TWiV 752 COVID-19 Clinical Update #61

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 8 May 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 752, recorded on May 6th, 2021. I’m Vincent Racaniello. You’re listening to the podcast all about viruses. Joining me today from New York, Daniel Griffin.

Daniel Griffin: Hello, everyone.

VR: This is clinical update number 61, Daniel. I am going to paraphrase former New York mayor Ed Koch. How are we doing?

DG: I knew Ed Koch quite well. My father actually worked for Ed Koch, so the mornings would often start with Ed Koch swinging by the apartment. He was quite a guy. He was a bit of a character. We will get right into the update on how things are, but let me start with my quotation, “Three things shine before the world and cannot be hidden. They are the moon, the sun, and the truth.” Now this is a modernization of a saying attributed to the Buddha. I think the eyes of the world are on India right now and it’s painful to so quickly see that Hegel was correct. The one thing we learned from history is that we do not learn from history.

This is recent history, and so many of the same mistakes are being made there. Many resources are being poured into unproven therapies, shortages of things that do really make a difference; vaccines, oxygen, no significant access, if any at all, to monoclonal therapy, and use of failed non-pharmaceutical interventions. We’re going to talk a little bit about what is a non-pharmaceutical intervention, what is an NPI?

Let me start with an update a little bit here in the U.S., and then we will make sure we keep mentioning what’s going on in the world because it’s quite different. One of the first things I’ve noticed is that the paywalls are starting to go back up. Some of these articles that, I don’t know if you’ve noticed that as well, but some of these articles I wanted to read, I had to go through the Columbia access to get the articles.

I think that’s unfortunate. I think people were getting used to the ability to access information. I think it’s critical. Maybe we should start trying to think about ways to keep those paywalls down and create other ways where people can get access to information when you publish something. You could pay, and it is a hefty sum to create an open access, but we need other ways to do that. A little bit of a change there. We are seeing a dramatic drop in numbers of cases here in the New York area, and actually, across the country.

I’ll get into this in a little bit later as we talk about modeling and the prediction that I think we’re on course for an incredibly low number of cases come this July. The rest of the world, if you look at it, they’re on the other trajectory. I think they’re going to start thinking of that first, what people called a wave, as nothing more than a swell before the true wave started to spread around the world.

This is tragic, but let’s hit each section. We’ve got a lot to cover today; children and COVID. I’m going to return to this in our vaccination section. I talked a little bit last time about the CDC camp guidance and oh my, the CDC is getting raked over the coals on that. This episode drops on Saturday, but I’m going to be on “The Brian Lehrer Show” on Friday here on NPR, that’ll probably be recorded. We’ll see how well I field the questions and criticisms of the guidance live on the air. Then I’m also going to be talking on Tuesday of next week on TV about what we are hoping the day– I’m going to predict the future again here. Next Tuesday we think that the EUA will expand for Pfizer down to 12-year-olds.

We’ll discuss a little bit about what that means. Let’s go right into pre-exposure period transmission. I think this gets back to our initial quotation. We have learned a significant amount regarding transmission, and this is, honestly, no longer an area clouded in mystery, or really just up for debate. We have science here, not just opinion. To just quote, the CDC and the WHO is in the same line with this, COVID-19 most commonly spreads during close contact. COVID-19 can sometimes be spread by airborne transmission.

COVID-19 spreads, less commonly, through contact with contaminated surfaces. In the MMWR, there was an article on, “Modeling of Future COVID-19 Cases, Hospitalization, and Deaths by Vaccination Rates, and Non-Pharmaceutical Intervention Scenarios,” United States, April through September 2021. This article is doing what Yogi Berra told us was the hardest thing to do. What is the hardest thing to predict? The future. That’s actually what they were doing here.

The authors presented predictive models of numbers of cases, hospitalizations, and deaths per week based upon different vaccination rates, either a high or a low vaccination rate and different non-pharmaceutical intervention levels or what they call NPIs. NPIs are things like wearing masks, physical distancing. I like that they’re not saying social and physical distancing, and this was just released May 5th. These models started their predictions March 27th. You actually got to see a little bit like how have they been doing since the models fired up?

