TWiV 811 COVID-19 Clinical Update #82

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 30 September 2021

pdf of this transcript available (link)

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

VR: From MicrobeTV, this is TWiV, This Week in Virology Episode 811, recorded on September 30th, 2021. I’m Vincent Racaniello and you’re listening to the podcast all about viruses. Joining me today from New York, Daniel Griffin.

Daniel Griffin: Hello everyone.

VR: I hesitated slightly because it’s the end of September, Daniel, and this is [crosstalk]

DG: Yes, 30 days has September, April, June, and November. [chuckles]

VR: Boy, it went by quickly, didn’t it?

DG: It did actually.

VR: How’s the pandemic looking from your end, Daniel?

DG: It’s really tough. I was actually thinking about this just over this last hour. There’s always the numbers, so like, what are the numbers, what are the waves but for me, a lot of COVID is personal, and so direct patient experience, having patients die, having patients not do well, and that that continues. I have a woman in her 40s unvaccinated in the ICU right now and we’re talking about is she going to get better? Is she going to end up on ECMO? Tragedies like that. Actually, I’ll share this story because I think it’s illuminating. A family friend has a niece, the niece has Down syndrome and the parents are anti-vaxxers and I won’t say vaccine-hesitant, I’m just going to say full-fledge.

The wife had to get vaccinated for work, but the father didn’t and the father about two weeks ago actually got infected with COVID. What often happens, he got better and this then reinforced his ideas that it was so much better to get infected with COVID, why get vaccinated? There was a lot of discussion about what about your adolescent daughter with Down syndrome? What about her? Potentially she’s at risk, you haven’t vaccinated her? I think we know where this goes. The adolescent daughter in her late teens ended up getting infected with COVID had a positive test, reached out to the pediatrician, encouraging monoclonal first week. The pediatrician was not comfortable with the data on monoclonal and decided not to. This young lady ended up in the hospital on oxygen. When she went into the hospital, they noticed that her lymphocytes were low.

They were concerned that maybe her lymphocytes were low because she coincidentally also had leukemia, and so they didn’t want to start steroids until they had a chance for a hematology consult, which did not occur until Monday. She was admitted Friday, hematology consult on Monday. Finally, Monday evening, they decided to start the steroids. By Tuesday, she’s in the ICU on high flow oxygen, she’s required CPAP, not doing well. This is all vaccine-preventable. I always tell the stories. I tell the stories about when everything goes smoothly. I think we learn from lessons like this. Unvaccinated putting a family member at risk and maybe our audience isn’t aware of Down syndrome, about four times more likely to end up in the hospital, maybe 10 times as likely to die. This is a high-risk condition.

This young lady, a little bit heavier than would be ideal also putting an increased risk, not getting the monoclonal, not getting the steroids with that delay, and then the question about should she be given tocilizumab and I’m going to get to some data on that, but by the time you’re requiring CPAP and high flow, actually probably missed the window we’re going to make a benefit there. For me, the pandemic is still continuing to be incredibly painful on a personal level. Looking around the country, we are seeing a little bit of light, we are seeing that things in many areas are getting better, but still an unacceptable high rate of infection in our younger population.

VR: Very sad story.

DG: We start off with our quotation. “Knowledge is no guarantee of good behavior, but ignorance is a virtual guarantee of bad behavior.” That’s by Martha Nussbaum. I love that and hopefully what we’re doing is we’re providing education. I was doing a talk for one of the California schools last week and the final question was one of those, there’s no right answer to this, but it was about vaccine hesitancy and having conversations. I guess my view has always been the long game. If you are respectful, if you continue to provide education, I think that you may not get people to make the right decision now, but you’re building toward better decisions, better behavior in the future. Children and COVID.

I like to say children are at risk for COVID. There’s no doubt. I think this is very clear and also wearing a mask is less traumatic for a child than being hospitalized. I think our story reflects on that. I was on a call earlier this morning with the consortium that I talked about where we’re really trying to get good data on COVID and children, and also whether or not as we’ve moved into the Delta variant whether or not that is somehow having a different impact. One of the things that came to my attention on the conversation is something we’ve talked about a little bit. There’s this idea that oh, maybe this will become the next endemic Coronavirus, maybe children, if they get infected in the first few years of life, they’ll have this immunity that protects them going forward.

