TWiV 926 Clinical Update #127

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 13 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 926, recorded on August 11, 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, we have COVID, we have monkeypox, we have polio. Now there’s a new henipavirus in China that’s infecting people, and it seems to come from shrews. Oh, my goodness. Viruses, they must be important, Daniel.

DG: [chuckles] I already put that in the show notes for the Puscast, and I’m like, “Shrews. The animals, not the people.”

[laughter]

VR: Excellent.

DG: All right. Let us start. A lot this week as, unfortunately, as always, and I’ll start with my quotation. I really like this quotation. I may have used it before, so let me know, but it seemed really appropriate with some of the stuff that happened this last week.

“When you tell a lie, you steal someone’s right to the truth.” That’s from the book The Kite Runner by Khaled Hosseini. Again, great book. Perhaps people have been paying attention to what happened in the news. Recently, it has come to light, and I won’t mention any names, that there are certain people who’ve been knowingly lying and feeding conspiracy theories that they know were untrue for personal gain. The idea that COVID has allies among individuals that value money and media appearances over the truth, and the life and well-being of others is very disturbing. Hopefully, we can be a voice of science in the midst of all these misinformation out there.

The monkeypox update. The Health and Human Services Secretary Xavier Becerra declared the monkeypox outbreak a public health emergency on Thursday, August 4, 2022. This is actually important for helping strip away a bit of the bureaucracy that’s been standing in the way of us moving forward. That bureaucracy, it’s important, right? I think we need to have a balance here. You just don’t strip it away willy-nilly. There needed to be a realization that the benefits outweigh the risks, and we’ll talk a little bit about that.

We’ll post again the monkeypox tracker, but I was just on a call with the CDC today from 1:00 to 2:00. Talking about the numbers are now over 10,000 confirmed cases here in the U.S. There’s a little bit of a lag there, because we’re starting to see some cases in children. There’s a lag before a confirmation is done because seeing a new population like this, it makes sense. You want to do a second test. We want to really make sure that this is actually what we’re seeing.

I will repeat what I hope everyone is realizing, monkeypox is not a gay disease or an African disease. Monkeypox is an infectious disease. We now have a formal monkeypox layout where we start with transmission. Recently, we had the MMWR,: “Interim Guidance for Prevention and Treatment of Monkeypox in Persons with HIV Infection – United States, August 2022.”

Here, transmission of monkeypox can occur through direct contact with the infectious rash, scabs, or body fluids through respiratory secretions during prolonged face-to-face contact, or intimate physical contact, or through touching items, such as clothing or linens that previously touched a patient’s infectious rash or body fluids. Patients are considered contagious until the scabs have crusted over and fallen off, and a fresh layer of intact skin has formed underneath. That could be two to four weeks, so we’re going to really have to be talking a bit about that.

I also wanted to mention, with a bit of commentary, the MMWR: “Epidemiologic and Clinical Characteristics of Monkeypox Cases – United States, May 17–July 22, 2022”. My commentary is that when you read the press, there is this comment about how the monkeypox is only affecting a certain population. Even when it is suggested that we should care, it is suggested we do so out of solidary and empathy with the impacted community.

Now, I’m going to comment that initially no cases were being diagnosed outside this target group, then 1%, then 2%. Then we see in this report that for 6% of the diagnoses, individuals reported no recent sexual or close, intimate contact. Six percent of the time, they were not in that target population. Even with this, the data’s already dated, and the authors acknowledge a number of limitations that I’m going to add to this list.

First, this analysis included only 41% of the U.S. monkeypox cases reported through July 22, and is not representative of all cases. They don’t even have all the data on these particular cases. Second, even on submitted case report forms, a bunch of information was lacking. Third, we’re already seeing more cases in women, children, men outside this target population.

As we have noticed, there’s a bit of a testing bias. We’re probably well past 6% outside the targeted population. I can share this from my vantage point that this perspective that this only occurs in a certain population is limiting testing. It’s also delaying testing. A lot of the cases that I’ve been involved in, it’s day 10 or 12 before that folliculitis is finally recognized and a DNA test is performed.

We really need to encourage testing so that we know the true number, the characteristics of people that are infected, risk factors, transmission, et cetera. We will get to testing as I move on, but still in the transmission section. I am going to – Is it OK if we recommend they listen to TWiV 925? I love the title, “First Kisses and Second Doses.”

