TWiV 741 COVID-19 Clinical Update #57

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 10 April 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 741, recorded on April 8th, 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: That’s right, Daniel, this is update number 57. How are things going this week?

DG: They are a little bit better. What TWiV are you at? What TWiV are we up to, Vincent? What did you say there?

VR: 741.

DG: 741, okay. I’m looking for the 747 because that’s the big one with the upper deck.

VR: Then, after that, there’s a 777, and then the 787. We’ll go through all of those, don’t worry.

DG: All right. Let me start with my quotation, and then I will give the update on where we are. This is, “Be kind, for everyone you meet is fighting a hard battle.” This is actually from Philo of Alexandria, 20 BCE to 20 CE. This goes back a ways, but I think maybe we need to remember. We’ve come out of this pandemic in a lot of ways worse, a lot of ways divided, hostile.

Sometimes, I feel like I’m in a Monty Pythonmovie, and someone sees their neighbors, they run away because this– I’ve actually developed what I’m going to coin, “The fear of the normal, FONO.” A lot of us are pretty traumatized from this last year, so ideally if we can all start working together. We are on the same side relative to the virus. My three quotations, as always, “Never miss an opportunity to vaccinate, never miss an opportunity to test, and never waste a vaccine dose.” Let’s get those vaccines into arms. The fridges and freezers do not need the vaccines, people do.

Where are we right now? What’s the update? I don’t often mention this, but worldwide, where are we looking, the world picture? Worldwide, the case numbers and deaths are rising with over 500,000 new cases per day, it’s probably more but that’s what we’re hearing. Over 10,000 deaths per day, again, probably higher. This is certainly not over.

What about here in the U.S.? I like to think that the experience in Israel is encouraging, they’re ahead of us. The experience in the U.K. is encouraging, they’re also ahead of us. The U.S., hopefully, we’re going to be next in line, a beacon of what happens with vaccinations. We are still on this plateau here in the U.S., thanks mainly to a few states. I call you out, that’s everyone in Michigan, Florida, New York, New Jersey, and Pennsylvania. We’re still seeing lots of cases, high positivity rates in these places.

Now, Georgia, oddly enough, is not reporting a lot of cases. They’re not in the top 10 in terms of cases, but they are in the top three in terms of daily deaths. I say that a little tongue-in-cheek, but there certainly are some issues with not doing enough tests around the country, particularly in certain places. You can’t hide the deaths, I guess you probably could as we learned, but when you see those deaths, it really suggests that we’re not capturing all those cases. I did want to point out, isn’t the CDC in Georgia?

We need to be doing a better job of testing, tracking, and everything else. Across the U.S., we have less testing but we still have the same number of new cases each day, so I’m not sure that this is as low a plateau as people might think. The same number of people are in the hospital across the board, certainly here in New York since February. There are fewer deaths per day. It’s odd that we’re celebrating that we’re under 1,000 and we’re still seeing 600, 700, 800 a day. That’s a pretty high plateau.

The things that have changed is the age of the patients in the hospital, and the age of those testing positive on average is decreased. That’s something that’s being reported, that’s certainly something we’re seeing. We still do a tremendous amount of testing here in the tri-state area at ProHealth and Optum Tri-State.

That’s my update. Now, let’s get into children and COVID. This is always a hot topic. We’ve covered that full in-person learning can be done safely and now, we have guidance from the CDC, but I’m getting lots of questions about how do we actually guarantee that this is done safely and not just done. This is interesting. I’m going to throw in, and this is thrown out of phase order, but it’s in the children topic.

We got some updates about the multisystem inflammatory syndrome during the COVID-19 pandemic in children. What I like to point out is that children certainly are at lower risk than adults, but they are not at no risk. Let’s put some context here. In JAMA Pediatrics, the article, Trends in Geographic and Temporal Distribution of U.S. Children with Multisystem Inflammatory Syndrome During the COVID-19 Pandemic was published.

This was a cross-sectional study of 1,733 patients with multisystem inflammatory syndrome in children, the MIS-C. The analysis included patients with illness onset from March 2020 to January 2021 that met the MIS-C case definition. Patients with MIS-C predominantly presented with gastrointestinal symptoms such as abdominal pain, vomiting, and diarrhea, as well as skin rash and conjunctival hyperemia. That’s a redness to the whites of the eyes.

