TWiV 978 Clinical Update

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 28 January 2023

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 978, recorded on January 26, 2023. I’m Vincent Racaniello, and you’re listening to the podcast all about viruses. Joining me today from New York, Daniel Griffin.

DG: Hello, everyone.

VR: Daniel, I spent the day on the campus of NIH. I would like to report that research is all well and good there.

DG: [laughs] I am glad to hear that. That’s perfect for our quotation because our quotation is actually about science, which is something that I think our listeners either share a love for or just are lost in listening to the wrong podcast. I’ll say the quotation, “The good thing about science is that it’s true whether or not you believe in it.” That’s Neil deGrasse Tyson.

VR: I love it. That is one of my favorite quotations,

DG: [laughs] I’m going to put this first article right up front, as I’m hoping we have effectively dispelled the idea that a patient can have only one thing going on at a time. As I like to say, Occam was not a physician. A patient can have as many diseases as they please. I’ve cleaned that up a little. The article, “Code Detections of Other Respiratory Viruses Among Children Hospitalized with COVID-19,” was published in the journal Pediatrics. Remember the days when certain large healthcare systems would not let you do a COVID test if the patient had a positive flu test?

In this study, the investigators looked at over 4,000 children hospitalized between March, 2020 to February, 2022 with SARS-CoV-2 infection admitted primarily for fever, respiratory illness or presumed COVID-19. They compared demographics, clinical features and outcomes between those with and without codetections who had any non-SARS-CoV-2 virus testing among a subgroup of 1,670 children with complete additional viral testing. They described the association between the presence of codetections and severe respiratory illness using age-stratified multi-variable logistic regression models.

Now this is important. This is what did they find. Of the children where they actually did those investigations, 21% of the kids with SARS-CoV-2 had codetections. This was clinically significant because children with codetections were more likely to receive increased oxygen support or be admitted to the ICU. Really the children less than 5 years of age where we’re really seeing this significant association with severe illness. We’re going to get back to this a little when we talk about a special exciting meeting that happened today, and thoughts about how we might want to time different vaccinations.

I also wanted to leave in a link to the article published in Nature by Richard Sever. “Preprint Review Should Form Part of PhD Programs and Postdoc Training.” Our regular listeners are aware of how often during the last few years we have discussed or reviewed preprints. It was really a first for me and many others to actually post preprints. I had never done that before the pandemic, and now I’m guilty as charged. I agree that the ability to review a preprint is a helpful skill. I think it is interesting, and that we usually bring a certain level of criticism to a preprint, and wonder if we should not be bringing that same level of criticism to published articles.

VR: Don’t we already, Daniel?

DG: [laughs] I know we do, but it is interesting. You and I have talked about this in the very recent past. A lot of times something gets published in an august journal and it is just felt to be truth. I still remember looking at a gram stain that was pulled from The New England Journal, and commenting that it was poorly stained, and the person saying, but it was published in The New England Journal of Medicine. I’m like, yes, still was done poorly.

[chuckling]

All right, influenza. Those that caught the MMWR early at increased influenza activity among children in Tennessee 2022-23 influenza season saw that this really impacted children preferentially with weekly pediatric influenza-associated hospitalization reaching 12.6 per 100,000 children aged less than 5; 6.9 per 100,000 person aged less than 18, exceeding the 90th percentile, so high intensity, and approaching the 98th percentile, very high intensity, of peak weekly rates for children reported during the previous influenza season. We are coming off this influenza peak but really disproportionately affected the children.

As we saw a little bit of evidence earlier, particularly a problem when these children are having more than one infection at the same time.

COVID. Two things right off. One of my colleagues shared with me a Reuters news piece in China. Doctors say they are discouraged from citing COVID on death certificates. This follows along with what we discussed last week suggesting that even the number of deaths due to COVID is not such an easy number to obtain. We hear that in China, doctors should try not to write COVID-induced respiratory failure on death certificates.

Instead, if the deceased had an underlying disease, that should be named as the main cause of death. If doctors believe that the death was caused solely by COVID-19 pneumonia, they must first report to their superiors, who will arrange for two levels of expert consultations before a COVID death is confirmed. The WHO responded by suggesting that we probably should just be looking at excess mortality. Lots of speculation suggesting that the real number might be greater than 30,000 per day. That’s per day in China. Maybe peaking around now after the recent Lunar New Year.

