TWiV 943 Clinical Update

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 8 October 2022

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 943, recorded on October 6, 2022. 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: Daniel, you heard Paul Offit. What do you think?

DG: I’m glad you ask. Paul Offit, if you’re listening, Paul Offit’s wife, if you’re listening, you should give him, “Only go on TWiV,” because what I worry is, on TWiV, his presentation was reasonable, there was a really good discussion. I think it would be very hard to take what he had to say wrong. I don’t think you’re going to end up with FDA advisor recommending against boosters. You’re going to get the message, which is measured, it’s thoughtful, and I agree with a lot of what Paul Offit has to say.

It’s that we would love if we could just have a blanket recommendation for everyone. That’s what the CDC has to do, but I think it’s a little bit more challenging, and he went through a few scenarios, I think. If you’re 30 years old and you got three shots already and you had an infection in June, should you be rushing out to get an Omicron booster? I’m not sure that’s going to do very much.

On the other hand, I think Paul was clear on this, is that if you are over 65, and maybe he should have mentioned this a little more, I noticed in the comments, or you have things that make you high risk. There’s younger individuals that have medical issues, immunocompromised, those people, the decision to get a booster is much more straightforward. I actually thought it was really good, but you can’t put it in a nutshell, you got to listen to the whole thing. Vincent, what did you think? You were there.

VR: First of all, you may have noticed we all asked him the same question multiple times because it’s a little confusing. There’s no more ancestral booster available, that’s it, it’s just bivalent. I think his recommendations are quite clear, if you’re elderly you should get this vaccine, but it’s not likely to benefit most other people unless you have special conditions, if you have comorbidities that make you particularly susceptible. I think it’s quite straightforward and very clear and his reasons for saying that are very clear.

DG: Hopefully, I’m going to hit on some stuff today.

VR: All right.

DG: Did you have any advertisements you need to do up front before I get to my quotation?

VR: I do. Let me tell you about a research assistant position available at the FDA in the laboratory of Amy Rosenfeld. The focus of research in the Center for Biologics Evaluation and Review at the FDA is to elucidate the mechanisms by which cross-species anti-enterovirus antibodies may affect pathogenesis. The research assistant will support work on picornaviruses such as Entero 68, polio and rhinoviruses, including genetic, biochemical, and cell-based studies for understanding multiple aspects of immune dysfunction associated with infection.

The individual will carry out experiments in cell culture, participate in the development of small animal models to study aspects of infection, including the cellular immune response, and all work done at BSL-2, and celebrate the molecule of the year, the spike protein of SARS-CoV-2, and support science education here at MicrobeTV by purchasing a Spike t-shirt from vaccinated.us. Profits during this month as well, October, it’s been extended, go to support our science education work. Use the promo code ‘MicrobeTV’ on checkout.

DG: Excellent. Go work with Amy and wear a cool t-shirt.

VR: Pretty straightforward. Yes.

[laughter]

DG: Exactly. I will start with my quotation, “No arts; no letters; no society; and which is worst of all, continual fear, and danger of violent death: and the life of man, solitary, poor, nasty, brutish, and short.” Thomas Hobbes speaking about natural infection versus vaccination. Next week we’ll be quoting Rousseau. [laughs] Polio, I’m not going to say much here, keep the message simple, get vaccinated. If you’re not vaccinated, get vaccinated. Influenza, it is time to get those flu shots. We are in October, we’re starting to see a rise in flu cases.

Monkeypox. For a while I’ve been saying, and I know people are like asking, “Why do you keep saying this, Dr. Griffin?” Monkeypox is not a gay disease, it’s not an African disease, it’s an infectious disease. The reason I say that is that it’s stigmatizing, if we go down these other roads. It limits the amount of testing that gets done. It delays the diagnosis. This is an infectious disease, and if we’re going to hear about today, we’re going to be discussing a couple of cases where no sex was involved.