Most patients develop hypotension or shock, with about 60% overall being admitted to the intensive care unit. I think I’ve mentioned that this went from early on being less to 50% to later on at being 80%, 90%, so evolving numbers. Myocarditis, inflammation of the heart muscle, cardiac dysfunction, and coronary artery dilation. These are the blood vessels that wrap around the heart actually dilating. That was reported in about a third of patients.

Now, most MIS-C illness are believed to result from asymptomatic or mild COVID-19. I think I want to reinforce that, asymptomatic or mild COVID-19 upfront, with hyper inflammation coinciding with peak antibody production several weeks after that initial SARS-CoV-2 infection. Patients with MIS-C were reported to have significantly higher titers of the SARS-CoV-2 receptor-binding-domain IgG antibodies compared with other patients hospitalized with COVID-19.

Just an update, this is out there, we’re getting more information on it. Let’s talk a little bit about the school opening plans. I was getting a lot of texts and messages about one of the local school districts that is planning an opening. They started laying out their guidelines. They’re going to separate the desk by three feet. The children are going to be wearing masks at all times. They’re actually going to have these plexiglass dividers. I’m hearing all these– this sounds encouraging, upgrading of the ventilation system.

But then, they had a very interesting quarantine outline. What they were saying was that, “Okay, we’re putting all these things in place, but if a child tests positive, anyone within three feet of them, the desk within three of them, they will all be quarantined.” Since the school is one where the children go to different classrooms, that one index positive case will then affect– I guess you could do the math on this, three in front, three behind, and one on each side. Eight kids from each class will be quarantined for the required quarantine period.

Some of the questions that parents were asking, “If it’s safe to be within three feet with all this mitigation, then why are these kids going into quarantine if our kids are going to actually have exposures in school?” It’s a back and forth. I think that one of the things that may be missing here for a lot of the schools is they’re being asked to open but they don’t necessarily have the professional guidance to help them put the whole plan together.

I think this has come up many times. If you do not have an exposure, you do not need to quarantine, and if you’re setting up a school plan that’s going to actually provide exposure opportunities for the children, that’s not a great school opening plan. Reach out if you don’t have the expertise. If you don’t know how to do this, and a lot feel they don’t have expertise – the superintendent, a principal, a teacher – I don’t want to be the one teaching your high schoolers or your middle schoolers. You probably don’t want to be the one coming up with school reopening plans during a pandemic without some communication.

I throw that out there. I do think that we can open schools safely, but you have to have the understanding and the science to do this. This ties directly into transmission. Today, we’re going to talk a lot about transmission. So much about COVID-19 has been controversial and even contentious, so remember my quotation, “We’re all in this together. The virus is the enemy, not your neighbor.”

I guess I shouldn’t be surprised. I still remember it was during my graduate training when I almost came to fisticuffs. I was having a dispute with another one of the graduate students about whether or not NF-kappaB activation was essential Th17 differentiation. Really? [laughs] That was enough to get in a heated argument. Here we’re actually talking about something that affects people’s lives and this is a scientific question, and I think we need to be level-headed when we discuss, “What do we know about this,” so that we can make appropriate decisions to protect everyone.

I think one of the issues, I will say, the issue of transmission was complicated by terms of art – there are certain words that we use in science. There’s certain words that we use even slightly differently in the clinical arena, terms of art such as airborne, and there are common usage of these terms by the general public. A lot of times people would ask that question, “Is this airborne?” I remember a wonderful article, It May Not Be Airborne, but It’s Borne by the Air.

There was a lot of confusion about what is happening here. In The Open Forum Infectious Disease Journal, the article SARS-CoV-2 Infection Among Healthcare Workers, Despite the Use of Surgical Masks and Physical Distancing, the Role of Airborne Transmission was published by a group out of Israel. This was a case study where the authors described a single source outbreak of COVID-19 from an asymptomatic patient to nine healthcare workers and room contacts in a general pediatric ward, despite meeting the current guidelines for PPE and the wearing of surgical mask.

Now, due to confirmation, I actually worry about this article. I think it’s going to be embraced by both sides of this controversy, right? Back to sides again. I’m going to take a moment here, and we’re going to have to learn, it’s little painful, but we’re going to do a little vocabulary here, but I think this is critical. This is important. This is how we keep ourselves safe, and I think understanding these terms are important.

