TWiV 972 Clinical Update

ThisWeek in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 07 January 2022

pdf of this transcript available (link)

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


VR: From MicrobeTV, this is TWiV, This Week in Virology, Episode 972, recorded on January 5, 2023. I’m Vincent Racaniello, and you’re listening to the podcast all about viruses. Joining me today from New York, Daniel Griffin.

DG: Hello, everyone.

VR: Here we are first episode of 2023. Is it all downhill from here, or uphill, Daniel?

DG: [laughs] Fortunately, it looks like we’re heading uphill again.

VR: Very good.

DG: Yes, we will be getting into that, but let me get right into it. At one point, I will fulfill my promise of making these briefer, but we’re not quite there yet. I’ll start off with my quotation. “I like the dreams of the future better than the history of the past.” Who is that by? Thomas Jefferson. I was a bit surprised when I ran across that quotation. I know a lot of people are still rehashing, what did we do wrong? What went wrong? Maybe it would be important to think about how to do this right when we reflect on what’s happening over in China at the moment.

Let’s start off with the influenza, what’s happening with influenza. Actually, for Vincent’s viewing pleasure, I put up actually this graphic where you can see the percentage of outpatient visits for respiratory illness reported by the U.S. Outpatient Influenza-like Illness Surveillance Network, the ILINet. They do this weekly national summary. The nice thing is they overlay prior seasons. Because I don’t want people to get lulled into a sense of it’s all over with flu.

Because characteristically we’ll have this rapid rise, things will start to go down, and other than 2021/2022 last year, which was a little bit odd, we then see a rise again. You just have to keep an eye on this. Why do we see this? What do we think explains this pattern? Part of it, we think, is travel. It goes up and then it starts to go down. We will see what happens with influenza. It’s still actually higher than it was in a few years here.

VR: It’s a very early peak compared to the other years, right?

DG: It’s the earliest peak, I don’t think we’ve ever seen peak this early in recent history.

VR: We have no idea what that means, right?

DG: We are learning, we are learning. COVID is jumping right in because we don’t want to have a lack of respiratory infections. I’m going to talk a little bit about the first article, the article, “Infectiousness of SARS-CoV-2 Breakthrough Infections and Re-infections During the Omicron Wave,” published in Nature Medicine. I’m hoping, Vincent, you and I can talk a little bit about, what do people mean when they use the word contagiousness and –

VR: Is infectiousness the same as contagiousness, Daniel?

DG: No. I think there’s a lot going on. What are they actually talking about in this article? What they’re looking at here is one individual gets an infection, and then other individuals get infections. You’ve got your index case, and then you’ve got a second person getting infected, or in this case many other people getting infected. What they were trying to estimate was what was the impact on transmission from one individual or group of individuals to another individual or group of individuals. How might that be reduced by certain variables, and what are those variables.

Vaccination alone, prior infection alone, and then prior vaccination and prior infection. What they estimated, based on this study, was that vaccination reduced that by 22%. Not as impressive as I would like. Prior infection, 23%. Combination of vaccination and prior infection, about a 40% reduction. They also comment that receipt of booster doses and more recent vaccination further reduced, and they use the word “infectiousness” among the vaccinated cases.

VR: Seems to me they’re talking about transmission, right?

DG: They really are. This is really a transmission study. It’s an interesting issue because it comes down to something that public health decisions are focused on, this whole idea that when you get vaccinated, is that just about you or does that affect society as a whole? Here we’re seeing, if you got infected, about a 20% if you got just vaccinated. If you got infected, then you get your vaccine on top. I understand the argument. People say, I already got infected, that’s just as good in this study at protecting others as getting my vaccine. Interesting arguments here.

All right, we’re going to talk about variants quite a lot because I think that people are, again, scaring the wrong people. I’m going to put on my glasses here as I look at this. What is going on right now with the variants and, shall we say, the Omicron subvariant? Here in region two, so that’s New Jersey, New York, Puerto Rico, the Virgin Islands, an interesting grouping here, we are seeing that about 75% of the variant infections that we’re seeing are XBB.1.5. They’re a little bit of BQ.1, a little bit of BQ1.1. I want to point out, what are we not seeing?

