Podcast Transcript TWiV 928 Clinical Update #128

This Week in Virology
TWiV 928 Clinical Update #128

Host: Vincent Racaniello
Guest: Daniel Griffin
Aired 20 August 2022

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

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From MicrobeTV, this is TWiV, This Week in Virology, Episode 928, recorded on August 18, 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. But Vincent, I'm not in New York. I'm actually in Glasgow.

VR: I'm such a creature of habit that I always say New York, but yes, from Glasgow, Daniel Griffin. Nice to see you, Daniel.

DG: No, I had to come down here because apparently, the internet in Edinburgh is not as quick as I would like. I'll start off with a very Scottish quotation from David Hume from his, An Enquiry Concerning Human Understanding. "In our reasonings concerning matter of fact, there are all imaginable degrees of assurance from the highest certainty to the lowest species of moral evidence. A wise man, therefore, proportions his belief to the evidence."

VR: I think we're holding humanity to a too high standard, Daniel. It's just not working.

DG: That might be true, but this is my hope is that I think we actually do the opposite, like the less certain, the more vehement, the more emotion we bring to a topic, and then when it's finally very clear cut we're like, "All right, whatever. That's the way it is." It really should be the opposite when we don't know we should be humble and just say, "You know what? We're not sure, we're learning, there's questions out there. This is what we know so far." We love that quick simple solution to our problems.

All right, but let us start with the MMWR, “Public Health Response to a Case of Paralytic Poliomyelitis in an Unvaccinated Person, and Detection of Poliovirus in Wastewater in New York, June-August 2022.”

Vincent, we were going to do polio, we're going to do monkeypox, we're going to do a bit of COVID. We got a lot going here. I will start with a little background here. This report from the MMWR or in the MMWR describes the recent case of paralytic polio reported to the CDC. That is the disease polio is the disease and the paralytic manifestation. The last U.S. case of polio caused by wild poliovirus occurred in 1979, and the WHO region of America was declared polio-free in 1994. This report, I encouraged people to read it, is very short, but it describes the second identification of community transmission of poliovirus in the United States since 1979.

The previous instance in 2005 was, they say, a vaccine-derived poliovirus type 1. In June 2022, a young adult with a five-day history of low-grade fever, neck stiffness, back and abdominal pain, constipation, and five days of bilateral lower extremity weakness visited an emergency department and was subsequently hospitalized with suspected acute flaccid myelitis, AFM. Some of our listeners may know that this can be caused by a number of other viral illnesses. In this case, this patient was unvaccinated against polio, and as part of the national AFM surveillance, the suspected case was reported. Sequencing of a stool specimen identified poliovirus type 2.

I'm going to say this is where it gets interesting if it wasn't interesting enough, based on the typical incubation period for paralytic polio, the presumed period of exposure occurred seven to 21 days before the onset of paralysis. Epidemiological investigation revealed that the patient attended a large gathering just eight days before symptom onset, had not traveled internationally during the presumed exposure period. This is something I want to point out, and I think this is a fact that many - there are many experts all of a sudden but these experts seem to miss is that the rate of paralysis for type 2 is different than for type 1 polio. Type 1 it's about 1 in 200, type 2 is different, approximately, I'm going to round up to 1 in 2,000 for poliovirus type 2 infections among unvaccinated persons resulting in paralysis. For every case of paralysis, we might estimate about 2,000 cases in unvaccinated people perhaps more in vaccinated people. Vincent, I thought I'd pull you in on these calculations.

VR: The type 2 is quite different from type 1 and 3, and the problem here is that in the U.S., we use inactivated polio vaccine and our intestines are not resistant to infection by any circulating poliovirus. If you are vaccinated, you're not going to contract polio, but the virus can reproduce in you, and that's why it's in the wastewater in this particular area. It's most likely in wastewater in many other parts of the U.S., and so you need to be vaccinated. These are mostly type 2 vaccine-derived polioviruses. They transmit very well after being excreted from people who get the type 2 OPV, which again, we don't use in this country and this community has very low polio vaccination rates for unfathomable reasons, and as a consequence, we have a case of polio. I would not be surprised if we saw more cases in the coming weeks.

