TWiV 964 Clinical Update

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 17 December 2022

pdf of this transcript available (link)

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

[music]

VR: From MicrobeTV, this is TWiV, This Week in Virology, Episode 964, recorded on December 15, 2022. I’m Vincent Racaniello and you’re listening to the podcast all about viruses. Joining me today from Uganda, Daniel Griffin.

Daniel Griffin: Hello, everybody.

VR: Daniel, where are you this week in Uganda?

DG: I am very far Western Uganda, very close to the Rwanda border just south of Lake Edward. If people were following the press, this is just very close to where the insurgents came across, but that was quickly dealt with by the military. As I told my worried wife, I feel very comfortable with the Ugandan military walking around in full regalia.

VR: That’s an interesting structure you’re in there.

DG: It is. This is a German expat’s ranch. They have many more cows than I have, so I’m a bit jealous. Of course, I’m wearing a warm jacket because I’m actually up in the mountains. It’s actually cold. I’m in the tropics, but I’m cold. Let me get right into it. Let’s start with our quotation. “Perhaps the easiest way of making a town’s acquaintance is to ascertain how the people in it work, how they love, and how they die.” That’s Albert Camus, The Plague. Let’s get right into polio. Great stuff out of the CDC recently with the MMWR, “Progress Toward Poliomyelitis Eradication, Afghanistan, January 2021-September 2022.” This will get a little complicated. I thought it got a little complicated, so I’ll slowly go through this. Got Vincent right here to help if I get caught up in anything.

Just for starters, Afghanistan and Pakistan are the only countries where wild poliovirus type 1 remains endemic. Two, wild poliovirus type 1 cases had been reported in 2022 as of September 30, compared with one case during the same period in 2021. No type 2 circulating vaccine-derived poliovirus was reported in 2022 compared with 43 cases in 2021. Now since the political transition in August 2021, 3.5 to 4.5 million previously unreachable children were vaccinated. This is the supplementary immunization activities and still restrictions persist in the southern region.

Just a little more on this. In 2016, Afghanistan joined the oral poliovirus-using countries around the world in implementing a synchronized withdrawal of trivalent OPV, so tOPV, containing Sabin strain types 1,2, and 3, and replacement with the bivalent OPV, so bOPV containing Sabin strain types 1 and 3 and greater than or equal to one dose of inactivated poliovirus vaccine.

Think about what we use in the U.S. This was as part of a containment effort for all type 2 polioviruses. However, in 2020, when Afghanistan began to report both type 2 circulating vaccine-derived poliovirus and wild-type poliovirus 1, the Global Polio Eradication Initiative authorized the use of the trivalent OPV for outbreak response. However, in 2020 when Afghanistan began to report both VPV2 and WPV1 polio cases, the Global Polio Eradication Initiative authorized the use of the trivalent oral poliovirus for outbreak response.

During January through December of 2021, there were five Supplementary Immunization Activities, SIAs, conducted including two after this political transition. After confirmation of the wild-type polio 1 and the CDPV2 polio cases during 2019 and 2020 in Afghanistan and Pakistan, both countries jointly reported five wild Poliovirus 1 and 51 VDPC2 cases in 2021 and this latest VDPV2 detection was in Pakistan in 2021. Transmission of the cVDPV2 in both countries is suggested to be likely interrupted. Thoughts on this, Vincent? Any way of making this more intelligible?

VR: The bottom line here is that in Pakistan and Afghanistan are the only places in the world that we know of where wild type 1 poliovirus continues to circulate. Actually, it circulates. There have been exportations to a few other countries in the past year, but those two countries seem to be the ones where it’s circulating. The reason it is is because we can’t immunize because the Taliban prevents the immunizers from doing their jobs, they shoot the immunizers. We have to get around that in some way.

There doesn’t seem to be any vaccine-derived polio 2 in those two countries. However, there are tons of vaccine-derived type 2 polio cases in other countries like in Africa. That’s a remaining problem that we’re going to have to deal with. That’s why we dropped type 2 polio from the Sabin vaccines because we had eliminated wild polio, but the vaccine-derived type 2 polio continues to circulate elsewhere, although it doesn’t circulate in Afghanistan and Pakistan, which is great. I think that’s the bottom line.

