TWiV 868 COVID-19 Clinical Update #102

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 19 February 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 868, recorded on February 17, 2022. I’m Vincent Racaniello and you’re listening to the podcast all about viruses. Joining me today here at The Incubator, Daniel Griffin.

Daniel Griffin: Hello, everyone, and hello, Vincent.

VR: Welcome back to New York.

DG: It’s kind of nice coming back to the city.

VR: Oh, this is a lovely place to work. It’s just me. Nobody to bother me. I don’t mind you being here.

DG: All right. On that note, shall we get going?

VR: Yes.

DG: Let me start with my quotation. “It is a capital mistake to theorize before one has data. Insensibly, one begins to twist facts to suit theories instead of theories to suit facts.” This is Sherlock Holmes. This is Arthur Conan Doyle speaking through the character of Sherlock Holmes. This is from A Scandal in Bohemia. As we go on, I’ll make a couple of references why I bring this up.

A big thing with science is you want to see what the data shows you and then you want to come up with your theory. You don’t really want to be a cheerleader. You don’t really want to go into science with an agenda wanting to have a confirmation bias and then being all excited when something supports your theory, your agenda, and then trying to discount it when it doesn’t. It’s important to, I would say, approach science with that maturity, that objectiveness. Let’s get right into our update.

Still, lots of people dying each day here in the U.S. from the Omicron variant. I want people to think about when they use the word “mild” relative to that variant. We had 2,802 deaths this Wednesday. Just yesterday, the day before we record this, looking at the date on Worldometer, about 100 deaths here in New York. The width of this Omicron peak in terms of cases and numbers has been about as wide as the Delta peak when you look at it, but much higher in terms of both cases and deaths.

This, I think, could have been predicted because the U.S. is a large country, so it takes time for a wave to spread across the country. If you look regionally, each region is going to have a slightly narrower peak. Pediatric deaths, this is really tragic. We are now up to greater than 850 pediatric deaths from COVID as of the 10th of February when we have the latest data. There were another 23 deaths just in the week ending 2/10. We’re still averaging over three children, three pediatric deaths per day from COVID here in the U.S. I was on a call with Mark Denison earlier this week. What a bright, pleasant guy. I like Mark.

VR: He’s been on TWiV.

DG: Yes, I brought that up.

VR: Twice.

DG: We were talking about the fact that– so he’s at Vanderbilt and he was talking about, “If this just affected children, the thousands of children hospitalized due to MIS-C alone would have really had us frightened.” Somehow, the fact that three children are dying a day, the fact that the numbers are higher in adults, I’m not sure the logic there.

As I like to always say and we’re going to get right into children, children are at risk from COVID. I think that needs to weigh in when people are making those vaccine decisions, which we’ll get into.

The first, we’ll start with a little bit of bad news. I was hoping we would be talking about the FDA discussion. Unfortunately, what we heard from Peter Marks, who heads the FDA’s vaccines division, when they were going to look at the data, potentially weigh in on vaccination for the under five, and I will quote Peter, “The data that we saw made us realize that we needed to see data from a third dose in the ongoing trial in order to make a determination that we could proceed with doing an authorization.”

Pfizer-BioNTech say they expect results on the three-dose series in April, so going to have to be waiting a little bit, at least for the mRNA vaccines here in the U.S. After that little bit of bad news, we do have, I’ll say, a little bit of encouraging data. This is the MMWR report, Effectiveness of Maternal Vaccination with mRNA COVID-19 Vaccine During Pregnancy Against COVID-19-Associated Hospitalization in Infants Aged < 6 Months – 17 States, July 2021 – January 2022.

Basically, what was the takeaway from this report and the takeaway that I think is reliable? Effectiveness of maternal completion of a two-dose primary mRNA COVID-19 vaccination series during pregnancy against COVID-19. Hospitalization among infants aged less than six months was 61%, a 61% reduction in these under six ending up in hospital. I think this really goes along with that maternal transfer of protection.

They do acknowledge several, “several,” I’m going to say seven limitations. The reason I give the data that I do is because of these limitations. Let’s go through. What are the limitations here? Encouraging women to get vaccinated before pregnancy, during pregnancy. One is we really don’t know about specific variants. That’s going to be data that’s going to have to come. Second, when during pregnancy, right? This was too small a sample to really know about timing.