We’re not seeing BA.4. We’re really seeing only 1% or 2% of BA.5. That’s going to come up in our discussions. Let’s talk a bit about, what is XBB? Because several folks are alarmed about the alarming antibody evasive properties, but we’ll get into that. Let me start off with a preprint. I think this is nice from understanding the science here. “Virological Characteristics of the SARS-CoV-2 XBB Variant Derived from Recombination of two Omicron Subvariants,” posted on bioRxiv. For background, this is what’s suggested. In late 2022, the SARS-CoV-2 Omicron subvariants highly diversified, and XBB began spreading rapidly around the world.

This analysis in the preprint suggested that XBB emerged by recombination of two co-circulating BA.2 lineages, so BJ.1 and BM.1.1.1, a progeny of BA.2.75. There will not be a test at the end, forget about those. The idea is this recombination event may have happened summer of 2022 in India. They present data suggesting evidence of a recombination break point between positions 22,897 and 22,941 of the Wuhan-Hu-1 reference genome. This is within the receptor-binding domain of the S protein. There’s data suggesting that many of the Omicron variants are undergoing convergent evolution with certain changes that may confer fitness advantages.

I like the word “fitness” there. L452R, people might remember that one, N460K, and R346T, they suggest improves binding to the ACE2 receptor. Some other changes seem to evade neutralization by antibodies induced by both vaccination and prior infection. In this preprint, and this is where the media gets excited, in vitro experimenting using pseudotyped virus, the XBB is poorly neutralized by antibodies induced by vaccination and/or prior infection. Then a bunch of stuff suggesting hamsters do poorly with XBB with lots of alveolar damage, hemorrhage, and congestion.

VR: Man, watch out hamsters.

DG: The hamsters are just – they’re done. I’m surprised there’s any hamsters left at this point.

VR: Can I just say that –

DG: Please. Please, do.

VR: – this improved binding to ACE2, we have no idea what that means. A certain immunologist in a state in the Northeast that will not be named has said this has implications for Long COVID, which I think is actually criminal to say because there’s no evidence that this means anything, and because this is in cell culture. Tell me in people if it means anything, and you’re never going to do that experiment. Do the hamster stuff too. Hamsters are not good for telling us how SARS-CoV-2 does in people. The only thing that’s interesting here is the recombination. I think this is the first variant to arise by recombination, not by single amino acid changes. That’s interesting.

DG: That, actually, I think is probably the takeaway from this. I think that is an interesting demonstration here. We’ve talked about this for a while that coronaviruses can change. They can become more fit through changes. Changes in amino acid, non-synonymous mutations in the RNA. Not mutations in proteins, but anyway, forget about that. Or in this case recombining. Viruses can recombine, coronaviruses can recombine.

Here, that’s what looks like happened here to create a variant which is demonstrating fitness advantage. It’s increasing. This happens every time, and maybe people have been here long enough to remember, everyone is ready to tell you now whether this is more or less virulent, pathogenic, more or less likely to cause Long COVID. It takes time. I think as long as we’re a little bit more honest and say, we will let when we know as opposed to just throwing darts at the board. I think that will be a lot better [crosstalk]

VR: Many of the pundits are saying this is bad, but there’s no data to say it’s one way or the other. I don’t understand, Daniel.

DG: I think my wife explained it. She said, you got to realize these pundits, they’re caught in this. They want to stay relevant. They know what to say to stay relevant, and they can’t help themselves. Please, help yourselves.

VR: They want to stay relevant. That’s very interesting.

DG: [laughs] When scientists become popularists. Now onto a publication in Cell. Oh my gosh, “Alarming Antibody Evasion Properties of Rising SARS-CoV-2 BQ and XBBB Subvariants.” Yes, Cell allowed that title and I’m –

VR: Unbelievable.

DG: – a bit perplexed. We’re not making friends, Vincent.

VR: I don’t care. I never had any friends, except you, so I don’t care.

DG: We covered this when it was a preprint and yes, they used the same title on the preprint, and reported that neutralization of BQ.1, BQ.1.1, XBB, and XBB.1 by sera from vaccinees and infected persons, was markedly impaired, including sera from individuals who were boosted with the bivalent mRNA vaccines. Compared to the D614G serum-neutralizing titers against BQ and XBB, subvariants were lower. A panel of monoclonal antibodies capable of neutralizing the original Omicron variant, including those with EUA, were largely inactive against the new subvariant. We’ve covered this. I’m not sure alarming.