DG: All right, excellent. Update there. Influenza, we are not doing great on vaccinations and numbers keep increasing and influenza has now overtaken COVID-19 as the primary respiratory illness in the U.S. As per the CDC, the weekly rate of hospitalizations for the flu have reached 5.9 per 100,000 people. A level not seen at this time of year in more than a decade. In comparison for COVID-19, the rate has fallen to 4.3 per 100,000. That’s 5.9 per 100,000 for influenza, 4.3 per 100,000 for COVID.

I think that this is really an interesting comment. This gets back to we’re scaring the wrong people. We’ve gotten to a point now and think about this historically, what did people do? What measures did people take during a bad flu season? We’re already in the midst of a bad flu season and we’re actually seeing now with the combination of vaccines and prior immune experience that flu is actually overtaking COVID. Part of this, I actually have to say is we are not doing great with our vaccinations.

We are going to move on to RSV. Actually good news here, perhaps, as we hear that the U.S. FDA granted priority review to Pfizer’s RSV vaccine. We’ve discussed the data. Pfizer is seeking approval for the use of the vaccine. This is the RSVpreF in adults age 60 years and older. The agency is set to make its decision by May 2023. It could become the first approved RSV vaccine in the U.S. for older adults. The vaccine was 85.7% effective among participants with three or more symptoms and 66.7 for two or more symptoms according to an interim analysis carried out by an external data monitoring panel. I do want to point out, so here, why are we talking about a vaccine for older adults? Doesn’t everyone think RSV is just a problem in children?

It’s a problem in both extremes of age. The youngest children can be hospitalized, they can die from RSV, but we lose thousands of adults aged 60 years and over every winter. Also want to mention that, well, we just talked about Pfizer, but what about Moderna? Moderna also announced that they received FDA emergency use authorization for their Omicron-targeting bivalent COVID-19 booster vaccine in children 6 months through 5 years of age. Let me talk a little bit about boosters today, and I’m going to be referencing the recent Paul Offit special episode, but now this is amusing thing because everyone is thinking about this issue about why are we having so many respiratory problems. Why so many respiratory virus, why so much influenza and RSV, and entero rhino, and metapneumo?

Everyone has ideas on why this is happening. They’ve even invented new concepts that don’t actually even exist. I’ve been curious to understand well, what would happen in Sweden where the schools and the daycare stayed open? Actually have some relatives there and we all heard about what the Swedish response was publicly, and they basically shared that at least for the children’s school, they were doing all this other stuff.

Well, according to the Public Health Agency of Sweden, they are also seeing a rapid increase in respiratory infections despite not really having a lockdown. Perhaps one of our Swedish listeners can shed some light on this. Were there lockdowns we didn’t know about? Is this information accurate? It certainly challenges the common wisdom on why we were having issues. Actually, next week, I’ll be covering a recent article about the concept of a post-COVID infection immune dysfunction that may last for many months.

Mpox update. As I keep saying, mpox is not a gay disease or an African disease. Mpox is an infectious disease. More data on the effectiveness of the JYNNEOS vaccine with the MMWR, “Reduced Risk for Mpox after Receipt of One or Two Doses of JYNNEOS Vaccine Compared with Risk Among Unvaccinated Persons, 43 U.S. Jurisdictions, July 31 through October 1, 2022.”

In this report, we hear that among JYNNEOS vaccine eligible men, aged 18 to 49 in 43 U.S. jurisdictions, mpox incidents among unvaccinated persons was 9.6 times as high as that among persons who received two vaccine doses, and 7.4 times as high as that among persons who had received only the first dose. Preliminary evidence suggests that, this is interesting, no difference in protection between subcutaneous and the intradermal administration routes. I have to say that was the part I found most interesting here.

VR: Daniel, is that a good number, 10 times better with vaccination?

DG: I think it’s hard for people to understand what that really means. If you said, “Oh, OK, 90% reduction, 75% reduction,” I think that that makes more sense. I think one of the realities is people sometimes have trouble understanding what do these multiples mean? Maybe the percent decreases a little bit better for communication. I would say the takeaway is more evidence that the JYNNEOS vaccine is protective, significantly protective, two vaccine doses better than one. The subcutaneous intradermal administration routes look like they are great ways to approach this.

