TWiV 803 COVID-19 Clinical Update #79

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 11 September 2021

pdf of this transcript available (link)

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

[music]

VR: From MicrobeTV, this is TWiV, This Week in Virology, Episode 803, recorded on September 9th, 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: How’s the week been, Daniel?

DG: It’s a little truncated here in New York. We had a long weekend. Well, most of the country had a long weekend.

[laughter]

DG: It was Labor Day, right? Monday was Labor Day. I celebrated Labor Day by not laboring. Let other people labor.

VR: Excellent.

DG: It’s nice to have a little– I did a lot of sailing, so that was very nice.

VR: Very good.

DG: Time with the family. All right, but we got lots to cover. I keep looking to that point when we have less to cover. We’re not there yet. Let me start with my quotation, “Life is a long lesson in humility,” and that’s by James M. Barrie. I think Peter Pan maybe was something that he created. It seemed appropriate because I think science is clearly an arena where this is very much true.

I think it’s fair to say science is a lifelong lesson in humility. That’s why we do science because we don’t know the answer. Science is really, I like to say, a journey of discovery, not a path to confirmation. If we know all the answers, we would not have to do the experiments or the trials. This episode is going to drop on 9/11, so I just want to take a moment there. I grew up in New York, so that was really a difficult day, well, for a lot of us.

All right, let’s get into a number of papers here. The quotation I start with, really, is something that has been addressed. I’ve seen a number of papers recently. One of them– actually, a couple of them, I think, are in Open Forum Infectious Diseases. The first, “Overlooked Shortcomings of Observational Studies of Interventions in Coronavirus Disease 2019: An Illustrated Review for the Clinician.” These updates, I don’t know if our listeners remember, they really started off theoretically as a clinician update.

I like to keep that focus, but I think we have non-clinicians that listen, right? Let me just read the abstract here because, over the last two years, this has been a rapid education, re-education for a lot of clinicians when something gets published. It gets thrown out there as a preprint. It gets interpreted in the media. A lot of clinicians are trying to decide what to do based, unfortunately, on a lot of observational studies that may not have been done that well. Let me just read the abstract here.

“The rapid spread of severe acute respiratory syndrome coronavirus 2 infection across the globe triggered an unprecedented increase in research activities that resulted in an astronomical publication output of observational studies. However, most studies failed to apply fully the necessary methodological techniques that systematically deal with different biases and confounding, which not only limits their scientific merit but may result in harm through misleading information.”

I am going to highly recommend that all clinicians take the time to read this. I think this is really critical. It’s only an eight-page paper. It’s not terrible to read. Our goal is discovering what’s true as clinicians. When you go see the clinician, you want them to tell you what’s true, not just what they’re excited about. Unfortunately, as we’ve seen over the last two years, there’s been a lot of poorly done studies that actually got people excited about stuff that turned out not to make a difference, right?

They talk in this paper about several of these issues. One, treatment selection bias. Maybe we remember that vitamin D study that we all got excited about, and then some savvy people in Spain realized that they were giving vitamin D to the people in the healthier, less acute wards but not giving it to people with severe disease and more issues, and so, yes, young, healthy people do better. [chuckles] Was it really the vitamin D? That was not helpful. If anything, that was misleading.

Then there’s survivor bias, right? You decide you’re going to enroll someone in a treatment and they have to live long enough to get the treatment, so there’s sort of this immortal period introduced. It’s important that we understand that. Then there’s these competing risks like if our endpoint is discharged from the hospital, what happens afterwards? Have we excluded them? Not followed them into discharge?

I think this is really great. There is a role for observational studies, but this paper just reinforces how important it is designing, conducting, and then, really, I’m going to say the integrity of publishing helpful reliable information. Because if you get something out there and it supports something because of one of these biases or poor study design, that’s not helpful. It’s more than not helpful. It actually can be harmful.