DG: Yes, and I think we complained about COVID 19 and SARS CoV-2, and why two different things, but I think here you see the confusion, is it poliovirus? Is it polio infection? Is it polio disease?

VR: Yes.

DG: My wife even made this comment like is paralysis binary. If you get paralysis, are you on an iron lung? Can you have just some residual weakness? Can you have a post-polio syndrome that doesn't--

VR: Oh, yes, no, no, no. You can have a whole range of paralytic diseases from mild limb weakness to respiratory failure requiring an iron lung. It's quite a long range, and people with mild paralysis can be rehabilitated and recover limb function, but you don't know what's going to happen. You might as well get vaccinated, that's this very clear solution in this case.

DG: Yes. I'm going to just echo that. The answer is simple. Get vaccinated, get your kids vaccinated, encourage your friends and enemies to get vaccinated, and for clinicians, never miss an opportunity to vaccinate. As we also may have heard, not only has polio been detected in Rockland, in Orange County, but now in New York City wastewater. I'm going to give you a little bit more credit, but a number of us have been suggesting that if wastewater monitoring occurred if the public was aware that polio was here and circulating, that would help with our vaccine efforts.

VR: Yes. I think a lot of people have this idea that polio is gone. Poliovirus is not gone. In the U.S. up until now, we didn't have paralytic disease, so the disease polio was gone, but the virus will continue to circulate because in most parts of the world they're using OPV, oral polio vaccine, which is shed, and this is a real problem for eradication Daniel. I don't know how we're going to eradicate. We've replaced wild polioviruses, essentially with vaccine-derived polioviruses, and now we're stuck because we keep using the vaccine, and so the virus continues to circulate, and if you don't stay vaccinated you might get polio. I'm worried about the eradication effort now, Daniel.

DG: Yes. Well, hopefully in future deep dives, maybe we'll discuss about some new approaches to vaccination that might help us here.

VR: Right, there are some, yes.

DG: All right, stay tuned. Monkeypox update, and as I like to say, right up front monkeypox is not a gay disease or an African disease, monkeypox is an infectious disease, and I've tried to point out from the beginning that though this initially was introduced into the men who have sex with men population, it's by no way a disease that will stay limited to that. We've already seen that beyond, and so as we know, well over 2,000 cases, just right here in New York City, over 12,000 cases in the U.S., the numbers keep climbing. We did actually, we heard about new virus variants, new names, we're getting a little bit of some movement here.

We heard from the WHO that consensus was reached to now refer to the former Congo basin, the Central African clade as clade I, and the former West African clade as clade II. Additionally, it was agreed that the clade II consists of two sub-clades, and then they go on. I think we're all used to naming conventions by now, the proper naming structure will be represented by a Roman numeral for the clade and a lowercase alphanumeric character for the subclades. I have to say, it's going to take me a little while actually. I think maybe we should start thinking about renaming before we're in the midst of a problem.

Transmission, let's move on to transmission. I have a couple of interesting things here. One, was the correspondence, “Evidence of Human to Dog Transmission of Monkeypox,” published in The Lancet. Now, people know for me, this hits close to home. I kept seeing these tweets and these pictures of our current president hanging out with his dog Commander while he had the COVID, think about your pets. Here we hear of two men from Paris, France, who owned an Italian greyhound, and these two men were diagnosed with the monkeypox. One man referred to as Patient 1 Latino aged 44, living with HIV with undetectable viral loads on antiretrovirals.

