TWiV 930 Clinical Update #129

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 27 August 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 930, recorded on August 25, 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: Yes, I’m back in New York. No longer in some Scottish city that I mispronounce. I was listening to Nels Elde and you on This Week in Evolution and we had a lot of fun with his “Edinburruh,” “Edinburr,” but it’s definitely not Edinburgh. All right, I am back. We got a lot to cover in addition to Scottish pronunciation. I will start with a quotation. “The old, the poor, and the sick were being relegated to second-class citizenship. Our real values are not the ones that disappear in hard times. They’re the ones that show up in hard times. All it took was one little pandemic and we started writing people off.” That is Andy Slavitt.” That’s from his book, Preventable: The Inside Story of How Leadership Failures, Politics, and Selfishness Doomed the U.S. Coronavirus Response.

I’ll admit I have actually been a regular listener to Andy Slavitt’s podcast in the bubble during the pandemic and I did enjoy TWiV 929: Empathyology with Andy Slavitt, but I did realize listening to that podcast that Andy was not a TWiV listener.

VR: No.

DG: Unfortunate.

VR: I think, at least, he should have listened to the clinical updates because that’s what he’s involved with and I think he’s misguided by his so-called experts.

DG: We could say that. You don’t have to hold back on that. I think that you tried to point this out because he kept saying, “Well, all the scientists were saying…”

I’m saying, “You know what, Andy, all the media echo chamber folks that you are hanging out with were saying the same stuff.” Part of staying in that media echo chamber, I know sometimes I get a call from someone in the media. I know what they want me to say. If you say it, then you’re going to be on Fox News like I was last night or CNN or something.

I still remember actually there was one time CNN wanted me to come on. I’m like, “I really can’t. I’ve got patient care responsibilities,” and it was like this pause. I was like, “I know you’re not familiar with that, but I’m actually a doctor.” I will throw some stuff back when we get to the COVID part, but let’s start off with polio, which is a little fishy, Vincent. A man who devoted their entire life to polio and that’s in the news here.

[laughter]

VR: You think I’m pushing it?

[laughter]

DG: I know what you’re doing up there or in Midtown at ‘The Incubator.’ Last week, we got an email asking about what someone should do if they’re not sure whether or not they were fully vaccinated as a child. It’s interesting because we’ve been in this practice in medicine where we often check titers, which, “Oh, just check your titers,” and then we think when we get this lab result back, we know what that means.

Our attentive TWiV listeners, unlike Andy Slavitt, certainly realized that for COVID, we can check serologies, but we do not have a validated commercial assay that really tells us what that means. I know it’s frustrating to people, and don’t worry, we’re going to hit on some new stuff there this week. We also know that there are many providers out there are not going to let a little bit of science stand in the way of their hubris and hubris is a fancy word for excessive pride or self-confidence. I had to actually look that up.

I’m going to talk, what is the current CDC guidance if someone comes to see you as a provider and they say, “You know what? I think I was probably vaccinated for polio, but I’m really not sure. What is the CDC recommendation?” I’m going to talk a little bit about it and Vincent, you’re going to weigh in as well. Adults who are unvaccinated or without any documentation of previous polio vaccination should be given three doses of IPV at these recommended intervals: two doses separated by one to two months, a third dose six to 12 months after the second dose.

Why? Why not just go ahead and check those serologies because I will tell you, last century when I went to medical school, that was the right answer. Well, we have a little bit of guidance here from the CDC. I can again quote them. “In the absence of the availability of testing for antibodies to all three serotypes, serological testing is no longer recommended to assess immunity.” They go on to say, “Serology to assess immunity for children with no or questionable documentation of poliovirus vaccination will no longer be an available option and therefore is no longer recommended because of increasing limited availability of antibody testing against type 2 poliovirus.”

This is actually interesting. I was looking and boy, in my Epic electronic health record, I can order polio serology. I started looking and you’re actually getting serology titers for only polio type 1 and type 3. There’s actually no type 2 in that polio that you order, which is really interesting because that’s what we’re worried about right now this, “Oh, my gosh. Am I protected against type 2?”

It’s interesting of the three wild poliovirus types, type 2 was declared eradicated in September 2015. To remove the risk for infection with circulating type 2 vaccine-derived polioviruses, which can lead to paralysis similar to that caused by the other, all of the OPV-using countries switched from the trivalent oral polio vaccine to this bivalent which only contains type 1 and type 3, so the OPV for type 2 only comes out for outbreaks of type 2. I encourage everyone – Vincent, I’m going to sell your other stuff. Vincent, you’ve been doing a lot of good stuff out there on YouTube. Go to the MicrobeTV channel and learn a lot more.