The other paper that I enjoyed this last week– I got all this extra time, right? I could read. “Critical Review of the Scientific Evidence and Recommendations in COVID-19 Management Guidelines.” This is really enlightening. I get to see some of this as I’m involved in the care of patients at multiple health systems, also involved in the outpatient setting. I talk to our providers across the Tri-State Area. Well, I tend to look to professional societies or government resources like the IDSA, the NIH, American Society of Hematology, or the CDC.

This paper gives a good description of the landscape. There are actually hundreds of different recommendations out there. Only about half of the ones out there really have any assessment of the supporting evidence. There’s actually quite a bit of discrepancies between different guidelines. I actually think this speaks to this vacuum created by a lack of well-designed randomized control trials.

It also might speak to an issue with who creates these guidelines, right? Each hospital, healthcare system, physician group out there creating their own treatment guidelines in this void. For instance, there are guidelines for treatment at Columbia University or recommended by a professional society, but then I go to a certain hospital, “Oh, we don’t do that here.” [laughs] This is a challenge and I think this is another area, but I shouldn’t complain, right?

I have colleagues in rural parts of the American West and they’re probably listening and saying, “Dr. Griffin, you don’t need to complain. We have it worse.” I won’t even go into the details. You can just use your imagination, but you can imagine some of the guidelines in certain areas of the world and our country.

All right, let’s get right into children, COVID, and mental health. As I’ve been saying for quite a while, “Children are at lower risk, but they are not at no risk.” I think everyone is really waking up to this. Wearing a mask is less dramatic for a child than being hospitalized. I’m going to add a new one. Children should not have to choose between health and education. I’ve talked a lot about the American Academy of Pediatrics, which has a COVID tracking.

The CDC also has a data tracking page, specifically looking at pediatric data. You can look at this and it’s outstanding. Over a quarter-million children were infected with COVID in the last week. Hospitalizations are going up. Just anyone who is still in this idea that for children, COVID is not a problem, their heads in the sand. The information is out there. Yes, two years ago, 18 months ago when our– I was giving moms the credit and I think I should in most cases.

When the moms were keeping the kids safe despite what people were saying. If a kid does not get exposed to COVID-19, if they don’t get infected with COVID-19, it’s not a problem. Now, an enormous number of children, I think, where over six million children have been infected with COVID in this country. We did get some data from the MMWR, two really informative publications, “Trends in COVID-19 Cases, Emergency Department Visits, and Hospital Admissions Among Children and Adolescents Aged 0-17 Years.” This is United States, August 2020-August 2021.

Here, the CDC analyzed COVID-19 cases, ED visits with a COVID-19 diagnosis, hospital admissions. Overall, COVID-19 ED visits and hospital admissions increased since June 2021 in children and adolescents. The rate, per 100,000 persons, of COVID-19 admissions in August 2021 in the quartile of states with the lowest vaccination rate was almost four times higher than the quartile with the highest vaccination coverage, right?

Think about it. Most of these kids are not eligible, so a lot of the impact here we’re seeing is adults getting vaccinated and the benefit that can provide. We also saw a second publication, “Hospitalizations Associated with COVID-19 Among Children and Adolescents,” COVID-NET, 14 States, March 1st, 2020-August 14th, 2021. Here, they reported that the weekly COVID-19-associated hospitalization rates among children and adolescents rose nearly five-fold during late June to mid-August 2021.

The proportions of hospitalized children and adolescents with severe disease was similar before and during this period of Delta predominance. Hospitalization rates were 10 times higher among the unvaccinated than among the fully-vaccinated adolescents, so that’s looking at the vaccine-eligible group. I think just important information that we have here. It’s great that this is being tracked. This is important when parents are making decisions when adolescents are involved in shared decision-making about vaccines. Yes, I’m not sure why people are so sensitive whenever I talk about children and COVID. I’m just sharing the information.

Pre-exposure period, transmission testing. Never miss an opportunity to test. I just did a keynote talk earlier today about testing. Usually, this is the area where I’m trying to reinforce antigen testing, talking about PCR detection, talking about how actually antigen tests maybe have been compared against the wrong gold standard. Maybe if you compare those antigen tests against viral culture, against contact tracing, against transmission– I think I’m going to say that antigen tests used during that two days before, three to five days after symptom, during the period of time we see transmission, even at-home antigen tests were in the high 90s.

