TWiV 850 COVID-19 Clinical Update #96

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 08 January 2022

pdf of this transcript available (link)

Vincent Racaniello: This Week in Virology, the podcast around viruses, the kind that make you sick.

From MicrobeTV, this is TWiV, This Week in Virology, Episode number 850 recorded on January 6, 2022. I’m Vincent Racaniello and you’re listening to the podcast all about viruses. Joining me today right here at ‘The Incubator,’ Daniel Griffin.

Daniel Griffin: Hello, everyone, and hello Vincent.

VR: Hi, Daniel. How are you?

DG: Doing well.

VR: Happy New Year.

DG: Thank you.

VR: The Incubator of course is our recording studio in New York City, and it’s easy for Daniel to get here. He’s sitting right next to me across the table here. We have a big table. You can see the phage pillow behind me is shared by Daniel.

DG: This is good.

VR: Daniel, this is update number 96. Before you start with your quote, I just wanted to ask you before I forget, this is a question. We’ve been getting a lot of Omicron. Does it cause serious COVID or we should say severe COVID? Does it cause Long COVID? Do we know?

DG: It’s hard to comment on Long COVID, so we’re doing it in reverse because it hasn’t been long enough. We think of Long COVID as lasting more than four weeks. Does it cause severe COVID? Certainly. When you look at these numbers and they say things like, “Oh, maybe it’s 50% reduction in hospitalization, maybe 50% reduction in deaths.” We’re going from what, instead of 2% of people dying, 1% of people dying?

I had a gentleman I saw this morning, and he almost died last night. This is a gentleman in his 50s, unvaccinated, no other medical problems, but he made that decision not to get vaccinated. He’s producing a thick plasticky mucus in the lungs. Everyone tells me, “Oh, but Omicron doesn’t really go to the lungs. In the hamsters, it’s up in the nose.” Well, in this gentleman, I tried to explain to him how mild this was supposed to be. No, he was coughing up thick, rubbery, nasty mucus.

He’s now on high-flow nasal cannula, we’ve done steroids. We’ve done Toci. We’re doing everything we can and we’ll see how he’s doing tomorrow. I had another woman whose family decided she shouldn’t be vaccinated. I talked to her. She seemed like she had capacity, so it would’ve been nice if she weighed in a little, but now she’s on a morphine drip, comfort care. She’s in the process of dying.

People are dying of Omicron, 2,000 people on some days. Hospitalizations, as we’ll talk about, are rising. There is severe disease. It’s this whole issue when we compare a population that had been vaccinated that maybe recently got through Delta, maybe a bunch of the most vulnerable died in the first few waves, the people still around, the people still standing. You’re going to see these impacts. We’ll talk a little bit about is that due to any intrinsic change in the virus, or is it immunity? Is it different populations being impacted? Yes, Omicron causes severe disease.

VR: It’s really a good point that the hamsters don’t tell you the whole story because they’re not people and they don’t actually get severe disease to begin with. We’re actually going to do that paper tomorrow on TWiV, but I think it doesn’t give you the whole picture.

DG: Yes. I think you’ve riled me up there.

VR: It’s good. Last night I was thumping on the table and someone said, “You’re like a preacher trying to make a point.”

DG: We’ll circle back to this, don’t you worry. Let me start with my quotation, and don’t worry, we’ll get right back into this. “The single biggest problem in communication is the illusion that it has taken place.”

VR: That’s great. I love it.

DG: This has actually been attributed to a lot of people, but I do believe it was actually the Irish playwright, George Bernard Shaw, who actually said this initially. Maybe people can email in and let me know. Let’s just start. Before I get into each section, I wanted to bring people up to speed. I think everyone is aware of the rising case numbers, but I do want to point out the hospitalization numbers are rising also and the deaths. We’re seeing days with over 2,000 deaths per day.

Where are we with the Omicron variant versus Delta? As far as the first of the year, the sequencing data we got from the CDC surveillance, we’re at 95% Omicron, so it’s almost all Omicron. I always like to check. I don’t trust anyone. Maybe I’m like Reagan, trust with verification. There’s some famous quotation where he’s talking about the Russians. Some of my colleagues are doing sequencing for research purposes, doing hundreds of sequences per week. We are in the 90s here in the New York region, so I believe this data. This is consistent.

As far as hospitalizations, because everyone is trying to paint this rosy picture about this disconnect, this exact topic that, “Omicron is not so bad. It’s the attenuated virus that the pharmaceutical companies could make. Go out there and get it for free.” Don’t. We peaked last January at about 128,000 hospitalized patients as a daily average, about 28,000 in the ICU. We’re already up at 100,000 in hospital and about 20,000 in the ICU. We have a lot of vaccinated people, so I’m having trouble with this narrative about how mild Omicron is.

Here in New York, here in Long Island, COVID hospitalizations are rising rapidly. Vincent, you can actually see if you look over. This is what’s happening locally. That’s pretty mild, that exponential rise in hospitalizations. There’s a disconnect from what I’m hearing in the media, speaking to an NPR reporter earlier this week. I’m so sorry. I know what you want to hear, I know what everyone’s saying, but this is not something to be taken lightly. Omicron is causing severe disease.

VR: The hospitalizations, you said some vaccinated people, but is the majority still unvaccinated people?