Third, they didn’t really assess whether the pregnant women had infection with SARS-CoV-2 before or during pregnancy, so we’re not sure about the role of prior infection. There’s a lot of other confounders here, right? This is not a big enough data set to know about, “Well, what about breastfeeding? What about child care attendants? What about prematurity?” This is reporting, so are we getting all the data? Anything being misclassified here?

What about immunocompromised during pregnancy? Then I think this is also a really critical question. What about boosting? What about the role of boosting? Let’s say you were vaccinated early in pregnancy and maybe you’re vaccinated before pregnancy. What about maybe a boost during that third trimester? That’s logically what we would think about, but it would be nice to have the data on those.

VR: Daniel, when in pregnancy is the best time to be vaccinated if you’re not yet vaccinated?

DG: I would say as soon as possible because we’re going to get into data on the fact that getting infected with COVID-19 during pregnancy not only puts the pregnant woman at risk but doubles your chance of losing the baby, right? Then do you want to maybe do a boost at that third trimester to get a high level of antibody transfer? That’s sort of the data I would like to see as well. We want to see women get vaccinated. Getting COVID-19 is not great if you plan on getting pregnant. Getting COVID-19 is not great if you are pregnant. Vaccination is much safer. I know this is a target of the anti-vaxxers, but vaccination is the safest thing to do for women of childbearing age.

All right, testing. I’m going to tell a little story here that I said, “This a great story.” Well, you can tell I’m an ID doc as the hospitalist laughed at me this morning. I saw a gentleman today, just ended up admitted to the hospital. His story was he started to feel not so great about a week ago. Last weekend, not feeling so great. He felt like he was fighting something off. He went to a party, big party. Where was this party, Vincent?

VR: Well, it must have been a Super Bowl party, right?

DG: In LA. He flew to LA.

VR: Oh, he flew to LA. Wow.

DG: He flew to LA, went to this big party. There were no masks involved in this big party. He wasn’t feeling great. Then now, he started having trouble breathing, ended up showing up in the ER, and he tested positive for COVID-19. This is a gentleman who showed up at that party, probably at that peak of contagiousness. It would have been great. Go ahead, do that test. Still a big role of testing, so that would have been–

VR: Was he vaccinated at least?

DG: No, he was not vaccinated.

VR: Oh great. Traveling, feeling lousy, not vaccinated, all great responsible moves. Not surprising, they’re a football fan. We’re going to get letters to sign.

DG: I’m a football fan. I enjoy the Super Bowl.

All right, so pre-exposure period, right? We’re actually expecting some updated guidance on masks very soon from the CDC. When that comes out, we’ll discuss it. Vincent, you have strong feelings on masks, right? Actually, my cousin called me the other day. He’s like, “All Vincent wants is to start teaching with his mask off.”

VR: I do. I think we have vaccines that work. You can disagree with me. Look, early in the pandemic when we didn’t have vaccines, I was all for masking. I still wear my mask because in the subway, you have to. At Columbia, I have to. New Jersey Transit, I have to. Wherever else, if I go to a restaurant, you don’t need to wear a mask. I feel we have vaccines that work.

There are people who have made the decision not to be vaccinated. I don’t particularly want to change my life for them. Why don’t they change their life for us, right? They don’t want to do that. Secondly, I’m of the opinion that vaccination reduces shedding and duration and level, so the transmission is very low unless there are two cases where a mask may be appropriate. First of all, of course, less than five years of age where you can’t be vaccinated, right?

We have to be careful about those kids and very elderly people and also immunocompromised people. We have to be careful in their presence. In my class at Columbia, none of those apply. I think it would be much better to have everyone’s masks off because you can see people’s faces and get a better sense if they’re learning or not. I really think that New York and New Jersey dropping the mask mandates is the right move.

DG: Yes, I was trying to stick to the science and keep my opinions to myself. As we talked about a little bit before, you take your class, which is perfect example. You’re sitting up front. Actually, ideal body weight, I probably should lose a few pounds.

You’ve been vaccinated. You don’t have any immunocompromising conditions. The students in the class, in general, are young, are healthy. They’re all vaccinated, required to be so. If someone was immunocompromised, they could potentially wear a KN95 or N95, make some choices. I think that the science is getting to the point where if people wanted to be vaccinated, they can. I was asked the question, it’s not rhetorical like, who are we protecting? You listed the right people. We’re still trying to protect those people under five.

A lot of adults are now saying, “Boy, I need to get my kids vaccinated because the masks are probably going to be coming off and they’re going to get exposed.” I think the science is very clear. It’s much safer to be vaccinated than it is to get COVID. We’ll be talking about more data today. Now, we’re getting to the point that tools are starting to become more available. We’ll talk a little bit about the small-molecule inhibitors. I think that’s where the science is moving us and I think the guidance– We’ll be talking about that as it rolls out.