Just check the seven-day average here in the U.S. for monkeypox, we’re now up to over 26,000 cases. We’re still averaging greater than a hundred new diagnoses per day. We’re considering that a victory. I actually wish we had maybe learned a little bit more and we’re not in this situation. We did get an update from the CDC, the “Technical Report 3: Multinational Monkeypox Outbreak, United States, 2022.” A couple high points from that technical report. One: Domestic transmission in the United States is unlikely to be eliminated in the near future. We’ve missed the ball on that.

Second, this is a little bit concerning, as per the CDC, they mentioned there is a possibility that the monkeypox virus could establish itself in one or more animal populations in the United States. Certainly has that biologic potential. The other, and I think this goes back to the, how did we do this time? We had COVID, and I thought we learned a lot, and then we got another slow ball pitch thrown at us, we heard that there was a two-month delay between the first case of monkeypox viral infection and our realizing that monkeypox virus had spread to Europe.

They went ahead, looked, and I’ll leave in a couple links for this, but through retrospective testing of a residual sample, the first case had a specimen collection date of March 7, 2022. The earliest confirmed case that we know about is actually May. It took us a couple of months before we realized it was here before we started making the diagnosis. We also had a third confirmed death, I’m going to say from monkeypox in Ohio, but qualify this. There was a death that was due to monkeypox in L.A. There was also a person in Harris County, Texas, who had monkeypox and died. The virus’s role in that death has not been confirmed. We’re looking at two or three deaths here.

That individual in Texas, just to be really– may have died with and not necessarily from monkeypox. The headline here of this news piece that was published in Nature, do you like this one? It’s a question, Vincent, “The monkeypox virus is mutating. Are scientists worried?” I thought you’d like that, Vincent.

VR: I can’t believe we are still doing these headlines, and Nature of all things. Come on.

DG: I have a question for you. You’ve studied viruses for a number of years, number of decades, do viruses mutate? Should we be surprised? Is this shocking?

VR: That’s the problem, viruses mutate every time the genome replicates. Every time, no matter whether it’s a DNA or an RNA virus. To say the monkeypox virus is mutating is a non-news item. It’s like saying the earth is round as a headline. Yes, we know this already, what are you telling us? This is awful. The headline writers, whoever is responsible for this shouldn’t do this because it makes people think that sometimes viruses don’t mutate and that’s wrong.

DG: Viruses always mutate. Actually, I’m going to quote, “Although scientists aren’t alarmed,” and I think maybe you’re hearing that here, “They’re monitoring the situation carefully.” I think that’s reasonable. I think if you cry wolf too much, pretty soon the wolves are going to show up and everyone’s going to ignore you. I think we have to be a little bit more reasonable and honest.

Now, as I’ve been mentioning, monkeypox transmission, this is predominantly through contact, no sex required. For those people listening, if you’ve had sex, there’s often a lot of contact that can feed into this.The dispatch, “Possible Occupational Infection of Healthcare Workers with Monkeypox Virus, Brazil,” was published in Emerging Infectious Diseases. Let us go through and see what happened here.

They say possible, but I’m pretty convinced. Here’s the story. On July 22, 2022, a lot of twos there, a man in Brazil, 40 years of age, exhibited genital maculopapular lesions. He had some enlarged lymph nodes, muscle aches, fevers, chills. On July 29, two healthcare workers, they’re going to be healthcare worker one and healthcare worker two, they visited the patient’s home to collect specimens and conduct an epidemiological investigation interview. Here they are. I’m thinking monkeypox, are you thinking, Vincent?

VR: Yes, I’m thinking.

DG: [laughs] I’m thinking monkeypox. Well, it was in the title, so we gave it away, but upon entering the patient’s home, they went ahead and they put on their personal protective equipment; their safety glasses, their disposable isolation gowns, their N95 respiratory masks. The patient is wearing a cloth mask, but they figure out, “Let’s wait before we put those gloves on.” After entering the home, the healthcare workers proceeded directly to the patient’s bedroom where the healthcare workers interviewed the patient and then collected samples from him. Now, during these procedures, the patient remained in bed.