They had numbers dropping from the peak in January to a nadir in April, and then a bit of a rise into May, followed by a rather rapid decline to very low levels by July. There were some error bars in these predictions and there were really four scenario lines that you could follow. You could either have low or high vaccination rates coupled with low or moderate NPIs, non-pharmaceutical interventions. She had each of those four scenarios, low-low, low-high, high-low, high-high. If anything, I have to say the future has turned out to be even better here in the U.S. than they predicted. If you look at the daily deaths, this has been decreasing since that peak in January.

I know there were some, we’ll call them pessimists, talking about the spring wave. The spring wave has not really materialized. I’ve been describing it as this spring plateau. If you look at numbers across the country, certainly regional areas, you look at Michigan, there was a second wave in Michigan, just in terms of cases and deaths. If you look across the country, we are actually experiencing, I will say their best-case scenario. Based upon this, we’re actually looking at a really good July ahead of us as I think a lot of us have been predicting for a while here.

This is the time for masks, distancing outdoors versus indoors, limiting group sizes, all these non-pharmaceutical interventions as we call them, and vaccination-both active. One day we’re hoping to get approval for passive, or I’ll say expansion of the EUA for the use of the passive monoclonal antibodies. All right, let’s move right into testing. Never miss an opportunity to test. We’re falling down a little bit. Compare our testing rates to the UK and they are doing much better.

They are doing a lot more tests per population than we are. Now, for a while, we’ve been talking about the way different tests can be used to answer different questions about COVID. A big disconnect still seems to come in people’s understanding of the rapid antigen tests versus PCR testing. The paper, “Performance Evaluation of Serial SARS-CoV-2 Rapid Antigen Testing During a Nursing Home Outbreak,” was recently published in the Annals of Internal Medicine. The authors reported on a prospective evaluation involving three facility-wide rounds of testing where paired respiratory specimens were collected to evaluate the performance of the BinaxNOW antigen test compared with virus culture and real-time PCR.

Real-time reverse transcription preliminary chain reaction, early and late infection were defined using changes in the RT-PCR cycle threshold values and prior test results.

They evaluated 532 paired specimens collected from 234 residents and staff. The authors reported on the percentage of positive agreements, a little bit of terminology, the PPA, and the percentage of negative agreement, the PNA, of the buyback BinaxNOW rapid testing, and the RT-PCR with viral culture.

They’re using viral culture here as really a potential infectiousness measure. Now, what did they find? What about sensitivity for a defect detecting infectious level of SARS-CoV-2? The BinaxNOW PPA, the percentage of positive agreement with viral culture used for detection of replication-competent virus, was 95%. I think that’s pretty stellar, right? You’re really asking the question, is this person contagious? However, the overall PPA with RT–PCR advantage in tests with RT–PCR, was only 69%.

I think this is consistent with what we have been seeing, which is that PCR is, perhaps, overly sensitive for asking and answering the question of infectiousness. The RT–PCR is great, late in the course, for picking up those people past that acute first week, who might now be in that early inflammatory phase. They might be showing up at the hospital. The rapid antigen test at this point may start to turn negative, but we’re asking a different question. We’re saying, “Is this need for oxygen due to an acute infection last week?”

The negative antigen tests that they did, where there was a negative antigen test, a positive PCR, those had a mean CT value of 33.2. An RNA copy number down only in the thousands. I think this really reinforces this model. The rapid antigen test within 15 minutes is really good at identifying those people who are contagious or infectious, getting them isolated before they spread. PCR is more sensitive, but it asks and answers a different question. Don’t think of the PCR as first-class, and the antigen test is sitting back in coach by the bathroom. The rapid antigen test is a very sensitive, really helpful tool for blocking spread of this virus.

