TWiV 908 COVID-19 Clinical Update #118

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 11 June 2022

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 908, recorded on June 9, 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, how many pandemics do we have right now in the world? Do you know?

DG: [laughs] That’s actually an interesting question. We still have the HIV pandemic going on that never ended. We’ve got the COVID-19 pandemic that has not ended. I don’t know if I’m going to say monkeypox is a pandemic. Everyone’s very excited about it but –

VR: What about hepatitis B and hepatitis C? They’re pandemics, aren’t they?

DG: That’s interesting that we don’t think of them as, but they are pandemic. The No.1 cause of cancer on the planet, solid or organ cancer, is hepatitis B virus, so yes.

VR: Yes. Well, WHO never declared SARS-1 a pandemic. 25, 26 countries, 8,000 cases wasn’t enough, so monkeypox can’t be a pandemic if that wasn’t.

[laughter]

VR: Anyway, that’s an interesting. Obviously, it’s a human thing, and there’s no biological basis for it, right?

DG: Yes. Calling something a pandemic now is just a bunch of people getting in a room and they’re like, “What do you think?” Well, let’s get right to it. “Ignorance is the parent of fear,” that’s Herman Melville from Moby-Dick. It’s I can say one of my favorite books, but I like to say the first 125 pages and then it drags, even for a man who enjoys nautical jargon.

Let’s start with our update. Novavax Tuesday. The FDA’s Vaccines and Related Biological Products Advisory Committee voted “Yes” in response to the question, “Do the benefits of Novavax’s vaccine given as a two-dose primary series outweigh its risks in people aged 18 and older based on available evidence?” Twenty-one members voted “Yes”, one abstained, none voted “No”. They go on to say, “We have reviewed the data previously from Novavax. It’s very similar to what we saw with the other” –  Well, I’m going to say with the mRNA vaccines –  “greater than 90% efficacy of preventing mild, moderate, or severe infection.”

A couple of things I’m going to throw in. We only have data on the older variants. We don’t have anything on Omicron or any Omicron-sub. None of the volunteers who got the vaccine experienced moderate or severe infection. The biggest issue I think that we’re still waiting on, I’m going to quote from the Washington Post, “It remained unclear when doses will become available, as a decision by the FDA is unlikely to happen immediately because a review of data regarding manufacturing remains ongoing.”

That’s really plagued Novavax, is their ability to show or demonstrate to the FDA that they have a reliable safe quality manufacturing process in place.

VR: Daniel, the ability to manufacture reasonable quantities, would that play into the FDA’s final decision?

DG: I think so as well. You can say, “We can make 10 a day.” That’s just not going to cut it. It doesn’t really make – You’ve got to show that you can produce a certain quantity and that this could be done in a safe, reliable, consistent manner. I will say there’s a lot of people who say, “Oh, those anti-vaxxers. They’re -” but I have to say, in my office, we’ve already gotten several calls. I have a number of people that are just waiting for Novavax. They’re not anti-vax. They’re hesitant with the current technology. They’re looking for Novavax as a solution for them.

How large will that number be? I certainly can’t tell you, but I’m optimistic, I think it’s positive that at some point here, hopefully before this month ends, we’ll have another option. Also, children COVID and other vulnerable populations, a couple of things exciting are going to happen next week. June 14 will be the meeting date for the FDA and its advisory committee of external experts to discuss Moderna’s EUA request for 6 years through 17 years of age. That’s been all Pfizer so far.

June 15 will be the meeting date for the Moderna EUA request for 6 months through 5 years of age and Pfizer-BioNTech EUA request for 6 months through 4 years of age. We’re hoping by some time at the end of next week we’ll hear all the way down to 6 months of age that there’ll be the opportunity for vaccines. Now, the pre-exposure period, transmission, testing, use those tests intelligently. Apparently, I have to repeat this. The incubation period is still two to 14 days. I’m hearing much too often, “It’s day five. If your test is negative, you’re done. The incubation period is only five.”

Apparently, people are obsessed with five days. “The incubation period is now only five days, the disease only lasts five days.” None of that’s true. Actually, the 14 days is a good one. The incubation period can last up to 14 days. In a lot of individuals, the acute illness lasts up to 14 days. Just, I guess, a refresher. I know a lot of people tuned in because of the promise. As promised, the article, “Diagnostic Accuracy of Non-invasive Detection of SARS-CoV-2 Infection by Canine Olfaction,” published in PLOS One. That’s by the noses of dogs.