They are not an issue with lack of sensitivity during that period. Once a person is past that period of stage, once the viral RNA is low and the viral antigen gets to a very low level, yes, the antigen test will turn negative. Use the right test at the right time to ask the right question. Today, I’m going to talk about serology. We had a couple of interesting studies looking at serology. It’s going to be serology positivity. One is the U.S. The other, Kenya. Both published in JAMA.

The first one, “Estimated US Infection- and Vaccine-Induced SARS-CoV-2 Seroprevalence Based on Blood Donations,” July 2020-May 2021. This is a repeated cross-sectional study that included 1,443,519 blood donation specimens from a catchment area representing 74% of the U.S. population. They reported that general population increased– This is really what’s the money here, 83.3% had a combined infection or vaccine-induced antibodies. It’s actually pretty high, I have to say.

The authors looked at both spike and nucleocapsid antibodies. Nucleocapsid being associated with infection, spike being from either. This is a very high number. I think there’s a couple of things to point out. People that donate blood are not necessarily representative of everyone, but there was, I’ll say, a little bit of a disturbing feature here. If you looked at this, the infection-induced seroprevalence was consistently highest in Hispanic, non-Hispanic, Black individuals, that Caucasians are getting their immunity from vaccination. Other populations are getting it disproportionately from infection.

Now, the second article, right? Here, most people in this first study are getting their positivity, their immunity from vaccination. I think we’re up to 75% of the U.S. population has gotten the first dose, 75% of eligible. Remember, we still have a large chunk of our population, the children, that are not eligible. The second article was a situation where there was limited access to vaccines. This was, “Prevalence of SARS-CoV-2 Antibodies from a National Serosurveillance of Kenyan Blood Donors,” January-March 2021.

In this article, the authors report about seroprevalence in Kenya. This is a surveillance study looking at blood donors aged 16 to 64. Slightly different age demographic in Kenya. We don’t have as many folks over the age of 65. The national prevalence of SARS-CoV-2 antibodies was estimated at various points in time, basically getting to the end. The crude seroprevalence had gotten to as high as 44.2. This is actually in-line with what we’re seeing in a lot of other areas, but remember, this is dominantly coming from exposure from infection. The Kenya COVID-19 vaccine program only began in March of 2021, so a little bit, and they were only up to 2% of the population by July 2021. Most of that is from infection.

All right, active vaccination. There’s always news on this front. Never miss an opportunity to vaccinate. Vaccination is how this pandemic ends. Wednesday, September 1st, Moderna announced its completed submission for full-approval of its mRNA vaccine, so we’re hoping we’re going to see that coming up on the horizon. Why does this matter, right? It actually seems like it does when I talked to my patients. I was talking to an unvaccinated woman earlier this week. She was not vaccinated and she said she was not interested in getting vaccinated until she heard about this new licensed vaccine called Comirnaty. She’s very excited to get Comirnaty as soon as that is available. [laughs] I think once we have the ability for people to get Spikevax– I was talking to one of the nurses today and asked, “What would you choose? The Comirnaty or the Spikevax?”

VR: I choose Spike Lee.

DG: [laughs] Okay, so I think this stuff matters actually. People seem to care. The other thing, I was not going to include– How can you not talk about boosters? That’s all anyone wants to talk about. What about the data from Israel, the boosters? This is my plug for Shane Crotty. I listened to the Shane Crotty episode. Shane Crotty is actually one of the people that I reach out to when I’ve got an immunology question.

He’s brilliant. He’s actually an individual that WHO and a lot of other people turn to when they really want to know what the science shows. If you go to the TWiV episode right before this, it’s great because everyone’s asking him questions. Shane Crotty is so good. He basically, “This is what the science says.” He doesn’t get ahead of the science. You don’t get Shane Crotty’s opinion. You get, “This is what the science is telling us.”

