This Week in Virology
Host: Vincent Racaniello
Guest: Daniel Griffin
Aired 5 March, 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 872, recorded on March 3rd, 2022. I’m Vincent Racaniello and you’re listening to the podcast all about viruses. Joining me today from New York, Daniel Griffin.
Daniel Griffin: Hello, everyone.
VR: This is update number 104. We’re making our way to 200, Daniel.
DG: I have to say I’m thinking, oh eventually we’re going to get to these short little five-ten minutes just what you need to know, quick little, but I’m going to apologize ahead of time, there was a lot that happened this last week.
VR: Seems there’s always something, doesn’t it?
DG: It does. I’m waiting for there not to always be something but let’s get right into it because I’ve got a lot that I want to discuss today. By discussing Vincent, I’ll be pulling you in because I’m not sure everything makes a lot of sense to me, but let’s start with the quotation. “The dogmas of the quiet past are inadequate to the stormy present, the occasion is piled high with difficulty and we must rise with the occasion. As our case is new, so we must think anew and act anew.” This is Abraham Lincoln. I was actually just down in Washington, DC last week instead of Kyiv, Ukraine where I was supposed to be traveling to.
We always try to theme our trips and we spent a lot of time with Barnaby, Jessica, visiting places where Abraham Lincoln had been and learning a bit more about him. He certainly faced a very difficult situation, and I think we still face one. I think as we’ll discuss going forward, this is new territory and we’re learning as we go. We’re learning on the fly, so this will hopefully be relevant to what we’re talking about today.
An update for our listeners/readers, we’ve gotten a number of requests for transcripts for the COVID-19 clinical updates, and we actually are almost through creating these, editing them, and so hopefully, very shortly, we’ll start posting those and we’ll be posting those going forward for the people that would rather read than listen to us, or maybe people want to do both. That’s what it is, for those that want to do both those, for listening and watching is not enough and they want to read also.
More on the BA.2, or stealth Omicron variant, worldwide this has increasing prevalence. I actually got a bunch of emails last time, we’re US-centric at times and people like, “Hey here in the UK, here in other parts of the world, it’s 30%, it’s even more.” There seems to be a fitness advantage, I love the fact that people are using that term now to this variant, but an interesting thing is we talk about as numbers go down, the percentage, the prevalence, the percentage is higher, but the actual numbers might be coming down overall, so interesting.
I always say for me one of the biggest concerns here is the impact on therapeutics, and so to bring it to, not only a US-centric but a Northeast-centric, we break down the US into these different regions and then we get updates on the prevalence of different variants. Region One, and that’s, people are familiar with the US that’s Connecticut, Rhode Island, Massachusetts like the very much Northeast, even a little more Northeast than New York, they’re up to about 20% of the BA.2 so that that can certainly impact our therapeutics or monoclonals.
Here in Region Two, that includes New York, New Jersey, actually interesting, Puerto Rico, were over 10%. Again, as people may remember, when you start to get resistance rates above 10% you start to have to rethink whether you’re going to put these resources there. Not just here, Region Nine, that’s out in California, greater than 10%, the great Pacific Northwest, I wish our region, the great Tri-state area, but the great Pacific Northwest also up above 10%, so really big issue here. I just want to let people know those percentages are moving in that way.
I did get a couple of questions, “Is this going to change the trajectory? Are we still heading down as far as case numbers and deaths?” We’re not seeing anything to suggest otherwise. I will say case numbers and deaths are down across the world, the US, and the New York tri-state area down but still high. Globally, the seven-day moving average for deaths is down to about 8,000 a day, that’s just crazy to say down to. Here in the US, on March 2nd, we had 1779 deaths that day, so we’re now down to below 2,000 deaths per day, so case numbers’ deaths are coming down.
A few changes I’ll hit on today, New York City’s coronavirus contact tracing program, it was announced that this will end toward the end of April. Officials citing a significant caseload drop, high vaccination rates, new treatments as well as aligning with CDC recommendations. The CDC actually has updated recommendations here, which we’ll hit on a little bit later maybe. We also heard about an upcoming test to treat program. I don’t like that name. I know it’s catchy but it’s really, test and treat, not test to treat. This is really what we’ve talked about, you really want to have therapeutics right there where people get their tests.
If the test is positive, you can immediately offer the therapeutics. We’ve talked about these challenges, someone tests positive and then you’re trying to figure out where can I send them. Ideally, they get a positive test, they get treatment right away and this may be pharmacists, they may be going throughout a brand maybe going to CVS. CVS has had a nice relationship with the government with regard to testing and vaccinations. Maybe this will be urgent cares but people get a test and immediately the plan is to be able to get therapy started right then. As you can imagine, a little easier lift with our oral antivirals, but this is also something we can potentially do as we move in IM, injectable monoclonals.
VR: Daniel, can I ask you, what’s the target for this? Is this someone who’s triple vaccinated, who was just tested for work for example, and has no symptoms? Do they get antivirals?
