TWiV 980 Clinical Update

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 4 February 2023

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 980, recorded on February 1, 2023. I’m Vincent Racaniello and you’re listening to the podcast all about viruses. Joining me today from New York, Daniel Griffin.

Daniel Griffin: Hello, everyone.

VR: Well, that’s one month of 2023 all gone.

DG: [laughs] Yes. One down, is it 11 to go? I have my count correct?

VR: One month of viral respiratory season gone also, right, Daniel?

DG: As we’ll get into, we really are dropping for a lot of things here. This is good, but let’s get going. I will start with my quotation, “Kind words do not cost much, yet they accomplish much.” That’s by Pascal of Pascal’s wager and a lot of other things. I like to try to remind people lots of times as we become so divided and angry and the rest. Little kindness goes a long way.

Polio, I’m going to start with polio. I want to encourage people to listen to TWiV 979. You can listen to the whole thing, but it was really the first part that caught my attention. It’s really a great discussion about polio. My favorite part is the reference to Poliopolis, the Poliopolis study. Now, Vincent, correct me if this is not the right study, but the Poliopolis study that came to mind was – I’ll describe this.

“In mid-2017, two groups of 15 strangers lived together for 28 days, each in a ring of shipping containers assembled in the parking lot of Antwerp University Hospital in Belgium. They had access to books and movies, a small courtyard for barbecues, a common kitchen and dining room, and a fitness room. All of it behind secure interlocking doors and under the watch of personnel in protective gowns. The 66 containers, which were prefabricated offsite, were assembled in just three days in April 2017 and were ready for operation a month after that.” This is really, I think, the catch. “Because of the length of time the virus can continue to be excreted, trial participants would have to stay sequestered for at least 28 days.” Is this the right study?

VR: Yes, that’s exactly right. As we saw, the virus actually was excreted for up to 100 days. I don’t know if they stayed there that long or if they let them go home.


DG: It’s kind of an issue, right? Because when we use the oral polio vaccine, we don’t sequester people. We don’t put them in – These actually looked pretty nice. If you go to the link I put in, you can actually see these shipping containers. I want one to live in. [chuckles] Look pretty nice.

VR: Well, this was, as you might imagine, a costly clinical trial, right?

DG: Yes.

VR: It showed, as we showed in that episode, that all these people had been immunized with IPV. Yet when they got OPV, this modified OPV, they shed virus. The IPV-immunized person’s gut is not immune. That’s why we have poliovirus in the wastewater in the U.S.

DG: I think it explains a lot of people – I was on The Brian Lehrer Show earlier today on NPR and someone called in, “I don’t understand. I got vaccinated. I did all I’m supposed to do. I still got infected.” I think this points out, vaccines are great at preventing severe disease, but we have yet to create a vaccine that will durably keep people from getting infected, particularly viruses that have these short incubation times, mucosal, et cetera.

All right, and we will get right into, as you pointed out, RSV influenza. Things are dropping down. The paper, “Prevalence and Clinical Outcomes of Respiratory Syncytial Virus versus Influenza in Adults Hospitalized with Acute Respiratory Illness from a Prospective Multicenter Study,” was recently published in CID. This is just one more study that may help people to have a proper respect, I like to say, for RSV in the adult population.

I have to say, a few years ago, people viewed RSV as something that only children got, but I think that that was a misplaced idea. In this study, over 10,000 adults, 622 with RSV, 1,940 with influenza, patients with RSV more frequently had longer admissions. Just an odds ratio of 1.38 for stays greater than one week and more likely to end up on a ventilator. Mechanical ventilation, odds ratio of 1.45 compared with influenza. RSV is a rather significant pathogen.

As we are seeing, and this is a nice thing, RSV has really dropped down. The most recent influenza-like illness surveillance network data suggesting that for this 2022 to 2023 season that the percentage of outpatient visits with influenza are actually really dropping back to baseline. Fingers crossed that it just keeps heading down that way. All right. We will get right into COVID. Pretty busy week actually. A lot of disparate things, so I’ll just basically put them out there.

“The WHO said on Monday that COVID-19 continues to constitute a public health emergency of international concern, its highest form of alert.” I’ll leave a link into the Reuters piece about that. “The committee acknowledged that the COVID-19 pandemic may be approaching an inflection point. Achieving higher levels of population immunity globally, either through infection and/or vaccination,” I sort of throw in and or both, “may limit the impact of SARS-CoV-2 on morbidity and mortality, but there’s little doubt that this virus will remain a permanently established pathogen in humans and animals for the foreseeable future.”