This is the little bit I put in italics, from the time they entered the patient home to the end of the interview, the healthcare workers did not wear gloves. After the interview they sanitized their hands with the 70% ethanol, they donned latex gloves to collect samples. Then they collect the samples, remove the gloves only after leaving the patient’s home and sanitize their hands with 70% ethanol. They wore their remaining PPE until they arrived in the labs. I’m just imagining this, climbing into your vehicle with all this stuff still on. When they get to the lab, they immediately wash their hands with soap and water.

Now, on the day of the visit, the healthcare workers had no known skin injuries, no skin breaks, no scrapes. They do confirm that this individual they visited has the monkeypox. Now, on August 3, five days after collecting the samples, healthcare worker one notes a single lesion on her left ring finger and this is confirmed to be monkeypox. Also, on August 3, healthcare worker two notices a papule on the forearm, develops fever, swollen lymph nodes, and then the next day gets monkeypox confirmed by PCR. Unfortunately, healthcare worker two, the lesion spread to her face and actually increase progressively until August 16.

I think this just really serves to highlight that monkeypox viral infection can be acquired through fomites, such as the patient’s belongings, surfaces. If you’re out there, if you’re thinking, “Oh, this person I’m going to be seeing in room two might have the monkeypox,” put the gloves on before you walk in the room. It’s interesting, they did all the stuff for a respiratory pathogen, they get their gowns, their masks, their goggles, but it’s contact. What do they leave? They leave their exposed hands.

Monkeypox testing. Remember, if you’re going to make the diagnosis, you got to swab, but put your gloves on then go in there and then swab and then wash your hands afterwards. Monkeypox vaccines. We’ve got them and we think they work. I’m going to mention from the CDC, we got the, “Rates of Monkeypox Cases by Vaccination Status” update. They have a really nice infographic. They report that unvaccinated people had 14 times the risk of monkeypox disease compared to the vaccinated. This data was for vaccinated, illness onset 14 days or more after first dose, illness onset 14 days after receiving just one dose. They excluded people that had been vaccinated for smallpox before 2022.

Now, I’m going to go right ahead and criticize this. I’m going to agree with Michael Osterholm, who said he believed it was too early to make any assumptions about the protection from a single dose of vaccine, commenting that there are too many unaccounted for variables in the CDC data. I will just quote Mike here, “People who seek out vaccines may be behaving differently from people who don’t. Did they also take a pause on sexual behavior?” I think that’s true. People that are aware, they’re concerned, they’re going, they’re getting, their vaccines are a different population from those who are not showing up to the vaccine sites.

Monkeypox clinical course treatment. Here we’re talking about TPOXX. Apparently, SIGA Technologies won a new contract for its oral antiviral drug TPOXX worth up to $10.7 million. We still don’t really know if this works. I am going to continue to encourage people, if you have a patient that you’re diagnosing with monkeypox, if you get diagnosed with monkeypox, go to stomptpoxx.org. Let’s get some science. We need to know. We just heard from the CDC that we expect this to be around. We’re seeing over a 100 new cases a day. It would be nice to know if this TPOXX stuff actually works, and if it does, when you need to give it, et cetera.

COVID. I don’t know if you’ve seen this, Vincent, but some people are putting in time length so they can jump right ahead to COVID. Tell people, listen to the first part too, but here we are. We’re at COVID, children, other vulnerable populations. I’m going to swing back a little bit to the topic of vaccines, because for kids, it seems like it’s getting complicated. I’m going to suggest that it’s not as complicated as it seems. Let’s go right into that pre-exposure transmission testing. That’s where I say use tests intelligently. I recommend people have a plan.

We got an interesting update on testing that actually, well, it’s impacting our organization and anyone paying attention, I should say. There was the announcement, “CMS Rescinds December 7, 2020 Enforcement Discretion for the Use of SARS-CoV-2 Tests on Asymptomatic Individuals Outside of the Test’s Instructions for Use.” This letter went out on September 26.