One of the things that was shared and this is consistent with what we’re seeing here in the U.S. if you would look at under 18 and you actually look at 0 to 4, so babies and really young children, that actually has for a while now had the highest associated rate per 100,000 population of ending up in hospital. This whole idea that it’s a continuum, the younger you are, the better you’re off with COVID actually breaks down in the zero to four. One of the gentlemen on the calls was from Brazil, and he was actually saying this has been a huge problem, really, particularly that first year of life they’re seeing a lot of hospitalizations, they’re seeing deaths, and so reflecting a situation. Vincent, did you have a thought on that?

VR: Yes, just one condition that might mitigate this, if, in the future when most mothers are immune, they will pass antibodies to their babies, and that may reduce severity, and then the baby is somewhat immune, and it reduces disease subsequently.

DG: I like that idea. That’s interesting, I know with Dickson, where we’ve been on This Week in Parasitism, we’ve talked about when do we see the mortality for childhood malaria? It’s after the children have lost that protective antibodies from mom. Hopefully, that is an optimistic and hopefully, that will pan out because this is if you think about it, what an incredible challenge to think that we’re going to continue to be able to keep our population. We haven’t even gotten there the first time but the idea that we’re going to be able to always vaccinate against SARS-CoV-2. Now I’m going to say in the child world, maybe this is the most exciting news for this week is on Tuesday, September 28, Pfizer and BioNTech submitted initial data to the U.S. FDA, from their pivotal trial on COVID-19 vaccine in children 5 to 12 years of age.

Then they wanted to say, and I think this is really important so that people have the clear message, formal submission to request emergency use authorization to follow in the coming weeks. The clock has not really officially started. That clock is when they request EUA, there’s a 15-day period of public comment and then we hear from the FDA if they’re going to extend it. We are all keeping our fingers crossed that there will be vaccines down to five years of age by Halloween. I guess that moves us right into active vaccination, vaccines, the jabs that keep you from getting sick.

This will be a public service announcement right here. It’s time to get that flu shot where by the time this drops, we’re in October and the current guidance from the CDC for the use of COVID-19 vaccines is that these vaccines can be co-administered with other vaccines, so COVID-19 vaccines, influenza vaccines, you can co-administer. Early on, we were spacing them apart and we were trying to understand the reactogenicity, things like that. At this point, don’t miss an opportunity, never miss an opportunity to vaccinate if the person comes in and they want to get a COVID and a flu shot. We can do both at the same time.

How are we doing with the third dose? We had the early release from the MMWR safety monitoring of an additional dose of COVID-19 vaccine. United States August 12, through September 19, 2021. Basically, the adverse reactions, the reactogenicity that we’re seeing with those three is really similar to what we saw with those two. During August 12th through September 19th, 2021, among 12,591 V-safe registrants who completed a health check-in survey after all three doses of an mRNA COVID-19 vaccine, 79.4% and 74.1% reported local or systemic reactions respectively. After the third dose, 77.6% and 76.5% reported local or systemic reactions after the dose.

This is really very similar. We’re seeing about the same. We know that now over half a million folks have jumped in now that there’s a booster, but we knew over a million had done it ahead of time. I think this is important. We’ve still discussed a little bit about unknown benefit but really critical was following and continuing to follow safety data. So far, voluntary reports have found no unexpected patterns of adverse reaction from this additional dose. The CDC is going to continue to monitor the vaccine’s safety for these additional doses as they go out.

Now, one of the things I want to talk about in the vaccine area here is one of these anti-vaccine tropes that’s going around. It seemed like there was a lot of it this last week as healthcare worker vaccine mandates were going into effect. This was this whole idea that, “Oh, I’ve already had COVID, why are they forcing me? Why are they making me get vaccinated? If you already have COVID, I’m never going to get this.” This is this whole idea. There’s a local infectious disease doctor, he always just seems to muse about, “I don’t understand how the vaccines can be better than just getting infected with COVID.” Most of us roll our eyes and wonder if he’s ever seen a second case of dengue or he’s ever seen someone with tetanus and where this comes from.