DG: No, and actually, this is interesting, we’re going to hit this again. There is this issue, we talk about people that are high risk for severe disease, and so what you described was not that. You’re 45 years old, you’re ideal body weight, you’re athletic you’re taking care of yourself, you don’t have comorbidities, you’re triple vaccinated, so that’s a large chunk, not everyone, a large chunk of people. They get COVID and then they say, “Well, what can I do? What do I get?” We’ve said, “Nothing. You’re not at risk of severe disease, you’re not risk of hospitalization.”
I have a friend who was telling me today, one of his lines is he says, “You know what? God is much better at taking care of things than we are, so just don’t mess.” Nobody is at low risk for long COVID, so as we get to some numbers later, this person may have a 10% risk of four weeks later still not feeling well. Will there at some point be an option for them to get something that can decrease that risk? Hopefully, but as we’ll probably talk about a little later, we actually don’t have any prospective randomized compelling evidence that there’s something that that other group can take. Really, I’m going to say we don’t have a lot of evidence that there’s a lot we can do to decrease the risk of long COVID.
I will say this will eventually be submitted, hopefully, I’m hoping the next week or two looking at the impact of monoclonals. I’m not even convinced that monoclonals have a significant impact on reducing a person’s risk of long COVID. Our data has really focused on hospitalization and death, so I think this is very relevant. Who is going to be so excited about test to treat? At the moment, it’s just a select high-risk population.
VR: Even antivirals do not eliminate long COVID, you think?
DG: I’m hoping they do, and I’ll share an anecdote because that’s an N-of-1, it’s not data, but I had a patient with long COVID and she was complaining to me on Tuesday, venting. She is a woman who developed long COVID after an infection early on, it’s been almost two years. She actually was saying, “Boy, it’s been two years, Dr. Griffin.” She has somewhat improved but still struggling. She had a friend of hers who was overweight enough to qualify as high risk, got put on Paxlovid and she’s like, “Dr. Griffin, 48 hours later, she felt 100% and she’s fine and she has no issues.” She’s thinking.
We don’t know yet, we have yet to see the data on those. It makes sense, but again, I’m humble enough to say a lot of things make sense to me until I see the science. I’m not sure.
VR: We had a lively discussion about this on the live stream last night, I gave them your position, which is it should be for the high risk, but people were saying, “How do I know I’m not high risk until I get really sick and then it’s too late for the antivirals, right?”
DG: Yes. That’s a tough thing you can’t do. I’m glad that discussion, you can’t say, I’ve heard Dickson says, “Well, why don’t we just wait and see it? If you get really sick–” If you get really sick, it’s too late. It’s an odds game. You say, “Oh, but I have a 1%,” but that’s 1% of often a big number. We have a lot of people who would not qualify for antivirals monoclonals, who end up in the hospital, who end up dying, who end up with long COVID. Now, I think this is an important discussion to keep in mind.
Children, COVID, and other vulnerable populations. For the week ending 2, 24. February 24th, we’re always about a week behind. We get the data and then we’re always a week behind. I have to say with the most current data from the American academy of pediatrics, we are still averaging three pediatric deaths per day. We’re now at about 900 pediatric deaths here in the US from COVID.
I really hope this drops, but I have to say we have over 200 pediatric COVID deaths from the Omicron wave alone. A lot of these deaths have been recent. Unfortunately, I’ve had a dramatic increase in number of questions and concerns from pediatricians and worried parents about a couple things that we’re going to talk about now. Let’s go into these. I hope that Vincent and I are going to be able to allay some of those fears with the science behind these concerns.
The first is a preprint that has caught a bit of attention. This was effectiveness of BNT162b2 vaccine among children 5 to 11, and 12 to 17 years in New York after the emergence of the Omicron variant. Now, this is a preprint. I’m going to put that right out front. For this investigation three, New York state databases were linked to examine out COVID-19 outcomes among children 5 to 17 years. The investigators reported that for the week of January 24 through 30th, 2022, 365,502 children aged 5 to 11, 852,384 children 12 to 17 years of age fully-vaccinated in New York State. For this context, when they say fully vaccinated, what does that mean? That means two doses for this study.
They looked at vaccine efficacy, and here’s what they’re going to report. Among these children, the vaccine efficacy against cases, we’re going to have to focus on that, declined from 66% to 51% for those 12 to 17. A little bit of a change from 66 to 51, and this is what it got a lot of people concerned and from 68% to 12% for those 5 to 11 years. This is what they’re claiming is vaccine efficacy against a case, an infection/case. Now, remember, and we’re going to get, I’m going to hammer this a little bit. We’re not talking about sick kids, we’re talking about kids with a positive test.
Now, they go on to say something else. Vaccine efficacy against hospitalization decline from 85 to 73 for children 12 to 17 and then they say from 100% to 48% for those 5 to 11. Actually, I’m going to throw in the confidence intervals on that last number, wide confidence interval. Maybe -12, maybe plus +75. I know a lot of people are saying it dropped in half. I’m not sure that our confidence intervals are going to allow such certainty there, but before Vincent and I do a deep dive on this, which you have to, I think, I want to bring up another report.
This is the mRNA “Effectiveness of COVID-19 Pfizer-BioNTech BNT162b2 mRNA Vaccination in Preventing COVID-19-Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Nonimmunocompromised Children and Adolescents Aged 5-17 Years” VISION Network, 10 States, April 2021-January 2022. A few takeaways from this report, two doses protected against COVID-19-associated emergency department and urgent care encounters amongst children and adolescents. However, the vaccine effectiveness for preventing these ed/UC encounters was lower during Omicron predominance.