Active vaccination, never miss an opportunity to vaccinate. In the U.S., we have shifted from arms searching for vaccines to vaccine searching for arms. We’re definitely seeing that we need to do a little better job here of connecting those arms with vaccines. Now, this might change for a brief time because I am hoping that prior to the next wave that we record, we hear that the FDA, like the EU and Canada, will have expanded the Pfizer EUA down to 12 year-olds, so 12, 13, 14, 15. We are expecting they will become eligible.

We’re already hearing that the states are getting ready. They’re expecting this as well. They want to be ready so that that morning, it’s usually 6:00am. We get up at 6:00am, so we can see that they hear that it’s expanded, that the states can then say, “Okay. We’re on board with this.” And all the pharmacies, all the state sites, could be ready to get that Pfizer into people’s arms because I have to say, a lot of Pfizer vaccine is sitting there. We also heard this is exciting news, that BioNTech, so it’s the Pfizer BioNTech Vaccine.

BioNTech has a new formulation that should allow them to store the vaccine for up to six months in a normal refrigerator, and they’re preparing the data packets for FDA approval on this upgrade to the vaccine. This will be a huge shift past these thermal shippers with dry ice, and all those concerns. Now, what about when we’re going to vaccinate kids? Are the kids going to want to get vaccinated, are the parents going to want to vaccinate them? I was talking a little bit with Jay Berger, the Head of Pediatrics for ProHEALTH New York, and I will mention also, an avid TWiV listener, about a lot of the conversations he’s had with parents about why they would want to protect their children from COVID-19 with vaccination.

There still is this perception that children do not get sick with COVID, or that children do not end up in the hospital with COVID, or that children are not at risk for long-term impacts following a COVID infection. I just wanted to take a moment here, and just get the numbers out here because this will be a discussion I think a lot of physicians, actually, a lot of family members will have with other family members. On May 2nd, the American Academy of Pediatrics reported that for the last week of April, the percentage of cases occurring in children had risen to 22% of the reported cases or up to 71,649 cases in children under the age of 18 just in the last week of April.

Now, I have to say, last year during April, children only made up 3% of all the cases of COVID-19 in the entire country. Actually, there were less overall cases. This is really a dramatic rise in the number of children that got infected that last week of April. This is really a dramatic rise in the number of children who are currently getting infected with COVID. I have to say, kudos to the parents out there. We really did a very effective job early on of protecting our kids from getting COVID. This involves school closures and all the other things we did, but now we’re letting the kids get COVID.

I want to say, even doing so much to protect the kids here in the U.S., here in the United States, we still had pediatric deaths, we still had hospitalizations, we still have children that developed long COVID, as I’ve previously mentioned, and this is one of those public health scenarios. When you do a really good job, and the outcomes are good, and I will say, only a couple of hundred children died, people say, “Oh, it really, it doesn’t affect children. It must not be a big thing.” That’s the problem with the public health success, which we have had to date for children.

If we look down at what’s going on in Brazil, we’ve already had thousands of deaths in children down there where they are not protecting the kids, over a thousand deaths in babies and Brazil is not the size of the U.S. Just use that as a measure of what happens if you don’t protect the children like we really did here. Now, let’s go into another article on this area. In JAMA, we saw “Antibody Response to 2-Dose SARS-CoV-2 mRNA Vaccine Series Among Solid Organ Transplant Recipients.”

This is a little bit of a downer, to be honest. The authors looked at transplant recipients. There’s a question we know in the studies, only certain people were vaccinated, certain people are excluded. Can the vaccine protect everyone, can it protect this particularly vulnerable part of the population? The authors looked at transplant recipients without prior PCR confirmed COVID-19. They recruited from across the U.S. to participate in– This was a prospective cohort study. They looked at those who completed the two-dose SARS-CoV-2 mRNA vaccine series between December 16, 2020 and March 13, 2021, and they followed them up through April 13th, 2021.