Oklahoma now has its weekly COVID-19 report, including reinfection data. I thought this was really interesting. This actually got quite a little bit of press. Actually, they now are reporting since May on the reinfection rate per 100,000 eligible cases. You can see this really had started to march up from 358 to 512, up to now in September, over 1,000 per 100,000 are getting reinfected. I think it makes sense that it matches experience. That first three months after infection, you’re at a low reinfection rate, but it does really seem like that protection drops off.

I have to say, there’s two aspects. One is it’s a little bit frustrating. I would like there to be better protection against reinfection. We do know that there is a benefit to getting vaccinated and we know that if you’ve been infected and then you go ahead and get that vaccination, you have dropped your risk of reinfection by about 2.34% in that nice study from the MMWR, so we are routinely asking people not to have this musing and just everyone, go ahead, get vaccinated. Do you have any comments there, Vincent? From The Incubator in Manhattan. [chuckles]

VR: That’s where we are. We’re at The Incubator now. Recording everything here. These are all cases in people who are not vaccinated but had previously recovered from COVID, is that correct?

DG: Yes.

VR: What is the overall in Oklahoma frequency again?

DG: What they’re looking here is the number of cases. It’s funny. They call it cases eligible for reinfection. These are individuals who had a prior infection and now looking at the reinfection cases and then counting them up over time. The test positivity rate in Oklahoma is about 15%, so they have actually a very high test positivity rate. Here, you had 453,927 eligible for reinfection and they had 1,035 that ended up reinfected.

VR: What’s that rate? Do you know offhand?

DG: That’s the rate per 100,000, so you could actually multiply that by, what, 4.5? Really, it was over 4,500 reinfections just in September.

VR: Can we compare that to vaccinated people?

DG: Yes, they do that. They compare it. We see a range depending on when you look of somewhere between 2 to 9.5 times as likely to get infected compared to the vaccinated people.

VR: Good. That’s good. I wish more states did that.

DG: Actually, it would be nice. It would be nice. All right, passive vaccination. We talked a little bit about monoclonals in our opening story. On September 29th, so just yesterday when we’re recording, it’ll be a few days for folks listening, the article REGEN-COV Antibody Combination and Outcomes in Outpatients with COVID-19. This article came out as a peer-reviewed publication in the New England Journal of Medicine. This paper describes the Phase III portion of an adaptive trial were outpatients with COVID-19 and risk factors for severe disease were randomly assigned to receive various doses of intravenous REGEN-COV or placebo.

We’ve talked about a little of this data in the early preprint and in the press releases but in the original Phase III portion of the trial, 3,088 patients with or without risk factors for severe COVID-19 were randomly assigned to receive a single intravenous dose of REGEN-COV. It’s either 8,000 milligrams or 2,400 milligrams. The difference in those, think about in parts per volume because we’re also thinking the potential that we can deliver these subcutaneous or IM [intramuscular injection] in some.

In the amended Phase III portion of the trial, there was an additional 2,519 patients. They’re growing the numbers here. The median follow-up was 45 days, so extending the follow-up from that initial 29 days, 96.6% of the patients got past that 28 days and had this longer follow-up. Now, this is I think critical, because timing, and I keep getting it. These patients had a confirmed SARS-CoV-2 positive diagnostic test no more than 72 hours prior to randomization and onset of any COVID-19 symptom no more than seven days before randomization.

They found that the COVID-19-related hospitalization or death from any cause, there was a relative risk reduction of 70.4%, p-value 0.02 with receiving the mAb, the monoclonal antibody therapy. Also, the median time to resolution of symptoms was four days shorter in the folks that got the REGEN-COV. This was similar at the two different doses. Serious adverse events, people are worried about giving people this, 4% in the placebo group, 1.1% and 1.3% in the two dosing groups for the mAbs.

Infusion-related reactions occurred in less than 0.3% of the patients in all groups. Just to reinforce, this is a very safe. Your patient is much more likely to have problems not getting the monoclonals than they are getting the monoclonals and the monoclonals continue to really do a tremendous job of reducing the risk of COVID-19-related hospitalizations or death. This really still remains our most effective antiviral therapeutic.