Overall, the two-dose vaccine efficacy against COVID-19 association hospitalizations was between 73% and 94% in this report. I will make a couple other comments very briefly before we get into a discussion. I just want to say most of the hospitalizations that we saw among the adolescents of the 12 to 17, those occurred during the Delta predominance, but two thirds of the hospitalizations among the children each 5 to 11, 66.7% actually occurred during the Omicron predominance. I know people just can’t help from using the word mild associated with Omicron. It’s just stuck apparently. Anyway, Vincent, I want to pull you in on this and maybe I just pull you in right now. What are your thoughts?
VR: What about deaths? What’s the effect? We’re looking at hospitalization and ed and all that. What about deaths, do they report that?
DG: We don’t get detail on that.
VR: I think that’s the key, because in my opinion, the bar for emergency room hospitalization for kids is a bit lower than for adults, wouldn’t you say? Your kids start to get sick and you rush them and then maybe they didn’t need to go there. I think that’s part of confounding this, but I do think that you’re right, this is mostly– The big drop is just PCR positivity. I’m not concerned about that at all, and it’s a bigger drop than in adults. It’s sooner, they’re younger, they have different immune systems.
I don’t think that is a reason to say, and I think the press is really off on this to say that this is showing that the vaccines are not working. Be careful what you’re saying. You have to analyze what working is. Now, the mRNA report is a little bit different from the New York state report. There’s a bit of variation in the data, and this is being reported, at least in some places. I think that we don’t have the final answer yet. I’m not sure the New York numbers are correct for the entire country.
DG: You and I, we’re on the same page. We always talk about, I was in a guidelines committee meeting today. We just talk about clinical decisions. Even parental decisions to bring someone for care, those are subjective. Those are a person makes a decision. It’s not a hard number. Death is a hard number. We certainly know that the vaccines are tremendous if that’s the endpoint we’re looking at, and durable. We’re seeing durability with regard to hospitalization. The thing, it is tough, because I know people say, “Oh, but I care because if I get an infection, I have a, let’s say 10% chance of getting long COVID.”
I’m not sure, to be completely honest, that we have the data that says a completely asymptomatic PCR-positive child has a significant risk of long COVID. I think the experience would suggest otherwise. Just think of the numbers. I’m certainly starting to see some long COVID cases now from people that got Omicron infections during December, January, we’re just getting into that two months out where they start to see. We’re not seeing 10% of those million people per day that tested positive.
I certainly don’t want anyone to get infected, but I’m not sure you can take the data and all the concerns from unvaccinated people having symptomatic COVID testing positive and say, “Oh my gosh, a positive PCR test has all those same fears and concerns.” I really do not think that we have data that says that a PCR-positive kid is at significant risk for Mis-C, the multi-system inflammatory of children, or for long COVID. I don’t think parents should be quite as concerned, as, well, unfortunately, a lot of them have been in the emails and discussions I’ve had since these reports came out.
VR: One last thing I want to point out is that, these are three week intervals in the 5 to 11-year-olds with no boost, and I just don’t think that’s correct. I think we’ve learned from adults that three to four weeks is too close. That’s why we’re giving a third dose to fix it. It’s just not clear to me why we’re doing this in kids.
DG: I think that’s a great point too. I think what we’ve started suggesting is that you get your first dose. You might want to wait eight weeks for that second dose. It might be more effective. It might be safer. This is turning into a three dose vaccine series. You get your first shot a couple months later, you get your second shot and then five months later you finish it off. We’re looking at old data here, so yes, I completely agree there.
VR: We should say that Daniel and I do not discuss this ahead of the show. We just spontaneously say what we think and we just turn out. We don’t always agree, but a lot of times we do.
DG: I think it’s better this way. It’s the raw, honest discussion. I’m sure I shared with you when I was doing these mystery cases at Columbia, they would want to give me the
result ahead of time. I’m like, “That’s cheating. Let them see me fumble through it.” They’ll say. Anyway, the next article, “Global, Regional, and National Minimum Estimates of Children Affected by COVID-19, Associated Orphanhood, and Caregiver Death by Age and Family Circumstances up to October 31, 2021” An updated modeling study was published in the Lancet Child & Adolescent Health.
This was really looking at how many children have lost either both parents or their primary caregivers resulting in orphanhood. Unfortunately, this report suggested that the number exceeded five million, so just another impact on the children. This was something that I painfully witnessed firsthand many times during the pandemic. A husband and wife would come in, they would have young children at home and they would not make it out of the hospital. This pandemic has just had enormous impacts on our children.
Now some good news, testing. A comparison of rapid antigen tests performance between Delta and Omicron variants of SARS-CoV-2, secondary analysis from a serial home self-testing study. They do make a point. This is Omicron BA1. This was posted as a preprint, so this was really an interesting study. 7,349 participants without any symptoms were enrolled from October 18th, 2021 to January 24th, 2022. They’re going to go ahead. They’re going to perform the rapid antigen tests and the PCR tests every 48 hours. They do this for 15 days. They’re actually sequencing so that we know whether it’s the Delta or the Omicron variant.
