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This Week in Virology
Host: Vincent Racaniello
Guest: Daniel Griffin
Aired 9 October 2021
pdf of this transcript available (link)
Vincent Racaniello: This Week in Virology, the podcast about viruses, the kind that make you sick.
[music]
From MicrobeTV, this is TWiV, This Week in Virology, Episode 814, recorded on October 7th, 2021. 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: How’s everything, Daniel?
DG: It’s actually all right right here in the immediate area. Actually, if you look around the country, things are on the way down. Actually, if you look around the world, there’s these sort of interesting cycles where things shoot up and then it goes down and we’ll see where we go. At the moment, particularly in the immediate area, but I was on a call earlier today, actually Shane Crotty was on the call. It’s funny because when things come up, people may think I know a lot but I always I’m like, “And can I call in a friend? Shane, can I call on you?”
In parts of the country, some of my colleagues on the call, not so great. There’s a lot of parts of our country where hospitals are still overflowing, where people just, not even COVID, just normal medical issues, they can’t be seen they’re waiting. It’s delaying care. Yes, by no means are we through this storm.
VR: Yes, we have an email about that sort of situation in a certain part of the country today.
DG: Yes, certain parts of the country not so great. Well, let me start with my quotation, and then I’m going to actually share what I think is an entertaining story, which has a certain, well, that’s a certain reason for sharing it. The quotation, “There are in fact two things, science and opinion; the former begets knowledge, the latter ignorance.” This is by Hippocrates. I just think this is very telling. I’m always a little disappointed when some of my colleagues seem to be searching for confirmation bias to support their opinion and not really just trying to move forward and learn. Hopefully, I’m trying to keep my opinions to a minimum and share the science so that people can form their own opinions based upon that science.
An interesting story I think I’ll share. These are dark times in many parts of the country, but this was a story that, actually, is the first time I laughed at work and, well, it’s been quite a while, but it was a friend-colleague of mine who was telling me a story. He’s embraced monoclonal even though he’s a cardiologist.
He’s like, “Dan, I sent this guy for monoclonals and I was all excited that we got that done, but then he left a message at the office. He went for the monoclonals. He’s doing great now, but he almost died.” It’s like, “Well, oh my gosh, what happened? That’s surprising because these monoclonals are so safe, what happened?” Well, apparently, this gentleman went for the monoclonals during one of these massive rainstorms that we had.
One of the things we do, we send people during that first week they’re feverish, they’re sick, and they’ve got to get into a car, and either go to a tent, or in this case go to an emergency room, get checked in, be there for a number of hours, get the infusion, which he went ahead and did, but as he was leaving, it was a torrential downpour. This feverish guy gets in his car and drives into an area of such degree of flooding that it’s actually up to the window level and his car completely stalls. He has to actually smash out the window and then climb out the window and swim to where it’s shallow enough.
Then the first person who offers to help him, he lets them know he has COVID and they drive away. The police then come and they offer to drive him home until he informs them that he has COVID. A little bit of a pause, they call his wife who then picks him up and takes him home. This was his harrowing monoclonal infusion experience, but then as he called my colleague, Dr. Sevilla said the next evening, he felt like 100%. He felt great despite having COVID, despite having to swim through these freezing waters.
VR: Good story.
DG: Yes, it’s a very, very entertaining story, but this is one of those reasons why it would be nice to be doing these in the home, bringing the therapies to these individuals, making it a little more accessible.
All right, some important updates, important dates for people to put on their calendar, they’re on my calendar. October 14th will be a discussion of the Moderna booster. Interesting enough, as I found out from my in-laws, everyone’s already getting their Moderna booster, so I don’t know what they’re talking about. Apparently, boosters for all, but this will be specifically– Moderna is requesting a specific Moderna third-dose, which would be half the dose of the first two. We’ll hear what the FDA independent advisory panel has to say on that.
The next day, October 15th, J&J is going to be having the FDA independent advisory committee discuss a booster for them. I think we talked about the data there, which is actually, I would say, rather compelling getting that protection for severe disease hospitalization, up into the 90s kind of at mRNA level if you give that second dose. That will be interesting to hear, but we’re getting positive signals on a J&J. One and you’re not done, I guess you need a second now.