What about the real antivirals? The traditional. Where are the pills? On September 27th, Pfizer announced that they were starting their EPIC-PEP trial. That’s Evaluation of Protease Inhibition for COVID-19 in Post-Exposure Prophylaxis. This is really interesting sort of moving on to the second level. We know we have a number of trials going on where people get acutely ill. We try to rapidly give them antivirals but now, we’re already moving on to this study where they’re looking at households.

This study will evaluate the novel protease inhibitor PF-07321332, co-administered with a low dose of Ritonavir. That’s actually a pharmacological boost. It keeps the drug from being metabolized so it can be present and effective for a longer period of time, something we’ve learned from the HIV days, for prevention of illness in adults living in the same household as someone with COVID-19.

The whole idea here is someone in the household, you’re at high risk, you give it to everyone as a post-exposure prophylaxis. This can potentially be administered at the first sign of infection, or in this case, exposure to SARS-CoV-2 without requiring the person to be hospitalized, without requiring intravenous therapy. We’re looking forward to that. This will be a Phase II/III trial. This is going to be twice daily for 5 or 10 days, so we’ll get some information on how well this works.

All right, the period of detectable viral replication. Hopefully, we keep through repetition reinforcing what are the evidence-based interventions at each stage. Here, now we have the period of detectable viral replication, the time for monitoring in monoclonals, not the time for antibiotics, they are not helpful, potentially harmful, not the time for steroids very clear that we can do harm. The monoclonals have now been added to the WHO COVID living guidelines.

The WHO now recommends antibody treatment for COVID patients at high-risk for hospital admission and for severely ill patients who have no natural antibodies to COVID-19. That’s a little bit different, so we’ll go into this in a little bit. What they have to say is a treatment combining two antibodies, and here it’s the REGEN-COV. The Casirivimab and Imdevimab is recommended by two specific groups of patients with COVID-19. This is the WHO Guideline Development Group, which is a panel of international experts and patients, and this was in BMJ on Friday, September 24th.

Now the first group are patients at high-risk of hospitalization, but the second group, these are individuals who actually have severe or critical COVID-19. These are those individuals which actually were getting into the next group. They’re getting hospitalized. They’re starting to get into that early inflammatory phase, but they’re still zero negative. They still do not have measurable antibodies, and it’s the second recommendation that is actually outside the current EUA in the U.S.

The second recommendation, so giving monoclonals to severe or critically ill COVID-19 patients who are admitted, but still our zero negative is based on the data that we discussed a while back, came out, became available in June the recovery trial, where we saw that Casirivimab and Imdevimab reduced deaths and they actually gave a range. They suggested that 49, fewer per thousand, maybe as high as 78, maybe 87, fewer in the critically ill, also reducing the need for mechanical ventilation. We’ll have to see when that gets updated here in the U.S., but WHO is actually recommending not just that first week, but if you check zero serology data on admission.

This is a group that we have data suggesting that they would benefit. Still outside the EUA here in the U.S., we have to wait for that. We’re also anxiously waiting for the data, as I mentioned, the other oral antiviral. We have Merck and Ridgeback Biotherapeutics with Molnupiravir. We have Roche and Atea Pharmaceuticals with AT-527 and Pfizer’s drug, as we discussed. It’s actually interesting. There’s a little bit of a challenge to recruit for these trials. Hopefully, we can get those trials done and we can get that information.

All right, let’s move into the early inflammatory phase. This is usually when people get hospitalized and we’re going to be talking about Tocilizumab again and really hitting as we keep hitting on how critical timing is for different therapeutics. In the journal of Respiratory Care, the peer-review publication, “Impact of Timing of Tocilizumab Use in Hospitalized Patients With SARS-CoV-2 Infection” was published. We’ve talked previously about the eight randomized control trials, including the recovery trial. Again, that demonstrated a mortality benefit for patients and led to the inclusion of Tocilizumab in the IDSA guidelines, the NIH guidelines, the WHO COVID-19 guidelines.

Now several healthcare systems, unfortunately, as Tocilizumab has been embraced there’s been some degree of rationing. Several healthcare systems have tried to create guidelines so that everyone doesn’t get Tocilizumab but hopefully that it’s going to the patients that can benefit the most. We’ll see if that’s working out. One of the rationings has been to wait until patients are on high flow nasal cannula, or higher levels of oxygen support before they get Tocilizumab. We’re going to see from this trial that maybe that is waiting too long, maybe it’s after the window of benefit has closed.