This means that our providers are running point of care waived tests on asymptomatic patients, for example, individuals, for example, and the package insert does not specifically state that the test is authorized for that patient population, no longer authorized for that. Just to mention a couple of those that we use locally that were impacted by this. The ID NOW, that’s that ID NOW instrument, that rapid molecular nucleic acid amplification test, the isothermal one. This is only now approved for symptomatic individuals during the first seven days of the onset of symptoms. You’re using an outside of authorization if you’re screening asymptomatic people.

The BD Veritor. They’re now saying you’ve got to actually pop those in the machine. You can’t just hold them up to the light and read them. This is also supposed to be mainly used during the first five days of the onset of symptoms, or individuals without symptoms, you’ve got to do two tests, so twice over two or three days. Not sure how that’s going to work logistically. Vincent, you’re shaking your head there.

VR: What is the reason for doing this and what are the data that are driving it?

DG: I don’t have much to say. [laughs] I’m beginning to feel like maybe we’re returning to a point in time where if you don’t test, it doesn’t exist.

VR: I remember those days.

DG: I do too. COVID active vaccination. Never miss an opportunity to vaccinate. I like to say vaccinated people still get infected, they are just less likely to die or have severe disease. Now, part of the idea behind immunity is that there might be some, I’m going to say, limited time protection, not just against severe disease, but also against infection and reinfection. People always ask me this, “I just had COVID, am I going to get reinfected?” Well, the article, “Protection of SARS-CoV-2 Natural  Infection Against Reinfection with BA.4 or BA.5 Omicron Subvariants,” was posted as a pre-print then published in Clinical Microbiology and Infection.

They’re actually looking, and people are curious about this, what is the impact of a previous pre-Omicron infection against symptomatic BA.4 or BA.5 reinfection? There was only about 15% against any BA.4 or BA.5. If you forget about symptoms, maybe you’re getting about 28%. Then they ask the other question because this is now relevant, effectiveness of a previous Omicron infection against symptomatic BA.4 or BA.5 or any infection between 76 and 79 for the limited time they were looking at. For some limited period of time, your chance of getting reinfected is somewhat lower.

Now, I’ve been getting inundated, Vincent, with questions about navigating vaccination and boosting. I’m not sure everyone is going to spend an entire hour listening to the wisdom of Paul Offit, though I do encourage them. The CDC created a guide, and we actually will leave a link in here. What you do is you go to this section of the guide, find out when you can get your booster. You click on find out when to get your booster. You then have a choice of different ages. Am I 6 months to 4? Mom’s probably doing it here, 5 to 11, 12 to 17, 18 to 49, 50 years and older? They really could have made this a lot simpler. Took a bunch of these and just really made it a binary. As per the CDC, everyone 12 and over is eligible for a booster. If you’re under 12, no bivalent booster has been authorized yet.

Now, this really comes down to this discussion that we’ve been having about how strong is this recommendation? I know everyone wants just a nice straightforward answer. Also, as we’ve been talking about, where does infection figure in the mix here? I wish during these last two years we’d really improve the primary care network in this country so that, as I keep saying, and I keep hearing people say, “That’s not as easy as you say,” it would be great for individuals to have a discussion, because, as Paul Offit points out, as the science shows, not everyone needs a booster. There certainly are people where it is a clear decision, but I will just recommend people go and they look at this site.

Passive vaccination. This is a little bit of a downer here. We’re talking about Evusheld, that’s tixagevimab co-packaged with cilgavimab. This is giving that passive protection to our individuals who are immunosuppressed through medications, through medical conditions, or for some reason cannot get that vaccine protection. This will not be a surprise to our listeners that have been following the science with us, but on October 3, the FDA updated the Evusheld Fact Sheet based on the increased circulation of B.4.6.