They were checking a semi-quantitative anti-spike, so looking at seeing what percent of these folks responded. The proportion of patients who developed a positive antibody test after the first dose was only 15%. They’re looking at 658 patients, only 15% of them had a measurable antibody level after the first dose. If they checked after the second, it was only 54%. Only about half of them had a measurable anybody level after the second dose. We don’t know what level of antibody might be a correlate of immunity. It’s a caveat here, but the level of antibody that these people were getting, those 54% who even did test positive, was below that of the general population.

Now, many of the TWiV listeners are pretty sophisticated. They want to know, “What about the T cells?” We’re not seeing T cell data in this publication. Unfortunately, the studies of T cell responses are even less encouraging. We’re concerned about these individuals. There’s questions about could we give them a third dose? Maybe we can somehow get that up, maybe, and some people have probably seen ideas that you combine an mRNA with an antiviral vector, maybe you can get different augmentation of different parts of the immune system, and that can somehow help these people.

Right now, this is potentially that group of people that the EUA expansion of the monoclonal cocktails might benefit. If you can’t make your own antibodies, maybe we can give you those protective antibodies. We will see potential expansion into this population in the future. All right, remember, post-exposure, a test does not predict the future, there still is that 2 to 14 day incubation period. Then you go into that next stage, should you get infected, the period of detectable viral replication or the viral symptom phase, remember, this is the time for monitoring and monoclonals, and I actually should say, and for education.

I will tell a couple of stories here about how this is not going as well as I would like it to be going. There is an issue with underutilization of monoclonals. I want to share it to share a couple of stories here, but the main one that I’m going to start with is a patient of mine that I’ve mentioned before. This was that gentleman in his 50s, who was diagnosed with his wife, the two of them went to an urgent care. They weren’t feeling well. This was not a ProHEALTH urgent care. They were diagnosed with COVID.

They both met criteria for access to monoclonals, they were offered therapy. Things going well so far. The wife said yes, that she wanted to go ahead. 36 hours later, she felt great, right? Got to know her a lot because she was FaceTiming with the husband. The husband did not do well. The husband felt like he would be just fine and wanted to take his chances. The urgent care physician did not, maybe, advise him strongly enough. He went on to get quite ill, ended up in the hospital, steroids, tocilizumab, oxygen, eventually, mechanical ventilation, and this Monday, this gentleman in his 50s died leaving behind his widow and his children.

I have to say, if this man came into a medical setting, and he had bacteria in his blood, if he had crushing chest pain, we were worried about a heart attack, I’m not sure the urgent care physician, or any clinician would be as willing to just let him go, take his chances. I think we really have to appreciate what an incredible impact the monoclonal therapy can have on these individuals. They’re sitting on shelves. It’s a phone call away. We need to make sure this happens. I just had another gentleman I admitted today. This gentleman had a BMI of about 40. He went to some urgent care I had never heard of before because he felt crummy and wanted to get tested.

When he did get a positive test, initially, it was a rapid, they signed off a PCR. They called him, they said, “Your test is positive.” He said, “Oh, can I come in? I’d like to talk to someone, find out what to do.” They said, “Oh, I’m sorry. We don’t see positive COVID patients in our facility. We’re worried about the risk of infection.” He asked what he was supposed to do. They said, “Remember that piece of paper you received. You should read that. Isolate for 10 days.” He got admitted today on oxygen. He’s in the hospital. Again, this is something that could’ve been prevented with just a phone call, just a little effort.

Early inflammatory phase, and now, this is that second week. This is for those folks who didn’t get monoclonals or weren’t eligible. If room air saturations are less than 94%, that’s when we have data, that’s steroids, six milligrams by mouth, one time a day times 10 days. You can do IV, but you don’t necessarily need to. Most people can just take that pill. This is associated with, not only improved outcomes, but a mortality reduction. This can, actually, sometimes result in rapid enough improvement that that person stating 92, 93, might come back up, might not drop into the 80s, might not require hospitalization. This is also that period of time when we use that remdesivir, $3,000 for a five-day course.