Ebola things are still quiet here in Uganda. I think this outbreak is perhaps passed. There was an interesting New York Times article, “Ebola Could Have Wiped Us All: Slow Lockdown Haunts Uganda.” Now, interesting, as I have a few comments. A sentence in the article reads, “Ebola, a highly contagious disease, mostly seen in Africa, causes fever, fatigue, and bleeding from the eyes and nose. The virus kills about half of those it infects.” I’m not going to agree. Perhaps the good thing about Ebola is it is not highly contagious. It’s not measles, smallpox, and probably only has a reproductive number of less than two.

Let me share the story of the two brothers that died of Ebola as related to me by the medical director of the Kakira Hospital. I say here in Jinja because that’s when I wrote this section. We heard about the two lads that ended up in Jinja dying of Ebola, and there was this concern that it was spreading. The story according to this physician was that two brothers hid in a truck to flee the Mubende District, and as he said, to flee danger, but instead to bring danger to their family and friends in Jinja where they died.

The other thing I want to comment about, which I think is really interesting, and this relates to a discussion I had with one of the Médecins Sans Frontières doctors that I had the ability to chat with recently. If you actually follow the case fatality rate over time, it starts at 100%, this highly deadly virus, but by the end of the epidemic, it had dropped to 47%. After a certain point, all the people diagnosed were surviving. It really seemed to support what was being suggested that early diagnosis and proper treatment turned a 0% survival into a greater than 85% survival. I’ll leave some copies of the links that show what I think is pretty impressive there. Vaccines, we did hear that a shipment of Ebola vaccine candidates set to be used in clinical trials have arrived here in Uganda.

The WHO has said it would send three vaccine candidates to Uganda to be used in a trial. One by the University of Oxford and Serum Institute of India, another by the Sabin Vaccine Institute, and a third by Merck. Uganda Minister of Health, Jane Ruth Aceng said the 1,200 doses that had arrived were from the Sabin Vaccine Institute, but, how to test vaccines when there are no more cases? Just sort of a, we need to be – I’m not going to say kind of. We need to be ready to go. Whenever there’s an outbreak, there are trial designs in place that are just ready to be triggered. This took months and months.

COVID update, a lot to say here. Maybe I should throw in just a little bit of the perspective here in Uganda. In Uganda, we really feel like COVID has moved on by. There’s a lot of other things here that the clinicians are focusing on. Still wearing masks and a lot of the patient care settings are getting mixed information about the vaccine coverage here, how many people were infected. In general, the perception, the behavior in Uganda is really moving forward past the lockdown times of pandemic. What about China? We have heard that China’s National Health Commission, NHC, announced the lifting of many of its signature Zero COVID measures, which comes in the wake of widespread protests and ongoing outbreaks in several cities.

They’re not related. Xi is just making his own decisions. Is definitely not buckling to the demands of the masses. People with mild or asymptomatic infections to isolate at home rather than in state facilities, no longer requiring people to show proof of a negative test for entry into public places. Also, allowing rapid tests to replace PCR tests in most instances, limiting lockdowns to narrowly targeted areas, shortening the lockdown period for outbreak areas, and allowing schools to remain open unless there are outbreaks on campus. Lots of concerns about vulnerable seniors, as many over 65 were viewed as too frail to be vaccinated. An interesting discussion here that I’ve had with some of my colleagues where – I understand it. The idea was that if we have a zero COVID policy, if my older patients are not going to ever be exposed to COVID, why do I need to vaccinate them?

They are now going to be exposed to SARS-CoV-2. They’re now be going to be exposed to a risk of getting COVID, so they need to be vaccinated.

Children, COVID, and other vulnerable populations. Children are at risk from COVID. As we’ve talked about – I think Paul Offit threw the right number out. Children are about 1,000 times less likely to have severe disease than adults. You can actually look at it. A million adults in the U.S. died. We think it’s about 1,000 for the children. Use tests intelligently and remember there’s more out there, not just COVID, and have a plan. Masks, we are starting to hear more about masks. The idea that they could protect us against getting sick or getting others sick with respiratory pathogens. Masks are not just for COVID anymore. Reasonable advice, but I worry about how political respiratory hygiene has become.

Along these lines, in New York City, the New York City Department of Health issued a health advisory on Friday, December 9, strongly recommending that all New Yorkers wear a high-quality mask in public indoor settings and crowded outdoor settings and take other proven precautions such as vaccination, testing, hand hygiene, and staying home when sick. Vincent, did you suddenly find that New Yorkers were all donning masks when they went indoors?