In short, they added that with BA.4.6, there is a greater than 1,000-fold reduction in neutralizing activity for Evusheld. We’ll mention this was done using a pseudo-typed virus assay. Unfortunately, we’re now up to B.4.6 being about 13% of isolates across the country, higher in certain regions.

VR: Daniel, what would you do? Would you genotype the isolate before treatment or just give Evusheld?

DG: The thing here is this you’re doing this ahead of time. You’re going to give it to your patient ahead of time based upon the regional prevalence. I had a discussion actually with a woman earlier today, number of issues on immunosuppressive medications. I said, “Before we used to quote this number, 94% reduction in your chance of even getting infected.” I said, “We’re going to have to drop that to maybe 80% reduction in your chance because we now have 13% of the time, I’m not sure Evusheld is going to provide you protection at all, should you get exposed to a B.4.6.” When we get to our treatment section, we’ll talk about what can you do should that person get infected.

Now we’re moving into the early viral upper respiratory non-hypoxic phase. I have to say, we are seeing a fair number of elderly, elderly or higher-risk individuals end up in the hospital during this first week, this early viral respiratory phase, maybe altered mental status, they’re not doing well at home. Sometimes this treatment is occurring in the hospital, but it is still, and COVID always has been predominantly an outpatient disease. You test positive, you’ve got your plan, number one, with a suggested 89% to 88% production in progression if unvaccinated, probably about a 75% reduction if vaccinated.

Paxlovid. We now have the results of the COSMO Study. I’m going to go through this a little bit with you, Vincent. Maybe people, if they’re not driving, can actually go to the link and walk through this paper, pause here, get that paper up, we’ll go through it. This is interesting. This article, “Paxlovid Significantly Reduces COVID-19 Hospitalizations and Death,” was published in Epic Research. Now, what is that? For starters, Epic Research is a non-traditional journal that is produced by the Epic Research Public Benefit Corporation owned by the Epic Systems Corporation, so those people that bring you EHRs.

Ideas are presented, and then two independent teams explore the topic, and then after the independent investigations, they come together, they compare their findings, and then it goes out for peer review. I’ll leave out a link to this. It’s an interesting approach to things. I think there’s a lot of potential here, as you’re going to hear, as far as numbers that people can look at. In this investigation, they looked at over half a million patients who were eligible for Paxlovid treatment between March 1st and October 1st of 2022, a little bit better than we were seeing before.

Of these, 146,256 received Paxlovid. Maybe doctors that use Epic tend to use Paxlovid, I don’t know, maybe there’s a connection there, and 421,304 did not. OK, not so great. It was going well for you there, guys. In adjusted analysis, patients who did not receive Paxlovid were two times more likely to be hospitalized and four times more likely to die compared to those who did receive Paxlovid. Let me walk through the data because I’m also going to be talking a little bit about the data on those that were vaccinated, those that were boosted, and we’re going to talk a little bit about age as well. Who are these high-risk people? I’m going to start off, put my glasses on for the small print.

The first figure one, those people that have your articles out, great. If not, I’ll walk you through it. The first, and I think this is important, realize we’re talking about a different end, so we’re talking about 146,000 versus 421,000. Hospital admissions, looking at 0.31% versus 0.65%. The absolute numbers are a little misleading, 451 versus 2,730. Remember, different ends, so you got to be looking at percentages. If you look at deaths overall, the folks with Paxlovid, 0.01% versus 0.04%.

Now let’s break it down. Rates of hospitalization and death by age group. Who are these people? If you go to figure two, you can see the vast majority of these deaths are occurring in these 65-plus. So, 1.62% is the hospitalization admission rate by age and the death rate for the 65-plus is 0.12%. You could see significant reductions. The most significant reductions you’re going to see are going to be in the older individuals. When you look actually at hospital admission rate, if you look at young folks, I got to say the 18 to 39, you’re only looking at 0.1% of the patients ending up in the hospital. You’re only looking at 0.01% dying in that population.