These are the results of a prospective cohort study in two community COVID-19 screening centers. Two nasopharyngeal swabs, one saliva, and one sweat sample were simultaneously collected. The dog handlers and the dogs were blinded with regards to the COVID status. [laughs] I love that they did not tell the dogs. The diagnostic accuracy of noninvasive detection of SARS-CoV-2 infection by canine olfaction was assessed as compared to nasopharyngeal RT-PCR as the reference standard, saliva RT-PCR and nasopharyngeal antigen testing.

Now, everyone place your bets. Drumroll. What happens here? Overall, 109 of the 335 participants tested positive on nasopharyngeal RT-PCR, either in symptomatic of 78 of 143 or asymptomatic, that was 31 of 192. The overall sensitivity of canine detection was 97%. Even, this is interesting, it reached 100% in asymptomatic individuals compared to the nasopharyngeal RT-PCR. This specificity was 91%, but interestingly, it was actually high. It was 94% in asymptomatic individuals. The sensitivity of canine detection was higher than that of nasopharyngeal antigen testing.

94% as we mentioned versus 84%, but specificity was lower, 90% versus 97%. A few details and comments. This is where I think it gets fun. First, this is not like you’re at the airport where the dog walks along the line sniffing people and their bags. What they actually did here is sweat samples were collected by these special dedicated sweat sample collection teams.

VR: Sweat teams.

[laughter]

DG: You could be, “What is your job?” “Well, you see, I work at the airport, and I have people put these two sterile surgical compresses under their armpits for two minutes. Then I take those samples and I store them in sterile, medical, anti-UV glass containers. They’re disinfected by the sampler’s helper, people have helpers, they’re anonymously coded, and then placed into a second plastic envelope.” So pretty involved. The dogs then, they go to these special stations. They have these cones, and the sweat samples are in these little boxes and then the dogs walk along.

Then as we learned before, the dogs need to be trained, and then they’re trained for the new variants. The time to train the dog depends upon the dog’s ability. Some are really good. Some dogs that are previously odor-detection trained, they can get up to speed in about three weeks. For the green dogs, those new at odor detection, it might take five to six weeks. It’s actually interesting if you see how they do this. The dogs go along, and then if they smell what they think is a positive, they sit down in front of the cone.

[laughter]

DG: Now, the other point that I think is really interesting is that the dogs were actually really good at picking up people even with high CT or low RNA copy numbers, really just as good as folks with high RNA copy numbers. This is where it gets interesting. A couple of times the dogs sit down, well, a couple of 20 times the dogs sit down and the people are like, “No, no, I’m sorry that person has a negative nares RT-PCR,” but they go ahead and they say, “What about if we check the samples, the saliva.

Of those 20 individuals, 17 were missed by nasopharyngeal, RT–PCR, but had positive saliva PCRs and the dogs picked those folks up. I thought that was clever like, “We’re thinking those nares PCRs, that’s the way to go. Only 97 here, 100% in asymptomatic. The dogs are picking up people.” 17 of the 20 people that got picked up by the dogs that we thought were clear had it in the saliva. Some of the studies that we’ve talked about, it may appear in the saliva a little bit sooner. A pretty exciting study. I will add for all the dog lovers.

I love this part. This is great. The welfare of the dogs was fully respected with toy rewards and a total absence of work-induced physical or mental fatigue. This study was carried out in strict accordance with the recommendations published in the Guide for the Care and Use of Animals, edited by French law. They followed the French Rural Code.

VR: Daniel, as we’ve said before, the dogs are likely smelling inflammation, cytokines, and chemokines. I think it’s really interesting that even with low RNA copy, you must be making some cytokines for them to smell.

DG: Yes. I’m curious what are these volatile organic compounds that they say are being detected because they’re not- [crosstalk]

VR: That’s something that could be sorted out.

DG: -Smelling variants.

VR: No.

DG: I think that’s important.

VR: It’s a volatile organic that’s somehow correlated with inflammation. It would be interesting to find out what. Right?

DG: Yes. I’m also thinking it can even go farther because I think your smell probably changes over time. A fresh infection probably has a different – Those ones in the saliva that had got it in the nasopharyngeal, do they smell different than those people who are on the other end of this. Can the dogs tell us? I know a lot of people are hoping there’s some way to find what are these VOCs that the dogs are picking up so that we can maybe even learn a little bit more here. I think it’s pretty exciting that the dogs are doing such a good job.