If anything, what we’re seeing, which is interesting, is that suddenly we don’t have 6,000 deaths a day. Where this is not a brand new virus, not a brand new sequence that our immune system has not seen. I think, if anything, reinforcing maybe a bit of the calm, the suggestion that, boy, our immune system is an orchestra. Your first flute player doesn’t show up that day, you can still go ahead. It’s not maybe what you are hoping for, but still going to work out. You still can hold the symphony. You’re still not going to end up in the hospital, you’re still not going to die. Those vaccines, those prior infections, they’re still protective.

VR: I think that’s a point. Now, there’s no data here about disease. Maybe it doesn’t matter, maybe the old vaccines still work against these variants, and in which case you’d have to take alarming away. This is not fair to say that. Maybe from a therapeutic standpoint, Daniel, the fact you can’t use monoclonals is a bit alarming. You have other things you can use.

DG: Yes. We’ll get to those. I think that we always talk about we care about disease, not infections. When we say we care about disease, we care about death, we care about hospitalization, we care about Long COVID, we even care about people being miserable for that week or two, or three that people are experiencing. Just infections, just testing PCR-positive. We’re still trying to sort out the importance of neutralizing antibodies versus the rest of the immune system. We’re going to learn a lot.

We are learning a lot, because right now, folks that have been vaccinated, people that have had bivalent boosting, people that have prior infection, they don’t have neutralizing antibodies against 75% of the infections we’re currently seeing. It is not looking as bleak as “alarming” would suggest in that title.

All right, children, COVID and other vulnerable populations. I do like to keep reinforcing that we have millions of children being born, so we have millions in that first six months of life coming new to the world. They can actually get a little bit of experience from mom if she’s got the antibodies too. Also, some parts of her cellular immune system to transmit.

Post-exposure period transmission and testing. This is when I say have a plan, now is the time to reach out. We are seeing a lot of infections, so have a plan. Talk to your doctor now. Find out how you’re going to access the right treatments. We get there. We’ll talk a little bit about various options for implementing those. Masks. I’m seeing a little bit more mask wearing going on. No one has to tell you to wear a mask. You can actually wear a mask. The science does favor mask use and suggests a hierarchy with N95s offering the highest level of protection.

Let me hereby give permission to everyone that still wants to wear a mask. If people ask why you are wearing a mask, feel free to tell them it is because Dr. Griffin thinks it is a smart and reasonable choice. I’m very happy to be thrown under the bus there if you’re being criticized. Remember, outdoors, fresh air, keep that HVAC fan turned on, open a few windows. Remember how much safer it is with better air quality. What works against all the variants? Masks, ventilation, and smart choices.

VR: You could throw in vaccines there. So far, we don’t know that they don’t work.

DG: We’re about to get to vaccines. I agree with you. Everything we’re seeing is they seem to be working. They seem to continue to offer durable protection against severe disease.

VR: In the U.S., Daniel, how many people are dying a day?

DG: We’re sitting at this about 400 a day. We’ve been there for a while, even as we keep getting these new variants.

VR: These people are largely immunocompromised, elderly-elderly, right?

DG: The majority are elderly-elderly. 90% are over 65, probably even over 75. Have multiple medical problems. I don’t want to sound like some other government-appointed person. I’m not government-appointed, but a government-appointed person who wanted to discount those individuals. There clearly are individuals who are at higher risk. Those are the individuals that we recommend, I think all of us recommend, well, not all of us, most of us recommend boosting. Most of us, I don’t know if it’s most again, recommend appropriate treatment. This clearly is a demographic that is at highest risk.

VR: If I understand, most of those people who die are not getting Paxlovid, right?

DG: That’s the really tough thing. We’ll talk a little bit about it, but there’s this idea you’ll most likely be OK. I was talking to a patient today and I said, you know what, you’ll most likely be OK. What do I mean by most likely? Here are your numbers. Do you want a 1 in 50 chance of ending up in the hospital? Would you like me to make that less? The answer is usually yes. You got to be careful when people say, “I’ll most likely be OK.” It’s like, what do you consider most likely? Is 1 in 30? 1 in 10 is most likely.

The article, “Comparative Effectiveness of Third Doses of mRNA-Based COVID-19 Vaccines in U.S. Veterans,” was recently published in Nature Microbiology. This is really a paper, a challenging venture where they’re trying to judge a one vaccine against the other vaccine. This is looking at vaccines for the prevention of COVID-19 outcomes in the largest integrated healthcare system in the United States. I’m not sure I’m so impressed with much of a difference, but this might figure into a public health calculation when selecting a vaccine for a population. It’s also nice to have choice. We have a very similar paper under review by the way, taking forever. We probably should have sent it to Nature Microbiology, but actually even a bigger and, very similar outcomes.