Ultimately, a number of participants met eligibility for the study. We end up with a number of positive PCRs. For this study, they actually used tests that are FDA approved. The BD Veritor at home COVID-19 test, the Quidel QuickVue At-Home over the counter COVID-19 test, the Abbott BinaxNOW COVID-19 Antigens Self-Test. What they’re looking for is individuals with a positive rapid test within 48 hours of a positive PCR. They found that for Delta, this was 79.3%, for Omicron it was 89.5. Yes, not worse during Omicron in any way. Just, I think encouraging those rapid tests.
There’s a lot of media stuff about, “Oh, we can’t trust them, et cetera.” I’m not sure that the science that the data supports that. I think these did continue to work. Certainly, no suggestion that they were inferior for detection of Omicron. I will say, apparently, there are tests out there that are not FDA-approved somehow being sold and used. Yes, use an FDA-approved, validated test. Don’t let somebody in a trench code sell you something on the street in New York City.
Pre-Exposure. Now, I know we’ve already been going for quite a while, but this is actually the meat of it. This is, I think, what has a lot of people really throwing up their hands, not sure what’s going on. I am going to tell people to go ahead and take a little time, read this for yourself. The CDC created a page called COVID-19 Community Levels, a measure of the impact of COVID-19 illness on health and healthcare systems. I’m going to go through a little bit about this.
This was actually updated February 25th, so actually, the day after we recorded our last TWiV. I actually felt it was good that I had a little time to read this a few times and discuss it with people a few times. Let me start by reading the first paragraph, which I actually– “With current high levels of vaccination and high levels of population immunity from both vaccination and infections, the risk of medically significant disease, hospitalization, and death from COVID-19 is greatly reduced for most people.” I put most people in italics. That’s my italics.
“At the same time, we know that some people and communities, such as our oldest citizens, people who are immunocompromised, and people with disabilities are at higher risk for serious illness and face challenging decisions navigating a world with COVID-19.” I personally would’ve added something about those who are still not eligible for vaccinations. I might have also wanted to throw something in about long COVID. People that don’t fall into some of these categories, but 10% continue to suffer. Now the CDC is going to use three metrics in this guidance.
I actually switch it around because then they actually switch it around to later. Let me go through it in my order. When you look at how they do this, the first number they’re looking at is the total new COVID-19 cases per 100,000 population in the past seven days. What they’re using as a cutoff is 200 new COVID cases per 100,000 people in the last seven days. I am going to say right upfront. I do worry that there’s no test positivity percentage here. One way to keep your numbers is just not to test. The test positivity used to be a check on this.
If you decided, “Well, I’m just not going to test anyone,” then your test positivity would trigger a risk issue. Here you could just not test and that keeps you below this cutoff. Well, it might keep you below the cutoff, but then you could potentially get hit with these, say, lagging indicators. The next one is the percentage of staffed inpatient beds occupied by COVID-19 patients. That’s talking a little bit about what’s going on here. New COVID-19 admissions per 100,000 population in the past seven days, again, a late indicator. Let’s go through because this was a big shift. I want to talk about the fact that people are showing these maps.
The entire country was red, and then it suddenly turned green with a click of a button. What were the old levels of transmission? We used to have low. That was zero to nine. This is all new cases per 100,000, so zero to nine. Moderate was 10 to 49. Substantial was 50 to 99. High transmission was greater than equal to 100. Now we have anything under 200 is low. For a lot of people, that was a very big change.
VR: They also used to have percentage of positive tests there.
DG: Exactly. It used to be low transmission. You had to be less than 5%. They forced you to test otherwise, so moderate was 5 to 7.9. Substantial was 8 to 9.9, high transmission was greater than 10. They took that out, which actually, I’m being critical, I’m sorry, CDC. Now, there’s the fewer than 200 and there’s 200 or more and then they put in those other, basically how are the hospitals doing, et cetera. Then ultimately, each color gets color-coded as green, which is low level, yellow, medium level, orange for high level. Then depending on where you are, they make recommendations about what individuals should consider doing and they make recommendations for the community.
The big takeaway from this is everyone looked at this and the mask came off. The mask basically was in here only being suggested if we’re in orange territory. More than 200 new cases, hospitals are starting to get overwhelmed. I have a lot of comments, but Vincent, before I do, did you have any thoughts? How has this impacted your thoughts?
VR: Do you think it’s realistic to take masks off and then at some point in the future masks back on?
DG: This is not the first time that the masks came off. We did this before. We did this last summer. Every time things go down, last summer we looked at this and we said, “Hey, mission accomplished.” I don’t know if it was a photo taken on a battleship or not but the mask came off. Then everyone got really upset because there was a recommendation for the mask to come back on. This is going to be a tough sell. At some point, this will settle into a seasonal respiratory pattern. Let’s say November, December. These are recorded, so people can go back and listen to this again.
It is likely that next December, January, we will be seeing high transmission as I would define it. We’ll start to see hundreds of people dying a day. We’ll see tens, thousands of cases. It’s going to be hard at that point to encourage people to wear masks again. Taking the masks off, trying to put them back on is a tough sell. An interesting issue. I was talking to my son, Barnaby, today on the way to school and we were talking a little bit about, “Well, Barnaby, what are you going to do at school?”