You particularly think in these, I think of limited-resource areas, it might be a little more reasonable to train dogs to do some of the work versus bringing in all the machinery. You just think about the amount of money we spend. What do we charge? $200 per PCR test? these dogs are cranking through.

Active vaccination, hot off the press. I got lots of questions about this. “Moderna announces Omicron-containing bivalent booster candidate mRNA-1273.214 demonstrates superior antibody response against Omicron.”

I will say this is a press release. This is preliminary data that Moderna is thrilled to share with us according to Stéphane Bancel, the CEO of Moderna. Now, in this press release, we hear that Omicron-containing bivalent COVID booster candidate mRNA-1273.214 containing mRNA 1273 (Spikevax) and a vaccine candidate targeting the Omicron variant of concern meant all pre-specified endpoints. Including superior neutralizing antibody response against the Omicron variant one month after administration compared to the original mRNA-1273 (Spikevax) vaccine.

The neutralizing GMT against ancestral SARS-CoV-2 for mRNA-1273.214 was 5,977 versus 5,649. The GMT against Omicron was 2,372 versus 1,473. Higher. I do not know what those numbers mean. I don’t know if anyone does [laughs] but more is better. I guess this is the opposite of golf. I do have to say, there, there’s this interesting. I think Amy sent me that article about people are growing tired of getting vaccinated for COVID-19. I thought that was an interesting comment.

There is a certain marketing aspect to this as well. People may be done with getting Spikevax or getting the Pfizer-BioNTech Comirnaty, but there actually seems to be some excitement about trying something new. We’ll see. [chuckles]

VR: Mr. Bancel is very excited because it means potentially more profits for his company. If you use this vaccine in six months, the titers will be down, and then where are you? What’s the difference? I bet – I would really like to see protection against disease. As you have said yourself, Daniel, I don’t care about neutralizing antibodies. I want to see protection against disease. For him to be so excited about antibodies seems to me misplaced in some way. I want to know if this is any better at preventing serious disease with Omicron or its subs versus the 1273. I think the FDA should demand that data before they approve this.

DG: It’s got to be a challenge. It’s interesting. What is the best vaccine? The best vaccine is the one that people take, I guess. Is there any difference in safety profile? Is there any difference in efficacy profile? I think these are all important, but it is interesting, this issue that if you have a new updated vaccine, will that improve vaccine update? Right now, we’re not doing great, to be honest, in the U.S. We have not done great in the U.S. If we have a new, updated vaccine, will we get more people? I think that’s even going to be part of the thinking here.

It is interesting, once you start putting more stuff in there, what will the safety side-effect profile be? I’m not particularly worried about that, but I think these are all valid points. Will this actually work better? The original vaccine still tends to be doing really well. It’s just a question, do we need anything new? Some people, maybe they’ll want something new. I suggest that they charge a little bit extra because that always drives– If you have to pay $10 extra, that means it’s obviously better. [laughs]

Now, the paper, “Association of COVID-19 Vaccination During Pregnancy with Incidence of SARS-CoV-2 Infection in Infants.” This was published in JAMA Internal Medicine. This is a registry-based cohort study of all live-born infants in Norway. Really impressive. Infants of mothers vaccinated during pregnancy had a lower risk of a positive test compared with infants of unvaccinated mothers and lower risk during the Delta variant–dominated period, 71% reduction. Then, during Omicron, it was a 33% reduction.

Just reinforcing what I think we’ve said for quite a while here, the best thing a mother can do to protect herself and her baby is to get vaccinated. Yes, during, not after pregnancy. Give our babies that precious immune protection. This week, I also wanted to discuss an article that talks a little bit about not only the personal benefit of vaccination but also the societal impact. John Mascola and I were emailing a little bit about this article because this is– I don’t know, maybe it’s not very American.

I thought it used to be very American, but we asked like, “What can I do for myself?” versus, “What can I do for -” the John F. Kennedy question Now, the article, “Population-Level Implications of the Israeli Booster Campaign to Curtail COVID-19 Resurgence” published in Science Translational Medicine. This paper relies on mathematical modeling and simulations. It relies on assumptions about the impact of vaccine efficacy against infection which I think we know may be short-lived. They also look at numbers of severe cases in these models, impacts on healthcare and hospital capacity.