Also, the heterologous boosting, the mix and match. What if you had one vaccine, can you get another? A lot of people say, “Boy, I got the Pfizer, can I just get the Moderna as my third dose?” My mother, actually, I was talking to my dad last night, “Oh yes, your mother, she’s already signed up for her third dose. She’s going to get a Moderna.” I’m like, “What?” I talked to my mother, she was, “Yes, they called me back. I had two Pfizers and I want to get a Moderna and they told me I can’t do that.” [laughs] What happens on the 15th, she’s going to wait a little bit longer to get a little more data before she and I make that decision.
Then October 26th for a lot of people, Pfizer vaccine for kids, 5 to 11. I’m going to talk a little bit about the fact that this is going to be packaged differently, a different dose, actually even a different amount will be injected, but we’ll get to that as well.
All right, let us start off with children and COVID. Children are at risk for COVID. I think that’s now clear. As I like to say, wearing a mask is less traumatic for a child than being hospitalized. We keep hearing about numbers in children, but as numbers go down across the country, we had been up to this quarter-million number for children, that’s dropping below 200,000, moving in the right direction there per week. Hospitalizations getting a little bit of improvement, but again, this is regional where we’re seeing problems.
One of the things I wanted to talk about is, I’ll say, success. And maybe when there wasn’t success with getting children back out there for in-person activities, we have some data now and how did we do this summer in places where there was good guidance, vaccination, masking, etc.– mitigation measures versus where there wasn’t? We’re going to talk about a couple of MMWR early releases. The first is “Multicomponent Strategies to Prevent SARS-CoV-2 Transmission – Nine Overnight Youth Summer Camps, United States, June-August 2021.”
As mentioned, this came out as an MMWR early release, and the authors reported on a total of 7,173 campers and staff that attended nine U.S. overnight camps that implemented multiple prevention strategies, including high vaccination coverage that was greater than 93% among eligible persons. Pre-arrival and frequent screening testing, there’s a total of 38,059 tests. Additional prevention measures during this time period. There were only nine laboratory-confirmed COVID-19 cases, and no secondary infections detected during this period. As I like to say, we can do this safely.
On the other side of the coin, we can also mess this up. “COVID-19 Outbreaks at Youth Summer Camps – Louisiana, June-July 2021,” came out also as an MMWR early release. And here, the authors were describing 28 camp outbreaks. There was a 31-fold increase in confirmed camp-associated cases compared with the previous summer, and the author’s comment that this period coincided with underutilization of preventive measures such as the vaccines, the masking, the physical distancing. You remove those mitigation measures and you can do this poorly.
All right, well, with the expansion, the impending, we hope expansion of COVID vaccines down to the 5 and 11-year-olds. There’s been a lot of discussions about trying to normalize the COVID vaccines, trying to get them into pediatrician offices because a lot of parents want to have that discussion with the pediatricians, not go to one of these mass vaccination sites. Actually, it’s coming up a lot, a lot of individuals don’t really feel that comfortable going to one of these large sites with the security presence. Maybe I have a little bit of this bias. If we’re lost, my wife will go ask a police officer. I will, if I see a police officer, maybe go the other direction. Maybe this is my upbringing. [chuckles] I always joke with the police officer when I see them, my last name is Griffin and we try to calculate how many Griffins were in the front seat as police officers, and how many of us were in the backseat causing trouble.
This vaccine, we are hoping, a lot of parents are hoping they will be able to access it in the pediatrician’s office. Just a little bit about what are we expecting on the horizon. The current Pfizer vaccine that we’ve been giving out has a purple cap, but we are hearing that the new caps for the children will be orange caps. These are going to be different vials. They’re going to be 10-dose vials instead of the 5/6 that we were doing before. It’s going to be a different amount to dilution. This is going to be a 1.3 mL dilution. The injection, rather than 0.3, is going to be a 0.2 injection. These can sit in the ultracold freezer for six months, but you can put them in the refrigerator undiluted for 10 weeks. That’s two-and-a-half months. That’s going to be a great way of getting these in pediatrician’s offices, getting those sitting there in the refrigerator. We all, as I think sort of embarrassingly say, “We have a lot of vaccines. We expect to have a lot of these.” We’re not expecting people to be quite as stringent with the like, “Don’t waste the dose.” It’s going to be more of a, “Don’t miss an opportunity to vaccinate.”
There’s also, for the over 12, there’s going to be a– we hear a new gray topped vial that is already pre-diluted. This can then sit pre-diluted in a refrigerator for 10 weeks. Undiluted, or, actually, let me see if I’ve got this right, already diluted can sit for 10 weeks.