VR: Quite a few are, especially on the trains. I noticed a lot of – I would say a quarter of people are donning masks, and even out on the street, many people are as well. It’s clearly increased in this holiday season. Yes.

DG: It’s actually reasonable. Let’s think about the date. When this drops, it’s going to be the weekend before Christmas. Those that celebrate, do you want to have the flu? Do you want to have RSV? Do you want to have COVID? Just think of all the respiratory pathogens. You can reduce your risk of a respiratory infection. You can increase your risk of having a jolly Christmas.

Transmission. I was very excited to see the article, “Reduced Airborne Transmission of SARS-CoV-2 BA.1 Omicron Virus in Syrian Hamsters,” published in PLOS Pathogens. The authors suggest that currently Syrian hamsters are the only rodent model in which airborne transmission can easily be tested. Is that true Vincent? Anyway, we’ll get back to you.

Now, I am hoping we get emails from our colleagues regarding how true that statement is. I’m not sure how many people are aware of this. Since January 2021, the National Institute of Health, SARS-COVID-2 assessment of Variant Evolution Initiative has evaluated the transmission potential of SARS-COVID-2 variants in Syrian hamsters. The results shared here actually go directly against the mainstream media suggestion, and what has quickly become common wisdom.

They report that their data suggests BA.1 airborne transmission is substantially less efficient in hamsters than prior variants. Similar results were obtained for the BA.2.12.2 and BA.5 Omicron variant of SARS-COVID-2. I like the figure. There’s a figure, so I’m sure you’re looking at this, Vincent, entitled “Inefficient Airborne Transmission of BA.1 Variant of SARS-COVID-2 in Syrian Hamsters.” My favorite is the data out of the Munster lab.

There’s four panels, so I’m going to focus on that, where they separate the hamsters by 16.5 centimeters to differentiate contact from airborne. They do acknowledge that the observation that BA.1 variant of SARS-COVID-2 does not transmit efficiently via the air in Syrian hamsters appears to contrast with human epidemiological data. Vincent, your hand is up.

VR: OK. There are two problems with this.

DG: Just two, you only found two?

VR: At least two. First, ferrets can also transmit SARS-COVID-2 through the air. It’s not correct that Syrian – Well, maybe they’re the only rodent model. Is a ferret a rodent, Daniel?

DG: I thought a ferret was.

VR: Let’s see. Is a ferret a rodent? Let’s Google it right here in real-time. Ferrets aren’t rodents, they’re weasels.

DG: OK, so they caught us on a technicality.

VR: Technicality, but ferrets will transmit in a cage. The second part here, this Omicron BA.1 being less transmissible. Well, first of all, we don’t know if hamsters tell us anything about people, but they say it’s in contrast to human epidemiological data. Well, you know what, in humans, Omicron is immune evasive. If someone has immunity, this virus will still infect them, so it appears to be more transmissible. The hamsters were not immune and so they don’t see any effect of immune evasion. That completely explains the difference between hamsters and people. Is that clear, Daniel?

DG: I think it is.

VR: OK.

DG: All right. Let’s move on to COVID active vaccination. Never miss an opportunity to vaccinate. Since we last recorded, the authorized updated bivalent COVID-19 vaccines for children down to 6 months of age. Children 6 months through 5 years of age, who received the original monovalent Moderna COVID-19 vaccine are now eligible to receive a single booster of the updated bivalent Moderna COVID-19 vaccine two months after completing a primary series with the monovalent Moderna COVID-19 vaccine.

Children 6 months through 4 years of age, who have not yet received their three-dose primary series of the Pfizer BioNTech COVID-19 vaccine, or have not received the third dose of their primary series, will now receive the updated bivalent Pfizer BioNTech COVID-19 vaccine as the third dose in their primary series following two doses of the original monovalent, Pfizer BioNTech COVID-19 vaccine.

Basically all the way down to 6 months of age, the boosters are now bivalent. The bivalent boosters are now approved all the way down to 6 months of age.

Now, I didn’t get a chance to discuss the brief communication, “Low Neutralization of SARS-COVID-2 Omicron BA.2.75.2, BQ.1.1 and XBBB.1 by Parental mRNA Vaccine or a BA.5-Bivalent Booster,” published in Nature Medicine.