First off, they looked at five measured COVID-19 outcomes. Documented infection, we’ve weighed in on that. Symptomatic COVID-19, COVID-19 required hospitalization, ICU admission, and death. Actually what I want to focus on was, what was the risk for death in each vaccine group? These are folks getting three vaccine doses. Less than 0.03% for death within each vaccine group. You could see the figures, you could see a little bit of a separation for hospitalization. Pretty much overlap when it comes to death. What is really impressive is just how low these incidents numbers are.

Now we’re going to move right into it. I think Vince was trying to jump ahead to the early viral upper respiratory non-hypoxic phase. This continues to be a lot of controversy here. The article, “Time to Negative PCR Conversion among High-risk Patients with Mild to Moderate Omicron BA.1 and BA.2 COVID-19 Treated by Sotrovimab or Nirmatrelvir,” published in CMI. This is this whole issue of, which therapy would more quickly drop down your probability of a PCR, or raise the cycle threshold value, so decrease the amount of nucleic acid detectable units?

What are people thinking before we do the data? Which is going to drop it down based on all the misinformation out there? What does this paper actually show? There are some really nice figures. Actually, it was Paxlovid, nirmatrelvir, that was associated with a more quick reduction, a quicker reduction in the amount of RNA copy numbers, and more rapid reaching of probability of negative PCR. If you follow them out, you’re not seeing any of these concerns that the people have raised out there.

VR: Using CT of 31 as a cutoff, right?

DG: Yes.

VR: Nirmatrelvir gets there in 10 days.

DG: Yes. It doesn’t get there with your monoclonal till 20.

VR: Yes.

DG: Interesting data, I think. That moves us right into the article, Paxlovid. This is a news piece that was published in Nature. “COVID Drug, Paxlovid, Was Hailed as a Game-changer. What Happened?” People should read this. It’s not a long read. I would say it was a page-turner, but you don’t even have to turn the page. It’s all just one page. It’s a pretty quick read. When clinical trial data for the antiviral drug, Paxlovid, emerged in late 2021, physicians hailed its astonishing efficacy, a reduction of nearly 90% in the risk of severe COVID. More than a year later, COVID-19 remains a leading because of death in many countries, and not only in low-income countries where the drug is in short supply.

In the United States, for example, hundreds of people still die from COVID-19 each day. I think they capture the misinformation, the misunderstanding of the disease, concerns regarding rebound. They talk about “the wait and see how you will do” mentality does not mesh well with the five-day window for starting the medication, and the concerns about side effects and drug interactions. I just see this as one more communication failure that is costing thousands of lives. Just a plug. When you’re thinking about public health interventions when you’re spending billions of dollars, spend some money on communication.

VR: Daniel.

DG: Yes.

VR: We communicate here. You have always communicated about the correct use of Paxlovid, but it doesn’t help just to communicate. People have to listen, and apparently, they’re not.


DG: Should listening to TWiV be required for people that take care of COVID patients? I think that if you’re taking care of patients with COVID, I think it’s incumbent on you as a clinician to stay up with the latest scientific information. Don’t get your information from mainstream media. Get it from the science, get it from the actual data. Number two, and I think maybe this is also – remdesivir. Really impressive data. The PINETREE data, 87% reduction in progression if you get three days within that first week. Where do you get this? I reached out to my buddy, Yuan-Po Tu, who’s in the Seattle area.

What happens if a person’s on dialysis? What happens if a person has a drug-drug interaction and can’t get Paxlovid? Any options there? We hear that maybe UW is going to roll it out, but it’s amazing. This is not rolled out. A lot of clinicians are not aware. This is a licensed-approved drug. This is not EUA. This is licensed-approved drug with compelling data for the ability to keep folks out of the hospital. No monoclonals at the moment. Molnupiravir, we’ve talked a little bit about that in the past. It’s convalescent plasma. I was entertained when I brought this up the other day.

We’re in the hallway outside the ICU. One of my colleagues reacted with, “Are we still talking about that?” Yes, here in the U.S. at this point, a very limited role, but perhaps we have stuff to learn for the next pandemic or even the next spillover. I wanted to share the article, “Fc-effector Function of COVID-19 Convalescent Plasma Contributes to SARS-CoV-2 Treatment Efficacy in Mice,” published in Cell Reports Medicine. I like that we are hopefully building on the theme that one cannot just measure those antibody levels, or even just measure neutralizing antibody levels. To assess the quality and potential benefit of this antibody-containing plasma, one needs to actually look a little bit harder.