Pre-exposure transmission testing, another nice paper looking at the impact of vaccination on transmission. This is really, I think, because we’ve discussed the community motivation behind vaccination and the pandemic rather than just looking at individual risks. We saw the pre-print, “The impact of SARS-CoV-2 vaccination on Alpha & Delta variant transmission.” This study was performed as part of the Public Health Surveillance and NHS Test-and-Trace Program quality assurance. The authors start by providing a little bit of background at the pre-Delta. There was evidence that there was some impact. Now, they’re going ahead and looking at the risk going forward.
They performed a retrospective, observational, cohort study of contacts of SARS-CoV-2 infected index cases using contact testing data from England. In this study, 37.2% of the contacts tested were PCR positive. They looked at two doses of the BioNTech Pfizer or the ChAdOx1, that’s AstraZeneca, in the Alpha variant index cases. The reductions they were seeing, the adjusted odds ratio, 0.18 versus 0.37. About 82% reduction, about 63% reduction. Then when they looked at the Delta variant, the odds ratio was 0.35 and 0.64. About a 65% reduction, about a 36% reduction, so not working quite as well.
There was an interesting comment– I think that this is important and maybe a place to talk to to think about boosters. Transmission reductions declined over time since the second vaccination. For Delta reaching similar levels to unvaccinated by 12 weeks for ChAdOx1 and attenuating substantially for BioNTech 162b2, the Pfizer-BioNTech. Protection from vaccination in contacts declined in the three months after second vaccination. There’s sort of this challenge, our vaccines are really great at preventing hospitalizations and severe disease. How long are we going to get this impact on infection? How long are we going to get this impact on transmission reductions?
I’m also making several questions about a couple AstraZeneca products. The first one is the MABs that they have, and these are these long-acting antibody therapies. AstraZeneca’s AZD7442, it’s very catchy, request for Emergency Use Authorization for COVID-19 prophylaxis was filed in the U.S. These are long-acting monoclonals for prevention. This request was based mainly on data from the PROVENT trial, P-R-O-V-E-N-T trial, where 5,197 participants in a 2:1 randomization received this AZD7442, which has two MABs in there. And I am not going to go into which they are because this has become a pronunciation challenge, and they compare this to placebo. The primary analysis was based on 5,172 participants who did not have SARS-CoV-2 infection in the baseline. In this trial, 77% reduction in developing symptomatic COVID compared to placebo.
What’s special here? We’ve already talked about how REGEN-COV can be used in the EUA as, and we will go to details on that, as a prophylactic. Here, this can be given IV or IM as opposed to subcutaneous. It’s a little nicer to give this IM. This was actually gluteal, so this was given in the tail. There’s also a longer half-life here. These antibodies were optimized to have an extended half-life, reduced Fc receptor, and complement C1q binding. They are actually suggesting that this can afford up to 12 months of protection following a single administration.
A lot of questions I’m getting from my colleagues who take care of individuals who are immunosuppressed– Let’s say cancer patients, patients with autoimmune disease, patients on immunosuppressive medications, patients that we do not think are going to get the protection that we would like from vaccinations or maybe even have a contraindication to vaccination. This is potentially a way of providing passive protection.
Little exciting news on the testing front. We’ve sort of gone full circle, and there’s been a lot of folks embracing and really seeing the power of the rapid test, but also the at-home rapid test. On the 4th of October, the U.S. FDA issued another EUA for the ACON Laboratories’ Flowflex COVID-19 Home Test. Per the manufacturer, they are planning, and they claim they have the capacity, to produce more than a hundred million tests per month. They think they’ll be able to ramp this up to 200 million per month by February 2022. Very exciting.
Because right now as we know, everyone’s excited about home test, but no one can get them. I even tried to do this myself. They are in short supply. Also, if you want to understand how to use this, because you’re going to be swabbing yourself, the same day the CDC updated their COVID self-testing page where you can see some really nice infographics about how to stick that Q-tip up your nose and get these samples.
VR: I presume this is an antigen test, Daniel?
DG: Yes. This–
VR: Is it going to be less than a dollar?
DG: [laughs] Let’s see if I have the money. Let’s see if I have the cost here. I do not know what the cost is going to be, but will it be– going to be less than a dollar? The answer is no. [laughs] Will it be maybe $5? Maybe, maybe. There is the potential that the U.S. Government will purchase a lot of these and then distribute them. That could be not quite free because we’re paying our taxes.