Minor impacts, but as I mentioned, huge expense and no compelling data on mortality. I hear about tons of remdesivir being used in India. Remember, that’s a $3,000-a-course medicine. Let’s talk a little bit here in a minute about some alternatives. Anticoagulation for our hospitalized patients improves outcomes and has a mortality benefit. The ASH guideline panel suggests using prophylactic-intensity over intermediate-intensity, or therapeutic-intensity anticoagulation in patients with COVID-19-related critical illness who do not have suspected or confirmed VTE. If they’ve got a clot, it’s straightforward. If they don’t, you want to get everyone on anticoagulation.

Then, they go ahead, and I think this is really important, an individual’s assessment of the patient’s risk of thrombosis and bleeding is important when deciding on anticoagulation intensity. The panel acknowledges that higher intensity, anticoagulation may be preferred in patients judged to be at high thrombotic risk and low bleeding risk. That might be where we’re seeing some of this new data. We’re waiting for peer review, may suggest floor patients on full-dose, and ICU patients on low-dose, but, of course, individualized. Keep up with the latest data, and look at your patient and make that decision. This should be made by the treating clinician, not by some institutional algorithm.

We perhaps do not give as much appreciation as we should, that supplemental oxygen is critical. I was talking to some of my colleagues in the ICU about that. If the patients start dropping those oxygen saturations into the 80s, we differently want to look at getting them on oxygen. Oxygen saves life. We’re seeing in India right now, what happens if you do not have enough supply of oxygen. Our listeners might remember how close we got last winter in some of the New York hospitals, and all the upgrades that the hospitals put in-place over the summer to allow us to have high-flow oxygen this winter. If we didn’t have those upgrades, we would’ve been like India a little while back.

To deliver the high-flow oxygen that we did that kept so many people off ventilators, we did not have that infrastructure in-place. I tipped my hat to the hospital administrators that made the decision to invest that money. There isn’t a great return on that as far as money goes, but a great return on that as far as patient care. Other pulmonary support measures, such as proning, have improved mortality benefit. They actually require the providers, particularly the nurses, to be involved.

If you just ask a patient and instruct them to lay on their belly, to turn on their side, they usually don’t want to. When you’re having trouble breathing, that’s not what you want to do. This, actually, is a person-intensive intervention. I could stop by the room, I could talk to the patient, explain how important it is, but this is the nurses telling them over and over, the medical assistants, “You got to switch positions. You got to do this, you got to do that.” This is associated with better outcomes.

I want to remind our listeners, antibiotics are not helpful for treating viral infections. Particularly, combinations of renal or kidney-toxic medications such as vancomycin, piperacillin, tazobactam, these can be harmful in a disease process already associated with a high risk of kidney failure, progression to dialysis, or death. You are not helping, you’re potentially harming your patients. It’s not safer to put them, to put them on these renal-toxic antibiotics just in case.

What about adding tocilizumab to patients already receiving all these interventions including steroids? We have some updates. We have some new data here. After the “Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia,” let’s just call it REMAP-CAP study, we saw a survival benefit in critically ill patients with the use of tocilizumab. After this, a number of the hospital systems, they stopped blocking its use, and they’ve started to allow its use.

They were using a very restrictive algorithm, only allow certain patients who met a rigid set of criteria oversight by a specific approval person not even necessarily involved directly in the patient care. Other hospital systems, really just much like restricted antibiotics, ask that a specialist be involved in the case, make that decision. The peer-reviewed results of the recovery trial have finally been published. The recovery trial was looking at the impact of tocilizumab in a broader hospitalized population. This was published in The Lancet. “Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY):, a randomized, controlled, open-label, platform trial.”

As this title says, let’s get it all in the title, this was a randomized, controlled, open-label, platform trial. Basically, the people the treating clinicians knew, either the person was getting tocilizumab or not. Randomized evaluation of COVID-19 therapy recovery assessing several possible treatments in the UK. Now, this was looking at tocilizumab, what we see published here, and the trial participants with hypoxia, so oxygen saturations here, they’re using less than 92%, evidence of systemic inflammations, they’re using C-reactive protein greater than, or equal to 75 milligrams per liter, were eligible for enrollment in this random assignment in a one-to-one ratio to either the usual standard of care that we’ve discussed.

