TWiV 957 Clinical Update

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 26 November 2022

pdf of this transcript available (link)

Vincent Racaniello: This Week in Virology, the podcast about viruses, the kind that make you sick. From MicrobeTV, this is TWiV, This Week in Virology, Episode 957 recorded on November 23, 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, everybody.

VR: Daniel, one of the questions I often get is, how are we doing? How’s the match between the flu vaccines and the current strains?

DG: [chuckles] We quoted some research a couple of episodes back actually, one of the best ways to get a sense of what’s going to happen here is to look at the Southern Hemisphere because they’re ahead of us. They just had their winter. It was about 50%, actually looked like a pretty good match, about a 50% reduction in progression to hospitalization symptomatic disease that required presentation to medical care. I think that is pretty encouraging. The only problem is if you don’t get the vaccine its efficacy is zero.

VR: Are you serious?

DG: [chuckles] You got to actually get the vaccine and we’re not doing a good job. Get those arms out there. I’ve talked about it, I was looking at this again today and I think I’m going to like take a picture of this and then keep it for, we’ll look at it in December, and then we’ll look at it again after the December holidays. They do a map and you can see the influenza is localized in certain areas and they actually have new colors now. Instead of just red, it now goes into like brown and purple. Not just high but very high and extraordinarily high. It’s like that old documentary where they turn up the stereo to 12. We’re now up to 12 on the flu tracker. What do you think is going to happen? I don’t think it takes a rocket scientist but a lot of these university college kids, a lot of people are traveling to be home with the family and then they all share a lot of stuff around that table. Some of those sharing involved respiratory pathogens and then they travel and so pretty soon everywhere is bright red.

VR: The same thing happens at the end of December again.

DG: Yes. We’ll get into that, these optimistic predictions, and where that fits in with reality. Let’s get right into it. I’ll start with my quotation. “No one has ever become poor by giving.” That’s a quotation from Anne Frank. I will suggest that as we celebrate Thanksgiving here in the United States people all throughout the world want to think about how by giving we do not ourselves become poor but rather we gain more than we give. Also right up front, I want to make sure I repeat my disclaimer right here as some may be introducing this podcast to family or friends during the holiday. With Twitter dying, I feel like this is going to be OK.

I may not have to answer my disclaimer anymore. Maybe they’ll still comment on the YouTube channel. If you are an anti-vaxxer, if you are an anti-Paxxer, that’s a new one, a COVID denier or dismissive when a person has Long COVID or after a child dies (you ask if they had other medical problems), this is perhaps not the right podcast for you. If you prefer chocolate-flavored, horse-based, untested remedies and anecdotes, this might not be the podcast for you.

VR: Which podcast should they listen to?

DG: I know which one they should. I don’t want to promote it here. Joe’s got enough listeners. Polio, get vaccinated and influenza, the same. We just talked about it. Get vaccinated. We are not doing great on vaccination and the numbers keep increasing. I actually pasted into our show notes, the influenza-positive tests reported to CDC.

It’s an exponential rise. We’re really rocketing up there. As mentioned, we are concerned and I just want to put this right out front here, people don’t feel well. I was just talking to my buddy Adam Fiterstein who’s the head of our urgent cares here on Long Island for – we’re now Optum Tri-State. People show up and they’re like, “Oh, I got to get a COVID test. I want to get a flu’s test because if those are negative I want to go hang out with my young relatives under 5, my aged relatives over 65.” We’re saying, if you are sick, don’t make them sick. If it’s COVID, don’t give them COVID. If it’s flu, don’t give them flu. If it’s RSV, don’t give them RSV. If it’s human metapneumovirus or all these entero rhinoviruses, don’t go to the holiday dinner if you are sick.

RSV. I could have just put this in again, I have not seen such a steep rise in RSV. The percent positive, the detection’s really rocketing up. We’ve talked quite a bit. The concern with the holidays is that this is a time when people say, I’m going to take the day off from good behavior. It doesn’t really work that way. I do have a little bit of good news, monkeypox as I’ve been saying for a while, monkeypox, it’s not a gay disease or an African disease it’s an infectious disease. If you look at the monkey pox tracker, we’re actually doing quite well. We really got to a high level. This is now endemic, but we are really, at least at the moment, doing well.