They calculated how much impact was felt to be direct protection to the vaccinated, how much are you doing for yourself versus indirect protection to others because a person was vaccinated or people around you are vaccinated. Interesting how even vaccine efficacy against infection short-lived properly timed vaccination on a population level. Even if that’s a small impact can start to have a significant impact. Small percentages, large numbers start to add up.

A big issue they raise that we experience firsthand is that during surge conditions, when you start to overtax a hospital, there’s a significant increase in mortality. I think they were using about a 38% increase in mortality. We do not do well when our hospitals are overtaxed. I have to say I was a little bit surprised at the limited number of hospital and ICU beds available in Israel. It is a much smaller country than the U.S. There are a lot of assumptions that go into these models. I have to say, here in the U.S, our biggest challenge is still getting people to step up for the primary vaccine series.

We have perhaps a third of our eligible population here in the U.S. still unvaccinated. As we move into the younger, that’s really a part of our population that we have done poorly. Really important when we start thinking about. There’s really two sides to vaccination. One is the personal benefits. The others, you start looking at the impact of vaccinations on our society.

VR: I think that’s really an important point. I can see where if you have a surge, you can immediately vaccinate but that’s not going to happen here in the U.S. I don’t think we would respond. In a country like Israel, you could do that. I’m not sure these are generally applicable. The other point is that I think this shows that the vaccines have an impact on transmission. Part of the narrative by many has been, “Oh, vaccinated people shed as much as unvaccinated.” It’s simply not true in terms of transmission, I think this study shows that in a nice way.

DG: Yes. Who was it who said vaccinated people are teeming with virus. OK, we won’t go there.

[laughter]

Passive vaccination, Evusheld, authorized for use in adults and pediatric individuals, 12 years of age and older, weighing at least 40 kilograms. Now remember, this is something that is not only for those with moderate to severe immune-compromised, but it’s also for those who do not feel can mount an adequate response to the vaccine. Or for whom you cannot vaccinate. Hopefully, with Novavax, we’re going to be impacting that number a little bit, but I’m still very much under-utilized, I’m still sitting on shelves in a lot of places.

This should not be as hard as it seems to be and as we’ve discussed several times, really impressive data. The post-exposure period, really limited here. You’ve been exposed and now while you’re in that period of time, two to 14 days, not just five, that’s when we’re thinking about testing, and keeping track. Then perhaps you test positive. The period of detectable viral replication. I’m going to tell a story about a patient I saw this week. This is a woman, right about age 50. She went ahead and she did not have many risk factors so she got COVID.

Had some degree of symptoms in the first three or four days. By about day five started to feel better and she actually felt better for quite a while until about day nine, day 10, she started to feel bad. She actually said, “You know what, by day nine, 10, I actually felt worse than I felt during those first few days. I felt bad for about three days, and then I got better from there.” I said to her, “Do you know what we call that? We call that Paxlovid rebound.” She said, “Dr. Griffith I never took Paxlovid.” I said, “Oh, no, it doesn’t matter, we still call it Paxlovid rebound.” [chuckles]

We had a nice long discussion and I saw several patients this week with a similar story, who never got Paxlovid. I just want to reiterate that this is something we often see, this bimodal illness. Particularly, I think in vaccinated individuals, lower-risk individuals, they don’t get a lot of that early inflammatory surge at the beginning of the second week. This is not a disease that is very linear so people can feel bad, feel better, feel bad, feel better. Certainly, I know a lot of our folks with Long COVID have experienced that feeling better, feeling worse.

Remember, Paxlovid’s still No. 1 recommendation. Get that in in the first three to five days if the person is at risk of progression. Remember, you can’t just wait, you can’t say on day seven, day eight, oh boy, now you’re having that early inflammatory phase, now you’re hypoxic. Well, you’ve missed your window. This is not a wait-and-see, this is a calculation. This is, you’ve got to step in, time really matters. If you can’t do Paxlovid and there certainly are situations where there’s complexities, there’s other drug-drug interactions, there’s renal function you may want to move on.