Active vaccination, vaccines, the jabs that keep you from getting sick. I like to say, vaccination is how this pandemic ends. I’m talking about those first doses, that’s where we get our bang for our buck. In the New England Journal, we saw the peer-reviewed publication, “Phase 3 Safety and Efficacy of the ChAdOx1 COVID-19 vaccine.” These are the– finally, we’re getting the peer-reviewed publication of the ongoing results from the ongoing double-blind, randomized, placebo-controlled Phase 3 clinical trial. Looking at the safety, vaccine efficacy, and immunogenicity of two doses of the AstraZeneca ChAdOx1 as compared with placebo in preventing– it’s important what are we looking at. The onset of symptomatic and severe COVID-19 15 days or more after the second dose in adults, including older adults in the United States, Chile, and Peru.
In this trial, a total of 32,451 participants underwent randomization in a 2:1 ratio to receive this vaccine or placebo, so we have 21,635 versus placebo 10,816. The overall vaccine efficacy for preventing symptomatic and severe was 74%. Interesting enough, the estimated vaccine efficacy for this endpoint was 83.5% in participants 65 years of age or older. They report that this high vaccine efficacy was consistent across a range of demographic subgroups. In the fully-vaccinated analysis subgroup, they reported no severe or critical symptomatic COVID-19 cases. You’ve got to think about our endpoints. That’s a pretty excellent endpoint for looking at severe or critical disease, 83.5% for symptomatic, so a pretty, pretty impressive data here.
On October 4th in The Lancet, we saw another article, again, on vaccines, “Effectiveness of mRNA BNT162b2 Pfizer–BioNTech COVID-19 vaccine up to six months in a large integrated health system in the USA,” retrospective cohort study. It’s a peer-reviewed article. This is a retrospective cohort study where they analyzed electronic health records of individuals who are members of Kaiser Permanente, Southern California. They were looking at the effectiveness against infections and COVID-19-related hospital admissions for up to six months.
This is a very robust dataset by an organization that, I’ll say, does an excellent job. 4,920,549 individuals were assessed for eligibility, and ultimately, 3,436,957 were included. For fully-vaccinated individuals, they reported that effectiveness against infections declined from 88% during the first month to 47%, so that’s effective against infection. Amongst sequenced infections, vaccine efficacy effectiveness against infections of the Delta variant was high during the fourth month, 93%, and that went to 53% after four months. Effective against other variants the first month, 97%, 67% at four to five months.
What about vaccine effectiveness against hospital admissions for infections with the Delta variant? 93% up to six months. I take away this as very encouraging. I know Pfizer vaccines has been getting a lot of bad press. People are a little upset that they get the Pfizer instead of Moderna, but vaccine effectiveness against severe disease, hospital admissions with the Delta variant, 93% from the six months. I found this rather encouraging.
What about reinfection? I get a lot of questions about this. There’s a lot of articles out there, but this article, “The durability of immunity against reinfection by SARs-CoV-2: a comparative, evolutionary study,” was published in The Lancet Microbe. We certainly see reinfections mainly starting about three months after infection and increasing over time. We know that if these folks get vaccinated, they can decrease their risk of infection by at least two-fold. We’re not sure one dose got us there, but two doses did in the MMWR publication we talked about. If prior infection, we know that these individuals can get a benefit from vaccination.
In this study, the authors looked at antibody data for six human-infecting coronaviruses extending from 128 days to 28 years after infections. It’s a pretty broad study, infection between 1984 and 2020. They used this data to estimate profiles of the typical antibody decline and probabilities of reinfection over time under endemic conditions. They estimated that reinfection by SARS-CoV-2 under endemic conditions would likely occur between three months up to 5.1 years, after the peak in the antibody response, suggesting a median of about 16 months. They calculated that this protection is less than half the duration revealed for the other endemic circulating coronaviruses, so, -OC43, -NL63, -229E, if people have those remembered.
What I’m going to say, for a deeper dive into the comparison between protection from infection versus vaccination, I’m going to recommend people go to TWiV 813, discussion with Florian Krammer. It’s really a popular topic that people are trying to sort out. Just to make it clear, we recommend that people who have been previously infected get the benefit of vaccination.
A popular question now. I don’t know, Vincent, if you are aware of this, but I keep getting “Am I still considered fully-vaccinated if I haven’t [chuckles] had my booster?” Straight from the CDC, yes. Everyone is considered fully-vaccinated two weeks after their second COVID vaccine in a two-shot series, or two weeks after a single-dose vaccine for the J&J Johnson for those folks here in the U.S.