The second man, Patient 2, white, non-Hispanic, age, 27 years, HIV negative. In Patient 1, the virus was detected in the skin and oral pharynx samples. Whereas, in Patient 2, viruses detected in anal and oral pharyngeal samples. Twelve days after symptom onsets for the first individual, symptom onset was very similar for these two men, their male Italian greyhound, aged 4 years, and with no previous medical disorders, presented with mucocutaneous lesions, including abdominal pustules and a thin anal ulceration, the dog tested positive for monkeypox virus by PCR.

The monkeypox virus DNA sequences from the dog and Patient 1 were compared by next-generation sequencing and the virus that infected Patient 1, and the virus that infected the dog showed 100% sequence homology. The men reported co-sleeping with their dog. They had been careful to prevent their dog from contact with other pets or humans from the onset of their own symptoms so we think this is going to stop here. A little bit of a warning that the monkeypox can go from humans to their canine companions.

We also have the disturbing MMWR early release, “Human Monkeypox without Viral Prodrome or Sexual Exposure, California, USA, 2022.” Now this made me think of Rich Condit on the last TWIV suggesting if we only change behavior, it would all be better. I'm not sure how optimistic I am after this and some very similar cases that I have seen so far myself, but this is another case where there was no obvious exposure, no obvious behavior that we had previously thought was associated. This is a man in his 20s. He sought care at an emergency department in Stanford, California USA on day seven of an asynchronous, I think that's important, diffuse vesicular rash.

These were not all in the same stages of development, but in different stages of development. After he had traveled to the United Kingdom, I hope he wasn't up here in Scotland. The first lesion appeared about 14 days after he attended a large, crowded, outdoor event at which he had close contact with others, included, close dancing for a few hours. He said that many attendees were in sleeveless tops and shorts. He wore pants and short-sleeve top. He did not notice any skin lesions on anyone present, not sure how well you can see that at such a venue, but the patient was ultimately diagnosed with the monkeypox. This patient did not report recent sexual contact, did not have evidence of genital lesions or inguinal swelling of the lymph nodes.

He did not have a violent viral prodrome. His primary risk factor was closed non-sexual contact with numerous unknown persons at a crowded outdoor event. I think this is still in line with what we talk about, but it really makes it clear. This does not require sexual transmission. This does not require that you're at any particular target group. I'll leave that there as we move on to testing. Remember, keep getting emails about this, remember to make the diagnosis, you have to do the test and send off those swabs in transport media and keep them refrigerated or frozen after collection. As I like to say, remember, Occam was not a physician. John Hickam was. A patient can have as many diagnoses as they please. Cotton swab, noncotton swab, couple of those for the monkeypox DNA, maybe a couple of swabs, if you're looking for the herpes and the varicella zoster, and you may even think about looking for MRSA.

Approach this as a clinician. As far as vaccines, we got them and I'm going to encourage people to listen to TWIV 927, Merchlinsky vs Monkeypox. I actually thought that was a great episode, so we have vaccines, they’re smallpox vaccines. We have a certain confidence about their ability to help us with the smallpox. We're hearing really encouraging things about different ways of administering them and also hopefully about increasing supplies as we go forward.

Clinical course and treatment. I like to say observation in most cases but in some cases, we may be using the TPOXX or the Viroptic eye drops.

The prospective “Tecovirimat and the Treatment of Monkeypox - Past, Present, Future Considerations,” was published in The New England Journal of Medicine. I actually thought that this was a nice overview. The authors start by explaining that Tecovirimat is an antiviral drug that was approved for the treatment of smallpox under a regulation known as the Animal Rule. This pathway allows for approval of drugs for serious or life-threatening conditions when it is not ethical to conduct efficacy studies in humans and not feasible to conduct field studies to study the effectiveness of a drug or biological product.

Now, tecovirimat's efficacy for the treatment of smallpox was established and the drug was approved on the basis of studies in animal models using related orthopoxviruses. Specifically nonhuman primates infected with monkeypox virus and rabbits infected with rabbitpox virus. Oh my gosh. In these studies, survival rates were markedly higher among animals that received tecovirimat than among those that received placebo. Safety in humans was evaluated by looking for adverse reactions in healthy volunteers. We have the safety data there. What they did is they actually made the recommendations about the dose based upon plasma concentrations in healthy volunteers ,comparing these to what was required to protect the animals.