Let’s talk a little bit about the paper, “Oral Nirmatrelvir and Severe Covid-19 Outcomes During the Omicron Surge,” posted as a preprint. This study included all Clalit Health Services members, 40 years of age and older with confirmed infection of SARS-CoV-2 during the Omicron surge, so how well is Paxlovid working in the Omicron surge? Clalit Health Services is the largest of Israel’s four state-mandated health service organizations. In this situation, we had 109,213 participants eligible for Nirmatrelvir, that’s Paxlovid, during the two-month study period, among the 40 –

Then they say 42,819 eligible patients aged 65 years and above, this is the older population, 2,504, not a lot were treated with Nirmatrelvir. Hospitalization’s adjusted hazard ratio 0.33 so 67% reduction in ending up in hospital. Real-world data; death due to COVID-19 hazard ratio 0.19 so 81% reduction. Really, really pretty impressive real-world data here. Big takeaways, this was during Omicron. I think the other thing and I think this is really critical too, 78% of the participants had COVID-19 immunity, either by vaccination or prior SARS-CoV-2 infection.

I know I hear a lot of people saying, “Oh, the person is already vaccinated. I know they’ve got comorbidities. I know they’re older. I think that I’m not going to really do the Paxlovid.” Here is real-world data in people who are either vaccinated, prior infection during Omicron, 81% reduction in chance of death. Really pretty impressive.

VR: Let’s wait and see, Daniel, let’s see what happens. [chuckles]

DG: Let’s just wait. We’ll see. If you die then I’ll have regretted my decision not to give you Paxlovid. Sorry about that. Two, Remdesivir. The order changed, remember, I don’t want people going to the ER saying, “I’m here for my monoclonals.” You’re there for evaluation and treatment with the best therapy for you. A PSA to people out there, patients and clinicians alike, respect your ER colleagues. Don’t send them there for the monoclonal and have them have a fight and then come away with nothing.

Remdesivir is number two. Number three is monoclonals and that’s Bebtelovimab at this point, but we have some new data, “Efficacy and Safety of Intramuscular Administration of Tixagevimab-Cilgavimab for Early Outpatient Treatment of COVID-19,” the TACKLE Trial, which is a phase three randomized, double-blind, placebo-controlled trial. This is Evusheld, published in The Lancet Respiratory Medicine. This is this question of perhaps Evusheld is not just for pre-exposure prophylaxis, maybe we can use it for acute therapy as well.

These are the results from the TACKLE study, which is an ongoing, phase three, randomized, double-blind, placebo-controlled study conducted at 95 sites in the USA, Latin America, Europe, and Japan. We’re hitting all the things that we want. Here, participants for Evusheld in the first seven days after symptom onset. Here we saw a relative risk reduction of about 50%. They concluded that a single intramuscular Evusheld dose, provided statistically and clinically significant protection against progression to severe COVID-19, or death versus placebo in unvaccinated individuals, and the safety profile was favorable.

I will say that protection, if you break down death, was also about 50% as well so composite and death.

VR: Daniel, for you to be able to use now Evusheld therapeutically, does it have to receive an EUA expansion?

DG: Yes, it really does, because it’s not licensed, so we would need an EUA expansion. Right now, we’re still using Bebtelovimab before going the monoclonal route. Molnupiravir, that’s number four, last option. Only about a 30% reduction so less impressive, no renal or drug-drug interactions. For those doctors out there, that are daunted by everything else, this is better than doing nothing. Remember to get that negative pregnancy test, not authorized for those under 18. The big issue, let’s avoid doing harmful things.

Let’s not give steroids during that first week and shut down the immune system. We’ve talked about data, we’re actually doing harm. Let’s not give people antibiotics, azithromycin, doxycycline, those are anti-bacterial, not antiviral agents by the way, and unproven therapies. We’re getting more and more data on those things that people were excited and optimistic about that just are not helpful. The article, “Efficacy of Short-Course Colchicine Treatment”. This is in hospitalized patients, so a little bit later in the course, with moderate to severe COVID-19, pneumonia and hyper-inflammation.

A randomized clinical trial published in the Nature journal Scientific Reports. These are the results of a prospective, randomized, controlled observer-blinded endpoint probe study. Basically, they found that adding Colchicine to standard background therapy was not associated with a lower risk of CPAP, BiPAP, ICU admission, invasive ventilation, or death. Colchicine we’re just not getting encouraging data there. Remember, isolation for the infected. Remember, that’s five days, but then another five days of wearing that tight-fitting mask.

People keep asking about antigen testing so I’m just going to throw in what is the story there. The CDC says. “If an individual has access to a test and wants to test,” I’m going to point out there’s only a downside that I’m seeing here. They say the best approach is to use an antigen test toward the end of the five-day isolation period. Collect a test sample only if you are fever-free for 24 hours without the use of fever-reducing medication and your other symptoms have improved.