I’ve been getting a lot of employers, interesting enough, who are now demanding that their employees get a third dose, otherwise, you’re not considered fully-vaccinated. Straight from the CDC, this is evolving, but at the moment, you’re still good. I know we’re up to 400,000 people getting a booster per day here in the U.S.
Anyway, passive vaccination. I want to remind people, remember monoclonals after high-risk exposures in high-risk people. We talked a little bit about AstraZeneca is applying for this, but we already have post-exposure prophylaxis as part of the EUA for REGEN-COV. Who are the people that they’re recommending eligible for post-exposure prophylaxis? These are individuals who are at high-risk for progression to severe COVID-19, including hospitalization or death. These are folks who are either not fully-vaccinated or are not expected to mount an adequate immune response to the SARS-CoV-2 vaccination, so individuals with immunocompromising conditions, those on immunosuppressive medicines. You’re looking at individuals who have been exposed.
I also want to point out, they also talk about for individuals in whom repeat dosing is considered because they continued to have ongoing exposure. Just a little bit of subtlety there. An individual who is immunosuppressed, who’s not getting that protection from vaccine, but continues to be exposed over and over, the first dose is the 600-600, but you can actually continue to dose them every four weeks with a 300mg, 300mg. That can either be by subcutaneous injections, so in this sense, then we have to get two instead of four shots, or they can get an intravenous infusion every four weeks. For a while, we were stepping back a little on prophylaxis because of shortages, but as the numbers are going down, as we’re getting improved access, we’re stretching back out the post-exposure prophylaxis.
The period of detectable viral replication, it’s not the time for antibiotics, it’s not the time for steroids. We can do harm there. This is, for a lot of people, exciting. The beginning of a new era. Merck and Ridgeback announced the planned interim analysis results from the Phase 3 MOVe-OUT Trial, looking at the use of the oral anti-viral. This is a pill, Molnupiravir, in the early treatment of at-risk, non-hospitalized adult patients with mild to moderate COVID-19.
This was a planned interim analysis. They evaluated data from 775 patients who are initially enrolled in the trial, the Phase 3 MOVe-OUT trial. At the time of the decision to stop recruiting, the trial was approaching full recruitment, a sample size of 1,550 patients with more than 90% of the intended sample size already enrolled. When they performed this interim analysis, and I want to point out, this is top-line data, this is not peer-reviewed, we don’t have the details that would be coming forward, they reported in this study that Molnupiravir reduced the risk of hospitalization or death by approximately 50%. We had 7.3% versus 14.1%. The little bit of details here in the individuals that received the antiviral, there were zero deaths, in the placebo group, there were eight deaths. We’re looking at 0% versus 2%, so 2% the expected mortality, 0% in the folks that got this therapy.
What about eligibility and timing? These individuals had to have laboratory-confirmed COVID-19 with symptom onset within five days of study randomization. A little bit longer than we would ideally want because you get randomized at day five. It may take you another day before you actually get the therapy. All the patients had to have at least one risk factor associated with poor disease outcomes. This is a slightly higher risk group. People did well, a very well-tolerated therapy. There is a recommendation to go ahead and look at possibly getting an EUA, so we will find as we go forward.
Just a little background because this is going to be one of the first drugs here that is being introduced. This is an RNA-dependent RNA polymerase inhibitor. That’s something that we mammals don’t have to worry about. There is going to be discussion about the safety of this drug. That’s why it’s going to go through the FDA. This is really the first in this class going forward. We expect there to be another very similar drug. We also expect another drug that we’ve talked about that’s going to target the protease on the horizon. Fingers crossed, we’re looking at about three oral drugs being available by December. Vincent, do you want to make any comments at this point? I thought this was an exciting bit of news.
VR: I think it’s great that these are in development. My only concern, and I’m sure as a physician who treats AIDS patients, Daniel, these will be initially used as monotherapy, and I’m just concerned that we’re going to get rapid resistance, which will render them less useful. What do you think?
DG: Yes. Hopefully we’ve learned from the HIV, and we’ve also learned from influenza, is that if you use these drugs all by themselves, you run a risk, particularly if they’re used widely, which we’re thinking they will be, of inducing resistance. I’ve already talked about the concept of maybe using this with maybe the protease inhibitor. Maybe, if we can use two drugs, we can put up a barrier to that resistance. I think that’s key. Anytime we use a drug, we can end up with resistance. It may be that we want to look at using two drugs, so that we’re not pressuring and driving that. I worry, particularly, if people use this more than just as a five-day therapy, what if you have a person who’s immunosuppressed and you start using it for a longer period of time?