VR: Very good [chuckles].

DG: There’s a CDC info page where they explain that monkeypox spreads in a few ways. Just go through this, and we’ll also leave a link to the CDC site. The monkeypox could spread to anyone from close, personal, often skin-to-skin contact, including direct contact with monkeypox, rash, scabs, or body fluids, touching objects, fabrics, contact with respiratory secretions.

Then they actually talk about the fact that this direct contact can happen during intimate contact, including, and they mention a bunch of oral, anal, vaginal sex, touching the genitals. They say anus, and then they put in “butthole”. Hugging, massaging, kissing, prolonged face-to-face, touching fabrics. Then they actually talk about a pregnant person can spread the virus to their fetus through the placenta.

Then they mention, I think this is important: Scientists are still researching. This is something we are trying to learn more about. We don’t want to know what is written in a textbook, but we want to know what’s going on right now. Scientists are still researching, and they acknowledge this if the virus could be spread when someone has no symptoms. Is there any degree of asymptomatic transmission? How often is monkeypox spread through respiratory secretions?

I’ve already seen this post, is it airborne? Well, I think what we’re seeing here is in general, no. Are there exceptions? Are there circumstances where it may? That is being investigated, and that’s why we recommend a mask if these folks are going out. Also, the potential contribution of semen, vaginal fluids, urine, and feces in the spread.

More to go on transmission as we learn. But, testing. I was talking to someone today. “I’ve been going from confused to frustrated, to confuse to back to frustrated on this front.” Remember, to make the diagnosis, you’ve got to do the test. Initially, it was doing these dry swabs, putting them in sterile urine cups, having a conversation with someone from the DOH, FedExing them to Wadsworth here in New York. Now, this has been updated. It is recommended that two swabs be sent off, put in transport media, and then either kept refrigerated or frozen after collection.

I was always like to say, remember Occam was not a physician, Hickam was. A patient can have as many diagnoses as they please. Now, notice I removed a word that Hickam was more comfortable using than I am. Currently, it’s probably four or five swabs that are being sent off. Sending off one for the herpes, one for the zoster, the shingles, a couple for the monkeypox.

Then because sometimes we’re looking at folliculitis concerns for MRSA, or MERSA, you maybe even sending off an MRSA PCR. Each institution, each clinic is going to have to look into the details of putting the right swabs in the right collection, getting the right codes. We had a bit of annoying case this week where a couple dry swabs were set off on a particular individual. Those swabs were discarded because now we’re only accepting ones that are refrigerated in liquid. Fortunately, that person was able to get another test. Did actually confirm the diagnosis, but that would be little bit of my frustration really there. I do like to say here, remember, a provider without laboratory backup is really just guessing, and we have a poor track record here. We’re still learning why some lesions can be so mild of those co-infected, where other lesions on the same person may really progress and be quite devastating and painful.

What about testing? Currently, as I just mentioned, we’re doing PCR of DNA, not culture. What about those rapid antigen tests? Maybe there’s somebody sitting around with a stack of lick-a-sticks for the orthopox on their desk somewhere, ready to sell them to the masses for a dollar each.

There was an article, and yes, 2013, that date was right, “Evaluation of the Tetracore Orthopox BioThreat Antigen Detection Assay Using Laboratory Grown Orthopoxviruses and Rash Illness Clinical Specimens”, published in the Journal of Virological Methods. Still would need some validation out in the field, but they went ahead and found that the monkeypox viral samples with 10 to the seventh platforming units per milliliter were identified reproducibly by visual and quantitative methods when applied to these biothreat strips.

I’m going to go ahead and just recommend that people keep this on the horizon. This will need to be validated, but it would be, I think, a lot easier, a lot less stigmatizing for people to be able to check rashes in the comfort of their own home than maybe coming to see us for confirmation and secondary testing. Looking forward to those days. I will say we currently have lots of monkeypox testing capacity in terms of PCR. If anything, we just need to start testing more. Tens of thousands of tests are available per day, per week.

Vaccines. I’m very excited about this part. We discussed last week ways to potentially stretch the number of the smallpox/monkeypox vaccine doses that we currently have. I don’t know if people remember the days of the low dead space syringes when we suddenly had 20% more vaccine doses just by using different syringes where you didn’t end up with air and vaccine left in the syringes. Here, we discussed the idea on the last TWiV that there might be a trick to increase the vaccine doses fivefold.