The first term, respiratory droplets, these are small drops or portions of liquid that are in the five to 10 micron range. These are expelled when a person coughs, sneezes, sings, or as we now know, I think is more generally appreciated, talking as well. People always think about this, you’re not coughing, you’re not sneezing, if you’re not sick, how are you spreading this? Just talking is creating these droplets. That’s why a person can be pre-symptomatic and still create them. You do not need to be coughing, sneezing.

Droplet nuclei, or aerosols, now we’re talking about a term of art. These are small drops that are less than five microns. Due to their small size, they can actually remain airborne for extended periods of time and transmit over significant distances. Then we have fomites, and these are contaminated surfaces. What about airborne transmission? Now, the CDC points out that this is a specialized use word in medicine and public health, and is used to describe infections capable of being transmitted through exposure to infectious pathogen-containing small droplets and particles suspended in the air over long distances that persist in the air for long times.

Where are we with all this? I just showed you an article. “Oh, my gosh, with that instance of airborne transmission, despite masks.” As per the CDC, the principal mode, by which people are infected with SARS-CoV-2, the virus that causes COVID-19, is through exposure to respiratory droplets, carrying infectious virus. They do go on to say, “Airborne transmission of SARS-CoV-2 can occur under special circumstances, and those were the special circumstances that we described.”

What are those special circumstances? In closed spaces, we keep harping on indoor versus outdoor. In closed spaces within which an infectious person either exposed susceptible people at the same time or to which susceptible people were exposed shortly after the infectious person had left that space. That indoor poor air circulation prolonged exposure to respiratory particles.

Remember, this is a continuum, there’s no plexiglass shield at this distinction between the different micron sizes. Shouting, singing, exercising, you’re actually going to increase the concentration of suspended respiratory droplets in the airspace, so prolonged exposure. Then inadequate ventilation, which all this is all tied together or poor handling. You’re allowing a buildup of suspended small respiratory droplets and particles.

That’s your suburban home without good air exchanges. I think that we can very clearly at this point say that the CDC, the WHO, and the science supports that the principal mode here is respiratory droplets. Airborne transmission is rare, but can happen in circumstances. Fomites, contact, I think the current CDC estimate is that maybe one in every 10,000 infections was due to surfaces.

Just rethink all that bleach and Clorox and everything else. On Monday, April 5th, the CDC published an updated science brief addressing fomite transmission. This was titled SARS-CoV-2 and Surface Fomite Transmission for Indoor Community Environments. I’m sorry to the makers of bleach, but this goes along the lines of what we’ve been discussing, instead of focusing on the distinction restaurant droplets and aerosols, it focuses on getting COVID-19. Getting that virus and developing COVID-19 from surfaces and the summary statement, the principal mode by which people are infected with SARS-CoV-2 is through exposure to respiratory droplets.

It is possible for people to be infected through contact with contaminated surfaces, objects, fomites, but the risk is generally considered to be low. This doesn’t mean we’re walking around with unclean hands. I still want people to wash their hands. But I think there has been a lot of resources put into hygiene theater, and they actually conclude in the statement that in most situations, cleaning surfaces using soap or detergent and not requiring this disinfection is enough to reduce the risk.

Testing. The Journal of Clinical Microbiology published a nice meta-analysis, Performance of Saliva, Oropharyngeal Swabs, and Nasal Swabs for SARS-CoV-2 Molecular Detection: a Systematic Review and Meta-analysis. Now, for starters, what is a meta-analysis? In the edited words of Mark Crislip, Persiflagers infectious disease puscast fame, this is when you pile a whole bunch of studies on top of each other and they suddenly turn into gold.

I think Mark will be turning over in his grave, even though he’s still alive. He just has decided to stop puscasting. He’s only died in a certain way. This was really a high level summary, where they looked through– they found 1,253 unique citations. They then drill down to identify 25 saliva studies, 11 nasal swabs, six oral pharyngeal, and four oral pharyngeal nasal swab studies. From all the different sourcings, what they were using is nasal pharyngeal swabs as the gold standard and saying, “If we do other methods, how much of the time are we able to pick that up?”

They basically came down with the nasal swabs, we’re picking up about 82%, the oral pharyngeal, we’re picking up about 84%, and the saliva, we’re picking up about 88% of those that were picked up with the nasopharyngeal swabs. They also reported a few things that I found interesting, they reported findings, several studies that the unsupervised self-collected nasal swab specimens had higher percent positives compared to those collected by healthcare workers.