All right, active vaccination. This is a reminder and, actually, it went up from Columbia. By the way, it was a little bit off. By the way, Magda, your signature is on there. Magda is the head of the ID department. It was a reminder that the CDC recommendations for the COVID-19 vaccination schedule for moderately or severely immunocompromised people is a little bit different.

The current recommendations are a three-dose primary series, and then they later get a boost. Actually, the timing of that boost has been recently updated. Actually, if you go to the website, and clinicians who are caring for these people really should go here, there’s a flow-through. It’s a little complicated, depends on the age, et cetera. That third booster dose is recommended, at least three months.

That’s a change after completing that primary series for adults. There are some specific recommendations for kids, certain situations where a booster is not recommended yet, but just keep that in mind. The general recommendations are a little bit different, so we have a nice resource to the CDC to help walk through that. They even have a little bit of a mention and algorithm for, what do you do when J&J is in the mix? Okay, this is a study– I really like this study.

Now, at the start of the vaccine rollout, I had concerns about this approach of cutting out the primary care providers and putting all the vaccines in the hands of governors, putting all our resources into these large state-run vaccination sites, I always say, with a military presence, which always makes me a little bit uneasy. I like the idea of giving people the opportunity to discuss medical decisions, including vaccine choices, with a trusted primary care provider. That could be an MD, a DO, a nurse practitioner, a physician assistant, et cetera, really giving people the chance to express, “What are my concerns? What are my questions?”

Because if we don’t, as health professionals provide this information, there’s plenty of people out there with an agenda to provide misinformation. The article, Association of Primary Care Physicians Per Capita With COVID-19 Vaccination Rates Among U.S. Counties, was published in the JAMA Network Open. The authors conducted a cross-sectional study of really over 87% of all the counties, county equivalents in the U.S. We have some interesting county equivalents. They really just looked at, say, how many primary care physicians per capita there were in a certain region.

We’re able to show that the number of PCPs per 100,000 population was independently associated with higher COVID-19 vaccination rates in the U.S. I think this just really reinforces that PCPs and the whole list that I mentioned can really play a critical role in counseling and building local community trust, partnerships, helping with access to vaccines. I think there’s a lesson here. Going forward, we can provide opportunities for discussion and education rather than relying so much on this stick-and-carrot approach. It’s a little opinion. I put a little opinion on that.

Okay, so safety information for boosters. This has been interesting because a lot of people now have sort of come down. They’re required to get that booster before a certain deadline. A lot of people had concerns about safety. It was nice to get this MMWR early release, Safety Monitoring of COVID-19 Vaccine Booster Doses Among Adults – United States, September 22, 2021 – February 6, 2022. It’s hot off the press. Basically, what they were seeing is really not much of a safety issue.

Really, the reactions that we were seeing with that third dose, people feel crummy. You feel crummy for a day. Some people feel crummy for a week or so. As far as serious adverse events, we’re not seeing much of a signal. If anything, this looks safer and even lower risk than that second dose. I would like to mention myocarditis because everyone worries about that. They mentioned myocarditis was very rare after third doses. Even when you get to that highest rate, people worry about men aged 18 to 24.

We’re talking less than one in 100,000 even as a high-incidence group. Then, again, this is that greater than 90% of the time, it self-resolves 24 hours or so. Now, we can say this. We’re not seeing long-term issues with this vaccine-associated rare event. Really, really safe. I don’t want people to have fear. Apparently, there’s a lot of misinformation. Even my, say, medical colleagues, social media, et cetera, they’re actually frightened. No, we’re all going through this. It’s being well-tolerated. It’s very safe.

VR: Is the incidence of myocarditis after dose three less than previous doses?

DG: It’s significantly less than after dose two.

VR: Two?

DG: Yes. Actually, a couple of logs lower, so it’s very uncommon, which is good. This gets back to a little bit of what we talked about, this misinformation. Targeting women of childbearing ages is very troubling. Here’s a paper that I think just reinforces that it is not good to get COVID while pregnant. This is the paper, Placental Tissue Destruction and Insufficiency from COVID-19 Causes Stillbirth and Neonatal Death from Hypoxic-Ischemic Injury: A Study of 68 Cases with SARS-CoV-2 Placentitis from 12 Countries. I find that word hard to say.