Since this idea was being covered in the popular press, I just wanted to discuss the science behind this. There was an article “Comparison of Lyophilized versus Liquid Formulations and Subcutaneous versus Intradermal Routes of Administration in Healthy Vaccinia-Naïve Subjects,” published in Vaccine July, 2015. The modified vaccinia Ankara is being developed as a safer smallpox vaccine, and is being placed in the U.S. Strategic National Stockpile as a liquid formulation for subcutaneous administration at a dose of 0.5 mls. I’m reading from seven years ago.

This study from seven years ago compares the safety and immunogenicity of the standard formulation dose and route with a more stable lyophilized formulation and with an antigen-sparing intradermal route of administration. This is important right here. I want to point out because we’ve had some little bit of issues so far. This vaccine is not intramuscular. Let’s remember those COVID vaccines from, well, right now. This is where you, that deltoid muscle, that muscle in your shoulder area. The needle would go in. It was actually a fairly long needle. You want to get into that muscle intramuscular.

This vaccine is you grab a bit of fat, grab some skin with fat, you pull it away. You do not want this to go into the muscle. You administrate subcutaneously. What about intradermal? What about like those PPD skin tests? What if you slide that needle, keep it in the skin, raise a little bleb, that peu de l’orange that we talk about? I think that might be French. Here in this study, 524 subjects were randomized to receive a full dose of lyophilized sub-Q, a full dose of liquid sub-Q, or 20% of a full dose intradermal. They did this day 0, day 28, so four weeks apart. Safety and immunogenicity were followed through 180 days, post-second vaccination.

First off, and I want to point this out because we are seeing this, this vaccine is associated with a significant amount of local reactions with moderate to severe measured erythema, so that’s redness, induration, that’s hardness, and some mild injection site skin discoloration lasting just for about six months or so. After a second vaccination day, the geometric mean of peak neutralization titers were 87.8, 49.5, and 59.5. Lyophilized was the 87.8, the liquid sub-Q, that’s the standard, it was 49.5, and the liquid intradermal was 59.5, so certainly not inferior. Respectively, the maximum number of responders based on peak titer in each group was 97.9, 95.3, 94.5, respectively.

At 100 days after the second vaccination, we had contraction down to 11.7, 10.2, 10.4. They comment about the lyophilized as well as the intradermal. I will go onto the immediate. Where did this go? Very quickly I will add for those critical of the FDA. The FDA news release, “Monkeypox Update: FDA Authorizes Emergency Use of JYNNEOS Vaccine to Increase Vaccine Supply”. The U.S. FDA issued an EUA, we’re all familiar with those now, for the JYNNEOS vaccine to allow healthcare providers to use the vaccine by intradermal injection for individual 18 years of age or older, who are determined to be at high risk for monkeypox infection.

This will increase the total number of doses available for use up to fivefold. We discussed on the CDC call today. This is basically when you’re ready to go. This is now the recommended approach. They did also modify the EUA to say the EUA also allows for use of the vaccine in individuals younger than 18 years of age. That’s new, moving vaccine down to folks under 18 but in that group, they’re recommending subcutaneous injection. What study do they reference? The one that we just discussed above.

Now, I will throw in a little story. I enjoyed just having this discussion yesterday with one of my colleagues outside of the hospital about how people were back and forth, “Oh, this is going to be so hard. No one knows how to do intradermal shots.” We were wondering if those people had ever, I don’t know. What he was saying, and I thought this was really interesting. We were discussing the fact that a lot of the current target population have such limited body fat, that it’s actually hard to find that subcutaneous tissue, and occasionally, these individuals are accidentally getting the injection into the muscle. When they do that, they can actually have a pretty significant amount of local reactogenicity.

Actually, I have to say from a sort of boots on the ground, I think intradermal is going to be a lot easier than trying to find sub-Q in some of these individuals that are really keeping that body mass down. The two of us did acknowledge that either of us would have problems if someone needed to give us a subcutaneous injection.

Revaccination after exposure. I just want to sort of combat a little bit of misinformation out here, because I know a lot of people in their 60s and 70s are saying, “Oh, I got a smallpox vaccine when I was a lad. I’m sure I’m fine. I don’t think revaccination after exposure would be required.”

