals, and they report that the neutralizing antibody levels were higher after the extended dosing interval. Here we’re doing six to 14 weeks, instead of just that three to four. They also looked at CD4 T cells.

One other things I will say is the big impact they saw was an increase in peak neutralizing antibodies and B cells, but we’re not really seeing as much of an impact on the T cell. I think that’s an important comment there. This relates to the fact that that has caught the air support, that great protection against hospitalization and death. There may be a lot more T cell involvement there than just the antibodies.

The letter to the editor, “Differential Kinetics of Immune Responses Elicited by COVID-19 Vaccines,” was published in The New Journal of Medicine. Here, the authors reported on antibody and T cell kinetics. They reported that the BNT162b2 and mRNA-1273, this is the Pfizer and the Moderna vaccines, were characterized by high antibody responses that declined sharply by six months. These responses declined further by eight months. Antibody titers and the recipients of the–

I’m going to switch over to brand names here, the Moderna, the Spikevax vaccine, were generally higher than those of the folks that got the Pfizer-BioNTech Comirnaty vaccine. Now the Ad26.COV2.S, the J&J vaccine, induced lower initial antibody responses, but these responses were relatively stable over the eight-month follow-up period with minimal to no evidence decline, and it will save you.

Actually, look at the figures of this paper. When you get out to about eight months, the Pfizer has dropped below the level of the J&J. The Moderna has dropped to the level of the J&J, but what about T cells? At eight months, the median CD8 T cell response was 0.016. With the Pfizer, 0.017, with the Moderna, 0.12, so about a log higher, about ten-fold higher, with the J&J vaccine. With all three vaccines, the T cell response showed broad cross-reactivity against SARS-CoV-2 variants. We are learning more about these different vaccines and the kinetics of the response. Why are we talking so much about this? Because now on Wednesday 10/20/2021, so the 20th of October, the FDA expanded the use of booster doses of COVID-19 vaccines in eligible population.

Let’s go through what exactly this means, and they do a reminder here. The agency is amending the EUA for the COVID-19 vaccines to allow for the use of, and we’re going to go through this here, a single booster of the Moderna COVID-19 vaccine that may be administered at least six months after the completion of the primary series to individuals who are 65 years of age and older, 18 through 64 at high risk of severe COVID-19, 18 through 64 with frequent institutional or occupational exposure to SARS-CoV-2. Think of your healthcare workers.

The use of a single booster dose of the J&J COVID vaccine may be administered at least two months after completion of the single-dose primary regimen or a single dose shot in individuals 18 years of age and older, and they don’t qualify. This is anyone who got a J&J, it’s been more than two months, you can go ahead and get that second J&J shot if you want, or the use of each of these vaccines as a mix and match booster.

Going back to those eligible populations, if you got J&J and you want to do a boost, if you got two shots of an mRNA-based and now you want to boost with instead of Moderna, of Pfizer, instead of Pfizer, of Moderna, instead of mRNA, maybe you want to do J&J at that point. They are basically opening this up and giving people options here. They do clarify that stuff we talked about before, all those people who’ve been eligible for that third dose of Pfizer-BioNTech, you can go ahead and get another dose of Pfizer-BioNTech if you choose.

VR: Daniel, does it make an improvement if you say got Moderna and then get Pfizer or Pfizer and then Moderna, within the mRNA vaccines, does that matter?

DG: We don’t really know. We talked a little bit last time about those antibody studies where there was a slightly higher level of antibodies if you did two Modernas and then a Pfizer at a slightly higher antibody level, if you did two Pfizers and then a Moderna, but it was really a slight– I’m not really sure that there’s compelling evidence. Certainly, no efficacy evidence. We don’t have the T cell data on that yet. If you’ve been doing Pfizer, Pfizer, and you want to do a third, or I think my mom, I think we talked about this.

She got her two Pfizers, now she wants to join the Spikevax, so she can get the cool t-shirt. She wants to get that third dose for Moderna. It’s going to be half of those first two doses, I think that’s fine. Interesting enough, some people want J&J because they’re starting to buy into this concept of heterologous boosting. Certainly a lot of buy-in and people who got their first J&J, wanting to get two shots of the mRNA vaccine.

VR: I think what you said is really important. Efficacy, we don’t know what the antibody levels mean. I think to say that mixing and matching is good requires some efficacy data and we don’t have that.

DG: I think that’s really key. We talked about last time, when– I think the J&J is a perfect example. You have an individual who got one J&J shot and now they’re trying to figure out what to do next. We talked about the Phase 3 ENSEMBLE to study data where we had efficacy, but this was a very limited number of people. The FDA was a bit critical about how wide those confidence intervals were, but that was at least I’m trying to present some efficacy if you get a second dose of the J&J.