I do want to mention a couple of things that I think are important before we get into Ebola and COVID. A quick mention of the article, “Human Monkeypox Virus Infection in Women and Non-binary Individuals During the 2022 Outbreaks: A Global Case Series,” published in The Lancet. I don’t know how many times this circular reasoning is going to occur. Where we say, oh, it’s, it’s only in gay men and we only test gay men and we only find it in gay men. I’m also going to leave a link to the more accessible New York Times article. This investigation suggested that thousands of women were also infected and many more cases were probably missed. They also suggested that only about 60% of the cases could be connected to sexual contact. About 40% of cases, roundabout half could not be connected to sexual contact.

Also, a little bit of disturbing news, in light of how well we’re doing, this was anticipated but here it is. The CDC has confirmed the presence of tecovirimat-resistant viruses in two patients. CDC was notified of one patient with persistent monkeypox, whose viral isolates demonstrated tecovirimat resistance. Isolates from this patient sequenced by the state lab, demonstrated genotype changes in F13L associated with the tecovirimat resistance. In addition, the CDC confirmed phenotypic resistance to tecovirimat in cell culture. CDC also confirmed resistance in another patient who was tested due to poor response to treatment.

Ebola, actually feeling pretty good here as I prepare to head to Uganda. Looking at the trackers as of today, the day we’re recording this, we’ll see if this stands the test of time: Zero new cases in the last seven days. Really feeling pretty good about this, but we’ll keep folks updated. When I’m on the ground in about 10 days, I’ll let people know what it looks like there in Uganda.

Here we are right into COVID. Let me start by mentioning predictions about the future. As Yogi Berra once said, the hardest thing to predict, the future. We heard that the White House’s COVID-19 coordinator, Ashish Jha, isn’t predicting a severe COVID surge this holiday season. I read the different media takes on this. Does it come down to what we consider a surge? I anticipate numbers will go up. We’ll see what happens. The next article I want to go, I’m going to take a little time because a bit of nuances here. Stay tuned.

I’m going to carefully pick my words as I go through this, really trying to make clear the message. The article, “Changes in Population Immunity against Infection and Severe Disease from SARS-CoV-2 Omicron Variants in the United States between December 2021 and November 2022.” As per this analysis, as of November 10, 94% of the U.S. population was estimated to have been infected by SARS-CoV-2 at least once. Combined with vaccination, 97% were estimated to have some prior immunological exposure to SARS-CoV-2. Pretty impressive. We’re not seeing many first-time infections at this point.

Also, on November 16, we got the COVID-19 data review, “Update on COVID-19-Related Mortality,” from the CDC. Despite a lower number of COVID-19-related deaths reported to date in 2022, as per CDC, COVID-19 remains the third-leading cause of death in the United States, trailing only heart disease and cancer. The majority of deaths are in those 65 and over. With widespread vaccination COVID vaccination in those 65 and over, the majority of deaths are in the vaccinated, right? How many of these unvaccinated people are still around? Only 20% of deaths are in the rare, vanishingly few, unvaccinated folks.

So to state this another way. The majority of people dying of or following a diagnosis of COVID are vaccinated and in many cases, this is not their first infection and we have a figure here and as I told people last time, if I put a figure, now as I read these numbers, Vince will be distracted because his PhD, he’ll be looking at the figure the whole time.

If we focus on the 65 and over, that’s where we’re seeing most of our deaths of those dying, 20% unvaccinated, 30% primary series only, 45% vaccinated, and boosted about 5% with two or more boosters. Now my comment, as we’ve discussed only about 3-to-4% of eligible high-risk people are getting early antiviral treatment. We’ll talk a little bit about that. It’s easy to run the numbers on what that means.