Now, here in the U.S., people may have heard that the U.S. plans to end the public health emergency in May. I should mention, it was a little bit of pressure. There was a bill called the Pandemic is Over Act, which was put forth by the Republican-controlled House of Representatives. It was actually put forth by Brett Guthrie representing Kentucky’s Second District and actually did pass in the House. Not sure this is going to continue moving forward, but that bill would abruptly end the public health emergency.

We’re actually expecting there to be a bit of a phase-out. There’s been some discussion about the fact that a lot of antivirals, vaccines have been stockpiled, purchased already. Hopefully, there’ll be a more gradual transition out of this. There’s a lot of concerns. This is going to be the end for a lot of people for access to care, a lot of access to testing, right? That person next to you may be sniffling and sick and potentially had COVID but not want to test because they don’t want to shell out the $10 for a test.

People may be sick and not want to shell out the $100 or $200 to go to a provider or an urgent care. This is going to transform. I’m hoping there’s some silver lining. Maybe there is, but we’ll have to see how that goes. Now, let’s move on to a topic of particular interest to me. The article, “Reconsideration of Antinucleocapsid IgG Antibody as a Marker of SARS-CoV-2 Infection Postvaccination for Mild COVID-19 Patients,” published in Open Forum Infectious Diseases. I put a nice figure in here to distract Vincent.


DG: In this study, a total of 182 adult participants who were, one, enrolled in the outpatient SARS-CoV-2 mild and asymptomatic immune response and transmission, the OutSMART cohort, had confirmed SARS-CoV-2 infection by either nasopharyngeal or saliva RNA test, were greater than or equal to 18 years old and had at least one validated oral plasma antibody result, and five had mild COVID-19 with a reported date of symptom onset.

While the patients were infected before vaccination or were never vaccinated maintained elevated antinucleocapsid IgG antibody responses, those who were vaccinated before infection had significantly lower antinucleocapsid IgG responses. I thought this is interesting. They say, “These data highlight that measuring N-specific antibody seropositivity may not be useful long term to distinguish vaccine-induced from infection-induced immunity in COVID-19 surveillance efforts.” They do reference a couple of studies. I’m going to leave links in for those as well.

They reference a seroprevalence study from Ireland, which showed that only 26% of individuals who were vaccinated then infected had detectable anti-N antibodies as compared with 82% in individuals who are only infected. They also reference another randomized, placebo-controlled mRNA-1273, that’s Moderna, vaccine efficacy trial showing that seroconversion to anti-N antibodies after infection was observed in here, 40% of vaccinated, then infected as compared with 93% of individuals who were infected, never vaccinated.

I’m just raising. I know a bunch of people are out in these studies where they’re tracking. Conversion to nucleocapsid positivity may not be as wonderful a test as we hoped. A lot of musing about what’s going on here immunologically.

All right, children, COVID, other vulnerable populations. Some of this is actually pulled from that FDA meeting we talked about last week. I mentioned there was a lot in there, so a couple of things.

I think a lot of the next three things I’m going to hit on are hopefully just reinforcing the impact of COVID-19 on the youngest among us as I like to say. One of the things that came up was the cumulative COVID-19-associated hospitalizations per 100,000 population by age group, COVID-NET. This is January 2 and it’s going through January 2023. I think they have an error on the slide because they have January 2002, but I don’t think we had COVID back then.

They look at the different age groups. The less-than-6 months, COVID-19-associated hospitalizations, was 902 per 100,000. We don’t get back above 900 per 100,000 until we get into the over 65 years of age. Really, that under 6 months is the really hard hit when it comes to hospitalizations. Then they basically show when we get to the youngest, the less-than-2, only about 7.3% have even gotten a single dose. Only about 3.3% have completed a primary series.

I’m going to circle back onto this as I talk about the article, “Assessment of COVID-19 as the Underlying Cause of Death Among Children and Young People Aged 0 to 19 Years in the U.S.,” that was published in JAMA Network Open. This is national data for the years 2019 to 2022 from the U.S. Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiological Research, the WONDER database, I wonder who comes up with these acronyms, on underlying cause of death in the U.S. to identify the rankings of COVID-19 relative to other causes of death among individuals aged 0 to 19 years.

COVID-19 deaths were considered in 12-month periods between April 1, 2020 and August 31, 2022, compared with deaths from leading non-COVID-19 causes in 2019, 2020, 2021. They report that COVID-19 was the underlying cause of death for at least 1,289 children and young people aged 0 to 19. I want to point out in this data, at least 821 deaths occurred in the one-year period from August 1, 2021 to July 31, 2022. That’s the majority of the deaths occurring in that period.