Wondering recently when people wish me a Happy New Year, which Happy New Year they’re wishing, but unclear how accurate any of these numbers are, so I’m going to leave in some links to articles with satellite pictures of stuff that’s going on in China. Might give someone some sense of where things stand. What about here in the U.S. before criticizing China? We should look at ourselves and we might need to admit we have issues here in the U.S. getting an accurate number of COVID deaths. Some are suggesting an overcounting, others are suggesting a significant undercounting.

Yes, I said undercounting. In some counties in the U.S., the coroner’s report that they do not do COVID deaths. We see large counties with significant excess mortality, but not a single death certificate with COVID as the cause. I’ll leave in some links to that. Who is currently dying? This is actually disturbing data that I screenshot from the VRBPAC meeting. Actually, who’s dying? This, little bit disturbing, but kids aged zero to 1, and then adults over 50. We’ve been talking about older individuals, but in the zero-to-1 years, we’re seeing 3.8 COVID-19 deaths per 100,000.

We were seeing over 12,000 per 100,000 population COVID-19 cases. Then you get into adults, the 50 to 64, 44.3. That moves us right into children, COVID and other vulnerable populations. I will start off this section with the article, “COVID-19 Vaccines versus Pediatric Hospitalizations.” Yes, pediatric hospitalizations, published in Cell Reports Medicine. Let us start with the highlights, and then we’ll do a little bit of a deeper dive as I think this article can inform some of the vaccination discussion. We do not have direct comparisons for all age groups.

What we have is an 86.1% vaccine effectiveness versus hospitalization for children 3 to 11 years old after two doses of CoronaVac; 82.4% vaccine efficacy versus hospitalization for adolescents 12 to 18 with two doses of the Pfizer-BioNTech; 90.7%, a little higher vaccine efficacy, for hospitalization for those adolescents with CoronaVac, two doses greater than 90% vaccine efficacy versus moderate to severe disease after two doses of these. Then this is really, I’m going to comment on, this is something to be thinking about, zero, no hospitalization or moderate to severe disease for almost 70,000 of these children after three doses of vaccine. I see a hand up. Vincent’s got a hand up.

VR: When was this done? What era of COVID?

DG: This is good. We are looking, where was it done and when was it done? I think that’s really important. We’re looking at this vaccine effectiveness against hospitalization in moderate to severe disease. This is over 1 million doses given to the children, adolescents, in Hong Kong. This is data up to April, 2022.

VR: This is ancestral vaccine against some Omicron, right?

DG: Exactly. I think that’s really important because we do, we have so many questions that we always need to ask. What vaccine efficacy are we talking about? What was the time period in circulating variant? How were we approaching this? Which formulation of the vaccine?

VR: I also want to know, how long after the last dose was this study done? Because if it’s a few weeks, then it’s artificial. You really want to know a few months after that last dose.

DG: Yes, durability as well. Another article. “SARS-CoV-2 Variant-Related Abnormalities Detected by Prenatal MRI: A Prospective Case Control,” published in The Lancet Regional Health – Europe. These are the results of a prospective case control study. Two obstetric centers consecutively referred pregnant women for prenatal MRI after confirmed SARS-CoV-2 infection. Thirty-eight prenatal MRI examinations were included after confirmed infection with SARS-CoV-2. They’re matching these one-to-one with 38 case controls. Of the included cases after SARS-CoV-2 infection, 52.6% were infected with pre-Omicron variants; 47.4% with Omicron, a big group.

Both pre-Omicron and Omicron groups showed abnormalities. Placentas in the pre-Omicron group were significantly thickened and showed significantly more frequent lobules and hemorrhages. This really caught my – fetal growth restriction was observed in 25% in the pre-Omicron group. This led them to suggest that women who contract COVID during pregnancy should undergo placental imaging, ultrasound, they’re saying, soon after testing positive for the virus. Suggesting ultrasound, but as we comment here, this was a prenatal MRI study.