Then the duration also extrapolated from here, but just to let everyone know there is a plan to go ahead and do a trial. This trial will be conducted by The AIDS Clinical Trials Group. This is going to actually assess the safety and efficacy of tecovirimat for the treatment of monkeypox disease. A trial is coming soon to an academic facility near you. Actually, Columbia University will be firing up pretty soon. I'll keep our listeners posted and actually maybe share some links. Hopefully, get people to help us move science forward.

All right. The brief communication, “Retrospective Detection of Asymptomatic Monkeypox Virus Infections among Male Sexual Health Clinic Attendees in Belgium,” was published in Nature Medicine. Now, here the authors point out that we do not know, that's OK in science. There are things we do not know but want to learn, but we do not know whether asymptomatic or otherwise undiagnosed infections are fueling this current spread of the monkeypox.

I know a lot of people are saying, "Oh, you can't spread this unless you have active lesions." We do not know that. That's what we think. Now they set out to assess whether undiagnosed infections occurred among men attending a Belgian sexual health clinic in May 2022. They retrospectively screened over 200 samples that have been collected for gonorrhea and chlamydia testing using a monkeypox virus, PCR assay, and they identified the monkeypox DNA from four of the men. At the time of sampling one, man did have a painful rash. Perhaps that was the monkeypox, but three men reported no symptoms.

They followed these folks out and upon clinical exam, 21 to 37 days later, these three men were free of clinical signs and they reported not having experienced any symptoms. Now serology did confirm the monkeypox virus exposure in all three men and monkeypox virus was cultured from two cases. I will agree these findings show that certain cases of monkeypox remain undiagnosed. I do not know if these individuals are able to transmit to others, these asymptomatic. I think we've really hammered home just because you could culture that virus does not mean there's enough virus to transmit to someone else. It's important as we move forward, but we should move forward honestly. I noticed Vincent was nodding there. I think he approves.

VR: I think that's perfect. Even though in this, now we do get infectious virus here because this can be cultured under BSL2 conditions. You don't need a special lab to do cell culture isolation of monkeypox. Even though we find infectious virus, we don't know, as you say, if it's enough to transmit, that's a very important finding and I'm sure they'll do the experiments to find out.

DG: Excellent. Well, it seems like we're starting in the right direction there and back to COVID. Now the CDC updated, it's what to do if you were exposed to COVID 19 and its isolation and precautions for people with COVID 19. And they're getting beat up. That's what happens. The update recommends that after being exposed to COVID-19, one should take precautions: wear a high-quality mask, respirator anytime you're around others, inside your home or indoors in public. Do not go places where you're unable to wear a mask, including travel in public transportation settings. Take extra precautions if they'll be around people who are likely to get very sick and watch for symptoms.

If you get symptoms, you go ahead and test. If you don't get symptoms, you test on day five. Quarantine for the unvaccinated is gone. It's the same level playing field for everyone. Some people are not happy about that. Isolation for the infected. If you test positive for COVID-19, stay home for at least five days. Isolate from others in your home. They actually say something we've been saying for quite a while. You are likely most infectious during those first five days. After you end isolation, when you are feeling better, wear your mask through day 10. Take the precaution remains in effect.

Then we get a little more on this test out after the day five, after the five-day isolations. Here, they say, "If you have access to antigen tests, you should consider using them with two sequential negative tests, 48 hours apart." Think about that. Day 6, day 8, you may remove your mask sooner than day 10. I'm almost at day 10. If your antigen tests are positive, you may still be infectious. I like the word, “may”. You should continue wearing a mask and wait at least 48 hours before taking another test. Continue taking antigen tests at least 48 hours apart until you have two sequential negative results. This may mean that you need to continue wearing a mask and testing beyond day 10. Now, after you have ended isolation, if your COVID-19 symptoms recur or worsen, they recommend restarting your isolation at day zero.