There definitely are a lot of people who are immunocompromised, who can’t get the benefits of vaccine, too young to get vaccinated or at home. Now they’ve got people out there in the world quite concerned. We’ve talked about the potential to use in N95. I talked to my son, Barnaby, a little bit about when he may or may not want to wear a mask. If he’s outside walking to school by himself, I don’t see any reason he needs a mask. We had a little debriefing at the end of school today and he’s like, “Daddy, when I was in class, we were spaced apart. The windows are open. I didn’t have the mask on, but then when I would go out in the hall and it’s crowded, I would put it back on.” This is going to be interesting and challenging going forward for a lot of individuals.
VR: I would like to know the science behind changing these numbers. I’m not sure there is any.
DG: I would like if they did. I can make up my own in these whole ideas that, as we’ve talked about a case in someone who’s vaccinated is different, but they didn’t put any of that into these numbers. If you said, “Well, we’re doing this because of the impact of vaccination on transmission,” well, then these numbers should have different thresholds based upon your vaccination uptake in your area. That’s one of the challenge. You and I, we want to see the science behind this, because I don’t want to just tell everyone what my opinion is. I want to share the science behind this.
VR: It’s interesting on our live stream last night, there was mixed opinion about this and that many people still want to wear masks. It was quite interesting. Now, it could be the people who come to the live stream or a selected group of individuals but I think as in many parts of the US, nobody’s wearing masks anymore. In certain parts and many people said, “I don’t want to get long COVID. I’m going to keep wearing a mask until this is sorted out.” I’m like, “I’m not sure we’re going to do any better than this. We have really good vaccines.”
DG: It will be interesting. I think that’s actually a good comment, let’s say it’s next February, it’s next December numbers are starting to go up. We have good access to oral antivirals. Let’s say, oh my gosh, you take a course of Paxlovid and your chance of long COVID really drops to minimal. That might, and I think we’re going to have those studies. I think we’re going to have studies, not only on prevention of long COVID, but hopefully, we’re going to have more understanding of how to treat long COVID, which I’ll talk a little bit about.
Let’s go right to passive vaccination. We had an update here, which I think is important. I’m not going to spend a lot of time on active vaccination, but Evusheld’s had it changed in its dosage. They revised authorized dosage, Instead of it being 150 milligrams, 150 milligrams, it’s now up to 300 milligrams, 300 milligrams. For those of your patients, who initially received you that 150, 150, give them a call, have them come back. We’ve already started doing this with our patients. Get them back as soon as possible. If you’re starting now, they’re going to be getting four shots instead of just two. I think we’ve talked a little bit about what’s science here.
The pre-exposure indication was based on the phase three trial that demonstrated a 77% reduction in infection with SARS-CoV-2, no cases of severe COVID-19, or deaths in the treatment arm. There were severe COVID and deaths in the placebo arm. There was some concern, there is some concern about reduced efficacy of the Evusheld’s, about a hundredfold drops. By doubling the dose, this is felt to potentially improve the protection there. Not based on another trial, but doing the best we can here.
Period of detectable viral replication, the viral symptom phase. When people test positive, the time for monitoring monoclonals, antivirals enrollment in clinical trials, this is not the time to give people steroids, not the time to give them antibiotics or other harmful, potentially harmful, or unproven therapies. We did get March 3rd, just right before recording this, Vincent, updated guidelines from the WHO. They have a living guidelines panel and people. Go ahead and take a look. Nothing surprising here, really the same things we’re about to talk about, but nice to just see the WHO and their guidelines. Actually, they’re really good about giving you the science behind the recommendations.
One of the things that I am, and we keep hitting on this is this whole issue that, “Dr. Griffin, I’m not at high risk. What do I do?” Nobody is at low risk for long COVID. We’ll talk about a study where you can reduce that risk with vaccination. We’re still waiting for trials to know if it’s better to do something, to keep your hands in your pocket. We’ve certainly learned during this pandemic that doing stuff can actually be harmful. Increased mortality with the HCQ, increased progression if you give people steroids in that first week. We need to be humble until we have the science. Hopefully, eventually, there’ll be more options for that larger group of people who test to treat.
Right now, number one is still Paxlovid. Try to have a plan ahead time with your high-risk patients, those that might qualify. Look at their medicine list. Are they on something that might be substituted? Do they know what to do if they get a positive test? We don’t want to wait five or six days until they start feeling bad. They should be educated about the prompt treatment being critical here, and then know where you can get those locally. I did share that story. We are seeing, people tolerate this quite well and feel better quite quickly. So far so good with the Paxlovid. Monoclonal therapy, we’re now actually in addition to Sotrovimab, we’re actually getting allocations of Bebtelovimab.
Bebtelovimab, apparently, I don’t always pronounce that O properly, but a cautionary tale here. Sometimes things seem better in our trials than they are in the real world. The publication of “The Impact of COVID-19 Monoclonal Antibody Therapy on Progression to the Hospitalization in a Population with a High Percentage of the SARS-CoV-2 Alpha Variant.”