Then the other aspect is – two other aspects I want to hit. One is a paper. I don’t know if you remember this paper, Vincent, but, Amy was the first author and you were the last: “Cross-Reactive Antibody Responses against Nonpoliovirus Enteroviruses.” I remember because I actually spend a lot of time hanging out with Amy discussing her grant proposals and the rejections, which are not always well-founded. This is one of those issues too, is when you get those tests back for polio, are they really telling you about antibodies for polio? Is it maybe a cross-reaction from other enteroviruses, but the short and long story here is we also do not know what those levels mean.

What is the level at which you are protected against polio? When you send off those titers and they come back positive, what is positive? Is it positive above a protective threshold? We have these same issues and maybe we’re starting to realize that, boy, a lot of our serology tests, we don’t necessarily have any prospective data saying that there’s a threshold at which you are protected.

The short answer is if you’re not sure, there’s really no downside to going ahead and getting your poliovirus vaccines. It’s interesting I was talking to someone today in their 40s and they’re like, “I don’t have records, but I went to public school here in New York.” They wouldn’t have let you go to public school if you didn’t have those vaccine records. If anything, it makes me realize it would be nice if we had a much better system, which we now have in New York State, of recording when people get their vaccines. Vincent, don’t know if you had any thoughts.

VR: I think that you’ve made a good summary. The bottom line from Amy’s work is that there are many, many different enteroviruses which are related to polio and they can induce antibody responses that cross-react with polio. If you do a titer and you get one to eight, who knows if that’s polio antibodies or another enterovirus or a mixture? I think this is an underappreciated finding that should get some prominence and CDC needs to look at it. I’m glad they don’t recommend doing antibody titers, but they say it’s because there’s no type 2 assay and that’s not the reason. The reason is cross-reactivity folks at the CDC.

DG: That’s polio. Make sure you’re vaccinated. That’s the way you cease to have to worry so much about the polio.

The monkeypox. We have a bunch here and I’m going to keep reiterating what I’ve been saying here for a little while. Monkeypox is not a gay disease or an African disease. Monkeypox is an infectious disease. If people have been following the tracker here in the U.S., we’re up to about 16,000 confirmed cases, approaching 50,000 outside of Africa which is interesting. We care more when it gets outside of Africa. About 3,000 cases here in New York. I was looking at CIDRAP earlier today down in Brazil. There’s almost 100 cases in children already confirmed.

Just people as we go through, I’m going to start this section with the article, “Clinical Presentation and Virological Assessment of Confirmed Human Monkeypox Virus Cases in Spain. A Prospective Observational Cohort Study,” published in The Lancet. I encourage people to read this article as I will give here a very biased review of certain things that stood out to me.

A couple of things I will say, 18% of patients reported previous smallpox vaccination. How can that happen? I keep hearing from some of my elder colleagues that smallpox vaccination when you’re a child will keep you safe from the monkeypox. Median age here was 37, so that’s not that long ago that these folks got those smallpox vaccines, but it was long enough ago.

The other I will say that they report no differences in any clinical features between the vaccinated and the unvaccinated that got the monkeypox. 8% were identified as heterosexual men or heterosexual women. As I keep pointing out, this is no longer restricted to just the MSM population. Median incubation was seven days. Interquartile range of 5 to 10, so giving us some sense.

This is interesting. All participants presented with skin lesions and I’m saying, “If they didn’t have skin lesions, what were you swabbing and how did you make the diagnosis? Why were you thinking of it?” I’m not sure what to make of that. 39% of the participants had complications requiring treatment. That’s tough because I know we’ve been saying, “Oh, 95% of the time, you’re going to be just fine.” We’re starting to see a more significant chunk requiring treatment.

A quarter of them were because they had proctitis, 10% of them because they had tonsillitis, about 10% had penile edema, about 3% had abscesses develop. We’ve actually been seeing that locally as well, and 2% required hospital admission. The other is, the median time from onset of lesions to formation of a dry crust was 10 days. The interquartile range was 7 to 13, but remember, we don’t just want a dry crust. We actually want to have that heal completely over.

VR: Daniel, just a comment on the 18% of patients who had previous smallpox vaccination. That’s in line with the 80% protection against monkeypox by smallpox vaccine that we have established from studies in Africa.