If people really want a deep dive, spend that– I think he’s on for about the first hour, but then stay for the rest of the show, but that is really great. What created all this fuss? And I’m just going to spend a moment on this, the preprint, “Correlation of SARS-CoV-2 Breakthrough Infections to Time-from-Vaccine; Preliminary Study,” was put up as a preprint. Now, a number of statisticians, mathematicians have got a chance to really look at this. Some of the other data you can bring down from the Israeli dashboard’s publicly accessible data.

Yesterday, I got to listen to a really great analysis of this data presented by one of my colleagues, Efrem Castillo. He’s one of the senior VPs at Optum with whom I work. He really explained all about how this data was not originally correctly analyzed, explained a bit about Simpson’s paradox, where if you don’t break it down and look at the data correctly, it could be concerning.

He went ahead and broke down the data by a number of narrower age bands and really looked at, “Okay, if you look at a place like Israel, if you look at the population, say, 90-plus, over 90% are vaccinated.” Actually, over 70, if you look at people over the age of 70. Really, if you go to people 60 and up, the majority, over 90% are vaccinated, right? These people, you’ve greatly reduced their risk, but they’re still at the high risk of ending.

If you go through each, what is the efficacy we’re seeing for prevention of severe disease? You’re seeing in the oldest population, an 82-fold reduction risk in efficacy versus severe disease of over 90% and you march all the way down. You actually get to the youngest individuals under 30, and you’re looking at close to 100%. In the 30 to 39, 96.8%. Properly analyzed, I continue to not be concerned by this data.

Shane Crotty talked a little bit about, are we concerned about infection? Is there a potential that that’s going to be tied in with transmission, potential for long COVID? We’ll have to see, but I think when you look at it correctly, there’s no reason for panic. The booster study, the booster decisions will be addressed, but you don’t need to run out. I get questions every day, “Should I run out?” If we’re going to follow the science, the science is not pushing us.

All right, passive vaccination. I’m almost delighted how much of my colleagues have taken advantage of the prophylactic indication for monoclonals. Let me just reinforce this here. A bit back, the Regeneron cocktail, REGEN-COV, was given an expansion of its EUA for post-exposure prophylaxis. The U.S. FDA issued an EUA of all these three-letter acronyms, TLAs, to permit the emergency use of REGEN-COV for post-exposure prophylaxis in individuals who are at high-risk for progression to severe COVID-19.

Who are these individuals? One, not fully-vaccinated or they were vaccinated, but you have doubts about their ability to mount an adequate immune response, an individual who is on immunosuppressive medications or, as they say, at high-risk of exposure to an individual infected because of occurrence in a, let’s say, nursing home or an institutional setting such as a prison.

I’ve actually added this as part of my history of present illness. Once I get through with the patient, I say, “All right, this is great. Now, we have a plan for what we’re going to do for you, but let’s talk about everyone else that you may have exposed, who is either exposed and might benefit for prophylaxis, or is already infected and might benefit from early treatment.” I have to say, this has really been tremendous in the Tri-State Area.

We are seeing a low number of our ProHealth and our Optum Tri-State Folks end up in the hospital because we are doing, I say, a tremendous amount of getting these individuals in for the monoclonals, keeping them out of the hospital. A lot of the health systems have really helped support access. Tip my hat again to the Catholic hospitals, really jumped in and helped us with this.

All right, I’m going to jump right to the early inflammatory phase, right? We did have an update from the American Society of Hematology, “Living guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19.” This was an update on the use of anticoagulation in critically ill patients. Full disclosure, I’m one of the authors on this. This was a recommendation regarding patients in the hospital who are requiring critical care.

These are either patients in the ICU, but it’s not geographic. It’s patients who require that level of support really in favor of prophylactic-intensity anticoagulation here. This is that issue that a patient in the ICU, though at increased risk of clotting from COVID-19, and we know that COVID-19 patients have an increased risk. We felt reviewing the available literature that the risk of bleeding and associated mortality was in favor of prophylactic intensity in that setting.

What’s the standard right here? A patient ends up in the hospital, right? They’re usually there because they’re hypoxic. Their room air oxygen level is below 94%. Somehow, they’ve either not been vaccinated or they’ve missed the monoclonals or that small percent of people that progress. The standard is to start anticoagulation. Here’s a little more guidance on dosing, the remdesivir, the dexamethasone.