The authors performed a retrospective chart review of 11,512 patients infected with SARS-CoV-2, who are admitted to a New York health system from March to May 2020. I will mention that the healthcare system is Northwell, I actually know the authors on this paper. Tocilizumab was administered to subjects at the nasal cannula level of oxygen support to maintain an oxygen saturation of greater than 88%. The primary outcome of interest was hospital mortality and the secondary outcomes were progression to mechanical ventilation, prevalence of venous thromboembolism and renal failure, the change in C-reactive protein, D-dimer, and ferritin levels. Propensity score matching was used to minimize any selection bias.

What did they find let’s cut to the chase here? The hospital mortality was significantly reduced in the Tocilizumab group when it was administered at the nasal cannula level. This was a drop from 22% down to 10.4%. A 53% mortality reduction when Tocilizumab was administered at the nasal cannula level. If they waited till the individuals were requiring a non-rebreather high-flow nasal cannula, non-invasive ventilator you actually were losing any benefit. The window basically was closed. We’re hoping we’ll get our guidelines updated with this.

Just a little shout out to the corresponding and lead author, Anup K Singh, he actually sent me this when it was still in the galley proof stage, so I got to see all the corrections, but he’s really been I think a leader, the folks at the Lenox Hill Hospital in the city have really done a good job of understanding the disease really being on the forefront. I think this was helpful, but just to reinforce timing really matters if you give it in that first several days.

There’s actually a wonderful figure. This figure one where it not only, and you see the mortality benefit relative to what level of oxygen support they give, but you can also see how important the timing was. If they got the Tocilizumab within the first couple days, even out to about day five with the nasal cannula you were seeing low mortality, but once you waited started giving it after day five you really see that mortality start to go up. Earlier at the right time, people who have maybe gone from two to six liters of nasal cannula who have inflammatory markers, who are progressing despite steroids but if you wait till they’re on high-flow nasal cannula, you’ve waited too long and you’re actually giving the medicine to people that don’t benefit from it.

VR: What does it mean nasal cannula? Is that nebulized?

DG: No, actually this is great. We’ve all seen the movies where the person has this plastic thing and they’ve got little prongs in the nose, so that’s nasal cannula and I appreciate you jumping in here because let’s talk about oxygen therapy and what I mean here. One of the most important things for us as clinicians treating patients with COVID-19 is what level of pulmonary support do they require? One of the first things I want to know when a patient shows up in the hospital is, what is there a level of oxygen saturation on room air? I’ll often turn off the oxygen because I want that number because I want to know, we had a patient yesterday, came in and he was on three liters of oxygen via that nasal cannula starting in the 90s, but then we turned it off and he was still 95% with it turned off.

You really want to get that baseline. Now, the next thing is once you establish that they do require oxygen. They do have a level of hypoxemia that warrants admission for severe COVID and oxygen support, how much do they require. Now that nasal cannula that we’re used to seeing in the TV shows can deliver, we say up to about six liters, sometimes we’ll turn it up to 10, and then the next level of support is something that we call a Venturi mask, which allows us with a twist of a knob to deliver a slightly higher amount of oxygen that we can regulate, and then we move to the full non-rebreather, which is the mask with the little bag below it, reminiscent of what you see on an airplane.

Above that, something we’re using more and more is a high flow nasal cannula, where instead of the small prongs, you actually have two larger prongs that really fit tightly in the nares, and we might deliver 30, 40 liters of oxygen per minute directly in through that device. Sometimes we’ll even put a non-rebreather on top. The next escalation is to the continuous positive airway pressure, the Biphasic Positive Airway Pressure [BIPAP] where there’s a different force in versus out. Then often we have to move on to mechanical ventilation.

VR: How do you get the Toci in the nasal cannula?

DG: Oh, so the Toci is intravenous. It’s just going in the vein. When the person gets to, they’ve gone from two to six liters, we’ve already given them steroids, you administer the Tocilizumab as intravenous medication.

VR: When they say at the nasal cannula level, it means that’s where they’re getting oxygen?