DG: You can actually tell when I walk in the room, if someone’s in the room and they’re on nano breather, there are these high-flow nasal cannulas requiring a lot of support, I pretty much know they’re unvaccinated. I usually try to gently say, “Hey, any vaccines under the belt?” They usually say, “No.” That person who’s on maybe just a little bit of oxygen or maybe not on oxygen, they’ve usually been vaccinated, so there really is a different presentation, certainly.

The other thing that I’ve started throwing in the mix which I’ve seen is, I say, “Is this your first infection?” Because we’re seeing so many reinfections now. I’m actually taking care of individuals that I met for the first time back in April of 2020 now back in the hospital with COVID again, on oxygen because they did not take advantage of the vaccination opportunity.

VR: One more. Can you say if you compare Omicron to Delta, whether there is more hospitalization in the vaccinated population comparing Delta to Omicron?

DG: Yes. I think it’s hard to see a difference there. Then what I would love to see is just remove all the vaccinated people and just with people who get infected, who are not vaccinated, who never had a bout of COVID before, how are they doing? Is it really milder in them? I think that’s what people are trying to intimate, they’re trying to suggest that there’s a difference in the virus.

I think we need that data. We need to say, “Let’s look at a population of unvaccinated individuals who got infected and let’s look at hospitalization rates, deaths in that population.” That really answers the question, I think, is the virus behaving in a less virulent manner?

VR: As you know, Omicron is better at evading antibodies than Delta, and so I’m just wondering how that translates, if at all, into disease severity. We don’t know yet, but I think it’s important to know because it tells you how important the neutralization is, right?

DG: Yes. We’re actually going to get to a paper, which is rather interesting. I’ll say the disconnect between waning antibody levels and rising protection against severe disease, so stay tuned. I know you’re about to jump off, but don’t go away. Let’s talk a little bit about the literature here. Wo the research letter, Characteristics and outcomes of hospitalized patients in South Africa during the COVID-19 Omicron wave compared with previous waves. This was published in JAMA.

There certainly are some limitations to this paper, but we’ll go through that. One of the things they acknowledge is difference in age and comorbidities, but what did we see here? I think this is one of those things that people don’t realize, and when I point this out, they usually seem shocked. There’s this perception that, “Oh, South Africa. We’re in Africa. Nobody’s vaccinated Africa.”

Well, if you look at this paper, 44% of the adult South African population had been vaccinated as of December 2021, and greater than 50% of the population had evidence of previous exposure to SARS-CoV-2. This is not an immune-naïve population that’s on Omicron. In this context, let’s go through it. They have a wonderful table. This is open access, so everyone can get to this. If you look at table one, you can see what happened.

Wave one, about 4,000 people get admitted. Wave two, 4,600 end up in hospital. Wave three, that’s the big Delta wave right before this, about 6,000 people end up in hospital, and then wave four, 2,351, so less people in the hospital. The initial perception is we’re seeing less individuals end up in the hospital. They give us numbers on this where they say, “Boy, during the previous waves, about 70% of people were admitted. During this wave, the Omicron wave, about 40%.”

That’s a nice reduction. That’s very encouraging, but then you start looking a little bit more into the details. Actually, Vincent, I have this up in front of us so you can glance over because we’re in the same room. If you look at, are these the same patients? One thing we just talked about was, they’re not the same patients in terms of immunity. We have ongoing vaccination campaigns, we had a recent Delta surge where a lot of people were recently infected, so they have memory of that Delta infection. What about the age? I think that’s pretty interesting.

In the previous wave, we were really looking at people in their 50s. This wave mainly impacted people in their 30s. Age alone would almost give me these results. The other is the proportion of male and female. In this wave, 61% of the infections were in females. We know women do better, we know they’re less likely to end up in the hospital. What about comorbidities? In the prior waves, the majority of the patients had comorbidities. In this wave, only about a quarter of the individuals had comorbidities.

It really leaves me with a lot of things to speculate about. Certainly, this was better. Less people ended up in the hospital. Is this because we’re looking at healthy 30-year-olds versus people over the age of 50 with comorbidities? Is this in part due to immunity, either that viral infection survivor immunity? And also, of course, the most vulnerable people have died in the previous waves, we’re left with the survivors. Is it all the vaccination that moves forward? Is it the female issue? Or I think everyone wants to say, “Oh, the virus has become less virulent.” Vincent, any thoughts?

VR: You cannot make the conclusion because of all these things you pointed out, Daniel. It’s not the same population. In animal experiments, when we try to determine viral virulence, everything has to be the same. The same inoculum, the same animals, the same age, sex, and obviously, that’s very difficult to do in animals and here, it’s impossible in people. No, you can’t say that. Then you throw in the immunity issue, and it’s completely clouded. When they first said it’s less virulent, I was doubtful. Now, I’m convinced it’s not.

DG: Alright. We keep getting CDC guidance updates on quarantine and isolation. This is a little bit contentious, so let me talk a little bit about it. In a sense, this happened backwards. They came out with these changes and then they waited a while, and then they told us why. When you ask your children to do something, they might often– particularly my children, they’ll ask why, we’ve taught them to do that. You don’t say, “I’ll tell you next week, but start doing this in the meantime,” right? You want to know before you do it.