Perhaps this could also explain why there were so many different results when the COVID convalescent plasma was studied, as we’re not always looking at the same product and need really a better way to assess its efficacy. Here they report that CCP, so that’s COVID Convalescent Plasma, with robust Fc function can protect mice, that FC activity can serve as a secondary defense when neutralization is compromised, maybe this is becoming more and more relevant, and that Fc functions facilitate cross-reactive immunity against SARS-CoV-2 variants of concerns. It really is a very complex and fascinating paper that one can spend hours reviewing, and I suggest doing that.


It’s a big, thick paper with great figures. A key point I was really interested, was their demonstration. They found that recruitment of innate immune cells through polyclonal Fc-FcR interactions can actually dampen the SARS-CoV-2-induced inflammatory response. We’re thinking about, this is great, you’re going to clear the virus, but the whole idea that, I’m a big fan of Niels Jerne and anti-idiotype antibodies, and the way the immune system can actually control itself. Say, in conclusion, the COVID convalescent plasma-associated polyclonal Fc-effector functions have the potential to mitigate SARS-CoV-2-induced disease.

VR: Daniel, are they still being used?

DG: Very limited in the U.S. We talked about this back a little. It’s only in certain patients, it’s a last resort if nothing else can be used if the person is shown to be immune-compromised, so very, very limited role. Number one, you would be putting someone on Paxlovid. Maybe you can’t do that, who can’t get remdesivir. Meeting that bar of someone who can’t get anything else. I’m not sure what situation that would be, because the convalescent plasma data was fine in certain contexts. It certainly was never 87% reduction in progression like we saw with IV remdesivir, 88%, 89% with Paxlovid. It really is the redheaded stepchild.

VR: We were a bit critical of CCP on TWiV, and Arturo Casadevall heard it.

DG: [laughs] OK.

VR: Did you know he’s a big proponent? They use it at Hopkins apparently. He said he would like to come back on TWiV to set the record straight. We’re going to have him on in the next couple of weeks.

DG: I think that would be great, actually. I think, and I’ll ask you to push this point, is you really want to say, let’s use the current bar, which is 87%, 88%, 89% reduction in progression, and start showing me the data where you hit that with convalescent plasma. I understand in resource-limited parts of the world, it actually is a lot less expensive than $800 per person, which is what we’re seeing with some of these other medications, but are you getting close to a 90% reduction? Then, again, I think this is really an interesting point, how do you look at your plasma and judge the quality?

Now that we’re seeing loss of neutralization of prior variants, you’re really going to have to couple someone who recently got infected, recently enough before the most current variant, has that same variant, and that you’re going to get either neutralization or here this Fc-mediated protection. I will look forward to that. That would be great. He’s a very enthusiastic, passionate man, so that’ll be a fun episode.

Not a lot of movement here on the COVID early inflammatory lower respiratory hypoxic phase. We are trying to prevent this with all the things we do during that first week. We don’t want to wait and see if a person ends up in this position. This is when we talk about steroids, anticoagulation, pulmonary support, remdesivir, if we’re still early enough, immune modulation, tocilizumab, maybe baricitinib. Actually, I should point about baricitinib. This is actually oral, but there are certain challenges with discharging someone to finish those 14 days if this was started in hospital. Something you want to get familiar with if that’s going to be what you go with. Then again, avoiding harmful unproven therapies. We are moving into the late phase, past Long COVID.

A mix here. I feel like we did this last time where I give bad news and good news, and balance it out. I’m going to be a little critical of this article, but I will share it. The article, “SARS-CoV-2 Infection and Persistence in the Human Body and Brain at Autopsy,” was published in Nature. Just the first, to comment, these are people that died. You’re not doing autopsies on people that had a mild infection. Here, the investigators carried out complete autopsies on 44 patients who died with COVID-19, with extensive sampling of the central nervous system in 11 of these patients.

Their results suggested that SARS-CoV-2 is widely distributed, predominantly among patients who die with severe COVID-19, and that virus replication is present in multiple respiratory and non-respiratory tissues, including the brain early in infection. They also detected persistent SARS-CoV-2 RNA in multiple anatomical sites, including throughout the brain, as late as 230 days following symptom onset in one case. Despite finding this distribution of SARS-CoV-2 RNA throughout the body, they reported little evidence of inflammation or direct viral cytopathology outside the respiratory tract.