DG: Yes. I think what it said, 84. Yes, it’s right there. Yes, 82, 84, so yes.

Transmission. The MMWR early release, “High-Contact Object and Surface Contamination in a Household of Persons with Monkeypox Virus Infection – Utah, June 2022.” In May 2022, the Salt Lake County health department – I used to live in Salt Lake City. Met my wife out there. Got engaged at the top of Alta. [chuckles]

Here they reported two PCR confirmed, travel-associated cases of the monkeypox to the Utah Department of Health and Human Services. The two persons with monkeypoxes, we’ll refer to them as patients A and B. They live together without other housemates. It’s interesting what they did here. They were going to assess the presence and degree of surface contamination of household objects contacted by monkeypox patients.

They basically went around- It’s like a House episode. They’re going around, they’re swabbing objects in the home of the patients. Unlike House, I think they actually got consent and told the people they were going. The patients identified high-contact objects and surfaces for sampling, but the patients also described cleaning and disinfection activities performed within the home during the illness. The patients had isolated at home for about 20 days before the home was entered for sampling. This is like about three weeks into it.

Specimens were obtained from 30 objects in nine areas of the home. They transported them to the Utah Public Health Lab. Sent them to the CDC where they were process and tested. They did – PCR viral culture was only pursued if the PCR test was positive. Among the specimens, 70% they had positive PCR results, including those from all three- they say porous items: cloth, furniture, blankets. 68% of nonporous surfaces, handles and switches, and one of two mixed surface types, different types of chair. They didn’t get any positive viral culture results.

VR: Daniel, there’s a similar study in Emerging Infectious Diseases and similar results except I think a few of the objects they got actually some PFU. Like 10^2 PFU, very, very low infectivity like this one, so that’s very curious that the – Not a lot of virus on these surfaces.

DG: It’s curious because there’s this mythology out there. There’s this story about giving Native Americans these smallpox covered blankets as a part of a bioterrorist activity. It certainly was the intent, actually, if you go back and read some of the correspondence. I’m not sure it was successful, so it’s interesting. In someone who has the active infection, when they’re using blankets, cloths, stuff like that, how contagious are those objects and for how long? I don’t think we know.

I’m glad they’re doing the attempts to culture virus, and I love that Emerging Infectious Diseases is doing quantitative attempt to culture virus. That’s really what we need. Yes, we’ll have to throw in throw in a link to the Emerging Infectious Diseases article as well. Hopefully, we’re going to learn more.

This is one of those interesting things, and I’m going to spend time on our next talking about transmission and the fact that there isn’t this binary that we like. We’ll talk about the history of the binary of transmission. We talked about this being predominantly close contact from one infected human being to another, and then they’re being less common. Nothing is a binary here.

We have CDC, Monkeypox Guidance for Schools, and it’s about hygiene, it’s about cleaning. We can actually put a link to the FAQ’s in our notes here. Also, there is a bunch of stuff going on here with testing, and why do I put this next one in testing? I will start of, remember to make the diagnosis. You actually have to do the test, so you’re going to be doing those swabs, you’re going to be putting them in the liquid, and you’re going to be refrigerating or freezing those, and that’s two non-cotton swabs that are being sent off for the monkeypox DNA PCR.

There was the article, “Clinical Characteristics and Comparison of Longitudinal qPCR Results from Different Specimen Types in a Cohort of Ambulatory and Hospitalized Patients Infected with Monkeypox Virus.” This was published in the Journal of Clinical Virology. In this study, 16 male patients, five were hospitalized, 11 out-patients, were included for serial testing for monkeypox virus DNA, carried out in various materials through the course of disease.

All the patients were male between age 20 and 60. Self-identified as men having sex with men. Two had a known HIV infection coinciding with an increased number of lesions and viral DNA detectable in blood. Remember it’s an n of 2. The data presented underscored the reliability of lesion swabs for monkeypox virus detection even in later stages of the disease.

Can I hit you with another article? This is, “Monkeypox Virus Infection in Humans across 16 Countries – April – June 2022”. This was published in El New England Journal of Medicine. I put it in here because if we do not know whom to test, so why is this in the testing section? We’re going to be missing cases. If we miss cases, we’re going to allow people to spread to others to needlessly suffer. We really want to be catching diagnosing these cases. This is a report of 528 infections diagnosed between April 27 and June 24, 2022 at 43 sites in 16 countries. We have case descriptions from Spain, France, and now a much broader experience.