This is going to be anticoagulation, oxygen, steroids, either plus tocilizumab at a weight-based adjustment, so 400 milligrams to 800 milligrams, depending on weight, given intravenously or not. A second dose could be given 12 to 24 hours later if it was felt that the patient’s condition had not improved. The primary outcome was 28-day mortality. I just want to point out, these are not just ICU patients. These are floor patients who are requiring oxygen. This is not people not on oxygen.

The people say it’s about half of the patients admitted to hospital in the UK would be eligible as per this criteria. 4,116 adults were included in the assessment of tocilizumab including the majority, I’ll say, receiving systemic corticosteroids as mentioned. Overall, 31% of the patients allocated to tocilizumab and 35% of the patients allocated to usual care died within 28 days. That was about a 15% reduction in mortality with the addition of tocilizumab to standard of care.

Consistent results were seen in all the prespecified subgroups of patients including those, the majority, receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from the hospital within 28 days, 57% versus 50%. Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death, 35% versus 42. That was a risk ratio of 0.84. Just to put this all together, this is extending the use of tocilizumab beyond just those critically ill patients.

Tocilizumab was associated with a 15% reduction in death, looking at all the patients, and a 16% reduction in the composite endpoint of mechanical ventilation or death in those not receiving mechanical ventilation at baseline. They reported only three serious adverse events, which all resolved with standard treatment, right? These were three infections. I like to point out that we can treat infections, but we cannot treat death.

When they did an analysis of all the trials today, there’s nine trials to date, they concluded that if you did a meta-analysis, basically, including this trial, tocilizumab is associated with a significant 14% reduction in 28-day mortality. I’m hoping that this trial will do for tocilizumab what the original recovery trial on steroids did for steroids, and more patients will have access to this life-saving therapy.

Now, they also have a preplanned six-month analysis. We’re also going to find out about the long-term outcomes of these patients. Are we seeing less long COVID? Are we seeing less pulmonary complications, less neurological complications? That is preplanned. We’re not going to see that for a number of months, but we’re going to, hopefully, have that data as we go into the fall of 2021.

Now, what about limitations? Right. This study was open-label. It was not blinded placebo, that sort of trial. The participants and the local staff knew who was getting what treatment. Among the 1,837 patients assigned to tocilizumab, not all of them actually got the drug, only 84% actually received the drug. We’re an intent to treat analysis here. The reported results may actually underestimate the true benefit of tocilizumab in reducing death.

Given that patients with COVID-19 often have a prolonged hospital course and may continue to have issues post-discharge, 28 days as mentioned, is not enough. We’re looking forward to the six-month analysis. What’s the long-term outcome with tocilizumab versus not getting tocilizumab? Now, I’m going to quote the comment in the issue of The Lancet by Shruti Gupta and David E. Leaf. In summary, the RECOVERY trial provides the most definitive evidence thus far to address the controversy over whether tocilizumab should be added to our armamentarium of treatments for severely ill patients with COVID-19. The answer is yes.

I certainly want to make a comment right here on the equity impact, right? Just like monoclonals, this is not an inexpensive, off-the-shelf pennies a dose treatment. Let’s look at this, as I think I mentioned before, remdesivir at $3,000-a-course with not really impressive benefit, no compelling mortality benefit, is being used like water over in India.

This is a therapy that, though the hospitals may charge thousands of dollars for, can be acquired for hundreds of dollars per dose. It’s a single dose. It’s not five days. This is something we should be looking at as far as equity and getting this out to individuals. All right, I have gone long enough today. I want to finish by reminding people of our fundraiser. We are now helping support FIMRC, Foundation for International Medical Relief of Children. As mentioned, this is an organization that had been funded primarily through young excited individuals ready to go out there and save the world, ready to volunteer in all these many parts of the world, and because of the pandemic, that has really been interrupted.