Here is the revaccination after exposure. This is from the CDC. Persons exposed to monkeypox virus who have not received the smallpox vaccine within the last three years should consider getting vaccinated.

Clinical course/treatment. Observation in some cases, TPOXX, or I want to point this out, if eye involvement, we might be using the Viroptic eyed drops, which is a trifluridine. A little credit to Jason Zucker on making sure I have that on the radar for people listening. A few other options are out there.

I do want to point out and I think this is really important. We do not know how well TPOXX works. We discussed confirmation bias. It seems to be working, but then again, when most people are getting better, who knows if we just stepped in at the right time. Let’s go through, who needs treatment, who is likely to do just fine. Again, we have good interim clinical guidance for the treatment of monkeypox from the CDC. We’ll leave a link in the show notes, but again, people with severe disease, people who are at high risk of severe disease. Also, when there is disease in certain places. If it’s in the eyes, if it’s in the mouth, or other anatomical areas where monkeypox might constitute a special hazard.

Go through, if you’ve got a patient, look through the list, try to decide. The vast majority, it seems so far over 90% are going to do just fine without any treatment. Certain people are not going to do just fine. Particularly in the eyes, if you look at some of the literature from the cases in Africa, there can be pretty significant scarring, so we want to keep in mind who should access treatment.

COVID still here and still a bunch to say. Children, COVID, and other vulnerable populations, remember to get those vaccinations in time for the start of school. Time is running short. It’s almost time for school to start. I’m always amazed at people that think getting COVID is a safer option than getting a vaccine.

El MMWR: “Post-COVID-19 Symptoms and Conditions among Children and Adolescents – United States, March 1, 2020-January 31, 2022.” Here, the authors used a large medical claims database and assessed nine potential post-COVID signs and symptoms, and 15 potential post-COVID conditions among 781,419 U.S. children and adolescents aged 0 to 17 with lab-confirmed COVID-19, compared with 2,344,257 U.S. children and adolescents without COVID-19. The highest hazard ratios were recorded for acute pulmonary embolism. The adjusted hazard ratio was greater than 2, myocarditis and cardiomyopathy, about 2, venous thromboembolic events, 1.9, acute and unspecified renal failure, 1.3, and type 1 diabetes. We’re seeing increased hazard ratios for all these issues in children that end up with COVID.

VR: This is post-COVID, right? You’ve recovered and now these are things that happen afterwards. Correct?

DG: Exactly. This is post-acute sequelae of COVID in children. Not great.

Transmission testing, use those tests intelligently. Remember, there’s more out there than just COVID. I’m hoping, Vincent, I could spend a little time on this research letter, a little time because, wow, with monkeypox, we’re pushing on the COVID. The research letter “Duration of Symptoms and Association with Positive Home Rapid Antigen Tests after Infection with SARS-Cov-2,” published in JAMA Network Open. Let me start with some background, or in this case, a modification of what these authors lay out in their introduction. “Current U.S. CDC COVID-19 guidance for non-immunocompromised individuals allows for ending isolation after five days if the individual is asymptomatic or afebrile with improving symptoms, followed by five days of precautions.”

They then go on to comment that, “Despite this guidance, culturable virus, currently the best proxy for transmissibility, is reported after day five.” We’ll get back to this assertion, because it’s a critical suggestion, and really important to know if it is actually a proxy, particularly if it’s only done as a binary without any quantification there. It’s been proposed that rapid antigen tests might assist in determining the isolation periods. More than just suggested, we have some pretty emotional people out there adamant that they already know that this is true. The authors go on to say that, “However, while rapid antigen tests correlate with culture positivity during early infection, there are minimum data after day 5 where persistent RAT positivity has been reported.”

Can this be true? That these people are really so confident in the absence of data? Here, the authors report in this investigation, they will compare the rates of rapid antigen test positivity, COVID-19 symptoms, and positive viral culture starting day six after COVID-19 diagnosis. Between January 5th and February 11th, 2022, these investigators enrolled 40 individuals. Of these, 36 had received a primary vaccine series and first booster. In this period, 96% to 99% of the sequenced isolates were Omicron BA.1.

Now, in this cohort of newly diagnosed with COVID-19 folks, 75% continue to have a positive rapid antigen tests, while only 35% had cultural virus on day six. Everyone with a negative day-six rapid antigen test had a negative viral culture. However, only 50% of those with a positive RAT result had cultural virus.