If your result is positive, you continue to isolate for day 10. You don’t go out with that tight-fitting mask. If your test is negative, then you can end your isolation, but you continue to wear a well-fitting mask around others, at home, in public until day 10. I want to reinforce that. There’s nothing good about – People have this idea, “Well, if I get that negative test, I can take off that mask. I’m no longer infectious. I can go to the workplace. I can have dinner with my 89-year-old relative.” No, [chuckles] if it’s positive, they’re actually extending the 10 days.

Now, I think that this whole issue of who continues to be infectious is actually critical. We might be getting past the relevancy here now that we have vaccines, effective antivirals, but I think we still have an important knowledge gap that may be less relevant for COVID. Might be more relevant for other things like, for instance, the monkeypox. [chuckles] If we looked at people day six through 10 with those negative antigen tests and compared those with those positive antigen tests, is there still a significant difference in transmission?

We talked about we just don’t have that data that we would really like. As we discussed last week, these studies are not easy to do. It’s really hard to document if transmission has occurred, when it’s occurred. Particularly when we have high background SARS-CoV-2 transmission in the community as we currently do. How do we know a contact got infected from this individual that we think on day nine versus another source that it occurred during day six through 10 versus after that? Not easy studies to do.

I’m already concerned that we did not learn this lesson, the distinction between a positive molecular test and actually documenting that a person is infectious to others. I read The Lancet, this was a recent study in The Lancet where I quote, and this is folks with the monkeypox, “Five patients spent more than three weeks range of 22 to 39 days in isolation due to prolonged PCR positivity, prolonged upper respiratory tract viral DNA shedding after skin lesions resolved, challenging current infection prevention and control guidance.”

We had an individual here, 39 days locked in a negative pressure isolation room by themselves because the PCR continued to be positive. I think we need to actually understand how to do these things, how to really make these determinations.

VR: Daniel, in the old days before PCR, we didn’t have this issue.

DG: [chuckles] Yes.

VR: “You are asymptomatic, no more lesions, goodbye, go out.” Maybe that was a better way.

DG: Yes. I do worry now that we do have more information, I’m not sure we know what to do with that more information. We need to learn what to do with that more information. The early inflammatory phase. This is still very much what we’ve talked about for a while. Hopefully, less and less people are getting to this point. If they do get to this point, oxygen levels drop. This is when steroids might be of benefit when we talk about anticoagulation, pulmonary support, maybe remdesivir if we’re still early enough, maybe tocilizumab. Again, avoiding those unnecessary antibiotics and those unproven therapies.

We’re getting to the tail phase, Long COVID, post-COVID. Now, my wife knows that the clap-outs have always bothered me, but she tells me to just keep this to myself. [chuckles] My perspective is that so many of these people would leave the hospital without being connected to post-hospital care. In the early days, a lot of physicians were not seeing patients in the community, so they’d end up struggling. Many would end up readmitted.

Some would even die once they got out of the hospital. For me, I felt like the clap out was people missing that this is really just one step and that these people need continued follow-up and care. The paper, “Factors Associated with Readmission in the United States Following Hospitalization with Coronavirus Disease 2019,” was published in CID, Clinical Infectious Diseases. This was a retrospective cohort study, risk factor associations with 30-day readmission and in-hospital mortality.

Readmitted patients were more likely to have diabetes, hypertension, cardiovascular disease, or chronic kidney disease and to present on first admission with acute kidney injury, congestive heart failure, or cardiomyopathy. Higher odds of readmission were observed in patients aged over 60, not surprised, and those, interesting enough, admitted in the Northeast. Maybe I’ve seen more of this than the rest of the country. 12.3% of the readmitted patients died during the second hospitalization. This is not without a problem.

In addition to readmission and death, perhaps our listeners remember when we first noticed post-acute COVID hair loss and how devastating this was for so many. A couple of months would go by, the person was out of the hospital, they’d been clapped out, and then suddenly, all their hair would fall out. I remember quite well, some young women, actually, a couple of teenage women that this happened to, completely devastating.

The article, “Management of Hair Loss after Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Insight into the Pathophysiology with Implication for Better Management,” was published in the Journal of Dermatology. Several things going on at the same time responsible for this hair loss. Maybe people remember the terminology telogen effluvium. That’s the post-trauma shedding of the hair that occurs during the resting stage. These people are also getting anagen effluvium post-trauma shedding of hair that occurs during the growth stage.