Here’s a couple of things that they stated in the rationale. CDC came out with a rationale, why do we change things? January 4, the rationale came out. Let me go through what they said. “COVID-19 cases due to the Omicron variant have increased along with seasonal increases in influenza and other respiratory viral infections. The potential for a large number of cases raises serious concerns about societal impact due to illness, as well as isolation and quarantine requirements.”

That’s interesting. That was actually a lot of what I think Anthony Fauci weighed in on is, we’ve got to change something because we’re about to enter a crisis. We think of ourselves as really critical in healthcare, but I think everyone realized how critical those pilots were, the airplane mechanics, people involved in the food industry. I think a lot of us are essential. This was a recognizing that we need to come up with some things, otherwise, our economy is going to just grind to a halt.

It’s not just about dollars changing hands, it’s about people getting where they need to go. It’s about people eating, it’s about all these other essential things. Then they go on to mention the data. I always like the data to come first, but that’s okay. “Data including a review of 113 studies from 17 countries show that most SARS-CoV-2 transmission occurs early in the course of infection.”

I think this is true, and I think the data supports us. Infectiousness peaks around one day before symptom onset and declines within a week of symptom onset. We’ve been asking people to isolate for this big block of time. They don’t necessarily know that two days before symptom onset and we asked them to isolate for 10 days afterwards. Who’s doing that? Maybe 20% of the people. It’s not working.

What they were saying, and again, this is what we’ll go on to discuss is that they are not saying at day six you are no longer infectious. This is actually a sort of, if you need to, this is an update and this is a little bit of the science. Let’s go through– what articles did they quote? The first one they quoted was actually published very recently, September 17, 2020.

That was a little bit back. I was a little surprised when I saw the date. This was, Transmission of SARS-CoV-2, a review of viral hosts and environmental factors. It is a really nice review. I would have liked maybe a little bit of an update, more recent data because they are saying they are basing this on what we know about Omicron. There’s a really nice figure one, and I do encourage people to look at this. There’s really a lot in this figure one.

I think we’ll link this on the Parasites Without Borders page. You can see this rapid ramp-up in the amount of viral RNA. In that day before symptom onset, you can see people entering that threshold of infectiousness. You can even see the correlation with the antigen test, which I’m sure we’ll talk a little bit about, and then you can see how that PCR can just stay positive for prolonged periods of time, well past infectiousness.

Just reinforcing that those PCRs, so many false positives as far as their active viral replication is their contagiousness. I think really putting the PCR in its place. It’s great for a sensitive test, but it’s not great for asking this question which we’re talking about is, are you infectious?

VR: Daniel, this is presumably an unvaccinated person, right?

DG: It’s unvaccinated, and it’s not Omicron, and it’s not Delta. Just look at the publication date. In a sense, it’s old.

VR: It’s likely to be very different in a vaccinated person and depending on the variant as well, right?

DG: We have a lot of data. We’ve talked about the famous Singapore study, and there’s a number of other studies as well. It appears that a vaccinated person, they may shoot up as quickly, but almost like the Omicron wave, they drop right down very quickly. You almost need different isolation recommendations for vaccinated versus unvaccinated.

VR: Let me point out here in this figure that by the time this period of infectiousness is really over, only shortly after that does the antibody go up. The antibody plays no role in containing this. It’s probably all innate immunity. Considering a vaccinated person when the antibodies are going to rise in a couple of days, that’s got to make an impact on infectiousness.

DG: I don’t know if people know as much about T-cell kinetics, but the T cells are coming up at about day three, four. They’re actually, you’ve got innate immunity, you’ve got T-cell responsiveness. My PhD is a B cell, so let’s be nice to them. This is really supporting the role of a lot of other arms of the immune system. Also, they have another reference in there. This is actually The Comparative Clinical Performance of Four SARS-CoV-2 Rapid Antigen Tests and Their Correlation to Infectivity In Vitro. That’s another one to look at.

They’re actually giving us their rationale, they’re giving us the science behind this. This is really a move forward. They then go on to say these data are from studies of prior SARS-CoV-2 variants. Some of the studies they looked at included Delta. We’re not talking specifically in these reference studies on Omicron. They do acknowledge the science is evolving, particularly for the Omicron variant, but then they go on to say that some of that data that is coming in now is suggesting, and this is consistent with what we’re seeing clinically, that Omicron has a shorter incubation period, two to four days, instead of that seven, five, four, which we’ve marched through.

This is that time from exposure to the time that you’re infected, infectious and have symptom onset. Then a risk benefit comment. This is not COVID-Zero, this is not the Taiwan approach where if you end up testing positive– actually one of my daughter’s classmates went to Taiwan to visit his family, and ended up testing positive on arrival, so he enjoyed his 14-day vacation in Taiwan in hospital. Then there were two PCR negatives required for him to leave, so this is not that approach. This is not a zero tolerance, this is a risk benefit.

They say the spread of the Omicron variant has the potential to worsen staffing shortages, increase supply chain challenges, jeopardize industry, education, and other systems that are essential to maintain a functioning society and economy. The pandemic has had a negative impact on the mental health of adults in the United States, largely due to economic and social concerns.

They go on to say, the study suggests that only a small percentage of people, they say small, but then they say 25 to 30%, isolate for a full 10 days. Yes, people were not following the old rules. They do also clarify that those masks should be well fitting, it’s not just any mask, it’s not just a bandana. If you are going to isolate for five days, if you’re then going to go back to work on day six – and the counting changed a little bit – you want to wear a tightly fitting proper mask.