This in my mind is a significant claim, and yes, they isolated virus from 45% of the specimens tested across four SARS-CoV-2 subgenomic RNA quantification cycle value intervals. CQ is what we’re supposed to say instead of CT, but anyway. With decreasing yield, with rising quantification cycle, CQ value intervals. Among the 55 samples tested for virus isolation with sensitivity and specificity weight equally, a ddPCR value of greater than or equal to 758n copies per nanogram of RNA predicted replication competence virus with 76% sensitivity, 90% specificity.

I think the thought there is maybe you won’t have to do a virus culture all the time, you’ll be able to use this weighted score. Really interesting and thorough, but a few limitations that the authors acknowledge we could maybe throw in more, but first the cohort largely represents older unvaccinated individuals with preexisting medical problems who died from severe COVID-19, limiting the ability to extrapolate findings to younger, healthier, or vaccinated individuals. Although it is tempting to attribute clinical findings observed in Pax to viral persistence, this study was not designed to address this question.

VR: I just want to make one point here, and that’s the authors did not quantify the amount of infectious virus. They just threw RNA onto cells, if they got CPE or not. It was positive. If there were a few PFU there, what would that mean in terms of pathogenesis? You can imagine macrophages picking up virus in the respiratory tract, bringing it somewhere else, it doesn’t mean anything. I don’t know what this means in terms of the pathogenesis of –

DG: I think it’s really important, and they comment too, little evidence of inflammation or direct viral cytopathology. People are looking and saying, see, I do. I’ve never seen a virus like this, it gets into the brain. I’m like, I’m not sure it’s getting into the brain so much as it’s being found there. That’s important.

VR: That’s right, because there’s no cytopathology, no inflammation. It’s probably not replicating.

DG: That’s what makes me really – You want to put this in context because I know people are been waiting for this, there’s this confirmation. I knew it was getting up, sneaking up through the nose and olfactory nerves, and getting into that brain. Here’s proof. It’s not proof, but anyway. The last is an article and Nature piece about a topic that is recently very timely with a recent tragedy. Actually, this article was published a while back, but I just thought it was good to put this out here. The article, “Long-term Cardiovascular Outcomes of COVID-19,” was published February, 2022.

This was the study that used national healthcare databases from the U.S. Department of Veterans Affairs to build a cohort of 153,760 individuals with COVID-19, as well as two sets of control cohort. We covered this before. Over 5 million contemporary controls, over almost 6 million historical controls to estimate risks and one-year burdens of a set of pre-specified incident cardiovascular outcomes. There’s a really nice figure where you can really see the excess burden per 1,000 persons, and pretty significant increased risk for several cardiovascular problems.

There’s actually a Nature news piece, “Heart Disease Risk Soars after COVID, Even with a Mild ase.” Again, a little bit of hyperbole there. It really helps, I think, because a lot of people might find it a challenge to go through this, but you can certainly look at the figure. Just to bring it, following COVID-19 survivors were 52% more likely to have had a stroke than the contemporary control group, and the risk of heart failure increased by 72%. I think pointing out a lot of people are going down the other road here, but COVID-19 is not a great thing for your heart.

I will close it out here with low- and middle-income countries. No one is safe until everyone is safe. Love everyone to pause right here. Go to and click “Donate.” Even a small amount helps. We are finishing up. This is January, the last of our three-month fundraiser for MicrobeTV. We’re hoping to get up to a potential maximum donation of $40,000. We’ll be doubling everything up to $20,000 to get us up to $40,000. Thank you. I just want to, here, just take a moment and say thank you for all the really generous individuals that allow us to do this. We don’t do advertisements. I don’t think Vincent is a trust funder with huge chunks of cash at his disposal, so this is all you. This show is all you. We’re able to do this because of your generous support.

VR: Yes, please donate to Parasites Without Borders. That would be great, because we only do this once a year. Time for your questions for Daniel. You can send them to Katie writes, “I recently got COVID, and because I’m breastfeeding, I was told by my GP’s nurse that I should not take Paxlovid. I’m vaccinated and boosted, don’t have any risk factors. Even so, I was laid up for several days. Needed several extra rest after a week. My baby’s vaccinated. The viral exposure, we both had barely registered a blip on her radar.