I was trying to analyze this, is this that healthcare workers are too gentle? Is it that when no one’s watching people are willing to get a much better, deeper sample? So you turn away, and tell them to go at it? I also thought it was interesting. A lot of times we have people hold a mask and they cough, or they try to get up this deep throat saliva, and we tell them you can’t eat, you can’t drink, you can’t brush your teeth.

That really didn’t seem to do much in terms of sensitivity. Maybe it’s a little nicer people can show up for their testing with brushed teeth and having some adequate hydration. There were a number of limitations, though, I thought in this study. My big one, and I think all the listeners will guess that it was, where are the CT values? I think we’ve learned over the last year that nasopharyngeal swabs are very sensitive, but sometimes maybe are they too sensitive to answer certain questions.

If saliva, for instance, is missing these low-level RNA PCR positives weeks after the acute infection, do we really care? Is that really a limitation? Is this really relevant if we’re testing to avoid transmission such as might be done for certain sporting programs? Now, we know New York, working with Mount Sinai, is going to develop this large-scale saliva testing availability for opening large venue events. If those people have a few thousand bits of RNA, am I concerned as someone going into a venue, particularly as a vaccinated person going to the venue, versus someone who has a high positivity, such a large amount of RNA that’s being picked up by antigen tests and all these others? I think we have a lot of good testing options and we just need to ask, what question are we answering or asking when we do these tests.

Active vaccination. There does seem to be some growing evidence that there may be an actual connection between the blood clotting and the platelet disorder and the AstraZeneca vaccine.

I used a lot of qualifications in there. It still appears that the incidence of this clotting and platelet complication is rare and the risk of a COVID complication in most cases is significantly higher if you remain unvaccinated, but this is evolving. The Medicines Healthcare Products Regulatory Agency, that’s the MHRA, regulate medicines, medicinal devices, blood components for transmission and the transfusion in the U.K. They reported 30 cases in 18 million vaccinated individuals.

We’re looking at a complication rate of 1 in 600,000, but there have been seven deaths. There may be an issue with the age skewing. This may be something that is clustered more in younger individuals. We’re actually certainly seeing some changes where there’s a preferential use of this vaccine in older individuals and a preferential use of other vaccines in younger individuals. This is an evolving story. As we learn more, we’re going to have to decide what to do here with this information.

Just an update on the Pfizer EUA expansion. Let’s get vaccines to younger individuals or the option to have vaccines in younger – 12, 13, 14, 15. As far as timing, we heard about the data. There is a required 15-day notice of intent to submit before the FDA performs their review.

Paul Offit, who’s a member of the Vaccines and Related Biological Products Advisory Committee was just saying the other day that so far, notice has not been given. Whether it’s later this month, I think it’s going to be May at the earliest, that we see a potential EUA expansion down to our kids, 12, 13, 14, and 15.

Passive vaccination. The monoclonals. This seems to be going much better as far as getting these off the shelves and to the patients. I think seeing the Phase III data, all the help that we’ve gotten from a lot of individuals to get the word out, has helped. I have to say, on our last Tri-state Urgent Care call, this week the comment was that our Hoboken Infusion Center was basically getting fully booked and there were questions about how much capacity did we have for our in-home infusion program. People are really getting out and they’re getting these treatments. I have to say this is tremendous.

When we see these individuals, the experience we have is they get the infusion and 36 hours later, they’re really reporting that Superman feeling. I actually spent some time recently over at one of the Catholic hospitals in our area, Saint Francis Hospital, speaking with Stefan Muehlbauer, he’s the head of the ER there, just making sure we have everything firing as smoothly as we can on all cylinders. I don’t know if I got that expression correct.

We have the ability with monoclonals to either go to outpatient infusion centers, to go to certain ERs, to go to certain infusion tents that are set up outside of ERs, and to get even in-home infusions. This seems to all be going very smoothly with getting people access to the monoclonal cocktails. Some exciting developments before we move forward. Right now, as mentioned, that’s great and all, but this is putting an IV in, it’s–  21 minutes we are allowed to but a lot of centers are spending a full hour of the infusion, plus the post-infusion observation time.