All this hair is falling out and not growing back in. While spontaneous recovery is the norm, there were several studies that mentioned that maybe topical minoxidil might be helpful in these folks. One of the things I will say, I know there’s a lot of discussion now about post-COVID, post-vaccine infection. What are we calling that? PVI, post-vaccine infection so PVI. I don’t think I’ve seen a single case of someone having all their hair fall out when they get COVID after vaccination, so we got that.

Now, this is my favorite Long COVID paper, “SARS‑CoV‑2 Infection in Hamsters and Humans Results in Lasting and Unique Systemic Perturbations Post-Recovery,” published in Science Translational Medicine. Now, I know a lot of people are getting frustrated like, “All this money. Where is it going? Where are we learning about Long COVID?” This I thought was, actually, I think a step forward. I think there’s helpful information here.

To better understand the mechanism underlying Long COVID biology, these investigators compared the short and long-term systemic responses in the golden hamster, following either SARS‑CoV‑2 or influenza A virus infection. I’ll give Amy some credit. I think she sent this my way. Results demonstrated that SARS‑CoV‑2 exceeded IAV, influenza A virus, in its capacity to cause permanent injury to the lung and kidney and uniquely impacted the olfactory bulb and epithelium.

I think this is important, despite a lack of detectable infectious virus, the olfactory bulb and the epithelium demonstrated myeloid and T-cell activation, pro-inflammatory cytokine production, and an interferon response that correlated with behavioral changes, extending a month post-viral clearance. These sustained transcriptional changes could also be corroborated from tissue isolated from individuals who recovered from COVID-19. This data highlighted molecular mechanism for persisting COVID-19 symptomatology and provide a small animal model to hopefully explain future therapeutics.

I felt like this was actually helpful and interesting science.

VR: I just want to tamper your enthusiasm-

[laughter]

-because-

DG: Of course.

VR: -previously another group showed that in the same hamster model, Omicron causes a mild infection. That was the basis of many people concluding that Omicron is mild. You realize now, Daniel, you’ve said this yourself, Omicron is not mild. I’m just not sure what this animal model can tell us, right? Just be careful about that.

DG: No, I think that’s true. We will say with a guarded optimism, we will move forward. We’ll conclude by bringing everyone back to a global perspective. We talk a lot about here in the U.S., but in the rest of the world, in many ways, we botched this one. Low vaccine throughout the world still continuing to be in the midst of a pandemic, still continuing to have the ups and downs. No one is safe until everyone is safe. I think this whole concept of we only worry about a disease until it gets here, we have to move past that.

We are a global community, for both moral and even selfish reasons. I want everyone to pause right here, whatever they’re doing, go to parasiteswithoutborders.com, click on that Donate button. Even a small amount helps. Actually, we’d love those small amounts. Every bit helps us continue to do our work. We are now running our foundation, International Medical Relief of Children fundraiser. I actually met with the CEO, the head of FIMRC, the other evening in a COVID safe. We sat out on my back deck six feet apart with a nice breeze blowing through and really discussed their challenges.

We are going to continue through the month May, June, and July to double donations made to get up to hopefully a $40,000 donation to FIMRC. We’re really focusing on trying to help the Bududa District medical center there in Eastern Uganda.

VR: Time for your questions for Daniel. You can send them to daniel@microbe.tv. Before I start Daniel, I got an e-mail today from a cardiologist.

DG: Was it the cardiologist or just a cardiologist?

VR: No, it was a cardiologist who, he listens to the live stream, and he said, “I just want you to know, Vincent, that not all cardiologists think they’re virology experts.”

[laughter]

Which I appreciated. The first one is from David, “My middle-aged friend who lives in South Carolina got COVID and then his 88-year-old father and 80-plus-year-old mother got COVID. Within one or two days of symptom onset, both went to their respective doctors who told them because they are doing well, they would not prescribe antivirals. The mother’s doctor went on to say that prescribing antivirals was too complicated and required too many blood tests and flat out refused to prescribe them. From what I’ve heard on Twitter these docs don’t know what they’re talking about. Am I wrong?”

DG: Let me respectfully say those docs don’t know what they’re talking about. [laughs] It’s time to get a new doc. It’s too complicated to take care of a person who has COVID? It’s too complicated to basically take a few minutes out of your day and look at drug-drug interactions? Maybe read about a therapy with a 90% reduction in the risk of progression in high-risk individuals that you just described. That’s just unconscionable, actually. This is why I have trouble sleeping at night just hearing stories like this.