VR: Daniel, I want to go back to a question I asked you weeks ago. How long are we going to do this? This virus is not going away, right? It's not disappearing. It's always going to circulate. Are we going to always hold to these kinds of rules? We don't know the answer to that, but I bring it up to question why we're doing it because if there's a good reason to do it, then that will stay in place forever essentially.

DG: That's one of those things. If nothing is going to change, why would we do something different a year from now than we're doing right now? I'm not sure something's going to change. It is true, we're there. COVID's here. Interesting enough, we are at a point right now where 450 people on average are still dying a day. Those are mostly the unvaccinated. If they are older individuals, they have not been offered Evusheld, they haven't had extra early treatment. We really are getting to the point. Here in Scotland, I was talking to Christina saying it really pretty much appears like COVID is over. In many ways, I think we need just to look at, is this sustainable? Do we want this to be sustainable? I know the CDC is being beaten up, but I'm not sure they should be beaten up. There's a certain reality when you've been offered all the tools. At some point, you've got to decide what you're going to do going forward.

I think we lost all our listeners right then, Vincent. Anyway, children, COVID, and vulnerable populations. As I've been saying for a while, children are at risk for COVID. We still have a lot to learn about COVID and kids. Remember, there are certain children that are at higher risk, where we may not just want to cross our fingers and see how they do. There are active studies. We're going to be talking a bunch about Paxlovid today. Active studies on Paxlovid in the pediatric population. This is one I'm going to promote here, Columbia, the kidsCOVIDstudy.org. They're looking for children with COVID-19 symptom onset within five days of study enrollment, who have at least one medical condition that would put them at high risk. That could be obesity, kidney disease, sickle cell, chronic lung, cardiovascular, et cetera. We still continue the need to do the research. For some of the kids, yes, things may change as we go forward.

Pre-exposure transmission testing. Use tests intelligently, and remember, there's more out there than just COVID. Remember masks and ventilation, particularly as we're headed here into the reopening of schools. They actually just opened Wednesday here in Scotland. The article, “Risk of SARS-CoV-2 Acquisition in Healthcare Workers According to Cumulative Patient Exposure and Preferred Mask Type”. A little shock here. You're going to find out that masks actually work. In this study of 2,919 healthcare workers, they reported that SARS-CoV-2 positivity in healthcare workers was associated with cumulative COVID-19 patient exposure. The more you're exposed, the more likely you are. If you go ahead and wear one of these respirators, they saw a reduction of about 40%, even when you adjusted for all the other issues.

Interesting, right? You're comparing this to wearing surgical masks. Also, I think what makes sense is the more exposure, the more you're at risk. This is as our schools open again. We've had quite a bit of time to improve the filtration, improve the air quality. That's not just about COVID, it's going to help us with a lot of pathogens. “Effectiveness of HEPA Filters at Removing Infectious SARS-Cov-2 from the Air,” was published in mSphere, an ASM journal. I'm not that familiar with mSphere, but here, the authors wanted to evaluate the removal effect of HEPA filtration on airborne SARS-CoV-2. They chose to disseminate infectious SARS-CoV-2 aerosols in a test chamber in a Biosafety Level 3 facility, and then they filtered the air with a HEPA filtered air cleaner in the chamber. They found that the air cleaner with the HEPA filter continuously removed the infectious SARS-CoV-2 from the air in a running time-dependent manner. The virus capture ratios were 85, 96, and 99.97 at 1, 2, and 7.1 ventilation volumes. Those are chamber volumes, actually. I spent a little time trying to understand these units. Actually, it looks you can filter the air with the HEPA filters.