Vir GSK, which is trying to get their product EUA, is also looking at expanding into an IM, an intramuscular preparation. Right now, they have COMET-PEAK, which is an ongoing Phase II trial and they’re really looking at safety, viral kinetics, pharmacodynamics, doing this as an IM. They’re about to fire up COMET-TAIL and this will be a Phase III trial, which is going to be starting in the next month or so and we’ll be administering these IM products to high-risk adults showing hopefully the same benefit for reducing hospitalizations and deaths.

You can imagine the improved access, you’re getting something like an EpiPen where it could be just delivered from your local pharmacy or maybe it’s what’s brought in by an infusion team or a home care team, and boom, just right into the muscle. We’ll talk about whether or not you need to withdraw that plunger, when you do that, and then going ahead with the treatment.

Incubation post exposure period. Remember, tests do not predict the future. I was on a call last night with a camp and yes, you got to keep saying that. I used the pregnancy test analogy. Once someone is exposed, there is a period of time when they can go on to become positive. If someone gets exposed, they immediately test, it’s probably going to be negative but that does not mean that they will not go on and become positive in the next two to 14 days. Once they get into that period of detectable viral replication, remember our passive monoclonals, our passive vaccinations.

Time for monoclonals and monitoring, no steroids, no antibiotics in that first week. If you do get into that early inflammatory phase second week, if the oxygen saturations drop below 94, then you think of steroids, oxygen, anticoagulation, perhaps remdesivir. Most of these folks are not coming in with infections, that is a later stage issue. We got a lot of information. I’m going to say, close on this but this is actually a big chunk, we’re going to talk what we’ve learned about tail phase and Long COVID.

In The BMJ, we saw the article, Post-covid syndrome in individuals admitted to hospital with COVID-19: retrospective cohort study. In this observational, retrospective-matched cohort study, they reported on the outcomes with a mean of 140 days for 47,780 individuals that had been admitted to the NHS hospitals in England for COVID-19 and had been discharged alive.

These are the individuals that got– almost 50,000 that got COVID, were in the hospital. Nearly one-third were readmitted and more than 10% died during this follow-up.

Those with COVID-19 were diagnosed with major adverse cardiovascular events, liver disease, kidney disease, diabetes after discharge. What were the rates? Respectively, 3.0, 2.8, 1.9, and 1.5 times more. Major cardiovascular, three times more likely; liver disease, almost three times more likely; kidney disease, twice as likely; diabetes, 1.5 times more frequently than in the matched control group. This is a bit of an issue. I’m looking forward to more data on this.

We also had another study, and I think this is getting a lot of attention and this was in theLancet Psychiatry Journal and this paper, Six-month neurological and psychiatric outcomes in 236,379 survivors of COVID-19: a retrospective cohort study using electronic health records. This is really robust data, almost 2.5 million survivors. This was a retrospective cohort study and a time to event analysis. They were using data obtained from the TriNetX Electronic Health record, so over 81 million patients in this database.

I should say this database exists. I think we were painfully hearing of some early databases that were figments, but the primary cohort comprised of 236,379 patients who had a COVID-19 diagnosis and they had one matched control cohort including patients diagnosed with influenza. Other matched cohorts included patients diagnosed with other restorative infections during the same period. They reported that the estimated incidence of a neurological or psychiatric diagnosis in the following six months was 33.6, a third of these survivors of COVID-19 hospitalization.

If you were admitted to an ICU, the estimated incidence was almost 50%, it was 46.4%. This is huge. Now, what were these neurological diagnoses? Intracranial hemorrhage, ischemic stroke, Parkinson’s disease, Guillain-Barre, nerve root, plexus disorders, mild neural junction and muscle disease, encephalitis, dementia, psychosis, mood and anxiety disorders, substance use disorders, and a lot of insomnia. Now, I have to say, this report is consistent with the work of some of my colleagues at UHG. I think they’re a little frustrated because their study is still winding its way through peer review. I had the opportunity earlier this week, the pleasure I should say, of speaking with our ProHealth neurology group. I always like to get, “This is what we see in the literature, this is what the studies are showing. What are we seeing in our clinical practice?”

Several of the neurologists were describing the challenges that we’re seeing here in the tri-state area, presentations consisted with small fiber neuropathies with burning sensations and a lot of issues with either new onset headaches or an escalation of headaches from intermittent to chronic. Unfortunately, a growing number of individuals who maybe had an intermittent and vascular or migraine disorder and now they’re in constant pain, really challenging to treat these individuals. I think this will get a lot of attention because it’s quite upsetting, I think, to not have your mind working, to be in constant pain, to be suffering.