The vast majority of those dying from COVID are those not getting early treatment. The science very strongly supports the incredible benefits from vaccination but why fail to treat high-risk individuals with effective early antiviral treatment just because they are vaccinated or survived the first infection? My call to arms, never miss an opportunity to vaccinate but also never miss an opportunity to provide effective early treatment for high-risk individuals before the opportunity window closes.

VR: Daniel, this fact that many deaths are occurring in vaccinated people is being used by anti-vaxxers to say, look the vaccine doesn’t work, right?

DG: That’s why I was so careful to walk through this slowly because that’s what they’re saying but there are very few unvaccinated people left who haven’t died already. This was always – I think this was good because, when we were in Seattle and one of our colleagues, who will remain nameless, ended up sick with COVID and so, “I’ve been vaccinated, vaccinated people don’t die of COVID,” and I was like, “You know what? The majority of people who are dying, those 300 to 400 people we talk about every who die of COVID, 80% of those have been vaccinated.” As we saw, 45% of them vaccinated and boosted.

I think it’s important because when we say what makes you high risk, a lot of people have this binary, you’re vaccinated, you’re not going to die of COVID. We need to realize the majority of people dying are 65 and over, they have medical issues, they are vaccinated, so just the fact that you’re vaccinated does not mean you should not be offered the benefit of early therapy. All right. I always like to mention children, COVID, and other vulnerable populations. Children are at risk of COVID and just to remind people during the period of Omicron predominance, that’s when the majority of the children that died, died.

Now that we’re going to be around the holidays, use those tests intelligently. There still certainly is a rule before going to one of these gatherings. Remember COVID can spread without symptoms so a COVID test is a great thing to consider before you spend time around high-risk folks. Even if you don’t have symptoms and boy, if you have symptoms and you’re sick, do you really want to make people you care about sick? Mask, we keep talking about lots of concerns about the quality of the studies, but in general, science favors mask use and suggests a hierarchy.

Ventilation. Oh, I love this story. I love this H and P, History of Present Illness. The story of a lady who presents with what she thinks is a bad cold and she tells us that she started experiencing symptoms shortly after opening a window which brought a draft in. Apparently, she caught a chill. I was in one of the patient rooms today and one of the nurses asked me if I could help open the window and I got it open. A nice little fresh air came in and I said, “Oh my, now this patient is going to catch a chill.”

[chuckles]

Shortly after this, she began to feel ill, over a week had gone by, no treatment, came into the hospital. She has COVID, she’s now hypoxic. I’d like to point out that around the holidays if people have those windows cracked, they’re trying to let the fresh air in, that will not make you sick. That will reduce your risk of getting sick, OK? Leave those HVAC system fans, just leave them on the “on” setting, not auto. That’s better for the fan. It’s better for you. All right.

COVID active vaccination. Never miss an opportunity to vaccinate. Vaccinated people still get infected, they are just less likely to die or have severe disease. I’m going to talk about a couple articles and Vince will certainly jump in because this is an area that I know Vince is very interested in. We’re going to be discussing boosters, so let’s talk about COVID vaccine boosters, timing, durability. The article, “Effectiveness of the COVID-19 Vaccines against Hospitalisation with Omicron Sub-lineages BA.4 and BA.5 in England,” was published in The Lancet Regional Europe.

I’m going to go right to Figure One. Incremental vaccine effectiveness against hospitalization. I had to add that in. That should have been in the figure, with BA.4, .5 and BA.2 in England compared using individuals who received a second dose at least 25 weeks prior as the baseline vaccine efficacy for all the manufacturers and we get to look through in A, is going to be the BioNTech Pfizer in B is going to be the Moderna and then in C, we’re going to look at third and fourth doses.

A couple of interesting things as I go through. Very effective during that first zero to one weeks. Interesting (chuckling), continues to be very effective in that two to 14 weeks. That’s what it’s doing, its job. But you really see for all of these different scenarios when you get to 15 to 24, you start seeing the efficacy effectiveness drop. When you get to 25-plus weeks, the vaccine effectiveness is really actually dropping quite low.

VR: Daniel, this is an ancestral vaccine, not a bivalent vaccine, right?