Then some people look at those levels and they say, “Well, if I have J&J as a background, I’m thinking of that as a natural infection, natural immunity, and then I get to mRNA is we’re extrapolating.” We do not really have all the efficacy data that we will get, and we will get this. I’d like to state that people should have a conversation with their trusted health professionals to help them make the choice that is best for them.

I think that, actually, I say that and it makes me think of my friend, Lucy McBride, who has this concept, which I agree with, that everyone should have a trusted health professional, a primary care physician that they can reach out to, maybe even by phone for a conversation like this, maybe a video visit, maybe even getting in face-to-face, depending on preference, because these are decisions that you want to feel like you’ve made the right choice for you.

I’ve had this conversation, let’s say you’re a woman who’s pregnant. You may be thinking, “I want to do a certain vaccination, get really high antibody levels, so I can transfer them to my unborn child. I want them to be in the breast milk.” Then again, as this has come up, I think on one of the IMMUNEs, there may be more than antibody that we transfer.

Maybe you want a really robust cellular response. Maybe there’s actually transfer of cellular protection to the newborn. A lot of this you really want to feel like you’re making the right choice and in a perfect context. Instead of giving people lottery tickets to get vaccinated, it would be ideal if we gave them the ability to have that conversation, to find out what the best choice is for them. What do you think, Vincent? Am I being too idealistic?

VR: Well, I think if they talk to you, they could make a good decision, but I’m not sure that most other primary care physicians are going to be well-versed. They’re going to just follow the CDC recommendations, I think.

DG: Hopefully, we’ll get them to listen to this TWiV. It’s challenging. You want to make sure you make the right decision for you and if you have questions, I guess they can email us here, right?

VR: Daniel@microbe.tv

DG: The viral symptom phase, the period of detectable viral replication. What we like to say is the time for monitoring and monoclonal. It’s not the time for antibiotics. It’s not the time for steroids. Little more information on monoclonal antibodies, and this was an article, “Administration of Monoclonal Antibody for COVID-19 in Patient Homes.” This was published as a peer-reviewed research letter in JAMA Network Open.

In this publication, the authors describe a program in Michigan and multiple hospitals within the Saint Joseph Mercy Health System, where they were providing home mAbs infusion to prevent high-risk patients from requiring ED care and hospitalization. I have to say this is a topic I’m very excited about.

I should give a lot of credit to Ben Wiegand, who I worked with at UnitedHealth Group, who was repeatedly talking with the FDA, expanding that EUA so that this could be done because remember, mAbs had to be done initially through the remdesivir network. The EUA was expanded to allow this to happen. Here, among the patients administered mAbs in the home, 5.6% were hospitalized following home infusion because of the worsening of the symptoms.

Of those folks, the median length of stay was 3.3 days, non-required intubation, all were successfully discharged. I think just give us a little bit of granularity. Not only did the monoclonal keep people out of the hospital, not only do they protect people from dying, but should they progress and end up in the hospital, it’s a much different experience, 3.3 days. This is similar to what we were seeing in vaccinated adolescents. Remember, these are high-risk patients.

The early inflammatory phase. This is often when people get hospitalized, when they have this cytokine storm or the pulmonary phase. We haven’t talked about tocilizumab in a while, but what’s going on with tocilizumab? The article, “Tocilizumab in patients admitted to a hospital with COVID-19 (RECOVERY): a randomized, controlled, open-label, platform trial,” was published in The Lancet Respiratory Medicine. These are the results of the recovery collaborative group.

I quote my wife, “What would we do without the UK giving us such informative results?” I have to say, the recovery collaborative group has really stepped up. Maybe we can move back into the UK’s basement and start to learn how to do trials like this. In this study, 5,610, 49% of patients were randomly assigned to the tocilizumab group, 5,730, so 51% to the usual care group, and what did they find?

Overall, 21% of patients in the tocilizumab group, 21% of patients in usual care group died within 28 days, so no difference as far as mortality. I’m basically going to go through median time to discharge alive, discharged alive from the hospital within 28 days, required mechanical ventilation at baseline going on to mechanical ventilation, basically, all the way across, no benefit on any parameter to using tocilizumab, but the usual side effects with tocilizumab.

I think it’s really important here to pause and say that negative data is critical. We need to know what works. We also need to know what doesn’t work, because a lot of anecdotes, a lot of stories, a lot of passion about a particular therapy can develop. Then we really need proper science to let us know, otherwise, we leave this vacuum and I think we’ve seen how disastrous that vacuum is. Here we are looking at tocilizumab, really great study, not seeing any benefit here.

Another one, and this is one looking at the, “Efficacy of interferon beta-1a plus remdesivir compared with remdesivir alone in hospitalised adults with COVID-19: a double-blind, randomised, placebo-controlled, phase 3 trial.” Now here this is also in The Lancet. These are the results of the double-blinded, randomized, placebo-controlled trial at 63 hospitals across five countries.