It’s published in the Archives of Pathology & Laboratory Medicine. As we’ve talked about repeatedly, there’s now a significant amount of information that getting infected while pregnant not only threatens the life and health of the mother but can also significantly increase the risk of losing the unborn child. Here, the authors looked at 68 placentas. These were placental autopsy pathology from 64 stillborns for neonatal deaths. A neonatal death, this is the baby actually is born but dies within that first 28 days. They have the micro and macroscopic, right?

You’re actually seeing the severe destructive placental disease involving the majority. They say, on average, 77% of tissue involvement, multiple thrombi, chronic villitis. There’s no paywall, so you can actually go. You can take a look at this article. You can actually see the microscopic and the macroscopic or, we like to say, gross findings. Pretty concerning here. Just more encouragement, more science behind the importance of getting vaccinated.

Passive vaccination. We still have EVUSHELD and we’re continuing to use that. Being very well-tolerated.

All right, the period of detectable viral replication. You’ve tested positive. You’ve got that virus. It’s that first week. I like to say, the time for monitoring monoclonals, antivirals, enrollment in clinical trials, not the time for steroids. Particularly, someone’s been vaccinated. Now, we’re shutting down their immune system. We know that that increases the likelihood of them progressing, not the time for antibiotics. This is a virus.

Today, we’re going to talk a little bit about one of the antibiotic meta-analyses. Not the time for zinc. We see a lot of GI distress. Not helpful. Not the time for aspirin. We’ll be mentioning the anticoagulation guidelines. Not the time for unproven therapies, but potentially, a time when you can get an individual enrolled in a clinical trial. Just an update on the antibiotics, I feel like I’ve got to keep reinforcing this.

Well, I’ll just say I’m going to keep reinforcing this. This is a virus, not a bacteria, not a fungi. This is the article, Azithromycin in Patients with COVID-19: A Systematic Review and Meta-Analysis, published in the Journal of Antimicrobial Chemotherapy. This is pretty extensive. The authors searched PubMed, Embase, the Web of Science, Scopus, the Cochrane Central Registry of Controlled Trials, MedRx, looking for randomized controlled trials, observational studies. Initially, they started off with 4,950 results.

They then narrowed this down to 16 studies that they considered. Five were randomized controlled trials. Eleven had an observational design, ultimately looking at 22,984 patients. Can you guess? The meta-analysis showed no mortality benefit for those treated with azithromycin, not helpful there. They looked at other outcomes, need for hospitalization admission, time to hospital admission, clinical severity, need for ICU, adverse events, et cetera. Azithromycin was not helpful. I like their conclusion, “Further research on treatment for COVID-19 may need to focus on other drugs.”

VR: How did we ever get to azithromycin in the first place, Daniel?

DG: I have to say, there’s this idea that azithromycin is this wonder drug. It’s anti-inflammatory, it’s antiviral. It’s the Swiss Army knife of therapeutics, but it is not. I was actually going to, “Here we are and I like to reinforce.” I was torturing the residents on the different services this week. I’m going through saying, “Okay, here’s this case. What do we do?” I’m going to share this text and then we’re going to walk through this case because I want all the listeners for TWiV to be basically up to speed on what to do.

I’m going to open up my phone here and get to this text that I got this morning. This is one of the things I really like about being the head of ID for the Optum Tri-State groups is I get multiple of these a day. I love being in this position to sort of reach out. This is an urgent care physician that I know and she reaches out, “What options do I have to treat a 75-year-old female visiting from Florida, who just tested positive for COVID-19? She has CLL,” so chronic lymphocytic leukemia.

All right, so what do we do? Let’s go through this case. We’re going to sort of go through the case based upon, what are the available therapeutics? What did I tell this provider? I said, “Okay, we’ve got three questions and you already answered the first one.” The first one is, is this a high-risk individual? Seventy-five, they have chronic lymphocytic leukemia. Even if they’ve been vaccinated, I’m concerned that they don’t have the protection. This is a person in the first week, confirmed COVID-19, symptomatic we want to treat.

Number one, what is the first thing that we did? We want to consider PAXLOVID. Second question, do we know the kidney function? Third question, what medicines are they on? We went through, discussed the kidney function. We discussed what other medicines they were on. Actually, now, I’m getting really good at even knowing off the top of my head which drugs interact with the cytochrome P450 pathway and then went ahead.