DG: This is true. Now it’s interesting. This is vaccine efficacy against hospitalization so it’s actually against severe disease and we’re seeing this drop over time. Now, of course, this makes you say, well, if I’ll just get a booster, it’s going to shoot right back up. Well, we can’t just make assumptions, we need science so don’t worry, we’re going to get into the science. What if we go ahead and we actually give those bivalent mRNA booster vaccines? We will cut to the MMWR early release, “Effectiveness of Bivalent mRNA Vaccines in Preventing Symptomatic SARS-CoV-2 Infection, Increasing Community Access to Testing Program, United States, September – November 2022.”

Here, they’re going to report the relative vaccine effectiveness against symptomatic COVID-19 of a bivalent booster compared with that of two or more monovalent vaccine doses among persons for whom two to three months and greater than eight months have elapsed since the last monovalent dose. Let’s, go through these numbers so they’re going to tell us 30% and 56% but let’s actually run the numbers here. I’m going to move right to Table Two. What do you think, Vincent?

VR: What are they defining as vaccine effectiveness?

DG: This is efficacy against symptomatic COVID-19 so we’re not talking about death, we’re not talking about hospitalization. We’re not talking about Long COVID, right? That’s another. I’m just saying symptomatic COVID-19.

VR: Any kind of symptom right?

DG: Any symptoms at all.

VR: All right, good.

DG: All right. Let’s look at the table. We’ll cut to the table so let’s say you are greater than 65 and now you’re going to get your bivalent vaccine. You’ve had a couple of doses, 32%. [crosstalk] doses –

VR: Previously two and then you’re getting one bivalent dose across all these, right?

DG: Yes. You’re going to find yourself on the table. You can say, how many doses have I had and now you are going to get the bivalent added on. You come and you say, what? I just got two doses. I didn’t get boosted. This is my first booster. I’m over 65. That’s what I’m going to focus on here because we’re focusing on the high-risk folks that effectiveness vaccine efficacy against symptomatic COVID-19, you’ve had two doses. You get the bivalent 32%. You’ve had three doses, this is your fourth shot, 19%. You’ve had four doses, this is your fifth shot, 23%.

VR: Doesn’t make any difference, does it?

DG: It’s just not as impressive data as I think we were being. We were told early on if you get your bivalent booster, we’re not going to have a surge this winter. It’s all going to be great. It’s going to be like 1999. What I want to do here is, I still and I’m going to talk to the point of, I still broadly recommend bivalent vaccines. I think we have to be honest and realistic. This is not a game-changer. This is additional benefit, and this is giving us actual numbers.

VR: What is the VE for people, say 65 and over, two doses, no bivalent booster? I want to know that number.

DG: To some degree, we got that from the stuff we looked at up above, talking about the durability as we went forward, just really a second dose after that baseline. We are seeing a drop. Unfortunately, we’re not seeing that – We were hoping really a restoration back to a 90% reduction. We’re not seeing that. All right. Let’s cut to some real-world advice. I’m going to respond to a listener who can’t send us an email. For my covert ops friend in the CIA who wants advice about when to get that bivalent booster after your most recent COVID infection. You know who you are. Don’t worry, no one else will know unless you get all awkward listening to this.

[chuckles]

Timing matters. If you’ve never been vaccinated, I actually recommend – you have been vaccinated – but for those never been vaccinated, I recommend going right away with those vaccines. I really reference the impact on Long COVID and those studies showing that people who are vaccinated and start that series soon after have reduced risk of Long COVID persistence. If you’re already vaccinated and you get infected, as we’ve talked about before, there’s no real benefit. There’s no raise in antibodies if you get vaccinated within three months of that infection. I think of this as a boost that infection. In general, the recommendations are now, and this is a change, if you get COVID, put off that booster three months at least.