This was published in medical research archives, The Journal of The European Society of Medicine, here, the authors, and, and I am one for full disclosure, performed a prospective study looking at the progression to the hospitalization in a high-risk treatment population that qualified for monoclonal antibody therapy and that consented to have their viral isolates undergo whole-genome sequencing to assess for genetic variants. A total of 125 patients consented to participate. Ultimately, we good data on 81 participants. Sequence data, they completed the follow-up.
Based on the high-risk profile, we anticipated about a 10% or greater progression to hospitalization without therapy. We expected about a 70-to-80% reduction based on the RCTs. We’re thinking maybe 2% to 3%, might progress and end up in the hospital despite therapy. We actually saw 6% of the treated patients were hospitalized despite monoclonal antibody therapy. The most common variant, in this group, was actually Alpha at about 81%. If you go ahead and take a look at the article, you can see a little bit more about it. Just some of our takeaways, so we’re not sure why we didn’t do better, why we weren’t doing as well as expected.
Was it that there was a little bit of delay in real world? In those studies, you’re getting the average treatment in about day three. We’re getting it in about day five. Perhaps it was some difference with the Alpha variant in progression to hospitalization or efficacy. I think interesting enough, it’s nice to see the data coming out now that maybe Alpha was not so much different than the early media reports suggested, but just really critical to keep an eye on how are we doing. I think particularly if we start using a lot of these antivirals. If we start having a loss of efficacy, we need to know that right away way, not months and months later.
After the monoclonals, Remdesivir, remember that three-day outpatient IV therapy, 85% reduction in progression. Impressive in that arena, as I mentioned, not so impressive later on. Molnupiravir, 2 million courses distributed out there to the states and actually now added to the WHO living guidelines that were just updated March 3rd. Early inflammatory phase, we waited, now they’ve ended up in the hospital. As we’ve talked about, steroids at the right time in the right patient if they become hypoxic. Anticoagulation, we have recommendations on the level of dosing, pulmonary support potential use of Tocilizumab in a select group.
Actually, some of our local facilities have actually, I would say, created better operations. Let’s say someone shows up for that five-day Remdesivir. If they’re doing better, they might get them out after day three, complete that therapy in the home, if they’re stable. That’s nice to do but we want to restratify. We want to know who is safe, who’s going to do poorly, who needs to stay in the hospital.
We had a nice publication in Cell Reports Medicine, the article, “Development and Validation of Scope Score: A Clinical Score to Predict Progression of COVID-19 Pneumonia to Severe Respiratory Failure.” We don’t want to send someone out who’s really high risk. It’s the person we might want to continue to observe. One of the big challenges for clinicians when we admit a patient with COVID-19 is predicting how well or poorly they might do.
Here, the authors looked at D-dimers, CRP, ferritin IL-6. Based on levels of a certain number of points between zero to three, were assigned for each biomarker. Having a score of six or more was predictive progression to severe respiratory failure or death within 14 days. Another tool much like the COVID-GRAM that used chest radiograph abnormalities, age, hemoptysis, dyspnea, unconsciousness, number of comorbidities, cancer history, neutrophil to lymphocyte ratio, one of my favorites, lactate dehydrogenase, and direct bilirubin levels to predict outcomes. Just another tool that we can use clinically.
Long COVID. Yes, this is a long COVID session and we are appropriately here. COVID is not just a two-week viral illness for many people. We usually talk a lot about past but I also want to include what I call the tail. We’ve hit four weeks. Everyone’s celebrating, maybe there’s some clapping going on, but are we out of the woods? The article, Delayed mortality among solid organ transplant recipients hospitalized for COVID-19, was published in Clinical Infectious Diseases. Here, the authors looked at solid organ transplant recipients that survived hospitalization for COVID-19. While 20% of the recipients died in the first 28 days, another 23% died days 29 to 90.
We also know that a lot of individuals who don’t die may get readmitted. They may have a number of other complications. This is, again, when those individuals get out of the hospital, they really need follow-up. They really need someone there taking care of them because they continue to be at high risk. Now, this is an interesting one, the preprint, along these lines of, do vaccinations reduce my risk of long COVID? Risk of long COVID in people infected with SARS-CoV-2, after two doses of a COVID-19 vaccine, community-based matched cohort study.
First off, people are like, “What about three? No one’s doing just two anymore, Dr. Griffin.” Anyway, this is an investigation looking at whether receiving two COVID-19 vaccinations before SARS-CoV-2 infection reduces the risk of developing long COVID symptoms. The investigators included COVID-19 infection survey, participants aged 18 to 69, who tested positive for the first time for SARS-CoV-2, between the 26th April 2020 and 30th November 2021.
Just really interesting there. We are seeing so many reinfections that they have to actually say, “Was this your first time?” Patients were double-vaccinated, greater than or equal to 14 days before infection. They were one-to-one propensity score-matched based on socio-demographic characteristics and time for infection to follow up for long COVID, to those unvaccinated at time of infection. This study sample comprised 3,090 double vaccinated participants. I think the demographics are interesting. Mean age 49; 54% Female, 92% White. Median follow-up from infection, 96 days, and matched control participants.