Really, if you look at deaths by age, you’re not really starting to see a significant number of deaths until you get to the 65-plus. This feeds into that whole issue of who’s going to benefit with Paxlovid. If your chance of ending up in the hospital is incredibly low to begin with, you can’t get much lower. If you already have a solid, finite risk, then the Paxlovid is really going to drop that. Really reinforcing Paxlovid in high-risk people. This is not something, “Oh, I’m 32 years old and I want to feel a little bit better quickly.” I’m not sure we have data to support that.

Now I’m going to move to figure three for folks. What about folks that are fully vaccinated? That’s the big question. We always hear from the docs out there, “Oh, you’re vaccinated, you’re probably going to be fine.” You can actually see here vaccinated patient hospital admission by age. I’m going to focus again on the old or high-risk folks, 1.78. Almost 2%, dropping that down to 0.65%. Over 400 patients, remember different ends, in the untreated end up in the hospital. Only 70 patients in the Paxlovid. If we go to deaths, we’re actually seeing 0.13%. We have over 30 patients die vaccinated who didn’t get Paxlovid. We drop that to only four patients if they add Paxlovid to that.

I think as I’ve been suggesting for a while, if your chance of something is already basically zero, you really can’t reduce that much further. Here, even in vaccinated patients, if they’re higher risk, and I really think there’s a big focus here on age and comorbidities, even vaccinated high-risk people still end up in hospital, still die. We can reduce that with Paxlovid.

VR: The younger patients, no death, no hospitalization, no need to give them Paxlovid, right?

DG: I think that’s the issue. I think people keep asking me, “What about Long COVID? What about me feeling better quicker? What about me being less contagious?” We don’t have any data to support that. All right. Now we’re all excited, but “Dr. Griffin, what about the rebound?” I hear about the rebound. You know what I heard today and I actually got a little emotional, had to take a couple deep breaths? Not only are we hearing rumors of Paxlovid, but now we hear Omicron is resistant to Paxlovid. Did you hear that, Vincent? That’s not true.

VR: No, no. It just ridiculous.

DG: How do you gently say that? I say things like, “Yes, that’s not true.” Let me start by repeating the mantra. It was actually – at Columbia – I actually heard a bunch of people sharing this false information. The plural of anecdote is not data. What is the science? The letter, “Nirmatrelvir, Ritonavir and Viral Load Rebound in COVID-19,” was published in The New England Journal of Medicine. Now, these are the data on the occurrence of viral RNA load rebound from a phase 2-3 double blind randomized control trial, so the EPIC-HR, which enrolled over 2,000 symptomatic unvaccinated outpatient adults at high risk for progression to severe disease COVID-19.

They have data on these patients, viral load measurements on day five, and then during the “rebound period,” they have relatively equal groups, almost a thousand patients in the treated, almost a thousand patients in the placebo. From baseline through 14, day 14, viral load, as they say, rebound occurred in basically the same number in both groups. If you look at the paper, if you look at the figure, you can’t tell them apart, you have to look at the figures to try to figure out what is going on.

I am going to quote the authors. The incidence of viral load rebound was similar in the nirmatrelvir, ritonavir and the placebo group. The occurrence of viral load rebound was not retrospectively associated with low nirmatrelvir exposure, recurrence of moderate symptoms, or development of resistance to nirmatrelvir. No antiviral resistance here. And I will mention, this is consistent with the ACTIV-2 study, and this is where they looked at folks that had received no viral treatment, no antiviral treatment. Rebounds in viral load and clinical symptoms were relatively common among participants who had not received any antiviral agents. Basically, I’m going to keep harping on this. This is the natural history of the disease. This is not Paxlovid rebound, this is COVID rebound.

VR: Daniel, do you think the press is going to get it?

DG: No, they don’t care. Doesn’t sell newspapers, Vincent. [laughs] I think, Vincent, if we jumped on the Paxlovid rebound, maybe we’ll get some more views and feel crummy about ourselves. [laughs] All right.