VR: Don’t you have to trial them in combinations to get them approved that way?
DG: Yes, we’re going to have to do that. This will be two different drug companies, three drug companies, all playing nicely, working together. It is interesting, with HIV, we’re often using three-drug therapy. That’s kind of the triple highly-effective, anti-retroviral therapy, where, often, historically, it was three different companies were producing each of the different drugs in the cocktail.
Timing, we’ve got exciting stuff because the IDSA meeting was just recently. This was data that was presented there, and it was “Risk-factor analysis for hospital admission, following severe acute respiratory syndrome, Coronavirus 2, so that’s CoV-2, monoclonal antibody treatment.” And this was really looking at timing.
If we get those monoclonals in earlier, does that give us better bang for our bucks? We look at this whole less 7 to 10 days after symptom onset, 70% to 80% reduction, but are we going to get even more reduction if we get them in the first few days? Here, they’re looking at patients that received, what they say is early, within days one through five of symptom onset, and comparing those to people who received them late, six to 12. Here, we were seeing getting the MAB infusion in the first five days resulted in a 54% reduction in progression, relative to those folks that get them late.
With the monoclonals, timing matters. I know a lot of centers closed down over the weekend. A bit of a tragedy. Person gets diagnosed on a Friday evening and they can’t get treated until Monday or Tuesday. We really need to focus on timing here. Of the patients that received the monoclonals in days one through three, none, zero, experienced disease progression. Sooner is better. We’re hoping this translates in the oral antivirals as well. See my ‘antiretroviral’ slip. My world of HIV is coming back. We’re really hoping sooner can make more of a difference than later.
All right, everybody, MIS-C and MIS-A, remember those multi-system inflammatory syndrome. We have actually, finally, got a little bit of guidance on treatment coming out in a publication of peer-reviewed article, “IVIG Compared With IVIG Plus Infliximab in Multisystem Inflammatory Syndrome in Children.” This was published in Pediatrics, the official journal of the American Academy of Pediatrics. This was a retrospective cohort study of 72 patients with MIS-C. They’re looking at IVIG alone versus IVIG plus infliximab. This is going to neutralize the TNF alpha. Basically, what I’m going to just nutshell this year, they were looking at better outcomes in the children that got REMICADE, the infliximab added to their IVIG.
They reported that patients with MIS-C, compared to those with IVIG alone, were less likely to require any additional therapy, decreased ICU length of stay, decreased development of left ventricular cardiac dysfunction, more rapid decline in their C-reactive protein– Following inflammatory markers.
A couple of exciting things here on long COVID. I feel like I’m going a little long today. COVID is not just a two-week viral illness for many people. First, as of October 1st, we now have an official code for post-acute sequelae of COVID-19. This is U09.9 post-COVID-19 condition unspecified. Going forward, we’ll have subsets.
Also, some exciting data on the impact of vaccination on long COVID. The article, “Efficacy of COVID-19 vaccination on the symptoms of patients with long COVID: a target trial emulation using data from the ComPaRe e-cohort in France.” This was posted on The Lancet as a pre-print. The authors used data from this long COVID cohort. This was a cohort in France. Vaccinated patients were matched to unvaccinated controls in a 1:1 ratio by using their propensity scores, and they looked at outcomes 120 days after baseline. They looked at the disease severity. You had 455 patients in the vaccine group, 455 in the control group. What did they find?
They reported that by 120 days, vaccination was associated with a reduction in long COVID symptoms. They saw double the rate of patients in complete remission. They saw reduced disease impact on patients’ lives and the proportion of patients with an unacceptable symptom score. This is encouraging. We probably will never get a randomized placebo controlled trial. There’s always the concern that there was some placebo effect. Also, people got vaccinated, unvaccinated. They’re not exactly matched, but this is something that is consistent with our clinical experience, where we’re treating hundreds, thousands of folks, and we’re seeing this report encouraging.
What about mechanism? That’s what we scientists care about. We do want our patients to get better, but we also like to know what is going on. We’re going to close with a couple articles on some insights into mechanisms. The peer-reviewed article, “Persistent clotting protein pathology in Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is accompanied by increased levels of anti-plasma.”
This was published in the journal, Cardiovascular Diabetology. This is not a journal I usually read, and I’m not as familiar with some of the platelet activation studies that they did. But, basically, going through the suggestion here was that hypercoagulability, a persistent hypercoagulability, was being driven by inflammatory molecules, circulating micro-clots, hyperactivated platelets, issues with the fibrinolytic system. Then the speculation here, which requires further study, is that with clotting pathologies involved, maybe some anti-clotting therapies can have an impact on long COVID. Hopefully this will give us some sense of what to do going forward.