Active vaccination. Updated boosters for the fall, details to follow. New this week, “Novavax Seeks U.S. Authorization for COVID Vaccine Booster.” This makes a lot of sense, and we talked about the science on this. There's a number of folks out there who maybe got one or two of those mRNA shots. They're a little bit hesitant. Maybe they got a J&J, dare I mention them on this show, and they're looking at moving forward with another shot. Here's the potential for Novavax to be that next shot that they get. Passive vaccination. I keep touting the Evusheld. Let's keep this “Evusheld” and not turn this into “Evushelf.” Now, I'm going to move into what I promised, the early viral, upper respiratory non-hypoxic phase. This is that first week you've been diagnosed. We say number one is Paxlovid, but what about Paxlovid if you've been vaccinated? Does that work?

Let me just mention a few of the bits of information we have. I will start with the, “Pfizer Reports Additional Data on Paxlovid Supporting Upcoming New Drug Application Submission to U.S. FDA.” Here, we get the report of a subgroup analysis from Pfizer of a non-significant 57% reduction, see, non-significant 57% reduction in hospitalizations and death observed in Paxlovid-treated vaccinated patients, with at least one risk factor for severe COVID-19. Not particularly overwhelming start. Now, we did discuss the MMWR, “Hospitalization and Emergency Department Encounters for COVID-19 after Paxlovid Treatment, California, December, 2021-May, 2022.” Now, this was that study, where electronic health record data from Kaiser Permanente, Southern California, was used to describe hospital admissions and emergency department encounters related to SARS-CoV-2 infections during the five to 15 days after pharmacy dispensation of a five-day course of Paxlovid.

Among the persons who received Paxlovid during December 31, 2021, through May 26, 2022, only 8% were unvaccinated. This is a real-world experience with vaccinated individuals getting Paxlovid. They reported that less than 1% of all patients who received Paxlovid during the study period ended up with hospitalizations or ED encounters for COVID-19-related illnesses. A little bit tough how much of that was due to Paxlovid. We also have the article, “Effectiveness of Paxlovid in Reducing Severe COVID-19 and Mortality in High-Risk Patients,” published in CID. This, I like the best. Among those given Paxlovid and who were adequately vaccinated in this study, they found a significant reduction in the primary outcome of decrease in the rate of severe COVID-19 or mortality hazard ratio of 0.62. About a 38% reduction. This was also during the time of Omicron predominance, so bringing Paxlovid and Omicron together.

VR: Let me ask you, Daniel, is the difficulty in showing prevention of severe disease or death with Paxlovid due to the fact that the vaccine is already preventing a good amount of that?

DG: I think that's the challenge. You're probably going to need a pretty big number or you're just going to need to target that proper high-risk group because we talk about a certain high-risk group, people over the age of 75, people with comorbidities. Even if vaccinated, we know we're still seeing a chunk of those people end up in hospital and die. You would need an adequate number. You also would need a high enough risk group to still see it, because, for a lot of us, I'm going to put myself in that category, fingers crossed, being vaccinated we're already in really good shape.

All right, after Paxlovid, we have remdesivir. We have monoclonals, now just bebtelovimab and molnupiravir. Let's not do those harmful things. I think we know what some of those are.

Finally, just off embargo, the article, “Randomized Trial of Metformin, Ivermectin, and Fluvoxamine for COVID-19,” finally published in The New England Journal of Medicine. We'll have to put in the link because I put all this in prior to the embargo being raised, prior to there being a link, the day that we're recording this for this article. This is going to be a bit of a surprise, Vincent. We're going to find out finally whether Ivermectin really works for COVID. These are the results of the COVID-OUT Trial.

In this phase three, double-blind, randomized, placebo-controlled trial the effectiveness of three repurposed drugs - metformin, ivermectin, and fluvoxamine - were tested to prevent serious SARS-CoV-2 infection in nonhospitalized adults who had been enrolled within three days after a confirmed diagnosis of infection and less than seven days after the onset of symptoms. The patients were between the ages of 30 and 85, and all had either overweight or obesity. The primary composite endpoint was hypoxemia, less than 93% oxygen saturation on home oximetry, emergency department visit, hospitalization, or death. All analyses used controls who had undergone concurrent randomization and were adjusted for SARS-CoV-2 vaccination and receipt of other trial medications.