Vincent, any thoughts on this?

VR: As you said, these are binary infectivity, right? They put the sample on cells, and there’s either yes or no. They don’t quantify it. I would think that even these 35% who had culturable virus on day six may not have enough to transmit. Maybe irrelevant, right? It could be –

DG: Yes, I think that’s one of the challenges. I feel like we’re back in the days of antigen tests compared to PCR positivity, and you need to know the quantity. We needed to know what the CT value is. Did they see one or two plaques? Were there really a high plaque-forming unit per concentration? It’s interesting to me that so many people know the answer to this when, as you and I keep discussing, there still is a science to be had.

VR: I think this needs to be quantified to have any impact. I think if you did quantify on these days, you would find very, very low infectivity, probably not compatible with transmission.

DG: I think this is really critical for us to know what really is going on as far as a quantified virus culture and transmission. Because just having just a few viruses that you might build a culture, we do not know if that’s enough to affect someone else. I think that’s critical.

Active vaccination. We’re still waiting on the updated boosters. We hear maybe next month. We’ll see.

Passive vaccination. Remember, Evusheld. Let’s not turn this into Evushelf. This may actually become commercially available, which may improve our access.

The early viral upper respiratory non-hypoxic phase. This is when the person tests positive that first week. Remember, Paxlovid. I’m sure you’ve heard that name a lot in various contexts. We have some links, some information tools for prescribers. The pre-print was sent my way, “Viral Kinetics of Severe Acute Respiratory Syndrome, Coronavirus 2 (SARS-CoV-2) Omicron Infection in mRNA-Vaccinated Individuals Treated and Not Treated with Paxlovid.” Keep sending me those emails. A very small sample of 36 mRNA-vaccinated individuals, 11 of whom were treated with Paxlovid, 25 were not treated. Not exactly matched groups with treated and untreated. The median age was 44 in the treated, 16 in the untreated. Participants in the treated group were more likely to have comorbidities, smokers, being vapers, being obese.

The data is interesting, so rather than reading their conclusion, which I’m not sure I agree with, I recommend one look at the data. In Figure 1 that I put in our show notes here, so Vincent can see it at the same time, they actually saw what they refer to as virological rebound in one of the young, healthy individuals who was not treated, in three of the patients who were older with comorbidities who were treated. It did look like in this small group, that those who were treated, even though they were older and had more comorbidities, that they felt better about twice as quickly. Unfortunately, a very small sample. The groups are not really matched, so really plums compared to prunes, and no symptoms, but a start in the right direction.

Remember, remdesivir is number two, poorly operationalized. Number three and four, bebtelovimab and molnupiravir. I need to keep reminding people, let’s avoid doing harmful things. I’m a little shocked at how much of this is still going on. I’ll share a little story that recently an individual in a Southern state, that shall go nameless, older individual had risk features over the age of 75. Went and saw their physician. The comment was, “I’m not that impressed with that Paxlovid, so instead, I’m going to recommend azithromycin-quinine and this proprietary box of vitamins that we sell right here in our clinic to you. We accept all forms of payment, including credit cards.”

Unfortunately, that patient reached out to me, and I’m sure the physicians are not happy because I recommended not taking that vitamin pack with high-dose zinc and high-dose vitamin C, stopping the quinine, stopping the Z-Pak, and actually, starting the Paxlovid, and making the appropriate adjustments. I’m just really shocked. I’m not sure where people are getting their information. I’m sure that the physicians thought the vitamin pack that they were selling and making money on was the right thing to do. I hope that’s what it was.

Number two. This is that second phase of the clinical spectrum, that early inflammatory lower respiratory hypoxic phase. We still unfortunately have some individuals that during that second week, as we’ve heard about, they can progress. They could have symptoms. They can be worse than that first week. This is when they might get hypoxemic and end up in the hospital. This is when steroids are considered, by time, the right patient, anticoagulation individualized for a patient’s risk, pulmonary support, maybe remdesivir for early enough immune modulation we’ve gotten a little bit into, and avoid those unnecessary antibiotics and unproven therapies.

I have to say this last weekend at some hospitals that I normally do not go to on a regular basis but do cover, I was just shocked at the amount of high-dose vitamin C and doxycycline and other high-dose zinc, and other actually studied and unproven therapies that were still being used. Let’s get up to date on the treatment here.