We know not a lot of young individuals are able to go to these places to volunteer. That source of support for these clinics has dried up. FIMRC needs your help, needs our help. Please go to We are going to try to double your money to get up to $40,000 to support FIMRC, and really, the tremendous work that they do throughout the world. Thank you, everyone, so far, and continue to help us.

VR: Time for a few emails for Daniel. If you want to send one, it’s The first is from an anonymous listener who writes, “My father was recently diagnosed with plasmablastic lymphoma. He received his first dose of Moderna three weeks before his diagnosis. I know that some people have had a lymphatic response due to the vaccine. My father’s hematologist doesn’t think the vaccine caused the lymphoma, but mentioned it may have caused it to increase the lymphoma’s fast growth. I have a couple of questions. “First, how likely do you think my father’s hematologist is correct in his belief that the vaccine may have sped the progression of the lymphoma?” Let’s take that one first.

DG: I’m going to say, I don’t think he’s right. I’m sorry. If you think about the way B cells work and you think about it, lymphoblastic lymphoma, now, this is going to be B cells that are basically growing out of control. B cells have a certain specificity, so you would have to somehow have the same antigen. This would have to be a COVID-specific, a SARS-CoV-2 specific B cell that was expanding and forming this cancer.

The coincidence there is just beyond belief. We’re talking about a one in a trillion chance that your vaccine is going to provide the antigen that will trigger the B cell receptor of that cancer. That does not make sense to me. What we’ve seen, right, if people get mRNA vaccines, is sometimes they’ll get swollen lymph nodes in the axilla, in the armpit of the area where the vaccine was given.

We’ve now learned from some studies out of the UK, that those individuals with the swollen lymph nodes, these are people that had COVID before. The vaccine can trigger the lymph nodes to enlarge significantly if they have B cells in there that have seen the spike protein of SARS-CoV-2 before. I just think the one in a trillion odds here that you’re happening to hit the same B cell receptor, I don’t think that’s a connection there.

VR: All right. Question number two, “My father didn’t get the second Moderna vaccine. He’s immunocompromised because of a kidney transplant. He also has diabetes. How much protection from COVID do you think he’ll have from just one shot?”

DG: Well, I feel like this is a planted question because it is perfect. The paper that we just talked about really would suggest that after one dose, maybe a 15% chance that we’ll even have any level detective antibody. I’m going to say, at this point, it is most likely that your dad does not have much protection. This is one of those situations where I would say going ahead with that second vaccine makes sense. This, again, your dad might be a candidate down the road here for an EUA expansion and a passive protection with monoclonal cocktail.

VR: All right. I think you answered his remaining question, “They weren’t planning to give him the second dose, but they’re not sure what to do or should he get a different vaccine?”

DG: Yes, actually, that’s good. There’s really two questions in there. One is, as I was suggesting earlier, there’s been a discussion lately about trying to combine different vaccines. We’re learning about mRNA vaccines in this population. Maybe we can get a better response with the adenoviral vector vaccines. Maybe we can get a better response by combining two.

You definitely got to ask that question. Right now, your dad is not protected. We’re in a pandemic. We would think that there’s some benefit to vaccination. If your dad gets COVID, his chance of dying is actually really high. Yes, I understand your hesitancy to get that second vaccine. I’m going to say that, in general, this is a situation where we usually would recommend going ahead with the second vaccine.

VR: All right. Next one is from Barry, who says, “I’d really like to hear your views on the role of budesonide and other inhaled corticosteroids in mild COVID. The three or so articles I’ve reviewed seem to reflect the favorable trend. Many of my colleagues in ambulatory and emergency medicine have prescribed budesonide. I’m uncharacteristically supportive, as well, even though I generally stay away from the sharp cutting edge of clinical medicine.” [chuckles] What do you think Daniel?