COVID toes. Remember COVID toes? I have special socks with COVID toes. The article, “Type I interferon response and vascular alteration in chilblain-like lesions (CLL) during the COVID-19 outbreak,” was published in the British Journal of Dermatology. This was an observational study conducted 9 through 16, April, 2020 at Saint-Louis Hospital in Paris, France. 50 patients referred with chilblain-like lesions were seen during the period of the COVID-19 pandemic, included in this study. They were comparing the skin and blood endothelial and immune cell activation in the chilblain-like lesions in these COVID folks to seasonal chilblains, that were cold-induced sporadic chilblains.
They reported that they found chilblain-like lesions were characterized in the COVID folks, higher IgA tissue deposition, a more significant transcriptomic activation of complement and angiogenesis factors. They reported systemic immune response associated with IgA, anti-neutrophil cytoplasmic antibodies, and 73% of patients an elevated Type I interferon blood signature compared to healthy controls. They found blood biomarkers, which they reported related to endothelial dysfunction and activation angiogenesis and progenitor cell mobilization, really supporting in their analysis a role for endothelial dysfunction in the chilblain-like lesions. Very, very interesting. This is something that actually, I think, a lot of the nurses noticed early on. They’re spending a little more time than the physicians looking at the patients. Something that was seen in the outpatient setting as well. Just interesting that we’re starting to get a little science to maybe help us understand.
I’d like to close by saying no one is safe until everyone is safe. We are going to continue during the months of August, September, and October to– donations made to Parasites Without Borders, doubled, and going to support Floating Doctors with their efforts down in Central America. Drop what you’re doing, go to parasiteswithoutborders.com, click on “Donate,” and help us continue to do our work, and help us to support this organization.
VR: Time for some email questions for Daniel. You can send yours to daniel@microbe.tv. Lisa is a nurse practitioner, a pediatric nurse practitioner, who writes, “I agree kids are at risk. The decision made by adults responsible for protecting them sadly, too often, put them at higher risk than they need to be. While numbers here in Florida are finally beginning to trend down, they remain much too high. We are in the middle of a mask debate with a local chiropractor handing out blank signed medical mask exemptions after a very contentious school board meeting in which our county school board instituted a mass mandate in defiance of our governor’s ban on this.
Parents continue to show up in front of our schools with signs that making our kids wear masks is child abuse. Parents and children, too often, refuse to abide by our request that they wear masks in our office. Now, our new state surgeon general, who says he is rejecting fear over COVID mania, has decided that as long as they are feeling well, our school children, many of whom, of course are unable to be vaccinated, or if they are able, are not, no longer need to quarantine or test simply because they’ve been exposed to this pesky little virus. I am curious as to your opinion on this brilliant public health policy.”
DG: I’m horrified, actually, just to be frank. When you see the movies, there’s always the physician who can outrank the general. You can’t do that because of this health issue, and somehow in the real world, there’s no outranking going on. Yes, 18 months ago, there was this myth that started to be spread that children were not at risk of COVID, or children don’t get COVID or they’re not at risk of COVID. Now that we saw children getting exposed to COVID, we saw hundreds of thousands of children getting infected per week. We saw thousands of children ending up in the hospital. We see multiple children dying every week.
There really has to be a certain point when you start off with, no, children are at risk of COVID, children can die of COVID, children can get hospitalized with COVID. Children can develop long COVID with long-term disabilities. This is a horrible thing to let happen to our children. We don’t really know what are going to be the long-term effects of having been infected with this horrible virus? The second is we do know things that work, things that reduce our risk. You shouldn’t have to choose between education and safety for your children. A child shouldn’t have to choose between education and safety. We know how to keep our children safe.
Wearing a mask is something that parents complain a lot more about than children. A lot of children actually like the masks with the different designs, and maybe it’s become an accessory. I just really think we have to step back and take this out of the political arena. This is not a partisan issue. This is not a political thing. This should not be something that gets you re-elected. What should get you re-elected and what should get you support is protecting our children, helping them get educated safely. We know how to do that. We keep talking about all the data behind that.
VR: Michelle writes, “I’m in a quandary trying to decide what the best option for my daughter is. She turns 12 in January. She’s 61 inches tall, 150 pounds, so she’s the size of a small adult. She attends a school in which masks are only optional, most kids are not wearing them. My concern is whether to get my daughter vaccinated in late fall with the children’s dose, or wait until January for the adult dose.”