The late phase, an interesting pre-print profiling post-COVID syndrome among different variants of SARS-CoV-2. This was posted as a pre-print, so a pre-print here. These are the results of a prospective longitudinal cohort study. They analyzed data from 336,652 subjects with regular health reports through the COVID Symptoms Study smartphone application. These subjects had reported feeling physically normal for at least 30 days before testing positive for SARS-CoV-2.

9,323 individuals subsequently developed Long COVID defined as symptoms lasting longer than 28 days. We’ve talked about that. 1,459 had post-COVID syndrome defined as more than 12 weeks of symptoms, so a little bit stricter there. Actually, I think it’s important, 9,000 versus 1,400. A clustering analysis of the time-series data was performed to identify distinct symptom profiles, and I thought it was interesting.

They suggested three main clusters or groups. A cardiopulmonary group with exertional intolerance, dyspnea, fatigue, autonomic dysfunction, tachycardia or palpitations, chest pain. Inflammatory group, which they suggested comprised multi-organ sequelae, gastrointestinal symptoms, dermatological symptoms, and fever, and a neurological group with brain fog, dizziness, memory cognition issues, mood disorders, paresthesias, fibromyalgia, chronic pain, or myalgia. There’s really a ton of data here interesting to mull through.

Also for those of us taking care of COVID patients, starting to see that they do seem to cluster in these different groups, and then by focusing on that group of symptoms, sometimes we think we’re being helpful. Again, hopefully, we’ll get some science, so we’re not just believing that we’re doing the right thing. What do we call that, confirmation bias? Yes.

VR: Yes.

DG: The article, this I like actually, “Neuropsychiatric Sequelae of Long COVID-19: Pilot Results from the COVID-19 Neurological and Molecular Prospective Cohort Study in Georgia, USA,” published in Brain, Behavior, and Immunity – Health. I think this is more of an available online ahead of printing thing. In this cohort, fatigue was the most reported symptom, I’m surprised, 68.5, followed by headaches, 66.5.

I see a lot of folks after COVID with new onset migraine-type headaches, or significant worsening from baseline. I remember talking to someone in the Long COVID field like, “Oh, we never see headaches.” We see a lot of headaches, and it was nice to just see in this series that that was a dominant thing. 30% of participants demonstrated issues with smell and taste, and there were self-reported neurological dysfunction as well as a few other things going on here.

As I always like to finish on, no one is safe until everyone is safe. There’s still a lot of parts of the world with poor access to vaccines, poor access to vaccine education, poor access to therapeutics. I keep repeating, and this may seem odd, but the most selfish thing we can do is care about the world because we’re all part of this global community. These borders are porous. You can’t just stay here and feel like you’re safe. You really have to reach out to these other folks, because not only does it help them, not only is there a moral imperative, but it’s actually selfish. It will make our world safer all around. I want everyone to pause the recording right here after that pedantry. Go to parasiteswithoutborders.com. Click on the Donate button. Even every small amount helps.

Right now, we are having our Floating Doctors fundraiser. I’ve been emailing a little bit with Ben LaBrot, who is now doing some other stuff as well as the Floating Doctors. During the months of August, September, and October, donations made to Parasites Without Borders will be matched and doubled by PWB up to a potential donation of $40,000.

VR: Daniel, I have a question for you. I’ll bring you back to Paxlovid.

DG: Yes.

VR: This is now a theme for the last two weeks. People are complaining that the phase 3 trials of Paxlovid were done in unvaccinated people. How can you give it to vaccinated people who get sick? What do you think about that?

DG: I think it’s a fair point. It’s interesting. I remember, and actually, I don’t know if people remember, Pfizer initially requested an EUA to use it in the unvaccinated. The discussion was that that does not make a lot of sense, that’s not going to go over well. This is something that 90% reduction in progression. If you have an individual who’s vaccinated, but still at high risk, you still want that 90% reduction.

As we’ve discussed several times, there now are post-marketing studies, where we have seen that in the vaccinated population, we’re getting those significant reductions in progression. We now have data. We don’t just have to rely on a few hundred people in an early trial that got the FDA EUA. Now we have data, millions of individuals treated. We’re seeing the benefit in the real world.

VR: Where can we find those data?

DG: We’ve thrown them in a few of our previous ones. What I will promise to our listeners is next time we will do an update where we will talk about Paxlovid, what’s the data in the vaccinated population.