They do say an estimated 31% of patients remain infectious. Here they reference a preprint, Mitigating isolation: The use of rapid antigen testing to reduce the impact of self-isolation periods. They are acknowledging testing and we’ll even get a little bit more into testing as we go forward because I know a lot of organizations have said, “Okay, this might be something we do in crisis mode, but as things get better, if we’re going to let people out earlier, we’re going to want negative antigen tests to reassure us that we’re not sending infectious people into these settings.”

All right, so this next I’m going to say, Occam was not a physician, this is our “flurona” section. Please don’t use that term. This was in the MMWR, this is Characteristics and clinical outcomes of children and adolescents aged less than 18-years-old, hospitalized with COVID-19, Six hospitals, United States July through August 2021. Now, yes, children, adolescents are being hospitalized with COVID-19, thousands every week. With Omicron, “army cold, mild variant.” No, this is not a mild variant. We have a rising number of children in hospital.

Now this was actually looking at over the summer, so this is prior to Omicron, this is July through August 2021. 77.9% were hospitalized for acute COVID-19. Among these patients that they looked at, approximately one-third, so one in three of the youngest children less than five years of age, had a viral co-infection. They had COVID and something else. Approximately two-thirds of those was something else, was RSV, which we’ve talked a lot on TWiV, and only 0.4% of the age eligible children that were admitted were fully vaccinated.

I hope people got that 99.6% of all these children that were admitted age less than 18 years of age that could’ve been vaccinated. This is unvaccinated children being admitted and I do want to point this out because people say, “Oh, but–” One-third of these children were completely healthy, have no comorbidities no obesity, no– just completely healthy kids ending up in the hospital with COVID and as we know, a third of those kids that end up in hospital end up in the ICU.

You can have COVID, you can have the flu. You can have COVID, you can have RSV. You can have COVID, you could even have metapneumovirus, one of my favorites. You could have– and we had a patient today with COVID and one of the common coronaviruses. You can have it all.

VR: You have names for all those Daniel

DG: I think we need to make them the metapneumorona, I like that one. I think the other one, and I want to acknowledge this. I had a gentleman who I’m still taking care of. He is getting better. He got his COVID vaccines, even got boosted, but he decided to forego the flu shot right because there’s not that much flu around. Unfortunately, this gentleman ended up getting influenza, ended up getting admitted to hospital, ended up developing a staph pneumonia, so a bacterial pneumonia on top, ended up being intubated in the ICU. He’s now extubated. He’s on oxygen. Keep getting those flu shots and realize Ahkam was not a physician. You can have more than one thing.

Okay, all right. Now we actually get to get into our normal stuff. Children, COVID, and mental health. Children are at risk of COVID. We just discussed all the hospitalizations and don’t feel this is a great time for your child to get Omicron. This is not something that you want to do willingly. We talked a little bit about the return to work guidance, but what about the return to school guidance? We need to compare these.

When the CDC shortened the recommendation to five days, if asymptomatic, following five days of wearing a mask when others are round, they then go on to update the quarantine guidance. This got a little tricky, but it’s going to be okay, because we’re going to get an update. They talked about unvaccinated people more than six months out from their second mRNA, more than the two months after a J&J, not yet boosted.

This had a lot of parents of younger children thinking, “My child, though vaccinated has yet been boosted. The eligibility had yet to open,” but we’re going to talk about that. “They’re going to end up having to quarantine again, if there’s a case at the school.” Let’s go through a couple of the updates that we got, and I have this in red in my notes. For people who need to quarantine, they recognize viral infection and do survivor immunity for the first 90 days, this the first time.

I know a lot of people out there, we’ve talked about in the U.K., if someone gets infected, there was about a six-month window. Here they’re giving you 90 days, so that counts. I know people out there have been saying, “Why aren’t we getting any credit?” If you had confirmed COVID-19 within the last 90 days, so you tested positive using a viral test, but this doesn’t cross over to the healthcare workers, but this is the first.

Then this update, they added this testing option because a lot of people were really frustrated. “What about testing? I don’t really want people coming at it day six, maybe if you add a testing option, I might be more comfortable with that,” and here we go. If an individual has access to a test and wants to test, the best approach is to use an antigen test toward the end of the five-day isolation period.

Collect the test sample only if you are fever free for 24-hours without the use of fever-reducing medication and your other symptoms have improved. Just a couple of comments. Loss of taste, smell may persist for weeks or months. You don’t need to let that delay your end of isolation. If your test result is positive, then you should continue to isolate until day 10. If your result is negative, you can then end isolation, but continue to wear that well-fitting mask around others at home and in public until day 10.

This makes people feel a little bit reassured, but then again, nothing is 100%, and that’s why they’re saying even if it’s negative, we’re sending it out there, wear that well-fitting mask, don’t go hang around someone who’s necessarily more vulnerable. They also changed this definition of how to count five days. I felt like I was in the days of how they counted malaria.

To calculate your five day isolation period, and I got to say, I don’t completely agree with this, sorry. But day zero is your first full day of symptoms. Day one is the first full day after your symptoms developed, and you can leave isolation after five full days. I usually ask people, was it in the morning? Was it at night? And I count from there. Apparently, if you start getting symptoms at 1:00 a.m. in the morning, that’s still day zero. If you got symptoms that 11:00 p.m., still day zero, you don’t start to count that full day.