This provider picked up the phone, called Walmart. They’re open in Jersey. This patient ended up on PAXLOVID. They drove over. Same day, started on therapy. Really nice here. We didn’t have to go, but we will go on our discussion to the other choices. Let’s talk about PAXLOVID. We talked before about the press release. Now, we have the peer-reviewed article, Oral Nirmatrelvir for High-Risk Non-Hospitalized Adults with COVID-19, published in The New England Journal of Medicine. That’s PAXLOVID. Nirmatrelvir, what a horrible name.

VR: [laughs]

DG: Maybe they make it so hard because, boy, it’s going to be hard to ever use the generic to talk about this drug, but anyway. These are the results of a Phase II/III double-blind randomized controlled trial in which symptomatic, unvaccinated, non-hospitalized adults at high risk for progression to severe coronavirus disease, COVID-19, were assigned in a 1:1 ratio to either receive the, I’m going to say “PAXLOVID” to make it easy, 300 milligrams PAXLOVID, plus 100 milligrams of ritonavir every 12 hours for five days, or placebo.

Then they’re going to look at COVID-19-related hospitalization or death from any cause through day 28 viral load safety. First, I think this is this nice Phase II/III. We’re sort of truncating our efficacy expansion trials here. It is double-blind, so people do not know what is going on, nor the patients, nor the people handing out these pill packs. It’s randomized, so you’re removing the bias here. Symptomatic, we’re getting within the first three to five days here.

I will point out a couple of things. Unvaccinated, right? We were concerned that maybe this would be limited to only that. As we discussed with a patient here, this is someone who may have gotten vaccinated, but I’m sure they got the protection there. A total of 2,246 patients underwent randomization, 1,120 patients received the boosted PAXLOVID, plus the ritonavir, 1,126 got the placebo.

There was a planned interim analysis of patients treated within three days after symptom onset. The incidence of COVID-19-related hospitalization or death by day 28 was lower in the PAXLOVID-treated group. A relative risk reduction of 89.1%. Zero deaths in the patients treated, seven deaths in the placebo group. This efficacy was maintained in the final analysis. We’re seeing about an 89% reduction. When they follow this out, zero deaths in the treated group, 13 deaths in the placebo group. I want to be in the treatment group.

They said “viral load,” but I fixed that. The RNA copy number was lower in the PAXLOVID than the placebo treated at day five of treatment when they got the drug going within the first three days. Maybe this helps with making these people less contagious, shortening, helping with the spread. There were a few side effects. The taste was off, dysgeusia. About 5% of people that got drug reported that. There was some diarrhea, 3% versus 1.6%, so a little bit of loose stool.

If you look at subgroup analysis, and I think maybe this reminds people of the molnupiravir discussion. It’s nice to look it down and say like, “Well, what about people with or without diabetes? What about people who are heavy, not so heavy? What about age, less than or over 65 years of age, male, female, et cetera?” Really, all subgroups looked like they were seeing benefit. Really encouraging. It doesn’t look like there’s any outlier group, so very encouraging. Now, we’ve got the peer-reviewed data that everyone can take a look at.

VR: How much was the RNA load reduced? Do you remember?

DG: I took it out because it was only about a log. I was not that impressed.

VR: Maybe in a challenge study, they could give them this drug and see how much infectious virus it decreases.

DG: That’s what I would love, right? With all the issues I might have in the challenge trial, I like the fact that they were actually doing viral isolation.

VR: Yes.

DG: That’s why I changed it too because all they’re doing is looking at RNA copy number. I don’t know. Is that defective virus? Particularly, if you think about it, it’s interfering with the protease. There may be a bunch of RNA, but I’m not sure how much of that RNA is defective virus.

VR: Sure.

DG: All right, PAXLOVID, number one. Let’s say for some reason, you can’t give them PAXLOVID and you need to drop down monoclonal therapy. Not much of a drop-down, really similar efficacy here. Right now, we’ve lost a number of our options. We still have sotrovimab. We do have more on the way, which we’ll be talking about. Is sotrovimab going to keep working now that we’re starting to have an increasing percentage, increasing prevalence of the Omicron sublineages?

I think it’s just incredibly humbling, this whole pandemic. The pre-PRA antibody evasion properties of SARS-CoV-2 Omicron sublineages was posted at David Ho’s lab with a number of authors, including Magda Sobieszczyk, the head of– I’m sure I’m pronouncing that wrong, Magda, so I apologize. Magda and I were actually supposed to be meeting right before this meeting that got postponed.