DG: Yes. Not in their nose, don’t squirt it in their nose listeners. I think that’s critical, just reinforcing timing really matters with this disease. All right, I’m going to try to keep this from going too long today because I think we’ve been getting a little bit longer. I know it’s helping some people’s fitness level and the dogs are liking me, but long COVID. COVID is not just a two-week viral illness for many people. Apparently, we need to keep reminding people of this because I’ve actually started to see literature now or again, this return to dismissiveness but the paper incidents, co-occurrence, and evolution of long COVID features, a six-month retrospective cohort study of 273,618 survivors of COVID-19 was published in PLOS Medicine.

Here, this was an electronic health record study looking at data from 81 million patients. Included in this, were those 273,618 COVID-19 survivors. It looked at the incidents and co-occurrence within six months and in the three to six months for nine core features of long COVID. Basically, just to reinforce, again, in this really large dataset, they found that COVID-19 was associated with long-term effects that were common and diverse with 57% of patients having at least one long COVID feature recorded in the 180 days after infection. 37% still having issues 90 to 180 days after diagnosis. I’m going to close this out here with, no one is safe until everyone is safe.

I’m going to give a shout-out to TWiV 807 like all the TWiV’s, but I really enjoyed the Shot Yearned ‘Round the World with Chadi Saad-Roy and Caroline Wagner. Really nice discussion about what would’ve happened in different scenarios where vaccines got to other parts of the world where there’s a little more vaccine equity? Along those lines with that theme, I’m going to remind everyone, go to during the months of August, September, October. Click that donate button and help us support Floating Doctors. They’re going to be working with the Ministry of Health down in Panama, getting those vaccines out, continuing to provide care down there. I have to say thank you so much because our listeners have been incredibly generous. We need the funds to do what we do. These organizations need the funds to do what they’re going to do. Be part of the solution. Thank you so much.

VR: Time for some email questions for Daniel. You can send yours to Ronald writes, “I’m writing from Florida where the Sheriff’s department bans masks, won’t let you in if you’re wearing one, and the governor is bent on endangering the lives of our children. I know you’ve discussed Ivermectin at nausea. I’m hoping you could take a look at a site that exists solely to promote Ivermectin for the treatment of COVID-19 and give me some tips on how to debunk it. is a site devoted solely to convincing people that Ivermectin is the cure. Spends a good bit of space listing countries that use it. The main method is to use web crawlers to find peer-reviewed studies on all sorts of sites. They mentioned straight out multiple treatments are typically used in combination, including monoclonals. I’ve pointed out to those citing this site as science that a treatment of tap water and monoclonals if given early will show benefit, not all due to the tap water.

I showed them your last assessment and the response was, “I don’t know why the fine doctor says there’s not enough evidence. There’s tons of proof and they point to the site.” It appears that they find any study that mentions Ivermectin, web scrape, the most serious outcome, the count of participants, and the percentage benefit do something they call exclusion-based on sensitivity, and then they add the counts and percentages to their total to give them one huge study that has supposedly meaningful adults.”

DG: At the end there, I was reminded of Mark Crislip. He always talks about when you take a whole bunch of cow dung and you pile it high enough, suddenly it turns into gold. That doesn’t work. You’ve got to look at each little bit of cow dung. If it’s cow dung, you throw it out. You don’t pile it on top of each other. I think hopefully, we’re going to learn from the Ivermectin story, that if you leave a vacuum, things like this happen. We needed to do proper randomized controlled trials in this country to assess whether or not there is, or is not a role of Ivermectin.

We haven’t done those. There’s been the Egypt study that never happened. The Peruvian study that seems to have never happened. There’s meta-analysis that used those studies that have not been retracted. I think this has really become a difficult situation. I think that Bill Gates was really smart early on to put the microchips in the Ivermectin horse paste so he’s accomplishing his microchip control that way. He knew those people would not take the – I’m joking.

This is really challenging. There are clearly people out there who cherry-pick to support their conclusion. Science is not about supporting your conclusion. Science is about discovering the truth, and the way you discover the truth is by being honest. Not looking for support for your agenda, but looking for reliable data that can allow you to find the truth. This is very challenging.