Just briefly, they showed that a BA.5 bivalent booster did not produce robust neutralization against the newly emerged variant. I’m going to suggest we put a link in here to Paul Offit’s special episode that I enjoyed a few miles from the Rwanda border. It’s really a great discussion. We are going to learn a lot in the next couple of months and I think we’re going to settle some issues.

Listen to that full episode. I’ll just make a few comments here for those of you that will not take my sage advice. One of the things that was brought up is by the time everyone gets these new updated BA.4.5, these updated bivalent boosters, will those variants even be circulating? What are we doing? Are we chasing our tail? Initially, they make a BA.1 and people point out that’s pretty much gone, and then they make a BA.4.5. Now, that’s pretty much gone as well. We have a bivalent updated booster against a variant that no longer is circulating at any significant level. Now here is where we’re going to learn a lot and I think, fingers crossed, that we’re going to learn something very positive here about the role of T-cells and non-antibody-based immunity.

It’s this issue that currently the vaccine currently prior infection are not generating antibodies that neutralize these newly emerging variants. If it’s all about the antibodies, if antibodies are critical, if people should really be out there getting their serology levels checked all the time, then we are in for a bit of misery in this coming winter. If it’s true that the vaccines are actually producing a durable T-cell cellular response, then we don’t need to keep chasing our tails. Maybe three shots is we’re done. If we look with the uptake anyway of these recent bivalent boosters, what? 30, 40 million and they bought 170. I think we’re going to learn a lot in the coming months. Vincent.

VR: I think that’s an important point. We need to have data on whether these bivalent boosters make a difference in severe disease or not because if they don’t help, you’re right, we just stick with the original three doses and we need that data. The CDC and the FDA are not doing us any favors by not giving us those data before they say we need this. This is not flu where you can change the vaccine and for a season, at least, that works. This virus changes way faster than influenza virus does. My feeling is you get those three doses and you have a plan. If you get sick and you’re going to get sick even with those three or with a bivalent booster, get Paxlovid or remdesivir or perhaps some new monoclonal that comes out in the future. I agree with that.

DG: Yes, this could be encouraging. We could in a few months from now have the answer because, boy, if we really need to keep vaccinating every fall, maybe even twice a year, I’m not sure how viable. If it turns out that Paul has been right all along and that three shots and then you’re done and that’s going to give you that severe protection and now we just add on our antivirals, I really think that’s going to be a positive future.

That’s not an anti-vaccine comment, that’s a pro-vaccine and maybe a very encouraging. The vaccines are even better than people think they are.

COVID early viral upper respiratory, non-hypoxic phase. I want to start this section with a focus on the publication, letter to the editor in the New England Journal of Medicine, “Efficacy of Antiviral Agents against Omicron Subvariants, BQ.1.1 and XBB.”

Just to point out, BA.5 is vanishing from the landscape. We have new variants. There’s really a nice figure, that really catches it all. You can go through looking at a lot of the different, monoclonals, and basically, there’s a wonderful figure when you move to the BQ.1.1, the XBB, you basically see that these monoclonal are no longer working. As you’ll see going forward, as we keep reiterating, we pretty much at this point, have lost Evusheld. It still hasn’t lost its EUA, but it doesn’t really make a lot of sense moving forward with that. But, if you look at the small molecule antiviral drugs the, remdesivir, think about using that three days in the first week.

We are not seeing any significant impact as far as the activity. molnupiravir again, not seeing significant impact. Nirmatrelvir, that’s our Paxlovid. Also, not seeing a significant impact. Really encouraging when it comes to those small molecule antivirals. As we get into the order, we’ll discuss, couple of things. One for this section we also have the article, “Incidents of Viral Rebound after Treatment with Nirmatrelvir and Molnupiravir,” published in JAMA Network Open.

These are the results of a cohort study of 12,629 adults in Hong Kong with COVID-19 who were hospitalized and had serial cycle threshold values measured, viral rebound, defined as a cycle threshold value of greater than 40 that then decreased back down to less than 40, occurred in 68 antiviral non-users, so 0.6% in 1% of the Paxlovid users and 0.8% of the molnupiravir users. I just want to point out, Paxlovid rebound is not a thing. It’s like Nelly in the Loch Ness or something. People talk about it, but it’s not a thing.