Pre-exposure period, testing, transmission. Remember those masks? We’ve talked a bit about those. People may have heard that the WHO has updated its guidelines on mask wearing in community settings. As we can read, WHO continues to recommend the use of masks by the public in specific situations. This update recommends their use irrespective of the local epidemiological situation, given the current spread of COVID-19 globally. Ventilation transmission. Remember here, the goal is not to inhale the virus, SARS-CoV-2, that causes COVID.

Simple stuff, clean hands, clean water, clean safe food, and clean safe air. COVID-active vaccination. It’s going to be the meat of what we’re talking about today. Couple articles. Then we’re going to talk about an important meeting. The article, “Protective Effectiveness of Previous SARS-CoV-2 Infection and Hybrid Immunity Against the Omicron Variant and Severe Disease:  A Systematic Review and Meta-Analysis,” published in The Lancet Infectious Diseases. In this review of the literature, 11 studies reporting the protective effectiveness of previous SARS-CoV-2 infection.

Fifteen studies reported the protective effectiveness of hybrid immunity were included. For previous infection, there were 97 estimates. Lots of moderate risk of bias. Serious risk of bias, so put some qualifications there. Putting that together, the effectiveness of previous infection against hospital admission or severe disease was estimated to be about 74.6% at 12 months. For hybrid immunity, this is vaccination and infection, there were 153 estimates. Also lots of moderate risk of bias and serious risk of bias. That taken, the effectiveness of hybrid immunity against hospital admissions or severe disease was estimated at over 94% at 12 months with primary series vaccination plus infection.

All estimates of protection against infection waned within months against reinfection, but remained high and sustained for hospital admission or severe disease. We seem to have a theme that we will keep hitting on. Maybe this point has been made before, I thought I’d throw it in here. The article, “Persistent COVID-19 Symptoms at Six Months After Onset, and the Role of Vaccination Before or After SARS-CoV-2 Infection,” was published in JAMA Network Open, again showing that vaccination was associated with a lower risk of long-term COVID-19 symptoms.

Participants who were unvaccinated prior to infection, risk ratio 1.39 of illness that lasted 28 days or longer. I’m even going to hit another later on showing the positive impact of vaccination on Long COVID. Big news, the day we are recording, I don’t know what everyone else did this lovely Thursday, but I was able to enjoy the Vaccines and Related Biological Products Advisory Committee meeting held January 26, 2023, to discuss COVID vaccines. We did hear multiple participants recommend that we need to get away from just looking at levels of neutralizing antibodies.

Because, as they point out, we are still seeing continued protection despite these dropping levels. There was a suggestion that vaccine protection against infection had a durability of about three months, but protection against severe disease was more durable. I was pleased to say a very sophisticated discussion about wanting more than, as I mentioned, those neutralizing antibody data asking about T-cell responses, Fc-mediated antibody effects, NK and other cellular responses, as well as a request for ongoing efficacy data, as correlates of immunity are not very clear.

I wanted to start, I don’t know if I’m starting, but I want to throw in, science is not stagnant. There really was a large amount of new data presented and discussed at this meeting, and some I plan to discuss in a little bit more depth next week. Just to give a high level there was one voting question and some discussion. Just to hit these points. There was only one voting question. We’re going to talk about a lot of stuff, but we do want to come away with at least a vote on the question of vaccine complication. Is there a way to simplify current COVID-19 vaccine use?

Vaccine composition is the question. Does the committee recommend harmonizing the vaccine, they’re now saying strain composition, of primary series and booster doses in the U.S. to a single composition? For example, the composition for all vaccine administered currently could be a bivalent vaccine. This was a 21 out of 21 vote in support. There was a discussion about updating the shots. Primary and boosters might provide some improved protection. They weren’t seeing safety concerns. Lots of concerns about how poor vaccine uptake has been in children.

I guess I’ll say a little bit more because there was some data here on a couple issues. We’re going to talk about the data next week, but are the bivalent boosters really better than the monovalent boosters? Was that a wise decision? Really they came away with, yes, it does seem like things are trending in the direction that it might be better. I think that was really couched in a might. Is to say most of the studies were trending in that direction.