What if they progress, right? We’ve talked about patients that are requiring more oxygen support. We’ve talked about tocilizumab in the past. What if there’s a shortage of tocilizumab as we’re seeing in many parts of the country? Are there other options? Well, there is another option that is in the guidelines, but let’s talk about a publication in The Lancet that just came out.

This was in The Lancet Respiratory Medicine, “Efficacy and Safety of Baricitinib for the Treatment of Hospitalized Patients with COVID-19.” This is the COV-BARRIER study. This was a randomized, double-blind, parallel-group, placebo-controlled Phase 3 trial. This is, as I like to say, the much-awaited results of the COV-BARRIER study. Really, in the title, this was a Phase 3, double-blind, randomized, placebo-controlled trial.

Participants were enrolled from 101 centers across 12 countries in Asia, Europe, North America, South America. Hospitalized adults with COVID-19 received standard of care, were randomized 1:1 to either receive once-daily baricitinib, 4 milligrams, or matched placebo, for up to 14 days. The standard of care included corticosteroids such as dexamethasone, antivirals, remdesivir. They reported the 28-day.

All-cause mortality was 8% for the 62 folks in the baricitinib and 13% for the 100 in the placebo group, reporting a 38.2% relative reduction in mortality. They’re saying one additional death was prevented per 20 treated, so a 20 number needed to treat to prevent one death. The 60-day all-cause mortality was 10% for baricitinib, 15% for placebo. The frequencies of serious adverse events were similar between the two groups.

“What is this drug, Dr. Griffin?” [laughs] Baricitinib is a Janus kinase inhibitor. It interferes with the JAK/STAT signaling pathway. The thought is this is actually reducing cytokine, particularly IL-6 production, thus the idea we were concerned using tocilizumab and IL-6 receptor blocker without steroids because the IL-6 levels would shoot up. Here, you’re using this agent that actually reduces IL-6 production.

In some other studies, if you’re unable to use steroids, this is still something that you could potentially use. Actually, I’ll say, this is something that the IDSA has in their recommendations where they’re saying among hospitalized patients who are progressing elevated inflammatory markers, this is something you can consider and also something you can consider in a patient for whom steroids cannot be given for whatever reason.

Long COVID. I think it’s become really clear, but I’m going to add this to my list of pithy quotations. COVID is not just a two-week viral illness for many people. Early on, we had a lot of people saying, “With COVID, you either live or you die,” and this perception that it was two weeks. In the MMWR, the article, “Long-Term Symptoms Among Adults Tested for SARS-CoV-2,” United States, January 2020-April 2021. This is hot off the press today as we’re recording.

In this report, the authors administered a nationwide internet survey to 698 U.S. adults aged greater or equal to 18 years of age with a positive SARS-CoV-2 test. They compared them to 2,437 with a negative test, 2,750 had never been tested. They reported for those with a positive test. 65.9% had symptoms persisting for greater than four weeks. Now, the usual suspects: fatigue, change in smell or taste, shortness of breath, cough, headache.

I’ll say the same challenges that we talked about previously in the adolescent study, there’s a lot of background. Now, we’re seeing this above background, but a lot of challenges in sorting that out. I will say, this is another point in the line that long COVID is a real thing. A significant percent of people are not just better after two weeks. Now, there was also a preprint posted, “Severe COVID-19 is associated with sustained biochemical disturbances and prolonged symptomatology; A retrospective single-centre cohort study.”

This is a paper that’s up as a preprint, but it’s submitted to the Journal of Clinical Medicine. It’ll go through peer review. I’m one of the authors, right? I talked to a couple of my publications this time, or preprint postings. This really describes a cohort of 168 patients with severe COVID-19 previously hospitalized and describes how in this cohort, they have sustained biochemical disturbances, elevated ferritin, D-dimer, elevated neutrophil-lymphocyte ratio.