I’m not sure why the midnight is calculated, but anyway, there’s this new counting. Our HR department is really good at explaining this to people and you’re losing a day if your symptoms start depending on what time of the day. Then, as we were saying, what about isolation of students or staff? Does this all apply to them? Actually, on December 29, so after the December 27 media release, we got some guidance.

Here we have a person diagnosed with COVID-19 who can be around others when at least 10 days have passed since their symptoms began. Still back at the 10 days for the staff and the schools. I’m not sure I understand this logic of de-prioritizing education. Maybe not, maybe the suggestion is we have a lot of remote learning options, we’re talking about doing this one time instead of five, 10 days, but ultimately this guidance, what people do, this is going to fall to the states to your local school district. In New York, we still don’t have a “test to stay” option. This is going to be something that comes up to your local school, so we have a lot of guidance here.

Let’s jump ahead to boosters. Have boosters for everyone Vincent, boosters for individuals 12 through 15 years of age. On January 3, 2022, the FDA expanded booster eligibility, and then on January 5, the CDC advisory committee on immunization practices endorsed.

I have to say, some of the children I know in the 12- to 15-years-of-age got boosted today, actually, a couple of brothers that I know. One of them did the vaccine Vortex, the other did not. This will be with an N of 2whether or not that vaccine Vortex really decreases that post-vaccination shoulder pain.

VR: Daniel, why did they reduce for the Pfizer five months from six, but Moderna is still six months? Does it really make a difference and can’t they make it consistent so people don’t get confused?

DG: I actually think it would make more sense to make it consistent. I’m not sure why Pfizer needs to be five months, Moderna six months. I do understand this concept and we talk about this a lot, vaccine efficacy against infection and our thought is that that service is a four-month window. Five months, I see where that comes from. Moderna, interesting enough, if you look at the antibody kinetics, it actually does stay up a little bit longer.

Actually, we’ll talk about a little bit of a study, a site coming up where maybe even Moderna is giving you a little bit better protection against severe disease. It just makes so much more sense to keep it all consistent. Never miss an opportunity to test. As my wife says, this is a certain way to become bankrupt. A lot of people are overcharging for those tests, please stop that. $50 for two tests in Port Washington at one of the pharmacies.

People are probably hearing about this, so I wanted to make sure I touched on this and this is this issue of, “Should I be taking that swab that’s meant to go up my nose and stick it in the back of my throat before or afterwards and then stick it up my nose and then put it in and see if I can get something?” My friend Yuan Po Tu, I call him Po, he’s out at the Everett Clinic in Seattle, he was sharing a little bit of saliva testing turning positive prior to the Nerius swabs and there was an actual preprint, Saliva swabs are the preferred sample for Omicron detection. That was posted.

I love when the title tells you their agenda here. In this study, the authors looked at agreement between saliva swabs and those wonderful mid-turbinate swabs. Remember those brain biopsy ones that went back there? They were finding higher levels of viral RNA in saliva with Omicron than Delta, but still the highest levels were in the mid-turbinate. We don’t have timing data, so this will develop and actually have that figure there which I really like.

We’re going to learn more about this and I think one of the challenges, no one wants to hear this, with different variants we have to redo a number of our studies to really see, but the different tests and there’s been a warning about this, the tests are validated for collecting a sample from a certain area. If you’re FDA-authorized, test is a nares test use it in the nares. If you really want to test the throat, you’re going to have to use a test that was validated to work in the throat.

Actually, there’s a lot going on under the hood as we say. You want to make sure you use a test that’s designed for procurement from that site. Have you been hearing much about this Vincent?

VR: People were asking last night on the live stream. Is it better to swab the back of your throat but really saliva is doing that, right?

DG: Yes, saliva is a way of getting.

VR: We don’t know how much of this is infectious or not so is it just in terms of a sensitive diagnostic that we’re talking about here because it’s not about saying you’re infectious or not, right?

DG: Yes, in the middle turbinate, if you look at this data, even though they go ahead, they say saliva swabs are preferred, I’m not sure why they’re preferred because in the data that they show us, the CT values are always the lowest for the middle turbinate. It appears more sensitive than saliva, so I’m not sure that the data supports the title. I like this idea of comparison.

I don’t know if you’ve heard the term “mouth breathers”, but maybe this is part of why everyone’s getting Omicron because the mouth breathers are talking and more virus in their mouth, I don’t know, but that came to me in a dream, Vincent.

Alright. Active vaccination. Never miss an opportunity to vaccinate. I’m going to add, we need to stop scaring the wrong people. We are clearly seeing with this Omicron wave that vaccines really do work to protect people against severe disease.

This actually is interesting because it says January 7, but we’re not there yet. Maybe I have this a day early, but this is an MMWR, Risk factors for severe COVID-19 outcomes among persons aged greater than or equal to 18 years, who completed a primary COVID-19 vaccination series, 465 health care facilities, United States December 2020 through October 2021.