Let's go through a little bit of the results because I know everyone's excited. Is this finally the study that shows us? A total of 1,431 patients underwent randomization. Of these patients, 1,323 were included in the primary analysis, median age, 46. 56% were female. 6% were pregnant of those 56. 52% had been vaccinated, a split there. The adjusted odds ratio for primary event was 0.84, 1.05, 0.94. Let's go through what were those different drugs. 0.84 with metformin, but with a wide confidence interval, P value 0.19. For ivermectin, it was 1.05, P value 0.78. For fluvoxamine, 0.94, confidence interval of 0.66 to 1.36, and P value of 0.75. They then go on. I know there are some press releases where they're going to look at a pre-specified secondary analysis, but I'm not going to go there.

I'm just going to go to where the authors go. The authors conclude that, I know this is a shock, none of the three medications that were evaluated prevent the occurrence of hypoxemia, an emergency department visit, hospitalization, or death associated with COVID-19. Just another study that did not show a benefit for ivermectin, did not show a benefit for fluvoxamine. All right, and if you end up in the hospital, that early inflammatory lower respiratory hypoxic phase, steroids, anticoagulation, pulmonary support, maybe remdesivir if early enough. Maybe further immune modulation if needed. Avoid those unnecessary and unproven therapies.

We will move to the conclusion, the late phase. The article, “Readmissions, Post-discharge Mortality, and Sustained Recovery Among Patients Admitted to Hospital With COVID-19,” was published in CID, among adults hospitalized with COVID-19 in eastern Denmark. All right, where they're building a sailboat. March 18, 2020, to January 12, 2021. They assessed all-cause mortality, recovery, and sustained recovery 90 days after admission and readmission and all-cause mortality 90 days after discharge. Recovery was defined as hospital discharge and sustained recovery alive without readmission for 14 consecutive days. I will point out in this study, among the over 3,000 patients included, of those discharged from hospital, 20% were readmitted and 10% died.

VR: This was all cause though. It's not just COVID, right?

DG: That is true. I think that's actually interesting because part of that is how much of that is directly COVID? How much of this is this immediate post-COVID? How much is just these are elderly, vulnerable individuals who are at a higher risk, to begin with? Then I will say, as I always like to say, no one is safe until everyone is safe. I want everyone to pause the recording right here, go to parasiteswithoutborders.com. You can also go to microbe.tv and at either site click the Donate button. If you go to the parasiteswithoutborders.com, we are now having our Floating Doctors fundraiser. 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: All right, it's time for your questions for Daniel. You can send them to daniel@microbe.tv. Will writes, “I realize you have addressed nearly every variation on the theme of should this patient get Evusheld, but my father-in-law's 83, had a splenectomy eight years ago. We've been cautious in managing exposure. My father-in-law's current with vaccination. There's a family memorial service this fall that my in-laws plan to attend. Because he has no spleen, he's enquired about Evusheld.

His PCP and local infusion clinic has been told that having asplenia but otherwise being in good health for his age does not qualify him for Evusheld unless an IgG test found that he had produced no antibodies. Because he demonstrated some antibodies against SARS-CoV-2, the clinic says he does not qualify. Physicians I've discussed this with, I'm in North Carolina, have universally said they'd recommend Evusheld for a patient like my father-in-law. What would you recommend?”

DG: I took my glasses off so I could smack myself in the head without hurting myself quite as much. I don't know why this medicine is sitting on so many shelves. Here's an incredibly effective medicine, here's an individual who's moderately immunocompromised. I'm not sure why you would not give this individual that extra benefit. We're trying to move forward. Part of moving forward is using all the tools. Don't leave the tools sitting there on the shelf. This is a situation where I would be on the side of all the physicians who are encouraging the use of Evusheld to protect this individual.