Remdesivir. Remember, three-day early IV data suggesting an 87% reduction in progression if given in those first five days. This is for our listeners out there. If your loved one, if you end up in the hospital during that first week and they put you on remdesivir, that’s good stuff that, that’s the way to go. That’s how we’re treating these hospitalized patients during that first week. Incredibly safe, well tolerated no significant drug interactions. We’re using it in individuals end-stage renal disease, so number two.

Number three, monoclonals as treatment as opposed to pre-treatment passive protection. We have bebtelovimab, and this looks to be effective against the B.4.6, so we still have monoclonal therapy going strong, head-to-head with Paxlovid. It looks to be slightly inferior, so given the choice. We also at some point will get our paper published on, does monoclonal antibody therapy prevent Long COVID? We’re not sure it does.

Molnupiravir, Thor’s hammer, a great name, but not as great a drug. Last and least, but still much better than doing nothing, we suggest about a 30% reduction in progression, but remember, be careful about those individuals of child-bearing age, not authorized for those under 18, and avoid harmful things. Remember, steroids that first week causes harm. It is not helpful. High dose zinc causes GI distress and vomiting. Not helpful. We’ll just skip the others.

The COVID early inflammatory, lower respiratory hypoxic phase. Unfortunately, we’re still seeing folks end up in the hospital at this point. Those who were “probably going to get better but didn’t,” might end up in the hospital. That’s when they enter the early inflammatory, lower respiratory hypoxic phase. When those saturations drop, we’ll look at a short course of steroids, anticoagulation, pulmonary support, maybe remdesivir if still in the first 10 days, immune modulation or toci or baricitinib, really limited role of antibiotics. There are not that many of these individuals with a secondary bacterial infection.

Then moving into the later, the late inflammatory, the secondary symptom phase. Actually, have an individual in the hospital with this right now. This covers that spectrum of the multi-system inflammatory syndrome. This is often a time when we need to be diagnostic-driven. Is this a secondary infection? Is this an inflammatory surge? Is this a clotting issue? We base it on that. I am going to wrap it up here with what I like to say every week, no one is safe until everyone is safe.

I do want everyone to pause the recording here. Go to parasiteswithoutborders.com. Click on the Donate button. Even a small amount helps. We are finishing off here in October, our three-month fundraiser for floating doctors. Donate now and we will match and double your donation up to a potential donation of $40,000.

VR: It’s time for your questions for Daniel. You can send them to daniel@microbe.tv. Brad writes a question that I think we just addressed here, but we’ll let Daniel take that. Brad is 51 years old. He has had five COVID shots, three Pfizer, fourth Moderna, a fifth bivalent Pfizer, and he got COVID from his daughter. He tested positive. He went to his doctor and said, “I was surprised to see how tricky it was for me to get a Paxlovid prescription. I felt like saying to one physician that refused to give it to me based solely on my age, but I listened to TWiV and I would like to have it. I eventually did get a prescription, but I felt some unnecessary stress in the early hours of a COVID infection. The question is, does Dr. Griffin use age-based guidance when prescribing COVID, rather, (laughs) Paxlovid?

DG: Yes, I’m not prescribing COVID, but I am prescribing Paxlovid. Yes, I go through the criteria. If someone falls into a category where there is a solid, finite risk that they’re going to end up in hospital or progress, then I will go ahead and use Paxlovid.

VR: Marjan writes, “Can Dr. Griffin explain his repeated references to Hickam and Ockham? Immigrant here.”

DG: OK, certainly. William of Ockham is or was a theologic philosopher from the Middle Ages, and he had this dictum that you should find one thing that explains everything, and ultimately he came back to God. This was carried over into medicine. It was this rule of parsimony. You would find out all the symptoms that a patient had and then you wanted to find one unifying diagnosis, and once you found it, you said that’s it and you stopped looking.