Eligible patients had to be hospitalized– that confirmed PCR test. They had to meet one of the criteria suggesting that lower respiratory tract infection, so radiographic infiltrates, a decreased oxygen saturation. They randomly assign them to the two groups, so they’re either going to get remdesivir or remdesivir plus the interferon beta. The interferon beta group in no way was superior to the outcomes of the remdesivir alone. Negative data here for interferon beta compared to the usual standard of care.

I want to close here by saying a couple of things, making a couple of comments. One is to say, “No one is safe until everyone is safe.” I think it’s really important that we continue to look out at the world and see what’s happening globally. We are here getting to the end of October. August, September, October, all donations made to PWB will support Floating Doctors.

I want to do a little shout-out here to Robin Trotman, who committed to making a generous donation to ensure we meet our goal. Dr. Trotman is an infectious disease specialist in Missouri, and he just won the Humanitarian of the Year award from the Community Foundation of the Ozarks for all the COVID work he has done. He’s actually going to gift that award, so that we can match it and help support Floating Doctors.

VR: Time for some email questions for Daniel. You can send yours to daniel@microbe.tv. Rachel writes, “Can an antibody test indicate if a booster is needed? What metric and what level would indicate if a booster would help?”

DG: That is an excellent question because I get it all the time. Actually, I have to say, when I was at Columbia this morning, I was getting a text, and this was actually from a physician saying, “I’m in my 70s. I just checked my antibodies based upon this level. Should I get a booster or not?” I think we need to keep reinforcing, we do not know what to make up with these antibody tests. We certainly see people with high antibodies get admitted to the hospital. These might be high antibodies from infection and may be high antibodies from vaccination. We seem, if we keep repeating it over and over again, it does not make it true.

We do not know that certain antibody levels are correlates of immunity, so I do not recommend people getting serology tests prior to getting a boost if they’re going to get a boost. This is a challenge because we really could use those correlates of immunity. It would be wonderful if I could do a blood test and then be able to tell my patients, “You are someone who would benefit from a vaccine. You are someone who would not benefit from that vaccine booster.” But no, there’s no antibody level below or above that we know can help us make this decision.

VR: Holly writes, “First, I love your weekly podcast on TWiV. 20 months ago, I’d never heard of TWiV, now I am a total groupie. As a nurse practitioner working in a busy primary care practice in the Greater Chicago area, your weekly updates have greatly helped my ability to provide scientific- and evidence-based medicine to frightened and concerned patients. Thank you. Today, I ordered a PCR COVID test on an older man that I suspect has SARS-CoV-2. I mentioned to him that if he tested positive, I would likely recommend a monoclonal antibody. He was all over it. He’s not vaccinated. He then asked me what he could expect his long-term immunity to SARS-CoV-2 would be after receiving a monoclonal? Would it provide protection? If so, for how long? We certainly know that immediate outcomes are better for patients infected after they receive monoclonal treatment. However, are you able to comment on immunity after monoclonal treatment for COVID?”

DG: This is a great question. When people go ahead and get the monoclonals, based upon the different monoclonals, and I’m going to use the Regeneron, the Eli Lilly cocktails here, the half-life of these products is in 24, 26 days, right there, a little less than a month. If you’re going to use them for recurrent prophylaxis, you’d have to give them every month. We’re thinking one month, you get to two months, you’re at a quarter, by three months, it’s pretty much down there at about one-eighth of that original dose.

We think that the people then become susceptible to reinfection. At that point, we’re recommending that people get vaccinated. To go into depth, what about the potential protection that they may have gotten? Actually, I have to admit, a lot of people have said, “Oh, I don’t want monoclonals because I want to get that natural immunity, now that I’ve gone ahead and gotten COVID.”

We do not really know the long-term protection that you’re going to get. We think that the sooner you get those monoclonals, the shorter period of time that your immune system is going to be exposed to it, being educated by this experience, but it’s really tough. It’s like getting educated in a war zone. You do not want to get educated in a war zone.

We are not sure how much protection, how much immunity you develop. The sooner you get those monoclonal antibodies, the better for outcomes, but also the worse for you developing any immunological memory. Across the board, we say, I understand you’re not vaccinated now, but when you hit that three months, we really want you to get vaccinated.

VR: Sounds like a good study to do would be to take patients who have been treated with monoclonals, wait until they diminish, and then check their serology to see if they’ve made their own antibody response, and if so, what level?

DG: It’s not a hard study to do because we could look at nucleocapsid, for instance, which is not going to be in the monoclonals. We could even modify your assay so that it’s not going to bind because we know, for instance, of the Eli Lilly, you can get around that, but yes, the nucleocapsid would be easier. This would be interesting. I think people would want to know the answer to this because as much as we encourage people to get vaccinated, there are certain people that are very resistant. Maybe this information would help them make that decision.