I think that’s enough bad news. I’ll throw a little bit of good news in here and I think this is some perspective on the good news as well. We’ve heard a little bit, and I’ve shared a little bit about the potential benefit of vaccination on Long COVID.

I’ve been seeing that a lot of us who take care of a large cohort of patients who are never sick enough to get in the hospital but continue to suffer with the brain fog, the fatigue, all these other disorders, we are seeing a large chunk of them report feeling better with vaccination. I reached out to Lawrence Shulman, he’s one of our pulmonologists. Talking to him about, what about people that were sick enough, now they have pulmonary scarring, now they have things that I just wouldn’t really think a vaccination would reverse.

In those individuals, a lot of our long-term care COVID or post-COVID recovery centers where they’re dealing with people who had cardiac insults and pulmonary issues, a lot of this I have to say, unfortunately, there is a subset of patients where this is not reversible by vaccination. Still encouraging all these individuals to get vaccinated, but it does temper that optimism. There does appear to be certain patient populations that are more likely to benefit from vaccinations, but there are certain other individuals where a lot of the damage is done, the scarring is there.

I will close by saying, thanks again for all the support we’ve had. This will be our final month, right? April? We are supporting the American Society of Tropical Medicine and Hygiene and part of that support will be providing scholarships for early-career women investigators from low-income parts of the world. We’re excited to do that, we’re excited to allow them to attend the fall meeting. Then hopefully, really give them a boost and do something about so much about the inequities that currently exist.

VR: All right, time for a few emails for Daniel. You can send yours to [email protected]. The first is from Alida in Canada, who’s a nurse and is curious about, you’re saying, “It is a must to aspirate before injecting an IM. In Canada, we have not done this for more than 20 years. I started nursing in 2000 and I have never aspirated. I’ve given thousands of vaccines and injections. CDC does not recommend aspiration. Just my thoughts.”

DG: No, they’re more than just your thoughts. You’re right. What is this issue of aspiration pulling back the plunger while doing an IM injection? As I mentioned, this is, and hopefully, I didn’t say it’s a must. Hopefully, I said this is fairly standard, still common. Should it be? What does the CDC say? What does the WHO say? What is the science? What is actually recommended? Actually, is not pulling back perhaps best practice?

Let’s go through this. Thank you for asking this question. As per the CDC, aspiration before injection of vaccines or toxoids, so pulling back on the syringe plunger after needle insertion but before injection, is not necessary because no large blood vessels are present at the recommended injection sites. Any process that includes aspiration may be more painful for infants. Actually, I think your timing on when you graduate is appropriate. They referenced a study back in the ’90s and the WHO does not recommend the plunger pull.

What does the science say? I have to say, based on what we know, the need for aspiration prior to administering an injection is dependent on certain factors. As a general rule, I’m going to say the science does not support that you need to pull back on the plunger and there’s ample evidence suggesting that. What are the couple little caveats? It still is fairly standard. A lot of people do this. Is there harm?

Well, as mentioned in the pediatric population, the original teaching was you held negative pressure for five seconds to make sure no blood would come up. That actually creates pain. That is painful, it is delaying. Some of us– I think this is interesting, what about epinephrine? You say, “Oh, this is epinephrine. If I got that into a blood vessel, oh, my gosh, that could be quite different than an IM injection of epinephrine.”

Now let’s all think about those EpiPens. Those EpiPens you basically put against your lateral thigh, you push a button and boom, out comes the needle, and out comes the medicine. Things are a little different now, I have to say. I have seen people put injections in the deltoid bursa. I’ve seen people completely miss the muscle and put it in the fat. Probably the pulling back on the plunger is probably a small issue. What are the big issues? Getting that needle into the muscle, using a one-inch needle so you actually get through whatever subcutaneous tissue and into it.

If you’re going to do IV, you definitely– I’m not going to use the word definitely. You do want to make sure you’re in the vessel because a lot of our medicines, if they’re infiltrating, can actually be caustic and cause tissue damage. If you’re going to put it into a muscle and you know what you’re doing and you’re actually in the muscle, do you really need to pull back? No. Is it better not to pull back? Yes, probably, actually. I think best practice would be no. If you’re going to give the shots in the deltoid, put it in the deltoid, not in the bursa, not in the chubby part of the arm.