DG: I have to say if it was April of 2020, everyone would be getting budesonide because there were a few small studies suggesting maybe some benefit. I think we don’t know. I think in May of 2021, I think we can say, we don’t know. We need to study this. We need to know. Then once we know, we’ll be able to recommend. I think it’s, hopefully, time to stop experimenting on our patients, and start providing them with science-based advice and guidance. If there’s something out there that looks interesting, we need to push and make sure it gets properly studied so we can then offer our patients therapies that actually have proven benefit.

VR: All right. Starve writes, “My question, my 52-year-old boyfriend has hay fever because of pollen. He takes daily antihistamines. He got an opportunity to vaccinate, and, of course, following your number one rule, received Moderna. I advised him to stop taking the antihistamines so that his immune system be it at its best, but after one day he felt so bad with hay fever that he continued. Was I right? Do antihistamines interfere with the efficiency of the body’s immune system to produce antibodies?”

DG: Not significantly. Let’s be honest, when we did these huge trials with 30,000 people per trial on average, people were getting the vaccine, they would take an antihistamine, they’d take ibuprofen, they’d take acetaminophen. I think, if anything, there’s been this huge concern that our immune system is so incredibly fragile. Our immune system is robust. We get sick all the time. Your boyfriend probably fights off the common cold, pollen with antihistamines. Can you imagine that?

Some people take antihistamines while they’re fighting off influenza. And if these antihistamines are not going to significantly impair a person’s ability to respond to a vaccine, we’ve been giving vaccines for decades, this has never been an issue. There really is no compelling science. Go ahead. Take that antihistamine. Don’t suffer. This has been the worst allergy season in history.

VR: All right. One more, sneak an extra one in from Pablo. Two questions, one, “Patient at high risk; cerebral palsy, tracheostomy, nonverbal whose parents are COVID positive. He was not admitted for bacterial tracheitis. According to EUA rules, I cannot use monoclonal because he’s COVID negative, but once he becomes positive, he is going to be inpatient and likely hypoxic. Suggestions?”

DG: This is tough. With the current EUA, we’re restricted. This would be one of those where we have the data. Like you’re saying, “Why can’t I give this person monoclonal so that they don’t get COVID?” This is probably one person we want to test maybe on a daily basis, catch them as soon as possible. If you catch someone in the first day or two, give them monoclonals. I think our studies have suggested the earlier you jump in, the better you can really avoid what here sounds like it could be a horrible outcome. Soon, fingers crossed, we’re going to get that EUA expansion to use this prophylactic based on really compelling data of the Regeneron cocktail.

VR: “Patient number two, on rituximab for autoimmune encephalitis, got severe COVID pneumonia one month after the second dose of Moderna. After remdesivir, went home, came back a few days later; CT 27, no spike IgG. Is he a candidate for preventive monoclonal? Does the EUA allow it?”

DG: That’s a great question, and actually, I have to say, let’s go back to what we know here. The CT of 27 is exactly what I recently was dealing with with a patient who has a GPA, who is not able to clear the virus. The woman that I’m taking care of, actually, was infected in December. Her CT value is still in the 20s. What do you do here? Up at Boston, there was a nice article where they gave convalescent plasma several times.

All they did was get the CT to go up a little bit, get the viral load a little down, and basically breed resistant variants with convalescent plasma. That was not helpful. We’re concerned that if you start giving someone who can’t mount a good immune response the cocktail, that you might do that as well. But this might be a little different, the patient you’re describing, this is a patient who seems to have an isolated impairment of B cell function, maybe the T cells are still there.

This is a little bit of a gray area. EUA would not allow access, compassionate use might, but this is going to be a little bit tricky, but we’ll see going forward. Right now, you’re in the gray, the experimental area. I am not sure, but there certainly is that risk, if you give a person who can’t clear the virus themselves the monoclonal cocktail with persistence that you might breed a resistant variant– But no this is one of those, but boy, what a challenge.

VR: That is COVID-19 clinical update number 61 with Dr. Daniel Griffin. Thank you, Daniel.

DG: Thank you so much. Everyone, be safe.


[00:43:53] [END OF AUDIO]

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