COVID passive vaccination. This is a bit of a sad part. There are a bunch of Evusheld package insert updates. Basically spoiler alert. We pretty much lost Evusheld. Let’s talk a little bit about the updates. The updates really tie in why we’ve lost this. Here they’re showing the susceptibility, the fold reduction in susceptibility, and this is now part or has been part of the monoclonal antibody package inserts. The BA.5 33-to-65-fold-reduction, but then as soon as we get into the BF.7, the BJ.1, the BQ.1, and particularly the BQ1.1. We’re starting to get up to greater than 5,000, several hundred folds, greater than 2,000, greater than 2,000. Unfortunately, with the current circulating variants, this is really becoming ineffective. I will comment on another thing, because again, as I’ve said, we are hoping there will be a new therapy moving into this space.

Another one of the warnings that was added was a warning with regard to cardiovascular events. Interesting it says this, I’m going to talk about the science. “Inform individuals at a higher proportion of subjects who received Evusheld versus placebo reported cardiovascular serious adverse events, myocardial infarctions, and heart failure. Advise individuals to seek immediate medical attention if they experience any signs or symptoms suggestive of a cardiovascular event.” I have to say this was noticed in some of the early efficacy trials. What about this being something we’re actually seeing? I want to mention the article, “Cardiovascular Outcomes after Tixagevimab and Cilgavimab,” so Evusheld, “Use for Pre-exposure Prophylaxis against COVID-19: A Population-based Propensity-matched Cohort Study.” This was published in CID.

In this large population-based propensity match study, they found no increased risk of cardiovascular events after Evusheld administration, including in patients with pre-existing cardiovascular disease. Important to have the science out there. Unfortunately, right now the variants really have made this pretty much obsolete. We’re giving out the last doses and then we’re probably going to stop doing that. COVID early viral upper respiratory non-hypoxic phase, so this is that first week of what is often a several-week illness. Number one, Paxlovid. We’ve got a bunch to talk about here with Paxlovid. Just the logistics here before we get into the literature. The idea is you’re starting that Paxlovid within the first five days. If you’re on a drug like a statin, for instance, you’re going to stop those for those five days plus another five.

It does take a little bit of a thought process to figure out what those medicines are, the risk benefits. This is why we got our Pharm Ds, this is why we went to medical school so that we could handle this. Who do we treat? I want to talk about the article, “What is the Place in Therapy for Nirmatrelvir/Ritonavir?” This was recently published in BMJ Evidence-Based Medicine. The authors are Todd C. Lee at McGill; Jason Pogue, U. of Michigan, Ann Arbor; Erin K. McCreary at U. of Pittsburgh; Andrew M. Morris at U. of Toronto. Really, it’s an interesting article and I think it does a good job of reviewing what we know, what we do not know. I like the way they start with the tensions between supply uncertainty of which patient populations optimally benefit time-limited effectiveness, don’t wait for that to close, due to need for rapid initiation of treatment on an individual level and viral evolution and potential development of resistance on a population level and action bias, i.e., most providers want to do something for an ailing patient.

Now action bias certainly got us into lots of trouble early in the pandemic. The article also does a good job of trying to outline numbers needed to treat and how challenging it is to extrapolate from the limited data we have to how effectively early Paxlovid is in lower-risk individuals vaccinated with multiple doses of vaccine or no multiple infections. They point out how we still need more data and mention the ongoing UK panoramic trial that may provide more clarity. Now with this as background, this is where it gets exciting. I will share another MMWR early release. The timing is perfect. Thank you, guys. “Paxlovid Associated with Decreased Hospitalization Rate Among Adults with COVID-19, United States, April-September 2022.” You asked for more data, so here is some. Note the dates.

This is Omicron. To examine the benefit of Paxlovid in adults aged greater than 18 years in the United States, a large electronic health record (EHR) dataset, Cosmos, was analyzed to assess the association between receiving a prescription for Paxlovid. Interesting. They didn’t say if you actually took it, just did you get a script? I bet it would be more effective if you actually took it. Anyway, just a script, and hospitalization, intention to treat, with a COVID-19 diagnosis in the ensuing 30 days. What was the association between writing a script for Paxlovid and whether or not a person ended up in the hospital during the next 30 days? They reported that among 699,848 individuals aged greater than or equal to 18 eligible for Paxlovid during April through August of 2022, 28.4% received a Paxlovid prescription within five days of a COVID-19 diagnosis, so pretty impressive.