Big takeaways here for whom to suspect and on whom to do a test. They reported a wide spectrum of skin lesions, and they actually have a nice clinical image web library. This is actually open access. It does not apparently impact your free article count, so everyone can check this out. They comment that the rashes included macular, pustular, vesicular, crusted lesions, lesions in multiple phases were present simultaneously. None of that stuff that in the textbook that it’s got to be all these vesicular and then pustular lesion in the same state of development.

Among the persons with the skin lesions, I’m going to say only 58% had lesions that were described as vesicular pustular, so forget about same stage of development. Only about half of them even had vesicular pustular, so 42% had a rash that was not even a vesicular pustular. The number of lesions varied widely.

Most persons had about 10 lesions or fewer, so this is not that child that we see pictures of covered with the pustules. A total of 54 persons, so about 10%, presented with just a single ulcer. They also, much like other series, found a second infection in 29% of these folks, so don’t do that test that comes back positive and say, “You know what it is,” and then fail to go on and look for the monkeypox. If you have a test-positive from a monkeypox, don’t fail to look for that secondary infection.

They also saw a couple of cases of myocarditis. I’m back to my mantra of never miss an opportunity to test. Our current 50% positivity rate means we’re not testing enough rashes. The only way to know if a rash is monkeypox or not is to do a test, and remember, Occam was not a physician, Hickam was. A patient can have as many diagnoses as they please.

Vaccines, we got them, and now intradermal, but limited access.

We get a lot of questions as clinicians like, “Hey, does so and so qualify?” We’re still rationing the vaccines, and per New York City rationing criteria, people have to meet all of the following criteria to be vaccinated. They have to be gay, bisexual, or other man who has sex with men, and/or are transgender, gender nonconforming, or gender non-binary. That’s number one. They have to be 18 or over, and they have to have multiple or anonymous sex partners in the last 14 days. Really sort of a high bar based on the limited vaccines we have and sort of tough. As we’re mentioning we’re seeing it in children, we’re seeing it in women, we’re seeing it in populations that currently would not have access to vaccines.

Clinical course and treatment. We’ve been talking about TPOXX, we’ve been talking about the Viroptic eyedrops. We’re getting more descriptions on what we’re actually seeing, and an article was published in CMI, “Clinical Characteristics of Ambulatory and Hospitalised Patients with Monkeypox Virus Infection: An Observational Cohort Study.” These are those folks from France, 264 patients from France. Fever, 68% of the time; adenopathy, so enlarged lymph nodes, 69%; overall 6% in this series were hospitalized; none of them were immunocompromised. These are people with normal immune systems who are actually ending up in the hospital. A little bit worse than we’ve been trying to reassure people.

Complications that ended up getting them to the hospital included cellulitis; paronychia, I was a little surprised by that, is an infection around the nail; severe anal and digestive involvement; noncardiac angina with dysphasia; blepharitis, that’s involving the eyelid; keratitis, is actually involving the eye. Surgical management was required in four of these patients, so 2% or so.

Here’s a question, how well does TPOXX work? Because we say we got vaccines, we got drugs, how well is it tolerated? Well, the article, “Compassionate Use of Tecovirimat for the Treatment of Monkeypox Infection”, was published in JAMA Network Open, and they start with the background, maybe a deeper dive in another context, but tecovirimat is an antiviral that inhibits p37, a protein involved in the release of enveloped virus, dissemination, and viral purulence.

Here the authors assessed adverse events and clinical resolution of systemic symptoms and lesions in an uncontrolled cohort study of patients with monkeypox who are treated with tecovirimat on a compassionate use basis. We have no control group, so we’re not seeing how does this work relative to folks that got nothing, we’re just seeing the experience.

The patients had disseminated disease or lesions insensitive areas, including the face or genital region, that’s why they were offered treatment. Oral treatment for adult patients was weight-based, it’s either every eight or 12 hours. Recommended that you take this medicine with a high-fat meal, so just people take note of that; the duration of therapy was in general 14 days, but was actually extended, I think, in one of the patients.

Nine patients had HIV, one patient had received the smallpox vaccine more than 25 years prior, and four received one-dose of the JYNNEOS vaccination after symptom onset. As we’ve discussed, a lot of times if there’s in a ring approach, someone’s had an exposure, the vaccination here, they actually got the vaccination after symptom onset.