There was evidence that, at least in certain populations, that there was some benefit to the boosters. There was lots of concerns about how poor vaccine uptake has been particularly in children, and a lot of, I’ll say, public health commentary about how do we improve communications, how do we make this simpler and more straightforward? Because it doesn’t matter how good those vaccines are, if you’re not getting them into arms, they’re not doing any good at all.

VR: Daniel.

DG: Yes.

VR: If all of the studies of the bivalent have been done at less than three months after the booster, you can’t say anything about whether it’s better than the ancestral vaccine because you still have high antibody levels after that boost. You have to let them go down and then you ask, is it any better than ancestral? I think they’re missing data there. They need to do that because if it’s not better than the ancestral, why update it at all?

DG: This is great because there was – here was this discussion, and it really was, they went into this, how durable is this going to be? What are we trying to do? Of course there was a split. Some people were saying, and you can guess who they were, the only thing we should be talking about is hospitalization, is severe disease. Hoping for anything beyond that is just we’re hoping for something we’re never going to obtain. Some folks, and actually I should say some folks who work directly for the pharmaceutical companies, were saying, if we’re three months we can actually decrease the number of sick days at work.

If we can maybe decrease the amount of spread of the virus in the community, that then prevents one of those more vulnerable people from getting infected. Maybe there is something about looking at three-month data and then trying to time the shots right before the winter peak so people aren’t getting COVID and flu at the same time. It was interesting because there was a couple things that came up as they got into immunization schedule. One was a lot of comments about saying, can we all agree this is not the flu, and lots of words of caution about not taking all the lessons we have learned from flu too far?

Also, and I think this was reassuring, a lot of comments that we have just learned that with flu vaccine, we know that when you miss, you miss by a mile. Even the original shots were still giving sustained protection, so COVID’s different. We may be able to keep people out of the hospital. We may prevent severe disease with more durability. Number of people saying, I know everyone’s decided already that we’re going to do yearly COVID shots, but I’m not sure the science is there yet. Thought that was interesting when they talked about the immunization schedule.

Those were points of discussion, the ongoing or future immunization schedule. The other discussion point was vaccine composition. What is going to be in there in the future? Part of this was a discussion about we need to make these decisions if we’re going to make them for a particular timed immunization with enough advance time for how long does it take for those mRNA vaccines? About 100 days. How long does it take for a protein-based vaccine? It may take six months, may need a little bit more. Then how closely do we need to be chasing those variants? Maybe just getting a little bit closer is good enough. There still is a lot a lot to be decided.

VR: Daniel, if we’re talking about someone who has never been vaccinated, OK, give them a bivalent vaccine shot one, two, and three, that’s it, fine. If you have someone who’s gotten a three-dose of ancestral, you give them a bivalent booster, most of the response is going to be against the ancestral strain. It’s imprinted. I guess that doesn’t hurt, so why not? What we’re doing and I think you said it, the flu strategy is really to give you protection for three months or four months during the respiratory season, and you just do it every year. Sounds to me like that’s what they’re heading for COVID. Three, four months of protection and that’s it. I’m not sure that’s the greatest approach though.

DG: Yes. Still lots to be discussed. Interesting, I’ll just throw this in because I found this curious is that, so the – you had all the data from Moderna, from Pfizer-BioNTech, but then you had Novavax and they basically showed that, you know what, even if we just give the original one we still get great neutralizing antibody against all the variants. They’re like, we’re not even sure we even need to update us, but if you want us to, we will. I thought that was interesting.

VR: I just think you don’t need to update. I don’t know why we bothered, but now we’re stuck in the middle, and I don’t know what the solution is.

DG: I think there’s going to be updates. Actually one of the interesting discussion was as we update if we’re going to have these multivalent, let’s call them multivalent, do we even need the ancestral? If it’s not around, do we just update with more updated which are closer to what we predict might be coming around during that three- to four-month window where we’re hoping to get some augmented protection? Unfortunately, when it comes to COVID passive vaccination, I don’t know if I should say unfortunate here, because this is something that we’ve known for a little while.