If you’re thinking about doing a buttock shot, actually consider moving that to lateral thigh.

VR: We actually got a lot of emails about that and they were divided between “we don’t do it” and “we do it”. It was very interesting. It’s one of those situations.

DG: Well, it’s come up I think, Vincent, because the whole AstraZeneca issue. One of the theories they have there is that maybe younger people, better-vascularized muscle, maybe there are large enough vessels that you’re getting it in there. It’s good to have the science and the current recommendations. We did, so far this week, 213 vaccinations in my office. We’re doing another 100 tomorrow afternoon into the evening. Have I been pulling back on that plunger every time? No. Have I pulled back ever? No. I’ll fessup.

VR: Deepa writes, “I have been advised by my most excellent rheumatologist to skip two doses of methotrexate after taking any vaccine, including the one for SARS-CoV-2 based on the attached publication. This is the first study I’m aware of that carefully evaluated the immune response to flu vaccine in RA patients. They randomized the two cohorts, one that skipped two doses of methotrexate, one that did not. There is quite a remarkable and significant difference in the antibody response elicited in favor of skipping methotrexate.

Key finding, methotrexate discontinuation for two weeks after vaccination significantly increases immunogenicity of a seasonal influenza vaccine in patients with rheumatoid arthritis, who had been on a stable dose of methotrexate without significantly altering, increasing risk of disease activity. I hope this is helpful to you, your patients, and listeners of the podcast. Not many people are aware of this study. We need more studies like this.”

DG: Now, this is great. Thank you. Actually Deepa, we do need more studies like this and there’s no reason that we can’t be getting them. We are currently vaccinating billions of people by the time we’re done here, and this is the time. I know a lot of scientists have talked about, “We need a rapid review, rapid ability to fire up these studies.” If you think about it, these are studies that are minimal harm, they’re observational studies.

Rheumatologists, physicians who are using these medications are trying to space these out. Some people, almost practice preference might be only a week, some people don’t do this, other people are getting this two week. This is data I think that would be very valuable in helping us just in immunizations across the board. We do not only influenza vaccines, hopefully, every year, but now we do COVID vaccines. We have a lot of vaccines. Having really good science-based guidance here would be tremendous.

VR: One more from Marianne, who writes, “I got my first dose of Pfizer March 23rd. At the time I signed up, Walgreens had a schedule for the second dose four weeks out and my next is scheduled 28 days.” She found out yesterday by the time that Walgreens had taken upon it themselves to schedule these second doses at their convenience rather than at the tested interval, which should be three weeks, 21 days. Marianne goes on to expressing her displeasure with Walgreens and wants to know, “Any advice? Should I be looking at a booster sooner than later? Should I be asking my doctor for antibody testing? What can I do? I was looking forward to getting out of my house again, now I feel unsure. I figure I’ll be wearing a mask forever.”

DG: [laughs] Okay. Don’t be so upset. This was interesting. Walgreens decided that it would be easier for them, for their scheduling system to just do four weeks between shots and just didn’t care whether it was Pfizer or Moderna, which is interesting too because they’re shipping those second doses out, and then they’re sitting on a shelf somewhere for like an extra week, not in people’s arms. Walgreens was basically taken to task when this became public and told that that is not what we recommend. You need to be giving those second doses 21 days or four side, four days, either side of those 21 days, not waiting until 28 days unless, as we say, extraordinary circumstances.

Go ahead, get that second dose when you can get it. Do I think scientifically it makes a difference whether you’re getting it at 21 days or 28? In a lot of ways, I compare Moderna and Pfizer to Coca-Cola in a can versus Coca-Cola in a bottle. You’re getting the same mRNA, the packaging is a little bit different, the size is a little bit different but the outcome– it’s going to quench your thirst, it’s going to protect you from COVID quite well.

Don’t feel like Walgreens creating this difficulty is going to mean that you’re going to be less protected at the end of the day.

VR: Marianne says, “Thank you and the whole TWiV team for being a calm place to find accurate information. You guys get an A++, Walgreens gets an F-.”

Okay. On that note, that is COVID-19 clinical update number 57 with Dr. Daniel Griffin. Thank you, Daniel.

DG: All right. Thank you so much, and everyone, be safe.