At the time of treatment, systemic symptoms, lesions, or both were present for a mean of about 12 days. I think give a range of six to 24. What were those systemic symptoms? Fever, 76%; headache, 32%; fatigue, 28%; sore throat, 20%; chills, 20%; backache, 12%; muscle aches.8%; nausea, 4%; diarrhea, 4%. Almost all the patients, 92%, had genital or perianal lesions. Like we saw before, about half of them had fewer than 10 lesions.

All the patients had pain. This seems to be something we’re hearing. They have people present with this rash, they say, “It really hurts.” It’s interesting. It’s not the burning pain that we often hear with shingles, for instance, it’s just more of this really deep incredible pain, so pain seems to be significant. One patient received 21 days of therapy, as I mentioned. Everyone else got 14. Complete resolution of lesions was reported in 40% of folks by day seven, while 92% had resolutions by day 21.

Treatment with tecovirimat was generally well tolerated. They mentioned some complaints, but they actually say it was really hard. Adverse effects could not always be differentiated from symptoms related to infection, and as we mentioned, no control group was included so really we don’t know from this study about the antiviral efficacy, the impact on duration of symptoms severity, infectiousness to others, et cetera, but fortunately there is a trial. The PLATINUM trial.

You know who’s going to do this? The same Brits that did the RECOVERY COVID trial, and they expect to have data for us by Christmas. That’s very nice of them. I will say, a little embarrassing. Really? We need to have data before Christmas. We need to get this done before the Brits show us up again. All right. [chuckles]

COVID. Now we’ll get back to COVID. Children COVID, other vulnerable populations. As we keep saying, children are at risk from COVID. The MMWR, “Safety Monitoring of Pfizer-BioNTech COVID-19 Vaccine Booster Doses Among Children Aged 5 to 11 years – United States May 17 – July 31, 2022.” This report provided safety findings from v-safe and theirs, data collected during the first 10 weeks of administration of the Pfizer-BioNTech booster doses to children aged 5 to 11. So, right, this is dose number three. During this period over 600,000 third doses were administered in this age group. No VAERS reports of myocarditis after third doses among children aged 5 to 11, zip, zero, so nice safety data there.

We also did get updated data from Pfizer on Tuesday, August 23. Pfizer and BioNTech announced updated COVID-19 vaccine data supporting efficacy in children 6 months through 4 years of age. This is a press release. I will read their press release. “Updated analysis from 34 cases occurring at least seven days following a three-dose regimen showed 73.2% vaccine efficacy among children aged 6 months through 4 years.”

I will clarify that this is the secondary endpoint of vaccine efficacy for prevention of symptomatic COVID-19. Also mentioned that the majority of these cases were during the period when Omicron was circulating, so this is Omicron data in children 6 months through 4 years.

Testing. We have Cell Reports Methods: The article, “Direct Capture of Neutralized RBD Enables Rapid Point-of-Care Assessment of SARS-CoV-2 Neutralizing Antibody Titer.” In this article published in Cell Reports Methods, the idea here is to use a lateral flow rapid test to quantify SARS-CoV-2 neutralizing antibodies, and potentially get information about how much protection a person has against infection or severe disease from SARS-CoV-2.

It is blood, so you’re going to actually require a finger stick, this is not a lick-a-stick, this is not a Q-tip up your nose. The way this works is they use an ACE2 extracellular domain construct, immobilized on a cellulose-based test membrane by protein fusion with a cellulose-binding domain. For Cell Reports Methods, of course, they have these really nice figures and cartoons so you can check this out, I encourage folks.

They did some validation in a pseudovirus neutralization system and suggest, not surprising, that this is much better than relying on total IgG serology tests for assessment of neutralizing antibody levels. The big thing and the next step is their suggestion that they’re going to follow up with large-scale studies to try to find a correlation between these quantifiable results and whether or not folks are protected against SARS-CoV-2 infection, and also hopefully against SARS-CoV-2-induced disease, COVID-19 moderate, severe disease.

VR: Infection is going to be a tough one to figure out Daniel. They’re probably not speaking clearly. They mean disease I would guess. [laughs]

DG: You know, what they’ve been listening to in the bubble instead of TWiV. I gave them the benefit of the doubt suggesting they might want to also look at severe disease. As I like to say, as we move into active vaccination, not only, never miss an opportunity to vaccinate, but vaccinations prevent disease, not all infections.