Today as we’re recording Thursday, 1/26/2023, the EvuSheld EUA was modified to the point of resulting in it basically being revoked. The FDA revised Evusheld’s emergency use authorization to limit it to when the combined frequency of non-susceptible coronavirus variants is less than or equal to 90%. It’s a pretty low bar. Only 10% of the variant’s susceptible, and you can still use it. Then they immediately comment on, all right, we’re already at 93%. This means that Evusheld is not expected to provide protection against developing COVID-19. By the way, therefore don’t use this anymore.

I think a number of us have read the tea leaves, so to speak, and have really stopped providing this ineffective therapy. For some providers, it actually requires an EUA being revoked. Not a lot changing or updated here in the early viral respiratory nonhypoxic phase. Remember, early antiviral therapy in that first five to seven days? Significant reduction in the risk of progression. Let’s not do harmful things. Remember, this is a virus. Those antibacterial, those antifungal, those anti-parasitics, need I say more?

COVID early inflammatory lower respiratory hypoxic phase, steroids at the right time in the right patient at the right dose. There was an interesting article, interesting. I won’t spend too much time because I’m not sure how this changes what we do. The article, “Effects of Dexamethasone on Viral Clearance among Patients with COVID-19: A Multi-center Cohort Study,” was published in the International Journal of Infectious Diseases. This study recruited consecutive patients from March 1, 2020 to July 31, 2021. Patients with mild to moderate severity and who received dexamethasone therapy had a longer time – they say to viral clearance, but it really longer decay of the PCR positivity, 17.2 versus 12.3 days.

Patients with severe critical severity had a similar duration of symptoms. Really just suggesting you’re not going to not use steroids in these individuals but you may want to rethink some of that isolation. I know some people have just easier to remember 10 and that’s it for everyone. For some of these critically ill patients or patients on steroids, this may just impact some of the thinking there. Not much change in the other thing. We will get right into PASC and Long COVID.

I mentioned one study but I’m going to even mention another study. Growing amount of evidence that getting vaccinated reduces the risk of getting Long COVID or continuing to have Long COVID or PASC in people here with immune compromise. The article, “Impacted Vaccination on Post-acute Sequelae of SARS-COV-2 Infection in Patients with Rheumatic Diseases,” published in Annals of the Rheumatic Diseases. Here, the investigators prospectively enrolled patients with systemic autoimmune rheumatic diseases from a large healthcare system who survived acute COVID to complete survey.

You’d think the results are even better because if you have combined endpoint of Long COVID and death. I think there’s a little caveat. It’s critical because the combined outcome, as I point out, but the symptom-free duration and the odds of PASC were evaluated using restricted mean survival time and multi-variable logistic regression respectively among those with and without breakthrough post-vaccination infection greater than or equal to 14 days after that initial vaccine series. They looked at 280 patients. I will cut to the chase. A fairly impressive 90% reduction in PASC in the group with vaccination.

What about disability from Long COVID? A study published just this Tuesday, couple days before we’re recording, by New York’s largest workers compensation insurer found that during the first two years of the pandemic, about 71% of people the fund classified as experiencing Long COVID either required continued medical treatment or were unable to work for six months or more. More than a year after contracting the coronavirus, COVID, 18% of Long COVID patients had still not returned to work. More than three-fourths of them were younger than 60.

The Government Accountability Office estimates that Long COVID has affected 7.7 million to 23 million people here in the U.S. Really a nice figure where you can actually see the peaking of the different waves when we’re seeing a lot of these COVID claims. I will wrap it up here. I think this is important. No one is safe until everyone is safe. That was something that I think troubled me and some of the people in the discussion today. When you’re updating these shots, which variants are you looking at? Are you looking at the variants in New York City, in the United States, the world? Obviously not.

How appropriate are going to be all these updates for the world in general? This is, I think, a big challenge. Let’s not lose sight of that when we have these discussions. The pharmaceutical companies made it very clear that it was the U.S. market that they were concerned about. I want everyone to pause the recording right here. Go to parasiteswithoutborders.com and click “Donate.” Even a small amount helps. I will say this is our last episode we’re going to record, I see Vincent getting sad there, before the end of the MicrobeTV fundraiser. We just have this tiny amount to double those donations up to a potential maximum donation of $40,000 from PWB to MicrobeTV.