What do we do if someone has that acute infection? What do we do if in they’re in the first three to five days? They’re high risk. Remember, this is not for everyone. This is not that 22-year-old college athlete. This is someone who falls into a high risk. We’ll be talking maybe a little bit more about Paxlovid and the fact that the majority of the people that got Paxlovid were not over 65. This is high risk. Age is one of those things.

Number one, Paxlovid. Number two, remdesivir. No monoclonals at the moment. Molnupiravir. Let’s not do harmful things. Early inflammatory, lower respiratory. This is that second week. This is the early inflammatory phase that people are calling the COVID rebound. It’s the immunological period, steroids and anticoagulation, pulmonary support, remdesivir if early, immune modulation, and not doing things that make things worse.

Let’s wrap this up with the late phase. This is my favorite article of the week, “The Effectiveness of Coronavirus Disease 2019 (COVID-19) Vaccine in the Prevention of Post-COVID-19 Conditions: A Systematic Literature Review and Meta-analysis. Published in Antimicrobial Stewardship & Healthcare Epidemiology.

Here the authors searched PubMed, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, Scopus, and Web of Science. Really extensive, from December 1, 2019 to April 27, 2022, for studies evaluating COVID-19 vaccine effectiveness against post-COVID-19 conditions among individuals who received at least one dose of Pfizer, BioNTech, Moderna, AstraZeneca, or the Johnson so the J&J vaccine. A post-COVID condition was defined as any symptom that was present three or more weeks after having COVID-19. Already a little bit of an issue that they’re looking a little too soon there, but that’s OK.

They found 10 studies with over a million individuals that evaluated the effect of vaccination on post-COVID-19 conditions of which six studies were ultimately included in the meta-analysis. The pooled diagnostic odds ratio, the door for post-COVID-19 conditions among individuals vaccinated with at least one dose, was 0.71. About a 30% reduction with an estimated vaccine effectiveness of 29%. The vaccine effectiveness was 35.3% among those who received the COVID-19 vaccine before having COVID-19. This is really critical and 27% among those who received it after having COVID-19.

This is just – my patients are familiar with this, if a patient’s referred to me with Long COVID, the first thing I ask them is are you vaccinated? Have you been vaccinated yet? If they haven’t been vaccinated, the first therapeutic intervention, and I’m doing this for treatment of Long COVID evidence-based, is to get them started on that vaccine series. Interesting enough, in an individual like that who has never been vaccinated, I will actually start rather soon. We’ve actually discussed the other studies where the sooner you get them going on that vaccination strategy. It’s not about getting antibody titers up there. It’s about jumping in therapeutically to help with that post-COVID condition.

Here I am recording from Uganda. I will say no one is safe until everyone is safe. Hopefully, we learned our lesson about just the horrible loss of human life that occurred with the hoarding of vaccines and therapeutics. There still could be some more equitable sharing of those therapeutics because there are high-risk individuals. No one is safe until everyone is safe.

I do want everyone to pause the recording right here and go to parasiteswithoutborders.com and click ‘Donate.’ Even a small amount helps. We are now in the midst of our MicrobeTV fundraiser during the months of November. Here we are in December and January. Donations made to Parasites Without Borders will be matched and doubled up to a potential maximum donation of $40,000 for MicrobeTV.

VR: It’s time for your questions for Daniel. You can send them to [email protected]. Michelle writes, “Hope you’re enjoying your time in Uganda. Here’s my question. Last week I asked my internist, an infectious disease doctor in Westchester County, if he could write me a prescription for Paxlovid that I could fill and take with me when I traveled to the Caribbean later this month. I’m a 63-year-old woman with mild kidney disease, fully-vaccinated and boosted, been very careful, have not had COVID. He said Paxlovid was FDA-authorized for emergency use only, and he would have to lie to prescribe it for me for travel and refused to do so.

I’ve been hearing from other people that their doctors readily prescribe them Paxlovid when they’re traveling internationally. Do you know if this permitted? He also said 50% to 60% of people he prescribes it to get rebound from it. Is it possible his anecdotal numbers are more accurate than current research suggests? Lastly, he said what he tells all of his patients about COVID is that if your symptoms are improving by day four, there’s no need to take it. Does an improvement in day four mean you’re definitely out of the woods?” There you go, Daniel.