Now, I’d like to point out that November 2021 is when Omicron emerged. For all those stuck on the idea of Omicron as mild, the majority of the deaths in children were due to Omicron. Now, among children and young people aged 0 to 19 in the US, COVID-19 ranked eighth among all causes of death, fifth in disease-related causes of death. Two percent of all deaths in this age group were due to COVID. The findings of the study suggest that COVID-19 was a leading cause of death in young people aged 0 to 19. This, I think, is really something I want to hit on.

It caused substantially more deaths in young people annually than any vaccine-preventable disease historically in the recent period before vaccines became available. I know a lot of people, “Oh, I don’t know. This is vaccine and COVID-19. Should I vaccinate my children?” Listen, if you’re vaccinating your children, this is something you want to be vaccinating your children to provide protection for them because over 1,000 children are no longer with us. Now, moving forward, I think I’ve been saying this for a while. Vincent, have I been saying for a while, “Have a plan”?

VR: Oh yes, and many people are echoing you. All over, I hear people say, “I have a plan. Thanks to Daniel.”

DG: Oh, well, I’m glad that people are picking up on that because the recent MMWR early release, “Information for Persons Who Are Immunocompromised Regarding Prevention and Treatment of SARS-CoV-2 Infection in the Context of Currently Circulating Omicron SublineagesUnited States, January 2023,” is suggesting that people should have a plan. Now, I know they’re focused here on the immunocompromised, but I like to extend that to everyone who is at risk and they go through. Get your COVID vaccine. Decrease your risk of getting COVID.

They talk about ventilation. Spending time outdoors. Always a big fan of that. Learn about where you can get that test. Get tested if you’ve been exposed or have symptoms. Some recent thing about, now, you can treat people for COVID even without knowing that they have COVID. Let’s get a test. Let’s determine what’s going on. Wash your hands. That’s always good. Let’s keep that. Then they make some other recommendations here, including masks, which we continue to echo. Talking about masking, talking about ventilation.

All right, let’s move in to the next article. It’s an interesting one actually. The headlines. Let’s just say you actually need to read the article before you just go put in those headlines. If you’re a surgeon, you can read the title, but then listen to TWiV and we’ll tell you what’s a little bit deeper in there. “Association of Culturable-Virus Detection and Household Transmission of SARS-CoV-2 – California and Tennessee, 2020-2022, published in JID, Journal of Infectious Diseases.

These are the results of two case-ascertained household transmission studies conducted in Nashville, Tennessee and San Francisco, California, from April 2020 through January 2022. Seventy households, 70 primary cases, 114 household contacts. Primary cases and their household contacts were instructed to self-collect nasal swabs daily for at least 14 days after illness onset or enrollment.

Specimens were tested for SARS-CoV-2 using PCR. Specimens meeting a pre-specified cycle threshold were inoculated onto Vero E6-TMRPSS2 cells and assessed for cytopathic effect. For starters, they report that in this study, 70% of secondary infections had serial intervals of less than six days, suggesting early transmission. What is a serial interval? This is, I think, important. This is not saying that that transmission from the first person to the second had to happen within those six days.

What was happening here? Serial interval is the time from illness onset in the primary case to illness onset in the secondary case, right? You got to figure your math there. This then is a combination of how soon after exposure transmission occurs plus incubation. The reverse here is that 30% of the serial intervals were more than six days. Not saying that people transmit past Day 6. Whether or not that is true is not determined by this paper, so I just want to point that out.

Interesting is that they report 40% of household contacts of primary cases with culturable virus detected became infected with SARS-CoV2 compared with how many of the primary cases that did not? Twenty-one percent. Not zero, 21%. People that the primary case had culturable virus and they’re not giving us a quantification, it’s, again, binary. You know how we feel about that. People that had culturable virus, 40% of their contacts went on to get infected. Of those who had no culturable virus, we still had 21% go on to end up getting COVID-19.

VR: Basically, their culture system is not very sensitive, right, Daniel?

DG: [laughs] A couple of different ways to look at that, right? I think that’s one of the interesting, right? Here you say, “Oh, this person. I don’t know. Maybe they have a negative antigen. Maybe they can’t culture it,” and then the other people are still getting positive. It doesn’t make sense biologically that you’re going to actually not have a virus there and still get someone else sick. I think it puts a little context to some of these other studies, but you can imagine how this was treated. All right. [laughs]

VR: Well, maybe, Daniel, they got infected by someone else. That’s also possible.

DG: That’s actually one of the challenges that’s come up. I think even we’ve talked about this in some of the mask studies with healthcare workers when there’s so much SARS-CoV-2 floating around. Just the fact that you may not have gotten it from that household contact you end up, that may not be the actual smoking gun.