VR: Jeff writes, “I’d like to clear up some things regarding doctors prescribing antibiotics to patients with known COVID infections. I’m getting hung up on why antibiotics are bad to prescribe in this situation. I assume and hope that doctors are educated enough to know that antibiotics are not going to help a viral infection, rather they are prescribing antibiotics to curtail secondary bacterial infections. Especially in patients that have progressed to viral pneumonia.

I saw one study that said 18% of COVID patients with pneumonia had a secondary bacterial pneumonia infection of which 15% of those 18% led to mortality. It seems logical to me that antibiotics would be a good prophylactic prescription, especially for those who unfortunately progressed to pneumonia unless the antibiotics make the COVID infection more severe. I’m not an MD and I didn’t stay in a Holiday Inn Express last night.”

DG: I like that.

[laughter]

VR: I’m wondering if you say that giving antibiotics is not the solution because antibiotics kill bacteria and thus just don’t help COVID or is it because they have negative effects on the outcome of initial viral infections.

DG: Can we say antimicrobial stewardship here. There’s a couple things. I understand the idea that people said, boy, early on, “I’m just not a great doctor and I can’t tell whether or not you have a bacterial infection at all. I’m just going to give you antibiotics.” I could understand that but we have done studies, we have science giving all comers antibiotics up front is not helpful. I think we even discussed the doxycycline where actually twice the number of people who got the doxycycline died versus those that didn’t, so that’s bad.

Remember doxycycline, azithromycin can have cardiac issues and a disease that can be associated with myocardial inflammation. That’s one thing. The other and I will address that 18%. When we’re seeing folks with those secondary bacterial infections, that’s not week one that’s not when they’re showing up at urgent care. That’s when they end up in the hospital when we can get a chest x-ray. When we can look at ferritin procalcitonin ratios. When we can really make that proper assessment.

I hear all the time a person goes to whatever urgent care doc-in-the-box. Even their primary who says, “Well, I’m just not comfortable with these new antivirals but I am comfortable giving you Medrol Dosepak steroids and Z-Pak antibiotics. That’s not helpful we’ve studied that. Despite these ideas that it seems to make sense, it doesn’t make sense. Then the other is we are losing our antibiotics. We are quickly heading towards a post-antibiotic apocalyptic world. This is a huge issue for us, where people come in and we are struggling to find an antibiotic that still works.

This is a problem, not only is it not helpful, but it’s actually incredibly harmful at a societal level.

VR: Daniel, you would not give a COVID patient antimicrobials unless you know they have a bacterial infection right?

DG: I have a high suspicion or the risk-benefit warrant. Let’s say a patient comes in, they end up in the ICU, I’m not sure. There it’s fine erring on the side of antibiotics. But not when they show up at an urgent care center, just throwing it in there.

VR: Andrea writes, “My elderly parents 85 and 86 are fairly healthy, just received their fourth booster. I guess that means their fourth dose. Our family is fully vaccinated and boosted third shots and want to visit them this summer. We’re respecting their wishes and will only visit outside in their backyard or inside with N95s. My question is, are they being overly cautious given the vaccines and therapeutics now available or is this age group still extremely vulnerable and not able to return to normal. Is this age group vulnerability accounting for the continued COVID fatalities?”

DG: As an age group, pick an age. Let’s say you’re over 85 but you’re in otherwise good health, don’t have co-morbidities, you take care of yourself, you’re keeping your weight where it should be. Eating right, exercising. No, with four shots of vaccine with the availability of antivirals as long as you’ve got yourself connected with a physician who’s actually willing to deal with the complexities and challenges, you’re in pretty good shape. Now it’s a little bit different if you say this is an 86-year-old, they’ve got lung damage from smoking.

They’re overweight they’ve got diabetes, maybe they’ve got an autoimmune issue and they’re on a medication that suppresses their immune system. I think there actually is an individual calculus. Yes, there are certain individuals I take care of who still are at high risk despite all these different things. Those are the people hopefully you’re adding Evusheld and you’re trying to get them. I think that the calculus is a little bit different. I, unfortunately, think that we have scared a lot of people to the point where they’re continuing to operate in a way where really the risk calculus doesn’t make as much sense anymore.

VR: That’s COVID-19 clinical update, Number 118 with Dr. Daniel Griffin. Thank you, Daniel.

DG: Oh, thank you and everyone be safe.

[music]

[00:47:21] [END OF AUDIO]

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