VR: John writes, “Are there numbers anywhere for the vaccination rate among those who have already had COVID? Does anyone who has already been through it refuse a jab or two? I suspect the percentage is higher than overall anyway, which might be another argument to the stridently obtuse.”

DG: We’re starting to get, as we talked this week about, a little more granular data. I do not know where to get really good numbers on the breakdown. I’ve seen numbers that break down by political party, which I’m not that interested in. I would definitely be interested in this. There is, I’m going to call this myth, that there’s just these hordes of anti-vaxxers who won’t get vaccinated. Most of us are getting vaccinated. The majority of people who are eligible in this country have gotten vaccinated.

With the mandates, some people that we’re not that excited about have either gotten vaccinated because they had to, or they’ve basically been given away to save face and get vaccinated. This would be interesting to see what those numbers are. Hopefully, what will happen here is that anti-vax trope about natural immunity being so wonderful will be dispelled and people will clearly see that growing numbers of individuals previously infected are getting reinfected. The data we already have is that vaccination even in a population that was previously infected, can significantly decrease your chance of getting infected again and having a bad outcome.

VR: Nick writes, “My wife is pregnant 24 weeks. She had COVID in January this year. We’ve read articles stating that immunity given after infection is better than the immunity given after vaccination. Based on that, she doesn’t want to get vaccinated until after she gives birth. I’m an ICU nurse, fully-vaccinated, who deals with COVID on each shift and I’m concerned, given how I see the worst of the worst with COVID.”

DG: I’m going to share your concern. What are the things that we know here? One that we just touched on it a little bit is people who like the idea that natural immunity is better than the vaccine do cherry-pick data. There was the famous Israeli preprint that suggested that natural immunity prior to infection was better than vaccine that has been touted and circulated out there. It’s not peer-reviewed. It’s not reliable. We actually talked about some state-level data in Oklahoma suggesting that vaccinated people are better off, are better protected.

We also know that if you were infected before and get a vaccine, you’re going to more than 2.3 times, more than twice as likely, decrease your risk of an infection. Remember, a pregnant woman is trying to make a decision for herself and for the newborn child. Pregnant women are at a much higher risk of ending up in the hospital. They’re at a much higher risk of ending up in the ICU and on a ventilator if they end up in the hospital, and they’re significantly more likely to die. This is a very high-risk period. This is not a great time to be relying on natural previous infection immunity when you can have that extra safety of getting a vaccine. We also know, incredibly safe. No safety signal. There’s no reason not to get that extra protection if you’re a pregnant woman.

VR: Finally, Jessica writes, “As a young nursing student, I was taught that when giving injections that were not meant to be IV, care should be taken after inserting the needle to pull back and make sure no blood came back. Now, retired, I’ve been told most people don’t bother with that anymore.” Then she says, “What do you think about this study, where mRNA vaccines were injected into mice, one group intravenously, one group intramuscularly? They removed heart tissue and they found that intravenous injection leads to acute myopericarditis in mice. It’s only one paper, it’s mice, but what do you think?”

DG: I feel like we’re circling back, which is interesting. I’m old. I was trained, “Put the needle in. Pull back.” Then they did a number of studies showing no obvious benefit. An increase is painful actually apparently when you pull back like that. The recommendation is currently a couple of things. One is don’t pull back on the plunger. The other is if you’re going to not be doing the deltoid, to do the lateral thigh instead of the buttocks. Things have evolved over time, but this is interesting with the mRNA vaccines. Would we be better off returning to that pullback, the plunger?

I don’t know, but it is worth studying because even though the incidence of myocarditis is incredibly low and most cases tend to be mild, that’s important to point out, a myocarditis that lasts 48 hours resolves with, “Now we’re months out and not seeing any sequela good resolution.” It’s quite different than the myocarditis that you get with COVID but still, anything we can do to reduce that risk, I think is worth studying, so I would welcome. That’s what we have to do. We have to keep studying. We have to put more money into the science because we certainly see how expensive it is to not put the money in the science.

VR: That’s COVID-19 Clinical Update #82 with Dr. Daniel Griffin. Thank you, Daniel.

DG: Oh, thank you, Vincent. Everyone, be safe.

[00:40:47] [END OF AUDIO]

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