By the time this drops, this will be available for everyone to read, but here, this is great. The authors looked at 1,228,664 persons who completed primary vaccination for COVID-19. They defined this as two of the mRNA shots or one J&J shot. They reported that severe COVID-19 associated outcomes were rare at only 0.015%. Death only occurred in 0.0033%. Risk factors for severe outcomes included age greater than 65, immunosuppression, and about six other underlying conditions. All persons with severe outcomes had at least one risk factor and 78%, so almost all of them, who died had at least four risk factors.

I want to try to put this fear in perspective. Prior to vaccines we were seeing 10% to 20% of people who got infected end up in hospital and we had a case fatality rate of about 2%. We went from a one-in-five chance of hospitalization to about one in 10,000 with vaccination, chance of death from 1 in 50 to about 1 in 30,000 with vaccination. Then I’m actually going to bring up the article because I want to go through this really interesting table because if you start looking at different things– and so I’m going to encourage people to go to this article, we’ll post the link on Parasites Without Borders, but there is a table.

If you go through this table, on the far right there’s an adjusted odds ratio. This is– can I do something that either increases or decreases my odds of having a severe outcome? I’m going to cruise on down to age. If you’re over the age of 65, that’s going to increase that. We’re going to say threefold which sounds really scary, but your risk of death went from 1 in 30,000 to 1 in 10,000, which is still really low. You’re over 65– and remember this is just two vaccines. Now, what if you decided to get my favorite vaccine, Moderna? You dropped that risk almost in half. Your risk of dying is now 1 in 60,000. Not really sure you need to be living in fear actually.

VR: This is through October 2021, so this is all Delta.

DG: Yes, this is all Delta data. The other thing, and this I love, if you wait greater than 120 days, you’re six months out, your vaccine efficacy against infection is waning, the antibodies are going down. Wait, your chance of death just went down 30%. Your immune system is maturing. Now your chance of dying is even lower. This doesn’t make any sense, Vince, and the antibodies are waning.

My vaccine efficacy against infection is going down, but there’s a population, their risk of ending up in hospital or death is actually being reduced. I think this data has to be really reassuring. People who’ve been vaccinated even without the booster, this is without the boost. Boy, the boost is just adding icing on the top of the cake. This is really reassuring data.

VR: Does this mean that neutralizing antibodies are not so important?

DG: Oh, Vincent. How dare you to say that. I think we’re really having to break down this issue and I think we have to break it down as a society as well. Vaccine efficacy against infection is one of those games that– what’s the end game? This isn’t Afghanistan. If our goal is to keep people from getting in the hospital, keep them from getting seriously ill, even reduce the risk of Long COVID, I think our vaccines are showing that they’re really good at this stuff.

VR: Antibodies will protect you against infection, but that contracts after four to six months, yet you’re still protected against severe death and disease even when your neutralizing antibodies have contracted. It’s saying that either the memory response is enough or memory plus T cells, B and T memory, must be enough to prevent severe disease, right?

DG: This is very reassuring data, yes. I think it does go along that line. This whole fear of, “Oh my gosh, my antibodies are decreasing.” “Oh my gosh, all these people are getting infected.” This is really reassuring data with regard to just how tremendous these vaccines are.

Passive vaccination. A lot of us are trying to ramp up to have EvuSheld just little tip to our antibodies there, but a lot of what is changing the game is the access now, the availability of oral therapy.

Now we move into the period of detectable viral replication. You start to get symptoms, you test positive, we now have some oral antiviral options and we’ve actually– they’re available, we’re using them, but I actually have encouraged a lot of the ProHEALTH physicians to listen to this show this weekend, because I am getting bombarded with questions. Let me go ahead, Anuja, I’m going to tell people to just listen to this instead of answering those 50 phone calls an hour. Let’s go through those options.

Remember, we now have options for people who are at high risk of severe disease. Remember, similar things we learned about with those monoclonal antibodies, over the age of 65, diabetes, immunosuppression, that obesity, renal failure, et cetera. Renal failure is going to come up. The drug that has the best efficacy from the trials is PAXLOVID. This is actually nice. It’s already in the epic EMRs across the country, so you can actually type in PAXL and it comes down.

It’s the PAXLOVID kit 150 milligrams, two tabs PO BID with ritonavir 100 milligrams, one tab PO b.i.d. These three tablets are packaged together in cardboard with a push out. All three of those are taken together as a single dose in the morning, a single dose in the evening. Things to think about, renal adjustment. Kidney function is fine, you’re good to go, but if the estimated glomerular filtration rate, our physicians will know what that is, so if the kidney function is below 60 milliliters per minute, but more than 30, you could still use this medication.

What the pharmacist is going to do is they’re going to pop out one of those 150-milligram tablets and they’re going to put a special sticker over the hole. There is a special sticker, I’ve seen it and then the person is going to be taking just two tablets, one PAXLOVID, one ritonavir twice a day. If the kidney function is below 30 for the estimated GFR, we’re not sure about safety, so we don’t recommend it there.

The other thing that I want people to be thinking about, and you’re going to be picking up a phone, you’re going to be talking to the pharmacist, you’re not going to be sending this off at this point. You want to know not only the patient’s kidney function, but you want to know what other medications is my patient taking because there are a number of medications that have interactions.

Some of the statins are fine, some of the statins are not okay. Those cholesterol-lowering, some of our chemotherapeutic agents, some of our opioids, some of our anticoagulants. You’re going to end up making a phone call, talking to the pharmacist, you need to know why the patient is getting this medicine, what’s the risk factor, you need to know the other medication so you can make some decisions on what to do there.