What did they find? Being prescribed Paxlovid was associated with a lower hospitalization rate among the overall study population, an adjusted hazard ratio of 0.49. Overall, 51% reduction in hospitalization in the next 30 days. Among those who had received greater than or equal to three mRNA COVID-19 vaccines, adjusted hazard ratio of 0.5. So 50% reduction in folks that have gotten three or more mRNA COVID-19 vaccines. Across all the age groups in those 18 to 49, a 0.59, so a 41% reduction; in those 50 to 64 hazard ratio of 0.40, so a 60% reduction. In those 65 and over, a 47% reduction in hospitalization in the next 30 days. There were similar reductions in the unvaccinated. There was a reduction in those with and those without prior infection. They have a really nice table too that breaks down all these subgroups.

With that as an outline, and with all that data in front of you, I will reference an article in El Atlantic, “Inside the Mind of an Anti-Paxxer,” by Rachel Gutman-Wei. I like the coining of the term anti-Paxxer. It’s really interesting. I do want to remind all these folks who have spread misinformation about COVID-19 rebound and wondering what could possibly be gone wrong at this point. I’ll read a quotation right from the article. “Those who outright refuse Paxlovid are not obsessing over microchips or government overreach.” Instead, they mostly tell her that they’re worried about treatment side effects and rebound infections of the virus.

Remdesivir, a little bit of good news here I have to say. Number one Paxlovid. We heard the data there, pretty broadly effective in a huge real-world observation. Number two, the next choice Remdesivir.

We’ve talked about the pine tree data where in the first seven days, only three days of remdesivir can get this 87% reduction. Probably a little lower if we really look at real-world in the vaccinated, et cetera, et cetera. Exciting movement here at Columbia Presbyterian, I’ve been talking about how the Catholics have rolled out early access for those three days during the first week, but effective Monday, November 21, 2022, a new ambulatory referral process for three-day remdesivir infusion in high-risk patients was rolled out at the Columbia Presbyterian hospitals.

Outpatient IV infusions, we can leave links, actually, so patients can actually access this through some of the links we’ll share there. Providers can actually use Epic to get this set for folks. Number one, Paxlovid. Number two, remdesivir, and as we’ve pointed out number three is gone, the monoclonals. We’ve really lost our monoclonals at this point. The Catholic hospitals in the area stopped using the monoclonals, then Columbia, then Stanford, most other parts of the country, and just today as I’m recording I got noticed that Northwell, the largest healthcare system in New York has decided they also will suspend providing monoclonals that are no longer effective.

Four, last, and least, I was a little shocked by one of the comments from a physician from Maine in the article in The Atlantic where he was touting that he thought that molnupiravir was really the best choice. Remember this is last and least, maybe a 30% reduction in progression. A lot of studies in real-world just not really showing much benefit. A last and least perhaps better than doing nothing and certainly better than doing something harmful. Remember no steroids during that first week. You are going to increase the risk of your patient doing poorly. If you take them you’re going to increase your risk of doing poorly. Remember this is a virus stop using amoxicillin, azithro, and doxycycline to treat viruses.

Week number two, the early inflammatory lower respiratory hypoxic phase. This is the second week. This is the inflammatory stage. The natural history of the disease is to feel crummy during that first week, start to feel a little better and then feel crummy during that second week. As we’ve discussed it’s also pretty typical for your antigen test to turn negative on about day five or six and then turn positive in a chunk of people during eight, nine, and 10. I’m not really sure why people keep checking those antigen tests, but remember this is COVID rebound.

This is not Paxlovid rebound. Do you know what the great thing about Paxlovid is? During that second week, if you start feeling crummy your chance of ending up in the hospital has been reduced by half. Paxlovid does not turn this from a five-day illness into a 14-day illness. This is a 14-day illness. If you end up saturations below 94%, steroids, some mortality reduction in the right patient at the right time, anticoagulation, pulmonary support, maybe remdesivir if we’re still in the first 10 days.