This experience made me wonder if breastfeeding mothers who do have risk factors would be unable to take Paxlovid. What information is out there on the safety of Paxlovid during breast feedings? How should clinicians weigh that information? Does the amount that the baby breastfeeds matter? It seems like the advice for an exclusively breastfed infant might be different from a baby who mostly eats solids and just nurses a couple of times a day, like my baby. Thanks, Katie in Virginia.”

DG: I think this is an excellent question. What’s going to happen is breastfeeding individuals, breastfeeding moms are going to be in a situation where they get COVID and they’re going to want to know what their options are. Here’s a couple ways to look at it. One, currently it’s not recommended to prescribe Paxlovid while breastfeeding. It’s not recommended that this is something given to very young children, so that would be a way that they ended up getting it, in the breastfeeding. You really want to look at other options. I think this was a reasonable decision.

VR: Dale writes, “I’m wondering if my son should get the bivalent booster. He’s 19, has had three doses, and had COVID in the late fall of 2021. Generally healthy. Has had mild asthma that is controlled. Do any of the new Omicron subvariants necessitate the bivalent booster?”

DG: If you’re a frequent listener, you probably have some context for this. We’re not expecting the booster, whether it’s bivalent or whether we still were using the original booster, to really do a tremendous amount for a low-risk individual. Is there some benefit? Potentially. If the individual tolerated everything really well, didn’t have any issues. Is it reasonable to get the vaccine? Sure. Are we out there like pushing it in this low-risk population? The answer would be no.

VR: Ellen writes, “My daughter, who I know listens to TWiV religiously, is taking a trip to New Zealand with a four-and-a-half-year-old and a five-month-old.” Wow. I’m impressed.

DG: That’s really close in age, but –

VR: That’s a long trip.

DG: Yes.

VR: She asked if she could give the four-year-old the booster 12 days before travel rather than the two full weeks. No one in the family has ever had COVID while taking maximalist precautions. Any advice for traveling with young children would be appreciated.

DG: We’ve talked a little bit, and I think this is a reasonable discussion about, what are we expecting from boosters? We are expecting some period of time, some temporary increase in protection against infection, and maybe that’ll carry over into disease itself, which we’ve seen in some studies maybe. I think that’s a reasonable consideration. The timing you suggest, I think makes sense.

VR: Steve writes, “My mother’s 86 years old in good health. She had a semi-annual visit to a primary care physician this week who recommended keeping an acetylcysteine on hand in the event she becomes ill with COVID. I find a few early reports 2020 suggesting reduced likelihood for hospitalization and ventilation in patients who use NAC. I’m a faithful listener to your updates but I can’t recall you ever mentioning it, nor do I see any recommendations on NAC from the CDC. I’m a bit confused why the physician would even consider recommending NAC when effective treatments like Paxlovid and remdesivir are available. Could you please provide insight and perhaps a reference on this that I could share?”

DG: Ideally, what physicians should be doing is looking at the recommendations of the Infectious Disease Society of America, so the IDSA, recommendations from the NIH, maybe you can even look at recommendations from the WHO. NAC is nowhere to be found. Just cherry-picking a publication that some particular individual found interesting, that’s not how you should be basing your medical care. When there are highly effective available therapies out there, that’s what you should be recommending to your patients. Not just throwing darts at the board and hoping some article that you found interesting translates into something helpful for your patients.

VR: Our last one is from Peter. “As an immunosuppressed person, no B cells after treatment for CLL,” I’m not even going to pronounce the monoclonal because it’s too hard, “I thank you for your frequent mention of these patients, but we don’t get much focused information. My question is, what is your experience treating immunosuppressed patients with Paxlovid and remdesivir? Is there a preference for one over the other?”

DG: Yes. For immunosuppressed individuals, you would, particularly now with current variants, we don’t have monoclonals, really that the top two choices are going to be Paxlovid, remdesivir. Paxlovid has slightly better data. We have tremendous experience with both medications. It’s a lot easier to take a pill for five days than have to deal with the three days of IV and even dealing with access to the three days. They’re just the normal approach would apply for someone who’s immunocompromised, and that’s actually who we’re often talking about here when we’re talking about the hierarchy of treatment in the viral phase. Number one, Paxlovid. If you can’t do Paxlovid, then you move to remdesivir.

VR: That’s TWiV clinical update with Dr. Daniel Griffin. Thanks, Daniel.

DG: Oh, thank you. Everyone, be safe.


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