DG: I have to say, we’ve talked about this, about– this is perfect. Is that person right on the line? There’s going to be no judgment. It’s going to be, this is the day it happens. This is even true with influenza. I have a colleague who’s a hematology oncologist and he turned 65 today, so happy birthday, Bruce. Bruce went to get his higher dose because they’re still using the egg-based vaccine at the health care system. He wanted to get over 65 high dose because they’re not using the cell-based flu vaccine. They said, “I’m sorry, it’s Friday, your birthday is not until Thursday. You can’t get it today, you’ll have to come back when you turn 65.”
It’s interesting, people are pretty rigid about this stuff. The children, all across, look to be getting a really robust response with the lower dose. I would say, don’t miss an opportunity to vaccinate, don’t miss an opportunity to give your child that protection. If it turns out in the future boosters are recommended for individuals as we get more information about correlative immunity, I would encourage you to go ahead. When your child is eligible, go ahead and get the proper dose for that age.
VR: Daniel writes, “In New South Wales, Australia at the moment, there are a number of people in ICU and dying after full-vaccination. I know this is to be expected, but I feel that discussion of this is avoided and leads my older friends, particularly, to feel confused and helpless. All the people who have died here post-vaccine have been in their 80s and 90s. They have also all had other underlying issues, but the underlying issues are never reported. My understanding of why this would occur at all is that the individual was unable to mount an immune response to the vaccine, not that the vaccine has a weakness, but the individual. Is this correct? Are there young healthy people who make no immune response and are protected for some reason? Is there a specific list of age plus underlying conditions that people can look at and clearly understand their level of risk?”
DG: Yes. I actually feel like you’re right on with this. We talked about the vaccines reducing your risk of death by, I’m going to say, 30. We’ll pick that as a number. You hate to pick one study, but that seems to be reasonable. If you’re 90-years-old, you’re obese, you have diabetes, you have Down syndrome, let’s stack them all together. If your risk was 60% that you were going to die if you got COVID, you take 60 divided by 30, you still have a 2%, you still have a 1 in 50 chance of dying. My wife and I were talking yesterday, we’re out walking the dogs. I was saying, “Jessica, when you get this reduction, so you’ve got your vaccine, you’re now at 95% reduction for ending up in hospital. When you start it off, you’re in your 40s, you’re ideal body weight, you exercise, you started off with maybe a 1%, and now you’re down to 5% of 1%, incredibly low.” This is that that risk reduction. People think, “Oh my gosh, 95 reduction, that means 5% of people are going to end up in the hospital.” No. You have to take your baseline risk and this is a reduction below that. Yes, we are going to see a couple of people a day here in the U.S., a large country, who are vaccinated and still end up dying, but we’re going to see thousands who are unvaccinated end up in the hospital and dying.
We’re also going to see a certain percent of people who are vaccinated end up in the hospital, but that’s going to be a 30-fold or a 10-fold reduction in that number. You’re really hitting right on it. This is a reduction in baseline risk. Who are going to be those people who still end up in the hospital? It’s going to be predominantly older individuals. It could be predominantly individuals with a lot of comorbidities. Those people that do die, they’re going to be those individuals who have the highest risk factors.
VR: Finally, Helen is the parent of a 34-year-old adult with Down. She has had two Pfizer vaccines, wondering if there are any data on how well people with Down respond to the vaccines. Daughter is in a day program where everyone’s vaccinated, but she’s still concerned.
DG: That’s an excellent question. I think you hit on one of the things that I touched on there. Down syndrome is a significant risk factor for hospitalization and death. I think it’s about a 10-fold. There was a British medical journal article in September where they were looking at these. Actually, it’s a great article, a British medical journal. I think it was the 17th of September the article came out where they were looking at all these different factors, Down syndrome was about a 10-fold increased risk of death.
When they talked about populations that they felt were at increased risk, when they started talking about the Pfizer booster, Down syndrome was one of those thrown in there. Yes, individuals with all these different comorbidities, particularly Down syndrome, are at increased risk. What about response to the vaccine? I haven’t really seen any really good data looking specifically at individuals with the Down syndrome response, but put it in that context of the overall risk.
VR: That’s COVID-19 clinical update number 83 with Dr. Daniel Griffin. Thank you, Daniel.
DG: Thank you, and be safe. I say that to all those kids who have to go to school without masks, be as safe as you can.
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