VR: Come on, folks. Give because we can’t fall short. This is our opportunity. It’s time for your questions for Daniel. You can send them to [email protected]. This first one is a joke, so you don’t have to answer anything here, Daniel.

DG: [laughs] I’ll take a break.

VR: James writes, “I’m writing on behalf of my hospital’s IPAC team in Toronto, Canada. I have faithfully converted our team into routine TWiV listeners so our IPAC program can be well informed. Our team has an inside joke I wanted to share with you. This respiratory season has been unlike others, and we have many instances that have multiple agents as the lab-confirmed cause of a respiratory outbreak. For example, COVID and RSV outbreaks on the same floor at the same time. As part of your clinical updates and as part of our IPAC team’s practice now, we routinely cite Occam’s razor and Hickam’s dictum.

Especially during this respiratory season. I’d like to add my colleague’s addition to your list of axioms. We were exasperated as one of our COVID outbreaks turned into a mixed COVID and parainfluenza outbreak, and Brigitte quipped, ‘An outbreak can have as many viruses as they damn well please.’ That’s Brigitte’s dictum. I thought I’d share, as this joke has legs but nowhere to turn except with TWiV listeners.”

DG: I think we’ve got a bunch of nerdy enough listeners that hopefully this was as enjoyed as I enjoyed it.

VR: Sweta writes, “Do you believe a fully vaccinated individual who is starting treatment biologics for Crohn’s disease should consider taking the bivalent booster before their first infusion therapy? Will such an individual be able to mount a response similar to that of an immunocompetent person if they get COVID while taking biologics and hadn’t been recently boosted?”

DG: That makes sense. We’ve had a lot of discussion about this in someone who’s about to go on a biologic. This isn’t unique just to COVID. We want to get vaccines in ahead of time to get as robust a response as we can get, because once you’re on immunosuppressives, there’s concerns that you’re not going to be able to mount as robust an immune response.

VR: John writes, “I’m disabled by Long COVID. I have tachycardia. I have found some relief with ivabradine.” Is that right, Daniel, ivabradine?

DG: It’s close enough. We’re going to give you credit on that one, Vincent.

VR: “If I get reinfected, my plan is to take Paxlovid to try to reduce the chances that my Long COVID gets worse. However, ivabradine cannot be taken with Paxlovid. NIH guidance says don’t use Paxlovid at all. ID Society guidance doesn’t even mention ivabradine as a conflict. Since I don’t really leave the house, if I am reinfected, it will almost certainly be by a family member. Everyone in the house is up to date with the vaccine. Hopefully, we’ll be able to identify them as sick early, and I have a few days during incubation period where I can plan to stop ivabradine. How long do I need to stop taking ivabradine before I start Paxlovid?

DG: You got to say that word a lot. Where’s a cardiologist when you need one?

[laughter]

Couple things like, what is this crazy medicine? It’s a heart failure, it’s an anti-anginal. It’s cardiac med. It works on these fuzzy channels. Big problem is that it is metabolized by the cytochrome 3A system. You’re going to potentially – if you get on the Paxlovid, it’s really the ritonavir is going to interfere with metabolism. Yes, it wouldn’t be safe to be on these medicines.

Again, this is one of those great situations where you want to have a plan because the recommendation would be to stop this when you start the Paxlovid, and that’s what you do. You’re going to get your Paxlovid. If you took it that day, just don’t take it the next 10 days, and then just talk to your cardiologist ahead of time, is that safe? Is that OK? Can you stop that medicine? If not, then we would be talking about remdesivir as the other option.

VR: Just a day of stopping is sufficient?

DG: A lot of times, a person will call me and we’ll have an appointment. They’ll say, “I took my statin this morning. Oh, my gosh. I’ve got COVID.” I’m like, start your Paxlovid. Just don’t take any more of the statin. I would say the same. Heck, if you’re this that morning, that’s fine. Just don’t take anymore and it will work its way out of the system. If anything, it’ll work its way out of the system more slowly, but it’s not suddenly going to rise to any higher level. You’re just blocking metabolism.