Immune modulation but avoid unnecessary antibiotics, unproven therapies. I am going to right here, discuss another article. The article, “Angiotensin Receptor Blockers for the Treatment of COVID-19: Pragmatic, Adaptive, Multicentre, Phase 3, Randomized Controlled Trial,” published in the BMJ. These are those ARBs. There was a lot of hope that there might just be some inexpensive, widely available drug that we already have sitting on the shelf there for some other purpose that we could repurpose for the treatment of COVID-19.

There are precedents here. That blood pressure medicine that you rub on your head that has the side effect of growing hair, Rogaine, I think it’s called. I tried that myself. Doesn’t really work. Just people who are watching on YouTube. Apparently, you have to actually use it all the time. I grew tired of that after a week. That angina medicine that we now know as Viagra apparently has some other uses.

Even aspirin for headache is apparently an effective treatment for people having heart attacks. Investigating repurposed drugs has, on occasion, worked. With COVID the time pressure really got people excited. Let’s try to find something. If we can only find something maybe just a stop measure until we develop effective targeted therapies like Paxlovid, for instance. Here are the results of the CLARITY trial, which was a pragmatic adaptive multicenter phase three randomized controlled trial conducted at 17 hospital sites in India and Australia.

Seven-hundred-eighty-seven participants were randomized; 99% were from India. Basically, this is India, nine folks from Australia. The median WHO scale score at day 14 was one. Basically, the trial was stopped with a pre-specified futility outcome. They concluded in patients admitted to a hospital for COVID-19, no evidence of benefit was found for treatment with the angiotensin receptor blockers.

VR: Not surprised.

DG: It seemed like it made some sense on some level but again they’re using it during the second week. That doesn’t make a lot of sense.

VR: If you know Daniel, people tried treating HIV with CD4.  It just didn’t work. Even CD4 blockers, it’s just not a good target.

DG: Now we will move into the late phase and PASC and I have some good stuff here to talk about. I always leave a link into that BMJ paper, “Long COVID – An Update for Primary Care.” I will also leave a link to STOP-PASC, a Long COVID treatment research study. This is a study looking, and we’ve been talking about this, looking at Paxlovid in folks with Long COVID.

Don’t know if it’s going to work but I do think it’s worth studying. The participants must have more than three months of Long COVID symptoms so meeting current definition, current criteria for Long COVID, PASC. Some of the folks are going to end up getting Paxlovid. Some will end up in the placebo. It’s two-thirds getting Paxlovid to one-third on placebo. This is actually a longer course. I think it’s actually 15 days of therapy.

One limitation that involves five in-person visits to the Stanford research site. Actually, on the intake form, they actually ask you, are you within two hours’ driving distance of Stanford University located in Palo Alto, California? It’s also adults. It’s 18 and up.

Also, this is a bit of reading if you can’t sleep, a report on Long COVID was recently published by HHS. It is an 88-page document. It’s a well-done report. We’ll leave a link, but I like their introduction.

I read the 88 pages. “Within weeks of the first documented cases of COVID-19 United States in 2020, people who had been infected from all backgrounds and communities began reporting symptoms lasting or fluctuating for weeks, months, and with the passage of enough, time years. Long COVID one of the many terms used to describe this infection-associated chronic illness is now estimated to affect between 7.7 and 23 million Americans at the time of this report’s publishing.”

People may argue back and forth what percent but just to give folks, there are millions of Americans still suffering. People may have heard that Biden officials have asked Congress for $750 million aimed at accelerating research and treatments for Long COVID, part of a broader $9.25 billion request for emergency aid to combat the pandemic. As I always like to finish, no one is safe until everyone is safe.

I do want everyone to pause the recording right here. Even those friends and family members who are listening for the first time, you can be part of this. Go to parasiteswithoutborders.com. Click on the donate button. Every small amount helps us continue our work. We are now doing our MicrobeTV fundraisers. During the months of November which is going to end soon, December and January, donations to Parasites Without Borders will be matched and doubled by Parasites Without Borders up to a potential maximum donation of $40,000 to MicrobeTV.