It’s okay, two things can happen. One is the pharmacist and you may decide that there’s a safety issue and that you don’t want to use this medicine. Or, what might happen is they might be out of PAXLOVID and the pharmacist will then say, “We don’t have PAXLOVID.” Or, if we decided not to use it, can we instead use molnupiravir 200 milligram tablets, four tablets twice a day for five days?

There is no renal adjustment here, there’s no drug interactions but remember, we don’t want to use this in women of childbearing age, we don’t want to give this to pregnant woman, we’re not giving this to children. Look in your area. In Nassau County, where a lot of our ProHEALTH practices are, I’ve mentioned there’s three CVS’s, one in Glen Cove, one in Hempstead, one in Freeport, and you’re going to basically need to know in your area, which of your pharmacies has been selected as a dispensing pharmacy.

The nice thing is, with a limited number of pharmacies, there’s been a lot of training. These pharmacists are going to really know what they’re doing, they’re going to help you work through this.

Now I’m going to jump all the way to the tail. I like to remind people that COVID is not just a two-week viral illness for many people. Unfortunately, individuals who’ve decided not to get vaccinated continue to be at high risk for this outcome and this really is devastating.

There was a nice review article published recently, Fatigue and cognitive impairment in post-COVID-19 syndrome, a systematic review and meta-analysis. This article really resonated because I read this right after I was on a call with a disability reviewer regarding one of my patients who previously had been very high functioning, and is still severely impacted. I just can’t imagine with their amount of cognitive dysfunction how they could return to their prior occupation.

In this paper, if you go to figure 3, always trying to get everyone to read the papers, there’s a nice view comparing the different studies, but ultimately, they reported that about one in five individuals were having long-term cognitive impairment. They assessed the cognitive impairment in several ways. They used performance-based cognitive function tools.

The Montreal cognitive assessment, the telephone interview for cognitive status, the screen for cognitive impairment in psychiatry, or in some cases, there was a clinical diagnosis of the cognitive impairment, but this is really devastating. As I point out, for a lot of people, this is a big push for the vaccinations. There’s the case fatality rate. There’s deaths, there’s hospitalizations, there’s all this to collate from that.

Long COVID is here in the mix. Vaccines seem to do a great job of reducing, but not completely eliminating Long COVID. I just want to comment on that as well. Then the WHO battle cry for vaccine equity. “No one is safe until everyone is safe.”

We’re going to continue through the rest of January, to continue to collect donations to help support Microbe TV. Now that MicrobeTV is 501(c)(3), you can either go to parasiteswithoutborders.com, click on “Donate” and we will increase that money and support MicrobeTV. Or, you can go to MicrobeTV and donate directly. The last thing before we get to emails is we are now going to have an internship opportunity.

VR: Excellent.

DG: This will be exciting. We are looking for a global health coordinator intern and this individual will need to be dynamic, committed, and have a passion for the global health, health equity, science communication, and our mission of addressing these with our educational programs. It’s going to be flexible, often asynchronous, but they’re going to actually be coming to the Incubator periodically, so we’ll need someone in the New York area. If you’re interested, send an email to daniel@microbe.tv and send your CV. We look forward to having you join us.

VR: It’s time for some email questions for Daniel. You can send yours to daniel@microbe.tv. The first is from Martin from the U.K. “Number one, please can you advise on a typical progressive dosing strategy with dexamethasone when COVID-19 reaches a stage where blood O2 drops below the 90s? I’d like to understand to what extent dosing is typically increased when a patient’s O2 drops from low 90s into the mid-low 80s or worse. Is it normal practice to dose higher, the greater the drop in O2, and if so, what dosing limits boundaries are typically observed to avoid risks of compromising the immune system’s battle with the virus?”

DG: This is great. This is very subtle, sophisticated, but I think it’s important. I know a lot of clinicians watch, so get out your pencil and take some notes. We’ve looked at what would be a standard dose. I think in many ways we were lucky. It does look like dexamethasone 6 milligrams daily times 10 days is in general, a really good starting dose. We’ve looked at other studies where they’ve used higher doses.

Doing that as a general is not great. Start with the 6 milligrams and then we see how they do over the next day or two. If they continue to progress, if the oxygen requirement escalates to, let’s say, a non-rebreather, the high flow nasal cannula we’ve talked about, then we will often escalate to 10 milligrams, so dexamethasone 10 milligrams per day. We will, at that point, often jump in with tocilizumab.

Ten milligrams is really what will do, but then becomes the issue when you reach day 10 at that 10 milligrams. Do you continue for a period of time? And do you gradually taper? And that becomes an individual management decision. Starting with 6 milligrams, if you want to escalate jumping up to 10 milligrams, consider adding something like tocilizumab in there and then continuing up to day 10 and making that decision.

Making that decision at day 10 is going to really depend, in many ways, on where you are in the world. If I’m doing my consultations in Bangladesh with all the concomitant parasitic issues, we’re really careful going past day 10, but in a lot of other settings you may continue, you may slowly down, but you’re going to be following neutrophil lymphocyte ratios, ferritin, other markers for that guidance.

VR: The second question, are you reasonably comfortable with substituting methylprednisolone or do you stick rigidly with dexamethasone?