VR: Very good. Thank you. Time for your questions for Daniel. You can send them to daniel@microbe.tv. Karen writes, “Is there any reason someone with eczema should not get the intradermal monkeypox vaccine?”

DG: I wouldn’t think so. You don’t want to inject it into an area where there is active eczema but no, I don’t see a problem there.

VR: Beth writes, “I’m a 57-year-old, and I was never immunized for polio. Is this a situation where I should run, don’t walk to a doctor? Is there a polio vaccine suitable for adults who are first immunizing?”

DG: Yes, all the way around. I’m not sure what happened there, but go ahead and yes, we do vaccinate adults. I’ll bring you through the whole series and get you up to speed, and you really need to do that. I think this is one of those education issues. There is polio out there. Polio is not gone. We haven’t seen a lot of the disease polio because of our vaccination efforts. As we just saw, we can get that disease, and so yes, go out there and get yourself vaccinated.

VR: In the U.S., you will get inactivated polio vaccine or IPV?

DG: Yes. Since 2000, we switched over.

VR: We switched in 2000, now we just give IPV, no OPV. Other countries continue to give OPV but not the U.S.

Ned writes, “I have multiple myeloma essentially in remission but on a maintenance chemo drug. I’ve had four vaccines, the last one in April. Three months after the fourth vaccine, my antibody levels were around 15,500 up from 850 when last tested eight months after my third vaccine. I’m confused about my next step to protect myself. Should I take Evusheld as you recommend for the immunocompromised, even though I know I make antibodies? My oncologist thinks it may not be necessary. Or do you recommend getting a fifth vaccine this fall that includes Omicron BA.5 ? Do immune compromised individuals need more updated vaccines? Or if we already have four, will the original version be sufficient? What’s the latest thinking on when to get boosted again if you already had four shots?”

DG: These are great, and I feel like I’m repeating stuff, but that’s fine. Number one, you are getting a false sense, I’m going to say, of reassurance from those antibody levels. Those antibody numbers, they’re high, but we don’t know what they mean. We honestly don’t. You’re protected against, I’m not sure. Are you protected against the ancestral? Are you protected against BA.5? We do not know. There is no commercially validated test. The FDA has been very clear. Stop doing that. Stop looking at those tests and thinking you know what they mean.

We’re going to forget about the test. We’re going to make believe it never happened. That’s the way you’re supposed to approach it. That is the clear guidance, and the FDA has said this several times. Your physician maybe needs to get up to speed, and I’m sorry if that seems pedantic, but this question comes up every week.

I know at certain centers, they have protocols, where they have actually clearly just in their protocol, defy the FDA’s guidance, but we do not know what those antibodies mean. After that fourth shot, if you are moderately to severely immunocompromised, which is what you are describing to me in this context, then the recommendation is go ahead. Get that Evusheld, it’s about a 95% reduction, and even testing positive, and then in the fall, you get that fifth shot for the BA.5 update.

VR: Finally, Jennifer writes, “As I continue to follow your COVID guidance and try to get my teenager to do the same mostly with success, I have a question as the school year approaches and said teen looks forward to his senior year on the wrestling team. It seems to me that if the monkeypox situation continues on its current trajectory, wrestling may not be a good idea this year. Skin diseases are already a problem for the sport. I’m worried school officials will have blinders on and think, oh, that’s just a gay thing as opposed to a contagious disease. Thank you for repeating that, and just let the kids sweat all over each other skin to skin. Do you have any thoughts?”

DG: I do. I have to say this is a little bit tough challenge right now, as we’re trying to come to grips with the fact that it does appear as though monkeypox is in children. We have confirmed cases. We actually have a case that we’re dealing with right now where the individual has a PCR positive for the monkeypox. It’s a 9-year-old here on Long Island. They have these pustules and vesicles. Clinically, it looks like monkeypox. The DNA PCR is positive for monkeypox. The DOH wants a second result because we want to make sure and confirm this, but if it’s in children, if it’s in kids, and those kids are wrestling, they’re going to spread the monkeypox. This would be a population that hopefully we get vaccinated, and then they could do the things that kids love to do, which is get out there, and wrestle, and play sports, and do all the things that they want to do.

VR: That’s TWiV clinical update #127, with Dr. Daniel Griffin. Thank you, Daniel.

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

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