VR: Ann writes, “I've heard Daniel say a million times, "Never miss an opportunity to vaccinate," so I was hoping Daniel would comment on this tweet from Shane Crotty, "In my opinion, if you had COVID a month ago, then a booster is pointless and potentialy disruptive to the ongoing antibody education the body is still doing. We know from multiple labs that the immune system is doing a brilliant job of improving antibodies for at least six months."

DG: Shane's a brilliant guy, and I understand where he's coming from when he makes that. I want to make a couple of comments. One of them is thinking about the different variants. We are all sitting here in pretty much BA.5. If you just got BA.5 and it's four weeks later, you can say, "Boy, I'm probably somewhat protected against BA.5." This was probably a boost. I think Dr. Walensky echoed something along these lines.

Prior in the pandemic as we kept moving from variant to variant, we had multiple circulating, we would see someone get over one infection, and then four weeks later, boom, they're hit by another variant. Then we didn't want to be the doc who told them to wait, and now they have COVID while they were waiting. The other side of this - I think there's two more sides I'm going to hit - is the impact on Long COVID. Unfortunately, we are seeing Long COVID in people who get infected.

We have seen evidence that the sooner you get your vaccination after that. Of course, if the person was unvaccinated, I would be encouraging them to start on a vaccine series. Then really the last I'll touch on is we are pretty close to having these new updated bivalent vaccines, which may actually increase our protection for some period of time. We're in a little bit of a gray zone. I know everyone would like a really simple straight answer to this, but it'll really come down to the individual details. It's great to make sweeping and say, "I can think of no reason," et cetera, et cetera, but each individual, you've got to look at the big picture and then make a decision.

VR: Steven writes, “I remember participating in a mass vaccination program for polio about '64 or '65. This was the Sabin OPV series. Each dose, we were handed a cup with a sugar cube to suck on. I have no written record of this vaccination, but I dimly recall having received only two of three doses. I was 8 or 9 years old. A year or so later, I was hospitalized for appendicitis. For a few days, I was moved to a ward next to a boy, my age, who was in an iron lung. This was an experience I will never forget. Most people have seen pictures of iron lungs, however, I doubt many of you have experienced one in operation. Iron lung machines in the '60s were big, noisy contraptions. My neighbor's iron lung made an incessant clunk-whoosh sound as the machine's valves and pumps work to provide pressure changes to assist his breathing. He lay on his back with a mirror over his head at a 45-degree angle so he could look around the room. We talked for hours about stuff that 10-year-old boys talk about, but we never talked about the iron lung or how long he might have to stay in it. I know what a terrifying disease polio was and I will never resist getting necessary vaccinations so long as they have been proven safe. I'm 66 now and here's my question, do I need an IPV shot?”

DG: Yes, this is a great question and we're actually we're getting a lot of questions like this. Thank you for putting this out there. There's a lot of folks who are not sure they don't remember and if you're not protected, then you should get protected. Maybe this is one of the positive things that's coming out of this tragedy is a lot of people are starting to say, "Boy, am I up-to-date with my vaccines?" Not just polio, talk to your doctor, find out because if you missed something, now is a great opportunity to be up-to-date with your vaccines.

VR: Guy writes, “Can an individual receiving their first JYNNEOS shot subcutaneously receive the second intradermally, or should the entire series follow the same administration method?”

DG: Now, we have clear guidance on this which is great. If you got your first one-way, you can go ahead. If you got subcutaneous that first time, you can go ahead and get intradermal for the second one. No problems and that's currently what's being recommended.

VR: That's TWiV Clinical Update number 128, Dr. Daniel Griffin. Thank you, Daniel.

DG: Oh, thank you, and everyone, be safe.

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[00:42:08] [END OF AUDIO]

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