VR: Yes, I think we put too much faith in people saying what they did is what they did, right?

DG: [laughs]

VR: I think people misbehave all the time. Remember at the beginning of the pandemic, these people in a Hong Kong hotel. Two people across the hall from each other. They said one infected the other supposedly. They said, “We never went out,” but I don’t believe them.


DG: Yes. It’s like all those STIs from toilet seats. All right.


DG: Perhaps everyone had a chance to digest last week’s FDA-VRBPAC meeting and look at the publications that came out around the time of the meeting. Vincent, I’m anticipating a lively discussion here.

VR: Well, actually, Daniel, we’re having Paul Offit on TWiV tomorrow, so he’ll contribute.

DG: Oh, this is great.


DG: I met a physician who’s going to head over to Uganda, who actually was inspired to go into medicine and become a pediatrician by Paul.

VR: Good.

DG: That was a nice connection, so I look forward to listening to this. I’ll be brief then because I know Paul will do a great job on this. If one is going to boost, this came up at the meeting, are the bivalent boosters really better? That’s a contentious item. As I mentioned last week, the discussion was that the data is not all that compelling. There was sort of a, “Yes, things seemed to be trending in that direction,” but there was a correspondence.

“Effectiveness of Bivalent Boosters Against Severe Omicron Infection,” published in The New England Journal of Medicine. This data was discussed at the meeting. Here, the authors report that they focused on new data collected over 99 days during which bivalent boosters were administered from September 1 to December 8, 2022, and over the preceding 99 days during which monovalent boosters were administered from May 22 to August 31, 2022.

I highlighted in this “99 days” because I think that’s this critical number to discuss. How long do we think this boosting effect will provide this boost? Actually, I think it’s probably a good way of saying it. They say here that booster effectiveness peaked at approximately four weeks and then waned, contracted afterwards. For all participants 12 years of age or older, they reported vaccine effectiveness against severe infection resulting in hospitalization over days 15 to 99 after a receipt of one monovalent booster was 25%.

They then said the effectiveness of the bivalent boost was 58.7%. A lot of challenges with this study, right? We’re looking at different times, different exposures. They reported similar vaccine effectiveness estimates when the analysis was restricted to participants who are 18 years of age or older or 65 years of age or older. Also, estimates of vaccine effectiveness were similar for the Moderna and Pfizer-BioNTech boosters, similar among the first, second, third booster doses.

I’m looking forward to a deeper discussion. Really, the big thing that was voted on at the meeting last week was, can we get this simpler? Can we come up with one formulation going forward? It was not that it all needs to be bivalent going forward. Even a discussion, do we need to keep the ancestral in there? We’re not seeing that circulating much in humans. Seems to be stuck in the deer at the moment. I also discussed the recommendations made at the FDA meeting were to try to make things simple.

Likely, we’ll see where this goes, but I’ll also leave a link into The New England Journal of Medicine perspective piece, “COVID Vaccines – Playing the Long Game.” One of the things that I left a figure in here because I was hoping we could talk a little bit about this concept of, “When do we boost if that’s what we’re going to do?” While I’ve distracted Vincent with that, one of the things that came up, which was interesting at the meeting, was this idea that maybe we boost in the fall.

Not because COVID is now seasonal, not because we only see a COVID boost in the December-January period, but we don’t want to overwhelm the hospitals with COVID at the same time that they’re dealing with RSV and flu. Raised at that meeting was, “Well, what about that peak in hospitalizations, infections, and death in August? Should we be thinking about that as well?” Vincent, any thoughts on this?

VR: Well, I think we can’t boost more than once a year. That’s not a good strategy, right? You have to pick your season and seems to me that we’re in a weird era now because it’s still a new virus. This is going to be a winter virus in the Northern Hemisphere, so I think it makes sense to boost in the fall. The problem is if you get 90 days protection, three months, which three months are you going to pick? The fall or the next year? That’s what we play with influenza, right? We boost in September. Then by January, the protection is gone, especially in older people, and that’s not really acceptable. I think it’s going to have to be the winter, but how are you going to extend it? Maybe they should make more potent vaccines that have a longer memory. I don’t know.


DG: All right, I like that. All right, and let’s move right into COVID. The early viral respiratory phase, right? You test positive, what do you do? This has really been sort of the same for a while. Individuals that are higher risk. Number one, Paxlovid. Number two, if you have access, remdesivir. monoclonals, really no options at the moment with the current variants. Molnupiravir as a really last and least option.