Now down to age 12 for Nova. CDC Director Dr. Walensky signed a decision memo that Novavax COVID-19 vaccine can be used as another primary series option for adolescents aged 12 through 17. What about Novavax as a booster? They’re still waiting to get that as an option. What about boosters, updated boosters for the fall? Monday, August 22, 2022, Pfizer and BioNTech submitted an application to the U.S. FDA for EA authorization of an Omicron BA4, 5 adapted bivalent COVID-19 vaccine.

A press release and I will read, preclinical data, which they’re not sharing with me, showed a booster dose of Pfizer and BioNTech’s Omicron BA4 or 5 adapted by Valent vaccine generated a strong neutralizing antibody response against omicron BA1, BA2, BA4, and BA5 variants, as well as the original wild type strain. I don’t know when did strong become a quantifiable term? What do they mean by strong? We also heard that Moderna submitted an application as well.

We’re hearing rumors. I’m sure this has nothing to do with the upcoming midterm elections, that an announcement will be made after Labor Day. Here’s where I want to make the record clear on vaccines as far as what they do and what we have been repeatedly saying in our clinical updates. I listened and Andy Slavitt said, you should go back and listen. Well, the nice thing we actually have transcripts, so I could go back and see exactly what did we say? So as Andy Slavitt suggests, I went back to the transcripts and looked at what we were saying right back in December 2020 when the vaccines were first available.

We have transcripts so let us roll the tape and look at Clinical Update Number 41, TWiV 695 and I say, here is a vocabulary for today. We have three words, and I want people to learn about: infection, disease, and severe disease. As we discussed the data on the vaccine, we pointed out again and again, and I quote, the endpoint was not whether or not people got infected, the secondary endpoint was not whether or not people got infected. It was whether or not they get the disease and whether or not it was a severe disease.

Finally, we point out that these are very important questions when we talk about herd immunity, because if a vaccine protects you against disease, but not infection. If it doesn’t knock down levels and interrupt transmission, then we really have to step back when we talk about herd immunity. Just remember, and this applies to COVID vaccines, polio vaccines, and probably just about every vaccine, including HPV, if you look closely. Vaccines prevent disease, they do not prevent all infections.

VR: Good job, Daniel. I’m going to send this to Andy in some way. I just found it a little bit obnoxious that he told us, we probably think we said it, but we didn’t. He’s not used to dealing with virologists. I think people he talked to are not virologists. We have another one in the same 600 from Allan Dove saying the same thing. I will send this to him and see if he starts listening or not. Probably won’t, he’s too busy.

DG: He won’t, too busy. He won’t, but I think it’s important, because, Andy he did a tremendous amount with getting the vaccines out there. I have a lot of respect for Andy but he could have done a better job if he was listening to scientists and not, political appointees or people in the echo chamber.

Passive vaccination, Evusheld. Let’s not keep this Evu-shelved. Just unfortunate another patient I’m taking care of who his physicians were going back and forth and deciding whether or not to give him the Evusheld. They finally decided maybe they would go ahead and now he’s got acute COVID. We’ve got him on the Paxlovid so we’ll see how that goes. Let’s get to the early viral, upper respiratory, non-hypoxic phase. This is that first week that viral symptom phase. This is when you want to jump in with Paxlovid but everyone keeps asking “what about Paxlovid in the vaccinated? I need more information, Dr. Griffin.” I’m going to give you more and thank you for all the researchers that are making this available.

The article, “Oral Nirmatrelvir and Ritonavir in Non-Hospitalized Vaccinated Patients with COVID-19,” published in CID. These are the results of a comparative retrospective cohort study. Put that in your qualifications. They looked at 1,130 patients, greater than or equal to 18 years of age who were vaccinated, subsequently developed COVID 19 between December 1, 2021 and April 18t, 2022, got Paxlovid in the first five days, versus 1,130 vaccinated patients that did not get Paxlovid.

The primary outcome was all-cause emergency room visit hospitalization or death at 30 days follow up. The primary composite outcome was all cause-ER visits, hospitalization, or death in 30 days. This occurred in 7.87 in the Paxlovid, in 14.4 in the non-treated. In odds, ratio of 0.5, they actually say consistent with a 45% relative risk reduction. They saw significant reduction in multi-system symptom burden, subsequent complications, such as lower respiratory tract infections, arrest cardiac arrhythmia, diagnostic testing.

I also will highlight that in this study, the 30-day mortality for those that got Paxlovid was zero and a number of the vaccinated people that did not get Paxlovid ended up dying. Ten of the folks ended up dying.