This investigation looked at the ability of different monoclonal antibody therapies to neutralize different Omicron sublineages. The WHO is looking at four sublineages of the Omicron variant. This paper looked at two sublineages. I’m going to sort of make this simple, the BA.1 and the BA.2, with the latter containing eight unique spike changes while lacking 13 spike changes found in the BA.1.

Basically, what they did is they did these pseudo-viral neutralization assays, which we’ve talked about before. The findings were, I’m going to say, depressing. I’m not encouraged by these findings. They reported that the sublineages were antigenically distinct and the polyclonal antisera from convalescent patients, patients that have recovered, and from mRNA vaccine recipients showed a substantial loss in neutralizing activity.

With regard to the neutralizing antibodies, they found that the BA.2 exhibited market resistance to 17 of the 19 tested, including sotrovimab. Are we worried about BA.2? We’re starting to see increasing prevalence. I was just checking the CDC variant tracker. Maybe 5% across the country. Somewhere between 3% to 10% here in our New York Region 2 area. Not encouraging, but I will say in contrast to this preprint, VIR came out with a press release suggesting that they have data showing sotrovimab retained neutralizing activity against BA.2.

This data was shared with the government regulatory authorities. They’re going to post this on the preprint server. They’re actually going to do viral isolate testing as well as pseudovirus. We’ll get to see that data, but it’s really probably a question of when we lose this and move on. Fortunately, we have other monoclonals waiting in the wings. Another monoclonal antibody just got an EUA. This time, for bebtelovimab for the treatment of mild-to-moderate COVID-19 in adults and pediatric patients.

This is nice, right? Down to 12 years of age and older, weighing at least 40 kilograms, so about 88 pounds. COVID-19, high risk of progression. The clinical data here was from a Phase II randomized, single-dose clinical trial. This was apparently compelling enough data. I think we do need to start moving more quickly with the monoclonals. We can’t wait right now. We get one that’s going to treat a variant that’s no longer around. We need to be ready to go. The U.S. government has actually gone ahead.

Lilly has announced a supply of up to 600,000 doses of the bebtelovimab to the U.S. government. This is going to be another option out there. All right, so we’re working down. We started with PAXLOVID. Now, we moved down to monoclonals. What comes next? Remdesivir. This is the new three-day outpatient therapy based on that New England Journal of Medicine article we talked about with an 87% reduction in progression, right? Remember, this is that three-day. You want to start it early. A number of centers are creating access for this.

Not so impressed with remdesivir once someone has gotten into that early inflammatory phase. Boy, this was pretty impressive and it makes a lot of sense. This is during viral replication using an antiviral agent. Then don’t forget molnupiravir. This is still considered the last option, perhaps a 30% reduction in progression, but it’s an easy lift. There’s over three million doses out there. No renal issues, no drug interactions. If someone’s high risk, go through this algorithm and let’s make sure we get them treated.

All right, the early inflammatory phase. Still very limited, right? Once someone gets to this point, we’ve really missed a lot of opportunities. We still will look at steroids. We still will look at anticoagulation. I’m going to discuss some updates there. Pulmonary support. Sometimes we might escalate to tocilizumab, the IL-6 receptor blocker. Again, only in the right patient, only at the right time. If you wait too long, we might be missing that window. Sometimes baricitinib, that’s that Janus kinase inhibitor.

We did get an update on IL-1 inhibition with the Cochrane database update, interleukin-1 blocking agents for treating COVID-19. People may remember a little bit of excitement early on, anakinra, canakinumab. Based on review of all the available evidence, the authors concluded we did not find evidence for any important beneficial effect of IL-1 blocking agents. Most of the trials have either been ended because they didn’t show much of a benefit or they’ve been terminated for futility. Really, the ship has sailed on those agents. Time to move forward.

A Thromboprophylaxis in Patients with COVID-19. A Brief Update to the CHEST Guideline and Expert Panel Report, this was just published. Critically ill patients should receive standard thromboprophylaxis for VTE, venous thromboembolism. Moderately ill patients with a low bleeding risk might benefit from therapeutic heparin. We see no role for intermediate dose thromboprophylaxis in either setting.

Really, we’re getting here alignment with the American Society of Hematology. Someone is critically ill, end up in the ICU. We’re looking at prophylactic dosing being the recommended starting point. Someone is moderately ill, low risk of bleeding. We’re looking at therapeutic anticoagulation in the hospital. Then, again, my little line that I force them to put in the ASH guidelines all the time, “Use your clinical judgment. Look at the patient and decide what’s best for them.”