Long COVID symptoms reported in double-vaccinated participants, 9.5%, compared with 14.6% in the unvaccinated, so a corresponding adjusted odds ratio for long COVID symptoms of 0.59, so about a 41% reduction. Activity limiting symptoms were reported respectively at 5.5 and 8.7 participants. First off, another study suggesting that COVID-19 vaccination is associated with reduced risk of long COVID, but I have a number of comments.
First off, let me just talk about, how did they assess whether or not someone had long COVID? The primary outcome was long COVID status. According to the survey question, would you describe yourself as having long COVID? That is, you’re still experiencing symptoms more than four weeks after you first had COVID-19, that are not explained by something else. Participants were also asked whether their symptoms limited their ability to undertake daily activities.
The interesting thing I have there, is this really lumps? You say, “Okay.” You had COVID. Let’s say it’s past those four weeks, you’re still not a 100%, you might say you have long COVID because what I think people are seeing here is they’re looking at this and they’re saying, “Wait, if I get vaccinated, I still have a 9.5. I still have about a 10% chance of ending up with long COVID. I’ve heard about long COVID and it’s really bad.” I’m not sure that all these people had the long COVID that we talk about. It might just be, “Boy, at 29 days, I’m still not 100%,” so I do think we have to take this with a grain of salt. I’m happy to say, this builds on this body of evidence that vaccination reduces your risk.
It also goes well with our studies where we say that getting vaccinated after infection reduces your risk but not all long COVID is the same. These are not the people who can’t function. I just don’t think people should be quite as alarmed and take that from this but, Vincent, did you have a–
VR: Yes. I think these numbers could go down substantially because as you move away from the time, maybe a lot of these people get better and there’s really a lower percentage that have actual long COVID. I think that’s a real problem. I agree with you.
DG: Certainly vaccination reduces, I don’t think it eliminates long COVID, but yes, I’m not sure. I do want to mention this next paper and this is the paper, “Peripheral Neuropathy Evaluations of Patients with Prolonged to Long COVID,” just published in Neurology Neuroimmunology & Neuroinflammation. This was really a case series, to be honest. It was 17 patients. The author’s reported that 16.7% of these individuals had abnormal electrodiagnostic studies, 62.5% at lower leg skin biopsies with pathologically confirmed small fiber neuropathy. They actually treated these individuals with some degree of success with IVIG and corticosteroids.
Now, one of the things I was having a conversation recently with another physician about how difficult it is caring for people with long COVID and our concerns about the difficulty going forward if we don’t have something objectively to use to document. I’m going to be on another call with one of these disability groups coming up. They always like, “Well, so, they say this, they say that, but what do you have objectively to validate? Maybe they’re just lying, maybe they just don’t like to work.” It is really difficult. Nice at least here, here you’ve got a biopsy, pathologically-confirmed abnormality.
Also, same thing. They’ve actually got some treatment success, so just very positive if we can get a little more understanding of this disease. Something objective to help these patients document what’s going on. All right, no one is safe until everyone is safe, and here’s where we wind it up. Good news, in terms of vaccines for Sub-Saharan Africa. They experienced what we did early on. I think I complained about this where vaccines would just show up. Here’s some vaccines, you got like a week to get them out. Here’s some vaccines, three weeks from expiration.
Previously, the WHO would just send vaccine doses to African countries as they became available, but now countries can actually go ahead, request the vaccines they need directly from the WHO, what quantity, when they’re going to get them. As a result, there’s the hope that this will be able to really ramp up vaccination efforts in a much logistically better way. Dr. John Nkengasong, the head of the African Centres for Disease Control said that he’s really calling for a coordinated approach to ensure that the vaccines arrive at the right time in the right place.
I’m optimistic going forward because, boy, we have not done a great job so far. On that note, as people are well aware, things are tough around the world. I don’t think anyone can miss what’s going on in Ukraine. We try to not just focus on the US. At Parasites Without Borders, we try to have a global perspective. Throughout the month of February, March and April, we will continue along those lines and donations made to Parasites Without Borders, will be matched and doubled up to a potential donation of $40,000 to the American Society of Tropical Medicine and Hygiene, including scholarships to the annual meetings. These will be Travel Awards, with priority placed on females from low-income countries who might not otherwise be able to attend.
VR: Time for some questions for Daniel. You can send yours to Daniel@microbe.tv. First is from Jennifer, who is a RN in a hospital in the Midwest, and she has questions about two individuals who have long COVID. First, a friend who was infected over a year ago and is still dealing with tinnitus that affects her entire life. She has seen an ENT, who basically said there is nothing to do. She is miserable, she’s afraid it will be permanent. It affects every area of her life and marriage and job. Jennifer’s husband had mild COVID in October and since then, has a low humming sound in his ears.
For example, they have to have the TV volume on, very high. All these people are in great shape. They exercise daily, good BMI. They’re vaccinated, they’re boosted. Any ideas, suggestions or referral would be greatly appreciated.
DG: I appreciate the letter here because it really brings up a lot of important issues. One is, no one is at low risk for a long Covid. People who, “Boy, I did all the right things and now I’ve got this debilitating,” and it is. The tinnitus, this buzzing can actually be maddening. There’s actually a famous individual, people may know who this was, who actually took their life that just tinnitus drove them to the point where they’re like, “I cannot live this way.” I have seen in some of my patients, spontaneous resolution of the tinnitus.