VR: Daniel, so this addresses the criticism that it wasn’t tested in vaccinated patients, correct?

DG: It does. I’m going to hit you with another study, but before I do, I’m also going to point out, and this is for those of you that listened to Fox News last night. This question came up and it was prompted by Jill Biden, who now had, there’s a different type of Paxlovid rebound, Vincent. There is Paxlovid symptom rebound, there’s Paxlovid test positivity rebound, and then there’s some kind of other rebounds where you get both at the same time.

As we saw with Jill Biden she felt better. Her tests were negative, a few days later she got a positive test. Oh my gosh, we haven’t been seeing that for the last two years, and suddenly there’s this whole question, instead of five days, should you be doing 10 days of Paxlovid? As I like to point out, that is a reasonable ask. The FDA has asked for the data on that to be available by the end of September. I think an important question, five versus 10, what would be the benefits of one versus the other? Do you need any more than five? Will 10 further reduce the progression to moderate and severe disease? Will there be a mortality? You got to do the science. We don’t know until you do the experiment.

The next time I will be also discussing another article Vincent. This study was published in the New England Journal article. Another study, looking at Paxlovid this time in a mostly vaccinated population. To move away from Paxlovid, remember remdesivir. We have monoclonal therapy, we have molnupiravir, and a big thing that I keep repeating week after week. Let’s not do those harmful things. Let’s avoid doing things that potentially harm our patients.

Not a lot new for the early inflammatory lower respiratory hypoxic phase, steroids at the right time in the right patient and anticoagulation, pulmonary support may be remdesivir if early, not if they’re on a ventilator, possible additional immune modulation, avoid those unnecessary antibiotics and unproven therapies.

We are continuing to work with our patients with Long COVID. We seem to be learning a little bit more every day, but we still have a lot to learn. As I always like to conclude every time, no one is safe until everyone is safe. I do want everyone to pause the recording right here and go to parasiteswithoutborders.com and click ‘Donate.’ Even a small amount will help us. We are now having our Floating Foctors fundraiser and during the months of August, September, and October, donations made to parasiteswithoutborders will be matched and doubled 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. Chel writes, “I have IBD (Crohn’s) and take Humira to control it. My GI doc has said that research on IBD patients shows that they, on anti-TNFs, like Humira, mount their response to the mRNA vaccines that’s similar enough to non-immunosuppressed response and therefore do not need Evusheld. However, the CDC states that people on anti TNF drugs do qualify for Evusheld. What’s your feeling on whether IBD patients on drugs like Humira should get Evusheld. I’m also 60 years old. Should that be a consideration?”

DG: Yes, it is interesting. I am concerned about the disease itself, having an impact on the immune system. As your physician points out, people on the TNF inhibitors, if you look at their serology response, they actually look pretty good. Also, if you look at how these patients have done with COVID infections, folks have done pretty well, but again, it’s one of those things. I don’t see any reason to keep the Evusheld on the shelf when potentially it could be a benefit. In a case like this, I usually think it’s wise to err on the side of providing the passive protection.

VR: Jessica writes, “If two people in a household test positive for COVID several days apart, should they isolate from each other to avoid adding to each other’s viral load?” It’s the situation as her parents live together with no one else, dad tested positive and he didn’t find out till four days later. They started to mask and isolate. Then the mom had symptoms, although so far she is rapid antigen tests negative. They’re wondering whether they should continue to isolate. If they stop isolating, the dad still has high viral load, will make mom’s disease worse in a few days, if dad is feeling better and mom now has a high viral load and they aren’t isolating will dad’s recovery be hindered? Thank you.

DG: All right. What would you tell him, Vincent?

VR: No need to isolate.

DG: I’ve got to agree with you. I think of this as, there’s a certain point where the two individuals at this point it’s the same virus. It’s the same variant. I actually think they’re going to be better off not isolating. They can go through the suffering together. This is one of those things when you’re up on the altar and this is the, in sickness part and in health. In this situation, I would not recommend that they isolate from each other. They can just enjoy or not enjoy this experience together.

VR: All right, now we have something completely different. This is from Adrienne who wants to know about Mycoplasma pneumoniae. She tested twice in the last few years. March 2020, she was ill in 2021. She had the same symptoms and then she also tested positive for COVID in December.