VR: Angelika writes, “Hello. Just a comment on death with/from COVID. In Sweden, the definition of COVID death has throughout the pandemic been ‘death in an individual who either tested positive for COVID or was presumed to have COVID within 30 days prior to death.’ “ This is from an MD-PhD in Lund, Sweden.” What do you think of that definition, Daniel?

DG: It’s interesting, because what you’d end up having, like right now, when everyone has COVID here in the U.S., by the way, just in case you’re thinking of coming to visit us, then everyone who dies that month dies from COVID. That might overcount. Also, the other is, I think Mark Crislip always made a comment about this, a lot of times with infectious disease, it can trigger this post-inflammatory stage where you see a significant increase of cardiovascular, you see strokes. When that happens at day 31 or the person’s on the ventilator, you don’t count it. It’s really going to be challenging. I thought this was great.

At the meeting today, one of the participants commented, interesting enough, about the Massachusetts data that I referenced on the last TWiV, saying, “Why can’t the CDC have data like that? Tell us a little bit more about who’s getting hospitalized with COVID, who’s getting hospitalized because of COVID, who’s dying with COVID, who’s dying because of COVID.” Because basically the question is, we’re going to need efficacy data on whatever strategy we employ. This is not for people who want to deny COVID or people who want to overcount COVID. It’s for honest people who are trying to make a decision about how to keep people safe. We actually need to know this data. We may be stuck with excess mortality.

VR: Kari writes, “I hear you say it’s important to have a COVID plan with your physician ready to go. I want to contact my nurse practitioner now that I’m no longer pregnant or under the care of my OB, but was hoping for a little more information to prepare myself for the conversation.” We have three questions here. We’ll take ’em one at a time. “One, what is your experience with side effects of Paxlovid? I’m not concerned about the taste, but more dangerous ones like vomiting, severe allergic anaphylactic reactions. How common are they? If I have a sensitive stomach and a number of food and medication allergies severe enough to carry an EpiPen, so new drugs always make me nervous. My reactions tend to be pretty severe.”

DG: This is great. Let’s walk through it. The first thing about Paxlovid is some people, a percent of people, can get a metallic, a bad taste. I still remember my wife, she got a bad taste. She did not enjoy it. She’s like, “I can’t take this. It’s giving me bad taste.” She’s in a high-risk group. We had a little discussion about that metallic taste versus that plastic taste of having a tube in your throat. That is something that I think people, you have to ask. Are you willing to tolerate a little bit of discomfort for a gradation of benefit depending upon your risk group?

As far as an allergic reaction, Paxlovid has been prescribed not to enough people, but it has been prescribed to millions of people. Allergic reactions are rare even if you’re someone who has allergies to other things. The allergic concern is very low. Lot of medicines can be stomach upset. We’re not seeing that as a huge thing, but we do sometime see stomach upset. We’ve seen vomiting, sometimes hard to distinguish.

Is that vomiting from the medicine or is vomiting because that could be one of the ways that COVID presents. These are all good points, good questions you’re bringing up. I applaud you. Have this conversation. Number one would be Paxlovid if you’re in a group. Number two, IV remdesivir. Just the hassle of the three-day, but again, you’re not getting that bad taste. Less concern is about different drug-drug interactions.

VR: Her second question is, “Is remdesivir less likely to cause allergic reactions than Paxlovid?”

DG: I think from an allergic reaction, it’s going to be incredibly rare with both, so I wouldn’t see a difference there.

VR: Three, what is your opinion on the new California guidance that everyone be given a chance to get Paxlovid. Specifically, would you recommend Paxlovid to a vaccinated healthy 42-year-old person of normal weight with very slight asthma?

DG: Let me answer the first one again for a second, just because it just came to mind. I’ve treated lots and lots of COVID patients. I’ve had one patient so far reporting of Paxlovid allergy. Just this week, someone reporting a remdesivir allergy. Credibly rare, just to put that. This is a challenge. How compelling is the data that Paxlovid is going to prevent Long COVID? We’ve talked a little bit about that data. I think the problem with Paxlovid really is that it’s sitting on shelves, it’s going to expire, it’s not being used. If someone went down that road, that’s what the data is.

VR: That’s TWiV clinical update with Dr. Daniel Griffin. Thank you, Daniel.

DG: Thank you. Everyone, be safe.

[music]