Now, John Hickam was down at Duke, and John Hickam rebelled against this dictum saying, “You know what? A patient can have as many diagnoses as they damn well please.” As we are learning over and over again, that is true. I remember the early frustrating days of COVID when they would test for everything under the sun. Once they found say, “Oh, can’t be COVID, there’s no way you can have flu and COVID,” and many, many months later, we came to learn about flurona and how many people can have more than one thing at the same time, so that’s the whole point of what I’m saying.

As we saw with monkeypox, as we’re seeing with monkeypox, one-third of the people have something else too. Just because they have something else doesn’t mean you don’t also have COVID or monkeypox or something else.

VR: Jenny writes, “How long do people remain contagious with COVID? I thought contagion was extremely unlikely after day five as long as symptoms were improving, but this study suggests otherwise. A small study, 75% of people with COVID had a positive RAT on day six. Half of those had culturable virus suggesting contagiousness. My emphasis, no one with the negative RAT had culturable virus. One person in my home has COVID, is still RAT-positive on day 16. Since I am very high risk, this person has been remaining in isolation. Is this prudent or is it overkill?”

DG: It is excessive. Cue the hate mail here. We had two years. We have lots of science here. The majority of transmission occurs two days before and up to five days after symptoms. There is a small amount of transmission that we think that case control studies support going into the day six through 10, so that’s the CDC recommendation. First five, full isolation. Maybe there’s a small amount of transmission day six through 10, but there’s no documented transmission in healthy individuals after day 10. The only time we see transmission after day 10 is in individuals who are immunocompromised.

I actually just had an issue like this today. The poor young man was locked away. It was definitely well past day 10, but they still had a positive rapid antigen test. A couple of things that Vincent points out here. One is, are we seeing transmission after day 10? No. The fact that you have a rapid antigen test does not mean that you’re contagious. I know there’s a meme out there, “Enough to detect, enough to infect.” That’s not true. Catchy things are not always true.

The fact that you might have a small amount of culturable virus, is that enough virus to infect someone else? If you can culture the virus, does that mean your technique is so good that you can say someone’s not infectious? I hate to say this, but at this point in the pandemic, time is the most predictive of when a person is infectious to others.

VR: Terry is a retired internist and writes, “Dr. Dan, I know you aren’t too concerned about Paxlovid rebound, but your colleague, Dr. Ho seems concerned. Please discuss how to manage, diagnose, and treat patients who have COVID/Paxlovid rebound. Do they need extended isolation?”

DG: I know that is the CDC recommendation. I don’t think the science supports it.

VR: OK. JP wants to know why Paul Offit, who was 71 and got COVID didn’t take Paxlovid.

DG: I understand his choice. Here’s a gentleman who got his three vaccines. He’s a smart guy, so I’m sure he did the calculation, “What’s my chance of ending up in hospital? What’s my chance of dying?” and felt like it was small enough that he was willing to move forward with that context. I would put it in that.

VR: Finally, Daniel writes, it’s not you Daniel, it’s another Daniel, “In a study reviewed in TWiV 941,” our last clinical update, “The rate of Long COVID from Omicron in the boosted was stated to be 4% at 12 to 16 weeks, and 95% of patients got better, even if it’s a process. Therefore, is it reasonable to say that the rate of “permanent Long COVID” is really only 0.2% or am I missing something?

DG: No, I think that’s actually reasonable and it’s optimistic. I’ve been taking care of a lot of patients with Long COVID for a while. We still keep getting newcomers, thanks to Omicron. It’s nice to have this growing amount of evidence where you can say, “Listen, I know you’re having a tough time right now; 95% of people are going to be better a year from now. Unfortunately, even if you take 0.2 and you multiply that by, what is it, 400 million people in the United States, you still end up with a really large number of folks that are just not getting better.”

VR: That’s TWiV Weekly Clinical Update with Dr. Daniel Griffin. Thank you, Daniel.

DG: Thank you, and everyone, be safe.

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