It’s nice to start having some objective data. There’s been a lot of ideas about what drives long COVID, discussion about viral persistence, continued antigenic stimuli. There’s always been a lot of thought that this is something with the immune system. It’s just nice to have some objective. Maybe some bread crumbs here to start to understand and, hopefully, be able to help these individuals.

What about low and middle-income countries and COVID? No one is safe until everyone is safe. I’ve been having this discussion quite a bit that it is the right thing to do, it is the selfish thing to do to immunize the world. Where are all these variants coming from that’s keeping everyone awake at night? We heard from the White House COVID Advisor, Jeffrey Zients, that the U.S. plans to invest $3 billion in the vaccine supply chain as it continues to work to position itself as a leading supplier of vaccines for the world.

I heard some interesting musings by Anthony Fauci about maybe using the PEPFAR Network to help with vaccines, but then we just heard that COVAX, a global program to distribute COVID-19 vaccines, cut its 2021 forecast for available doses by one quarter. There was what I thought was an interesting, disturbing The New York Times article by Benjamin Mueller and Daniel E. Slotnik.

Let me quote, “In its latest projection, the global immunization program known as COVAX said that it expected to have a total of only,” I’ll throw again “only,” “1.4 billion doses available by the end of 2021. In June, the program had said that it expected to have access to 1.9 billion doses this year. Experts have said 11 billion doses are needed to slow the spread of the virus.” Just to give people perspective, as of now, less than half of a percent of all the doses have been administered in low-income countries, so this is not great.

Maybe with that, I will just go into a reminder– During the months of August, September, and October, please go to parasiteswithoutborders.com. Go to “Donate.” We are going to continue to support Floating Doctors. They’re a group down in Panama. As we discussed last week, they’re going to be working with the ministry. They’re going to be getting vaccines out there, really help us because the COVID pandemic is a global pandemic. If we don’t treat it as such, we’re all at risk.

VR: Time for some email questions for Daniel. You can send yours to daniel@microbe.tv. John writes, “I’m 71. Due to colon cancer, I’ve lost my spleen, pancreas, half of one lung, and a couple of feet of colon. My health is not great, but my diabetes and blood pressure are well-controlled. I received my second dose of Moderna vaccine in February. Is there a test that I can request that will show the condition of my immune system?

As of now, I don’t feel at all convinced that the vaccine has or will work for me as well as intended. The third dose is available or soon will be. I will get one if only for additional protection against infection and, yes, I do understand the difference between infection and disease. I really don’t want the infection. I’m fairly certain that the disease would knock me off my perch. I would really appreciate any information on available tests. It would help me to understand my position.”

DG: Okay. Good, and I appreciate that you added the sophistication at the end because I think that sophistication is required. We do not have any great tests for telling how well does the vaccine work against preventing disease, ending up in a hospital, death. There is, I’ll say, some information supporting the idea that there’s a certain correlate between antibody levels and infection, but I’m going to say that with trepidation. This is growing. We’re learning about this. I’m going to leave it there.

We do not have that test, I think, that you want. You want to go ahead and have a test and have that security. There’s certain ideas that certain levels of antibodies above a certain threshold might be associated with a lower risk of infection. What am I going to advise you to do? You would probably be an individual, as you described, who would qualify for that third shot. We do not know exactly what that results in, right? We’re still waiting for the science as far as efficacy because you don’t want to know, “What happens to my antibodies?”

You want to know, “What happens to my risk of infection? What happens to my risk of disease?” The second thing, you want to continue to act cautiously. You do not want to have a run-in until we have antivirals, until we have some other things that we can offer. I mean effective antivirals, not remdesivir. Hopefully, a product by Merck or Pfizer that comes out in the next couple of months. Continue to wear a mask. Continue to make smart decisions. Hopefully, individuals like you we will have more to offer.

VR: Debbie writes, “I’m an internist who has been educating the physicians in our medium-sized primary care practice since the beginning of the pandemic. As I look to the future of this virus becoming endemic, I’m trying to think how to frame this and what measures to follow. It occurs to me that hospital strain,” and that’s not the strain of virus, by the way, that’s strain on the hospital, [chuckles] “is one of the most important things to follow. In my home state of Texas, our non-medical governor has decided 15% of beds being occupied by COVID patients was a measure of distress.”