“Now, why does the USA state that Mycoplasma pneumoniae so common, yet here in Australia ,no one, no doctor, no GP, no specialist has been able to tell me anything other than it’s rare here. Don’t know how you got it twice. Do you own an exotic bird? No, I don’t. Two: Does M. pneumoniae have long-lasting effects? Have not felt the same since: fatigue, weight loss, congestion diarrhea, constipation, or is this what an actual doctor, (not a telehealth GP consult in OZ Australia) would say, possibly Long COVID? And what causes platelet ESR WCC levels to rise and fall? Please answer my questions.”

DG: OK. Please answer all my questions. This is like a full consult here. Mycoplasma pneumoniae, “walking pneumonia,” different prevalence in different contexts. This is something where we think we see more of the community-acquired pneumonias in younger individuals, as we get into older individuals, we see less. We do not see a lot of adult hospitalized patients with Mycoplasma pneumoniae in the U.S., but this is something that is suggested to be more prevalent in younger folks.

Again, I’m not sure how great the surveillance and testing is. This is one of those reasons why we often will think about adding a macrolide like azithromycin for the Mycoplasma pneumoniae. The mycoplasma actually can have some pretty significant inflammatory impacts on the immune system. We sometimes see agglutination, we see impacts on red blood cells and platelets. There’s a whole complex interaction with the immune system with Mycoplasma.

Is it really uncommon in Australia? Is it really more common here in the U.S.? I think one of the things we’ve realized over the last couple years is we probably don’t have the surveillance systems at the level that we should to really know what the amount of confidence about those comments.

VR: Do we know if it causes long-term effects? Long walking pneumonia, for example?

DG: Yes. Is there post-Mycoplasma? Every infection, interesting enough, has some degree of post-infection issues. Is it very common as we’re seeing with COVID? No. Is it less common with Mycoplasma? Yes. Is it zero? Certainly not.

VR: All right. Ron writes, “I have a question related to COVID booster doses, third dose for children ages 5 to 11. Health Canada recently approved booster doses for this age group. If it has been six months after the primary series is complete, I ask as my 5-year-old son would be eligible for his booster in January. His history of infection and vaccination is as follows. COVID infection mid-February confirmed with rapid antigen test. First dose in May, second dose 12 weeks later, end of July. Are there any updates regarding efficacy of the booster and preventing hospitalization, death, and specifically Long COVID for this age group? Would you recommend a booster?”

DG: Yes, we talked a little bit about the safety in this population. Incredibly safe, zero myocarditis in over 600,000 individuals. The big thing, and we’ve been talking about this for years is the vaccines even just two doses tend to do quite well against, we think severe disease, but again, this is a population where you need huge numbers to see that. I think I’m going to be on the same page that Paul Offit has been where with the advent of Omicron, really the COVID vaccines have turned into three-dose series. Does that one infection count as one of the three? I don’t think we know. In general we would say very safe, recommend finishing off getting that third dose.

VR: We have a flu question from Lily. My brother, 58, mentioned he recently got his first ever pneumonia shot and he got a flu shot this past April. My question is, the flu shot comes around October. I learned on TWiV that they decide on the vaccine as far back as February for the following season. Am I wrong in thinking that a shot in April would be from last season’s vaccine? Since the virus changes, it might not be the same vaccine needed for the upcoming season. Also wouldn’t antibodies from getting the shot last April have waned by the upcoming flu season, this fall and winter, I guess the shot wouldn’t hurt, but is he really still protected?

DG: Yes. This is a great thing. Vincent, you jump in on this, because I know you have opinions about timing of flu shots, but the flu shot, just like we’ve learned, seems to have a dependence on timing. Each month after that flu vaccination, so you can start two weeks after the flu vaccine, you’re going to be losing about 10 or 50% efficacy against what is the endpoint, what’s the efficacy we’re talking about? It’s upper respiratory influenza-like illness-related medical visits. Not necessarily confirmed influenza cases.

We don’t have great data on influenza, severe disease. I always historically say there’s decent data that 90% of the folks that die of flu were not vaccinated, but what’s the actual hard endpoints for those, but timing matters with flu. If you got a vaccine last April, even if it was matched to the variance, quite a bit of diminishing returns, antibody contraction for this coming winter. Vincent, any thoughts?

VR: Yes, I would say you should get it in the fall again, between the contraction of the antibodies and perhaps reformulation of the vaccine, I think that would be recommended.

DG: OK. All right.

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

DG: Oh, thank you, Vincent. Everyone be safe.

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