A lot of the data was based upon severely ill, surge condition, unvaccinated COVID patients. If you’ve got someone who’s walking, talking up at the window wondering when they can get out of the hospital, just on two liters of oxygen, make the right decision for them.

All right, we are going to move to the tail phase. We’re getting there. Another reassuring report, The Effectiveness of Vaccination Against Long COVID: A Rapid Evidence Briefing, out of the U.K., 15 studies were identified that reported on the effectiveness of vaccination against Long COVID.

They looked at a number of studies. Seven studies examined whether vaccination before infection reduced the symptoms or incidents of Long COVID. Seven studies examined whether vaccination of people with Long COVID reduced or cleared the symptoms of Long COVID. One study looked at both just to sort of the high points. This is worth looking through.

Six of the eight studies assessed the effectiveness of vaccination before COVID-19 infection suggested that vaccinated cases, and this would be one or two doses, were less likely to develop symptoms of Long COVID following infection. Less likely. It’s not getting rid of it but is significantly reducing the risk. In studies examining the effect of vaccination among people with Long COVID, this was that early observation where people who have Long COVID got vaccinated, they might feel better.

Three of the four studies comparing Long COVID symptoms before and after vaccination suggested an improvement in symptoms after vaccination either immediately or over several weeks. Don’t give up hope if it isn’t immediate. It might take several weeks for that to develop. If you are concerned about Long COVID, get vaccinated before you get infected. If you get infected, get vaccinated. That can reduce your risks of going on to develop Long COVID.

All right, another preprint, reinforcing how risky it is to get COVID in terms of post-acute infection risks. It’s not just about hospitalization and deaths. Not only do we have all the risks of acute infection, hospitalization, death, but the preprint, Complications following SARS-CoV-2 infection in Victoria, Australia. A record linkage study was posted. Here, the authors looked at laboratory-confirmed COVID-19 cases identified during this period of time in Victoria, Australia.

They looked at several outcomes in the first 90 days following COVID-19 illness onset. They looked at incident rate ratios comparing the risks. This was a pretty large study. So they looked at 20,594 COVID-19 cases with 2,992 COVID-related hospitalizations. They looked at elevated risks, which they saw for myocarditis and pericarditis, right? This was almost a 15-fold higher risk of ending up with myocarditis or pericarditis.

Thrombocytopenia, that’s those platelet levels dropping. Pulmonary embolism, a greater than six-fold increased relative risk. Acute MI, about four times as likely during this period. Cerebral infarction, a non-ischemic stroke, was more than twice as likely during this period. Just making it through those first couple of weeks, those first 90 days are incredibly risky. What about mental health? I think this is really important.

The pandemic has been really difficult in terms of mental health, but what about if you actually get infected with COVID-19? We have an increased baseline. Here, the research article, Risks of Mental Health Outcomes in People with Covid-19: Cohort Study, was published in the British Medical Journal. There’s a linked opinion piece. There’s a linked editorial. They’re all worth reading. Actually, read the actual research article.

Our listeners are probably familiar with this cohort. This is the U.S. veterans cohort and this has that 153,848 people who survived the first 30 days. They have these control groups. Basically, the cohort was analyzed before and going forward. They reported that people that survived COVID-19 were at significantly higher risk of a number of mental health disorders after the acute period.

I think the editorial piece is nice to point out that Long COVID is not in your head. This is not validation of that gaslighting approach, but really showing anxiety, depression, a lot of these other issues are increased in the period of time after COVID 19.

All right, well, I’m going to start to wrap it up there. No one is safe until everyone is safe. We’ve got to vaccinate the entire world. Lots of people in the world have not even had an opportunity to get that first dose.

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VR: It’s time for some email questions for Daniel. You can send yours to This first one came last night during our live stream and I said I would ask Daniel. The question is, “My school has a 95% vaccination rate in a highly-vaccinated area. We also have good ventilation. Should we remove the mask mandate?”

DG: We touched on this a little bit. I think that this is actually where the guidance is probably headed. There’s a couple of factors here. That is great, 95% vaccination coverage is excellent. It really gets to this question that I ask and I say not rhetoric about, who are we protecting? People have had the opportunity to get vaccinated. Ventilation is improved, which is fantastic.

I think we’re going to see guidance going forward that those masks are starting to come off because it’s a risk-benefit. It’s not like wearing the mask is innocuous and no one cares. I think it’s important that people who want to wear a mask, there will be certain people who– It makes sense. They may even get advice from their physician. You should be wearing a mask for whatever health issue. I think that this is where things are moving.