I can follow this number on the Johns Hopkins website for my state. Locally, it’s harder to follow. It seems that hospital strain numbers are not universally agreed upon and also seem to change. Hospitals are used to growing capacity during surges and emergencies. Is there any agreed-upon and standardized measure of hospital strain? If so, any reliable website for looking at it?

I’m also following the percent positive rate only as an indication of adequacy of testing, and then looking at cases per 100,000 per seven days on the CDC website or globalepidemics.org. Additionally, home testing or very easily accessible testing is going to have to be a much bigger part of the solution moving forward. $20 for two tests is too expensive. Here in Texas, it’s hard to find home tests. Scheduled tests are two days out and turnaround times are increasing.”

DG: Okay, so a lot in that email. Talking first about hospital occupancy and how that correlates with how much a hospital can handle, so that’s really the number. What is the percent of beds? What’s the hospital capacity? What’s the percent of filled beds? The other is actually looking at ICU. What percent of the beds? In New York, they actually have good sites that you can go to keep track of that. That’s one of the things because, remember, it’s not just about COVID.

You break your leg. You’re in a car accident. You need chemotherapy. There’s a myriad of other reasons why people end up going to a hospital. If those beds are all full of COVID, that’s a problem. That does strain the system. Yes, there is a certain ability to deal with increased capacity surges. We see this a lot of times with influenza respiratory season, so that’s helpful.

Testing, yes. I think as you went through that, it’s a very sophisticated analysis. If you’re in the UK, you go to a website, the next thing you know, you’ve got free testing. Here in the U.S., $10, $11 per test, that does not encourage people to get tested. If anything, it’s penny-wise, pound-foolish. It is incredibly expensive when someone ends up in the hospital with COVID and it is a lot cheaper to prevent that.

VR: Jamie writes, “I am a primary care clinician, a family nurse practitioner of 19 years with a doctor in translational research. Two clinical questions. One, we are in California and have vaccine mandates for our public employee sectors. I had my first patient asking for a medical excuse from the mandate, which, as of now, can be religious or medical. This 30-something patient is currently undergoing infertility treatments and wants to wait until after she is either pregnant or gives birth to get the vaccine, asked me to put in writing that there are no risks to pregnancy or fertility treatments, which, of course, I cannot do.

I discussed with her the risks of COVID while being pregnant and asked her to talk to her reproductive health provider and come back in two weeks prior to the mandate’s effective date so we can make a determination while I do more research. I wanted to talk to our fellow clinicians and have an office-wide approach, knowing that the only real CI to vaccination is allergy to vaccine ingredients. This person is in a forward-facing public law enforcement position. What would be your guidance for this case as well as to guide policy protocols, knowing there’s always some flexibility for clinicians when we issue protocols here?”

DG: This is a great question because this has been coming up. The patients are angry, right? The way our healthcare system works like, “Well, I’m going to find a doctor or a clinician, a provider, basically someone who’s going to sign this.” As this email or as you write in, there really are only these two exceptions. Either you have an anaphylactic issue, an anaphylactic reaction to this vaccine, you have had an anaphylactic reaction to that first dose you got, or you have an anaphylactic issue with one of the components.

Well, you’re going to have to look at the mRNA. That’s going to be the PEG 2000. Look at J&J. You’ll have to see if there’s an issue there. In general, there are very few individuals, even individuals that have had other allergic issues, most of them can successfully be vaccinated. What you were being asked is really the wrong question. Guaranteeing this person a long, healthy life, and successful infertility treatments, none of us can do that.

The vaccines are not without risks. This is like them asking for some sort of guarantee that that seat belt will not cause sternal bruising if they get into an accident. No, I think what this person is requesting of you is not reasonable. What we’ve tried to do as organizations is just put it in writing. These are the exceptions. There was a recent call for Northwell. It was an email that went out by David Battinelli, a really superior clinician and leader.