VR: Marios writes, “A friend of mine has gone on a cycling tour. All the cyclists were fully-vaccinated, but the organizers decided that every cyclist should have a PCR test prior to participation. I felt this was a bit over the top. Should an asymptomatic, fully-vaccinated person ever have to go for a PCR test to do anything, like fly, etc.? I wanted to know what I thought about this. Maybe a rapid antigen test might be better in this situation?”

DG: I like this. You’re thinking this through. What do we know? We do know that people who’ve been vaccinated can get infected. We do know that people who have been vaccinated can get infected and can transmit, because we have studies showing a reduction in that, but it’s not a reduction to zero. We certainly have case contact series showing that that can happen. We do think that that risk of infection is significantly lower, at least for a period of time. We do think that risk of transmitting to others is significantly reduced, but it’s still there.

The antigen tests I love. As you bring up, antigen tests really tell us if this person is contagious, if this person is capable of transmission. Do you really want a PCR, maybe done within the 72-hour window, or do you want that antigen test right before you get in that plane? Right before you go on this bike course? I actually think there’s a lot to be said for the antigen test. You get an answer right then. It tells you what’s going on right now, but yes, there are reasons to test people who are vaccinated.

VR: Bill writes, “I have a 40-year-old patient who had COVID last year and has long COVID. Should she get the vaccine?”

DG: I’m going to say yes, and let me talk a little bit about this. There was a recent TWiV, we had David Tuller on. Great guy. He and I have chatted several times. There came up this question, “Is there evidence that the vaccines impact in a positive way long COVID, or is it just anecdotes, what we’re seeing?” There are two studies now. There was the original Bristol study, it was smaller.

Then a couple of TWiVs back, I talked about the French study. No placebo group, so we don’t know how much of this is a placebo effect. But what we’re seeing, what the French study was demonstrating, if people get vaccinated, they are twice as likely to report complete resolution of symptoms. We are seeing in that study with all its flaws that people who got vaccinated were more likely to report improvement in a number of scores.

There is evidence to support a therapeutic impact of vaccination, but there’s also the other– If a person has long COVID, they had COVID, they’re at risk of reinfection. We know that getting vaccinated will drop that risk of reinfection by more than half.

VR: Finally, Lori writes, “I wrote in the summer, I’m a Canadian who works in Kazakhstan, was vaccinated with two doses of Sputnik in April, May, went home to Toronto, and I asked you whether it was bad for the body to add another two doses of an mRNA vaccine. I got the two doses of Pfizer before we returned to Kazakhstan in August. We were meant to have a holiday next week, but my PCR test today came up positive. I’m stunned and, honestly, a bit freaked out.

I teach online, I’m careful to wear masks, but I did have a couple of dentist appointments last weeks. I don’t think dentists here are as careful as they are in Canada. I did some quick reading after I got the result and was further dispirited to find that people with breakthrough infections are often older with underlying conditions. I’m 53, maybe that’s older, but healthy. I don’t have symptoms yet, but wonder, how true those findings are? Are breakthroughs usually in people with weakened immune systems? Is Delta messing with these initial stats?”

DG: First, I want to start up by reassuring that 53 is very young, but here’s, and I think we keep returning to this, is vaccines historically have never really been touted as preventing you from getting an infection. They’ve always been designed to protect you from getting sick, to protect you from hospitalization, death, paralysis. It was actually a bit of a surprise at how effective these vaccines were shown to be at preventing people from either even getting a positive test.

I want to put this in context, the more and more people that get vaccinated, the more often we will see positive tests. I was on a call this week with our urgent care doctors and one of the urgent care doctors was quite upset, “I’m seeing all these positive tests.” Yes, we are seeing positive tests in people who’ve been vaccinated, they tend to have a much milder course than you would expect compared to someone who is unvaccinated if you think about their age, their comorbidities, etc.

Certainly, people who’ve been vaccinated have died, but I like to put this in context, if you look at the number of people, unvaccinated deaths in the United States, it’s over 700,000. If you look at the number of vaccinated individuals that have died of COVID, it’s maybe in the 7,000 range. We had that really tragic loss this week of Colin Powell, and that was again an individual who had an immune issue, a cancer of his immune cells that prevented him from getting that protection.

At 53 with what you’re telling us, I really expect that the vaccines in your case have defanged the SARS‐CoV‐2, have defanged COVID-19. I expect that for you this will be, in most likelihood, just the sniffles, a mild cold. In a sense, this will be, I guess, your fifth boost and you should be good going forward.

VR: That’s COVID-19 clinical update number 85 with Dr. Daniel Griffin. Thank you, Daniel.

DG: Oh, thank you, and everyone be safe

[music]

[00:42:07] [END OF AUDIO]

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