VR: All right. Ken writes, “How safe is it to vaccinate my three-year-old with inactivated COVID vaccine in China? Are there any solid clinical reports on the safety and efficacy of these inactivated vaccines for children below five? What do they say? What’s your recommendation?”

DG: I think that it’s actually great that they ask this because sometimes we neglect the vaccines are not available here in the U.S., so Sinovac, the Chinese-inactivated vaccine. They’re actually studying this. They’ve been studying this down to six months of age. They actually had some interim data that came out back in the late fall, November. So far, it’s showing very good safety data all the way down. Efficacy data, we’ll have to see because that’s still moving forward. From a safety point of view, I don’t see that there’s a concern. This tends to be at least in the data we have to be a safe option.

VR: Charles writes, “I am a pissed-off taxpayer. It looks like a few doctors are making money off of the vulnerable by pushing unproven COVID-19 treatments.” He provides some links to their websites. “Personally, I would like to see these people strung up by their short hairs, but I know that won’t happen. To prescribe unproven drugs when we have five,” and he lists some of the ones that you’ve already mentioned, “drugs that work seems to be malpractice to this layperson. Short of having their licenses to practice medicine revoked, I would like to know your opinion on the following:

Have the Centers for Medicare & Medicaid Services only pay for treatments for COVID-19 that have been FDA-approved, including EUAs, or for treatments in an approved clinical trial. After the FDA lost their minds and approved aducanumab for Alzheimer’s, CMS, the Centers for Medicaid & Medicaid Services, save the taxpayer and patients by only covering the drug when it’s given as part of a clinical trial. This seems like a good compromise for ivermectin and hydroxychloroquine when treating COVID-19. If you think this is reasonable, I will start writing to my congresspeople.”

DG: I’ve always encouraged people that if they are interested in these other approaches, they look at enrolling people in a clinical trial. I’m not a big believer in some stuff you just know it’s true. I think there needs to be humility. We don’t know. That’s why we do science. None of us have the ability to just know what’s true. Science is our ability to figure that out.

It’s unfortunate. I actually was reading stuff lately. There’s been a lot of pressure, and I’m sure where it’s coming from, to not the discipline clinicians that are not treating people in accordance with the latest science, the latest evidence-based guidance. I know early on, we talked about the different ways that physicians practice the evidence-based, the eminence-based, et cetera, et cetera.

I think it’s really important that we really focus on that in our training so that clinicians, when they end up in a time like this, they understand that you can do harm if you don’t follow the science, if you don’t follow a really positive approach. It’s embarrassing that people took an oath and yet, apparently, they are willing to sell out their patients to the almighty dollar.

VR: Tanya writes, “Good afternoon from Mexico. I have a doubt about booster shots. I’ve seen in most developed countries, the recommended booster is an mRNA vaccine. My problem is that in Mexico, our government doesn’t want to spend money and is applying AstraZeneca and Sputnik V doses as boosters. I’ve read those vaccines aren’t very effective against Omicron. I’ve been delaying my booster shot, waiting to see if I could get an mRNA vaccine, but it’s taking a long time. Could you please explain to me the benefits versus risks that an AstraZeneca or Sputnik V booster provides at this point in the pandemic? Why is an mRNA booster more effective against variants?

DG: The V is for “vaccine,” not for five.

VR: Sorry, it’s Sputnik V.

DG: This is the first time, I think, you’ve made a mistake in two years, Vincent.

VR: No, I make plenty of mistakes. Sputnik 5.

DG: Sputnik V.

VR: Why don’t they just call it “vaccine” then?

DG: Interesting. I think that you bring up an interesting point and we’ve talked about the science here. I’m not sure that that booster needs to be an mRNA vaccine. I think I may have shared. When I went for my booster, I got Moderna. So many weeks later, four weeks later, I got my second shot. Then it was booster time, I went in unprepared. I’m like, “I would like the J&J as my booster.”

They said, “We don’t have J&J.” I was like, “Oh, okay, whatever you have, I’ll go for it.” I’m not sure that the mRNA– if you look at the science and we’ve looked through and we’ll hopefully get more, there’s that nice NIH study, which we’ll wait actually for more information. Looking at T cells, looking at antibodies, the rest, I’m not sure that that third dose needs to be an mRNA vaccine.

VR: That’s COVID-19 clinical update number 102 with Dr. Daniel Griffin. Thank you, Daniel.

DG: Oh, thank you. It’s a pleasure. Everyone, be safe out there.

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