He basically said to all the Northwell physicians, “These are the exceptions. If you’re giving exceptions, if you’re making up reasons for medical exceptions, that’s not okay.” That really sounds like what this person is saying. They’re saying, “Please give me a medical exception while I go through these fertility treatments.” That is not in the list of exceptions.

VR: All right, question number two, more personal. “On July 4th, my 45-year-old otherwise healthy husband developed chest pain, brought him to the ER. He had elevated D-dimer, multiple R PE on CTA. Nodule and the thyroid currently being worked up. He had received a J&J vaccine 10 weeks prior to this incident and had been feeling fatigued. Reported to VAERS and they followed up right away, but we don’t know and may never know if this was a causative factor. The question is, should he opt for one of the mRNA injections instead of another J&J?”

DG: Hearing this story, it’s hard for me to know if there’s any connection. It does not sound in any way compelling for there to be a connection here, but this is that gray area of medicine where we always work where there’s no reason not to use an mRNA vaccine in the future. I think that’s a reasonable choice, but there’s nothing you’re telling me here that connects the dots for me and makes me worry that this is J&J-related.

VR: All right, one more from Lynn. “Just listened to an Andy Slavitt podcast with Johns Hopkins epidemiologist Jennifer Nuzzo, very worthwhile discussion of post-vaccination infection. Note that I don’t use the word ‘breakthrough.'”

[laughter]

VR: “There was some discussion as well about boosters and my impression was that global vaccine equity plays too small a role in the booster decision, but that’s not where my two questions for you lie. After the interview was over, Slavitt opined on several COVID-related matters. He did a good job explaining waning, neutralizing antibodies, and memory T cells responding to viral attack. He then went on to say that the memory B cell and T cell response is slower to appear and that could lead to symptoms and disease before full immune response kicks in.

His argument for boosters is that those antibodies that appear directly after a boost will afford more protection against symptoms and disease. If you’re dead set against symptoms, then a booster is your thing. Is this correct? To his credit, Slavitt gives a very well-articulated discussion on the pros and cons politically and medically of boosters. He feels that boosters for the immunocompromised, vulnerable elderly, and healthcare workers in the U.S. is fair. Boosting everyone else before the rest of the world has vaccine access is not.” All right, let’s do that one first.

DG: Okay, so first, I’m going to say Jennifer Nuzzo, she’s fantastic, right? I remember, I actually listened to that podcast. Everything Jennifer says, I’m going to thumbs up. She really gives an expert scientific basis to what she has to say. Now, I love Andy. Andy actually is an old Optum executive, so he did a great job helping with the vaccine rollout. I worry about Andy, he’s very articulate. He’s very charismatic. He’s very persuasive.

He’s not a doctor, [laughs] so I often feel like he oversteps, right? It’s actually interesting if you go back and listen to his older podcasts and watch as it evolves. I actually listened to his podcast. He does a great job, but everything Andy says, take it with a grain of salt. He’s a great logistics guy. He’s the guy you call if you want help, maybe using PEPFAR to get those vaccines out there. If you want good science, if you want good medical advice, listen to his guests.

VR: I would say if you can only listen to one podcast, listen to TWiV, not Slavitt.

DG: [laughs] Yes.

VR: All right, second question. “Slavitt said that smarter people than he are pushing for the J&J vaccinated to get an mRNA vaccine. Where is the data that supports this and would it be one dose or two?”

DG: [laughs] Yes, I remember when he made that comment and he sort of– say he talked to a whole bunch of really smart people. Again, Andy Slavitt, he’s charismatic. He’s a great public speaker, but take it with a grain of salt. There’s no science that supports that recommendation. I don’t know who these smart people are.

VR: By the way, Lynn Hoff has written into TWiV. She is the retired molecular biologist from Western Massachusetts and grandmother to the epitope-obsessed grandson.

DG: Oh, I love that.

VR: Isn’t that great? That’s COVID-19 clinical update number 79 with Dr. Daniel Griffin. Thank you, Daniel.

DG: Oh, thank you. And everyone, including you Vincent, be safe.

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