DG: No, actually there are some studies, head-to-head comparison supporting the use of methylprednisolone. Solu-Medrol, some of the other formulations, even prednisone instead of dexamethasone. No, you don’t need to specifically just use dexamethasone. There’s a lot of data out there supporting alternatives.

VR: Next one comes from Nolan, who is at the National Institute of Environmental Health Sciences, and he writes, “I’ve been thinking about ‘you’re scaring the wrong people’ formulation. I agree many of the stubbornly unvaccinated are not going to be persuaded by new data, while the boosted and masked remain in a state of anxiety. I think the PTSD being experienced by the latter is caused by an inability to address one’s risk, once you’ve taken the basic precautions – vax, mask, test, distance.

This is exemplified by people asking about a fourth or fifth vaccine dose. Epidemiology shows obesity to be a major risk factor for COVID outcomes. Working on your BMI is something you can do alone or with your PCP. Personally, I’ve doing my best to get my BMI out of the COVID danger zone since this pandemic started. I appreciate PCPs are regularly asking their patients to lose weight, this may seem outside of TWiVs interest, but the extra motivation of any avoiding bad COVID and giving people the urgency to get their worries under control might be effective. Two birds.

Additionally, we now have some mechanistic data indicating serious COVID too might be infecting adipose tissue and causing local inflammation which begs the question whether viral replication and inflammation might scale with large deposits of fat.” Nolan provides a few references for papers on that, surgical means of weight loss also help and provides a JAMA paper for that. Thanks for your thoughts.

DG: This is great, and actually I’ve seen a lot of those studies. I find them really interesting. I’m hoping that the MMWR release that we talked about gives people some concept, gives people a number of the risk post vaccination. We are scaring the wrong people. For a lot of individuals, if they’ve been vaccinated, they could really calculate, what are these risks? Risk calculations are tough for people, but yes, we’re scaring the wrong people. People who are vaccinated are in really good shape, people work are unvaccinated, …. yes, you can’t talk someone out of a position they were not talked into.

VR: Allen is an MD at the Bronx VA Medical Center. He writes, “As COVID-19 evolves, your podcast becomes even more relevant to clinicians. My questions relate to the choice of therapy for COVID for a patient with moderate disease who has risk factors such as age greater than 65 or obesity. If either PAXLOVID or sotrovimab were available, which one would you prefer? I will also assume the patient would be willing to come in for the infusion if this was the better option. Do you see a role for combination therapy for immunocompromised patients?”

DG: That’s perfect and that has come up in the last couple days because we’ve had exactly that choice. Sotrovimab, which is the Vir GSK monoclonal antibody that is effective against the Omicron variant, is available in incredibly limited supply. But let’s take a person who might qualify, got people stratified. Let’s say this is a renal transplant, an organ transplant patient immunocompromised at high risk.

One thing you’d say, “Oh, why don’t we just give them both?” But there’s limited supply, so we’re not recommending that. If you look at the data on the PAXLOVID, you can very quickly get that into a person 88%, 89% reduction in progression. If you’re within the first five days, the data is a little bit stronger, I’m going to say on PAXLOVID. This was not head-to-head, so we’re hedging there a little bit stronger, but there’s a window here.

Let’s say it’s day six, we might go with sotrovimab, but it’s a really easy lift to get people on the PAXLOVID, on the oral agents, there is a little bit of a sense that the PAXLOVID might be superior, but there’s another side to this, and I think this is reasonable for discussion. Is the PAXLOVID only going to work for those five days? The sotrovimab is going to actually be in the system probably for many months.

I think you want to make an individual assessment with your patient, particularly a patient like that. Let’s take someone who can’t really generate a lot of their immune response. You may not only be addressing the acute issue, but you may be giving them that prophylactic antibody protection for months ahead.

VR: The last one from Marsha, “My daughter-in-law had at her two jabs prior to getting pregnant. Now, she’s halfway through her pregnancy due on Mother’s Day, just over six months since her last jab. Her OB doctor doesn’t want her to get a booster as he is worried about the booster vaccine affecting the fetus. I believe she should get the booster now, but I can’t overrule her OB doc. They have a two-year-old and a three-year-old and I want all of them to have protection. COVID is not a good thing in pregnant women.

Where do OB docs get their information about giving boosters to their patients? He said he’s checking into this. We think he’s a good doc. He delivered her first two children. What do you think? Can you let me know?”

DG: Sure. I’m going to suggest that maybe you can send a link to this podcast to this OB. We are seeing a lot of this. There was a recent study really showing how incredibly safe vaccinations are during pregnancy. We also know that pregnant women are at a much higher risk, and the other thing is that if a pregnant woman gets vaccinated, not only are they getting a certain amount of protection, but there is passive antibody and passive cellular protection for the newborn.

Getting vaccinated during pregnancy is the right thing to do as a mother, it’s the right thing to do to protect your unborn child. As we know, if a woman gets infected with COVID during pregnancy, this is the unvaccinated data, they’re twice the risk of losing that baby. You really want to get vaccinated.

VR: That’s COVID-19 clinical update #96 with Dr. Daniel Griffin. Thank you, Daniel.

DG: Oh, thank you, Vincent and thank you, everyone. Be safe out there.

[pause 00:57:36]

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