VR: MicrobeTV is the company that does all these podcasts including this one and the other TWiV, TWiP, and TWiN, et cetera. We’d love to have your support. It’s time for your questions for Daniel. You could send them to [email protected]. Jeremy writes, “Do you think it’s safe to reuse clean N95 masks if they are set aside for a few weeks in a bag?

DG: Early in the pandemic what I was actually doing is I had seven brown paper bags in my car and I had a different N95 and I was rotating them that way. We can use them for up to two weeks. There’s how they’re packaged, there’s what we did during the pandemic. Would the science say it’s safe to do what you’re thinking about doing? I’d say yes. Was it something I did and still have not gotten COVID? Yes, but don’t use someone else’s N95, use your own N95.

VR: [laughs] Rebecca writes, “My 18-year-old vaccinated daughter got COVID in mid-September, was sick for about eight days. She had a gradual recovery but six or seven weeks later, when the weather started to turn quite cold here in Ohio, she suddenly developed cold urticaria. Really terrible hives breaking out wherever her skin is exposed to the cold. She also seems to have developed other skin rashes, and eczema-like symptoms. Have you seen anything like this in your post-COVID or Long COVID Patients?

DG: Yes, so certainly, actually, quite a bit of this. Enough of this, that actually, this is one of the subsets described in the Long COVID update for primary care. There’s even subtleties here, is this being histamine driven? Actually, sounds like some of it is. This is something we see it’s something that is described and it’s also something that we’re getting experience successfully treating. Reach out to someone with experience treating post-COVID conditions.

VR: Dave writes, “I’m a CVS pharmacist but not an official representative of the company, and I don’t speak for them. I can clarify how Paxlovid prescribing is being handled. First, you take a home test if that’s positive, you go to CVS’s website, click on the section to schedule a test. From there, you can scroll down to treatment, make an appointment for Paxlovid, all of those appointments are handled via phone call. We have to be able to find recent kidney function tests in Epic somehow,” not sure how that works.

“If you qualify for a Paxlovid script, we send it to ourselves, you can pick it up through the drive-through or have a friend or family member pick it up. It does cost approximately $60 for the appointment, and that’s not paid for insurance as far as I know. I think most pharmacists are glad our scope of practice is expanding to be able to help do this, but we’re pleading with people to understand that our computer system will allow for up to four Paxlovid appointments per hour, in addition to eight vaccine appointments per hour as well as our normal job duties, including but not limited to filling anywhere between 500 and 1,000 prescriptions or more a day with very little staffing, so please be patient with us.” Hope that helps, Dave.

DG: Now that’s fantastic. Thanks, Dave. That is fantastic. Just a shout-out to all our pharmacy colleagues out there. What a tremendous job they’ve done, what they’ve been through these last three years, and things sort of unappreciated. What is this Epic, just clear clarity there. A lot of healthcare systems Columbia uses Epic. The Catholics use Epic. We started a joke that everyone’s on Epic except for Northwell.

Within Epic, when you get labs done, you as a patient can actually share access to different providers. This is just a great electronic health record where folks can get information, what medicines are you on? Sometimes you find that they were prescribed something by another provider that you didn’t know about, important to know for drug-drug interactions. You can also access labs, radiology, so really a great way to get that information, so excellent.

VR: Finally, Kevin writes, “In Ontario, the Moderna multi-valent booster used targets BA.1. The Moderna BA.4-5 targeted version is not approved here. The Pfizer multi-valent booster targets BA.5 and is approved in Ontario. I imagine that was why the doctor in question,” that was our last episode, “was recommending Pfizer over Moderna. It’s a question of interest to me since I got the Moderna BA.1 booster in October, just an FYI.”

DG: Now, that’s great. I don’t know if that person was from Canada, but if they were, kudos.

VR: I think they were, something like that.

DG: Then it would make sense.

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

DG: Oh, thank you. Happy Thanksgiving to all our listeners. Even though you’ll probably be listening to this after Turkey Day, be safe.

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