We do not have a great understanding of the mechanism, but tinnitus is actually a common complaint among the patients that I care for with long COVID and actually it’s something well described in the literature. Right now, we’re still struggling to understand the mechanism. We are desperately waiting for those trials to get started, where we can look at potential therapeutics. Just holding pattern for the moment, I’m sorry. What is being recommended is actually what we’re recommending, increasing background noise, all the normal things we do for tinnitus while we’re waiting for these trials, and this science to hopefully give us an explanation what’s driving it and what can we do.
VR: Gil writes, “I’m a regular listener of Q&A with A and V in your weekly updates. I hear Vincent repeatedly say that he thinks the fully vaccinated should be fine without a mask. I hear you say that all the risk is low, the fully vaccinated can get long COVID. I’ve seen studies that show likelihood of being diagnosed with diabetes or other conditions is higher for those who’ve had COVID. As the mask mandates fall away, I’m trying to decide if being fully vaccinated is enough. What are your thoughts?”
DG: You hit on the science. The science is that vaccination does significantly, we do think there’s a number of studies now, does significantly reduce your risk of long COVID, but doesn’t make it zero. I certainly have seen individuals who’ve been vaccinated. Even the studies we’ve talked about, vaccinated people have a lower risk, but that means there are people who are still developing long COVID symptoms. We’re optimistic that the severity is reduced. We’re optimistic that the duration that they suffer will be reduced, but it’s not 100% unfortunately, and so this is what a lot of people are struggling with.
Even a person who is otherwise young and healthy and they’ve done all the right things, they can end up with tinnitus, they can end up with the fatigue, they can end up with the cognitive disturbances and the hair loss, et cetera. This is something I’m hoping that we can have a next layer that maybe there’s an antiviral, and that just really gets us down to a much lower level. That’s where we are with the science.
VR: Hiam writes, “What’s your criteria for when you will personally stop wearing a mask?”
DG: That’s tough, because I’m one of these bleeding heart, trying to save the world, I’ll wear a mask just because I want to reduce the risk to others. Hiam, you don’t have to follow my guidance. I’m going to continue to wear masks probably a lot longer. I’m going to look for situations where I feel like someone might be at high risk and wear it. I may end up wearing it a little bit longer, so.
VR: Our last one is from Gabrielle who writes, “I’m someone who isn’t technically in a high risk group for severe COVID, but I am a C-6 quadriplegic from transverse myelitis. Due to the damage to my spinal cord, I have impaired coughing abilities, any respiratory infection is concerning for me as I have a harder time clearing secretions than the average person. My question is about Paxlovid. I know the immune response from vaccination is superior to that of infection in terms of durability, et cetera.
I was wondering if Paxlovid interferes with the potential durability of immunity from infection, if one becomes infected despite vaccination, or if it just reduces the virus’ ability to replicate without having an effect on initiation of the immune response. I’m just weighing my options in case I happen to get infected if Paxlovid makes sense to me. On a side note, I also hope we start seeing more accessible or easier to use home tests, as someone with impaired hand function, it’s quite difficult to squeeze little bottles of liquid into other little bottles to take a home test. I know home tests can be a problem for those who are blind or visually impaired as well.
DG: That’s great. Let me make sure I hit both. The first is, and this states back an interesting qualification of what you’re supposed to tell people when you gave them the monoclonals about how getting the monoclonals may reduce your chance to have a response to the vaccine, to the natural, or say, virus survivor-induced immunity that might follow. If you want to boost your immune system, get a vaccine, get a booster, don’t get infected. Don’t see getting an infection as your opportunity to get a better immune memory, because it’s pretty risky, and we’ve talked about this before.
Someone like you, as you describe, you’d be at risk of ending up in hospital, you’d be at risk of ending up with a lot of problems, you actually would be at risk of not surviving. Go ahead, get the Paxlovid. In my mind, there’s no reason you wouldn’t and your description would put you at a high-risk category, so I don’t see a problem there. Don’t go ahead and just let the virus run rampant. The actual hope, is that the sooner we treat it, the less immune response is going to be triggered because the immune response is what is actually causing so much of the problem.
We don’t know yet, and those are the studies. We have the study showing on reduction in progression, which we would think means that that immune system hasn’t been fully triggered, the dysfunctional part. We see some impact on the RNA copy numbers, but I will say that. Now the second one, which I think you bring up, which is really good is a lot of these home tests are not that easy.
There is a test that we were using quite a bit as part of the United Health Group wellness at home program. This is a Medicare Advantage where we would have these individuals at home. What it just involved was this little device where you would swab your nose, and then there was a little device you put it in, and as you put it in, you push down and then there was a light and a beeping that would happen.
If you’re visually impaired, that’s hard. If you’re having small motor skills, that becomes hard. We actually need to address these issues, and we address these issues, bathrooms, ramps. I’m not sure that during the pandemic this large population of individuals that have these challenges should not be considered as well.
VR: That’s COVID-19 Clinical Update Number 104 with Dr. Daniel Griffin. Thank you, Daniel.
DG: Oh, thank you, Vincent. Everyone, be safe out there.
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