DG: At the moment, I’m not enjoying my time in Uganda. The first thing, and I will just point out, so the EUA is, “For someone who has COVID.” It’s for someone who has a positive test, they have symptoms. The EUA does not say this is authorized for you to give this to people to have with them when they go travel. In a few months when it gets licensed, then yes, this’ll be seen.

Are a lot of clinicians doing that? Are they basically, stepping over that line and saying, “Listen, you’re a high-risk individual. I’m concerned you’re going to be in a situation where you’re not going to be able to get that.” People at high risk, let’s say you’re going into a holiday weekend and there isn’t going to be good access to a physician. I think you’ve got to use your judgment there, but yes, I think what the physician is saying about the EUA is accurate, but the rest of what is being said is not accurate.

Let’s pull that apart because this is a little bit painful. One is you do not wait. The sooner you start the Paxlovid, the higher the efficacy. Even just going from three days to day four or five, you shouldn’t be waiting to day four to see how they’re doing. You should have already started that Paxlovid in the first three days because it is better, it is more efficacious than waiting to day four and five.

The other is, I don’t know what he’s talking about with his anecdotes, but what is the plural of anecdote? It is not data, it is anecdotes. We have multiple, well-designed, really good studies looking at the fact that COVID has an early viral phase. It has a second-week inflammatory phase. That is the disease. That is not the medicine. There is no such thing as Paxlovid rebound. You lose that ability to reduce the progression of hospitalization severe disease by waiting, by not prescribing. Don’t use anecdotes, use evidence-based medicine.

VR: Chris writes, “In the past I’ve heard if you test negative for COVID using a home rapid kit, you essentially have a free pass for the day, meaning you’re not likely contagious. I’ve been involved in multiple occasions where a person has obvious symptoms, they test negative for several days, and then finally test positive. Is it safe to presume that someone with mild symptoms and tests negative that day is likely not spreading the virus that day, even if they test positive the following day? I know this is tricky, but I am wanting to live by the ‘test negative and you are OK for that day” guidelines.’ What do you think?”

DG: It’s funny the way this was worded. I want to believe. We’ve talked about the science here and the antigen tests are not 100% and that’s just very few things in life are. We say death and taxes but not even taxes as Al Capone taught us. There is a certain sensitivity, the sensitivity of those antigen tests is best first thing in the morning, but it’s not a 100%. When you test positive that next day on an antigen test, you may have missed something. That’s why when we were in these, I’ll say, financial high-risk situations, trying to get Netflix and Lionsgate up there, we were using the sensitivity of a PCR to try to catch people early, so no. An antigen test is great, multiple antigen tests are better, but it’s not a 100%.

VR: Bill Wrights, “I’m a recently retired Johns Hopkins-trained surgeon, and I find you’re poking fun at surgeons is funny and unfortunately true. When I trained in the ’70s and ’80s, we were proud of the fact that Hopkins-trained surgeons were internists who operate. When I was in practice, I would get referrals from family practice physicians for internal medicine consults. In one week, I prescribed Paxlovid three times for friends. Their doctor didn’t believe in the medicine unless you were in the hospital.”

DG: [laughs]. Thank you for writing in. I was wondering if you were going to brag that you got all the way through the abstract. No, it sounds like you’re an individual who actually reads the full article and who follows the science so I applaud that. Paxlovid actually is not authorized for use in the hospital. It’s a little disturbing. Thank you for staying up to date.

VR: One more from Will who is in China but has a question that he believes is relevant to everybody. “Are there known possible sequelae for those who’ve only experienced asymptomatic COVID? I know there’s abundant evidence of some quite serious possible consequences for some who’ve only had mild infections. I’m asking because a well-known Chinese expert, Zhong Nanshan, is being quoted as saying there are none. Even though I’m a complete layperson, I just doubt that an expert would actually say that. Sure, sequelae may be rare compared to those who had serious infection but to say none is beyond believable.”

DG: I’m going to disagree with that expert. This is one of the things that we’ve been talking about for quite a while now, is you can have asymptomatic, you can have a situation where your spouse tests positive, you get tested because of that contact, you feel fine, four weeks later you start having issues. We certainly have people with post-acute sequelae of COVID, with Long COVID who had either an asymptomatic or a barely symptomatic acute event and then they go on to suffer for months and months.

VR: That’s TWiV weekly clinical update with Dr. Daniel Griffin. Thank you, Daniel.

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

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