I think, at some point, we’ll have a little bit of discussion on the limited role of convalescent plasma here in the States. People move on into the hospital. I really say, you’ve missed your window if you haven’t jumped in in that first week. I was using the analogy of the physician who wants to wait to treat your blood pressure until after you’ve had that stroke and then they say, “Oh, well, most people with blood pressure don’t have a stroke can get paralyzed.”

I’m trying to say, “Listen, when you’re that doctor, when you’re that patient who ends up with a bad outcome during that second week because you most likely were going to do well, we have tools that can really improve your odds.” That’s really been a paradigm of medicine for decades. Stepping in before it’s too late. Because once it’s too late, sure, steroids, anticoagulation, hospitalization, possibly with pulmonary support, immune modulation.

Again, I feel like I have to keep saying this. Well, you’ll see why I have to keep saying this. Under the do-no-harm section, let me share the article, “Efficacy and Safety of Antimicrobial Stewardship Prospective Audit and Feedback in Patients Hospitalized with COVID-19 (COVASP): A Pragmatic, Cluster-Randomized, Non-Inferiority Trial,” published in The Lancet Infectious Diseases. These are the results of a Canadian prospective. They do things differently up there.

Pragmatic, non-inferiority, small-unit, cluster-randomized trial comparing prospective audit and feedback plus standard of care with standard of care alone in adults admitted to three hospitals in Edmonton, Canada with COVID-19 pneumonia. Basically, what we’re going to have here is one group is going to have antimicrobial stewardship stepping in, making recommendations, saying things like, “Maybe not treat that virus with antibiotics,” and then the other group is just going to be a free-range standard of care, which unfortunately involves a lot of antibiotics.

Three hundred one audit and feedback events were recorded in the intervention group; 215 recommendations were made, of which 84% were accepted, so that’s great. There was, as one might expect, lower antibiotic use in the intervention group than in the control group. They saw length of stay, 364.9 versus 384.2 days per 1,000 patient days. Clinical status at post-admission Day 15 was also non-inferior.

More evidence that antibiotics are actually not required for a good outcome with COVID-19. Well, I like to say, considering that one of the hospitals where I occasionally will visit, the head of that antimicrobial stewardship program still puts all of their COVID admissions on doxycycline, high-dose vitamin C, and zinc. Yes, antimicrobial stewardship is good, but you actually need to have someone competent doing it.

OK, moving on to the late phase, past Long COVID. The article, “Severe Fatigue and Persistent Symptoms at Three Months Following SARS-CoV-2 Infections During the Pre-Delta, Delta, and Omicron Time Periods: A Multicenter Prospective Cohort Study,” was published in CID. These are the results of a multicenter prospective cohort study of adults with acute illness tested for SARS-CoV-2.

They compared fatigue severity, fatigue symptoms, individual and organ system-based symptoms, and the presence of, this is an interesting criteria, greater than or equal to three total symptoms across variants among COVID-positive and COVID-negative participants three months after that SARS-CoV-2 diagnosis and the COVID-positive folks. The study included over 3,000 participants, about 2,000 COVID-positive, a little less than 1,000 COVID-negative, and then it was scattered with 19% pre-Delta, about 50% Delta, about 30% during Omicron.

Interesting. In multivariable models, there was no difference in severe fatigue between the variants. There was decreased odds of having three or more symptoms in Omicron compared with other variants. This was interesting. This was not significant after adjusting for vaccination status. It’s a really nice figure where they look at the three-month symptom prevalence just at odds ratio by variance at three months among COVID-positive patients. They really go through a number of different joint pains, ache, musculoskeletal, loss of smell and taste, chills, fever, shakes, shortness of breath. Really interesting to look at.

VR: I think it’s important to point out that many people, as each variant arose, said this will give more or less Long COVID. Just guessing, instead of looking at the data like we have here.

DG: I think that’s the big thing is that vaccination has really reduced the amount of Long COVID we’re seeing. Then once you look at people who are vaccinated, you’re seeing Long COVID with all the variants. I think it’s tough now. A lot of patients, we talked about this before, are a little bit hesitant to see providers because we have not done a great job of listening. We’ve done a horrible job of being dismissive for these folks. There’s millions of people out there that are struggling after COVID. All right, and I will close it there. No one is safe until everyone is safe.

We actually finished our MicrobeTV fundraiser. It went well. It was sort of nice last week there. Thank you, everyone who jumped in. Right now, we are starting our American Society of Tropical Medicine and Hygiene fundraiser. February, March, and April, donations made to Parasites Without Borders will be matched and doubled up to a potential maximum donation of $30,000 from PWB to ASTMH. We’re going to be supporting those travel scholarships for individuals from low- and middle-income countries wanting to come to the annual meeting. Go to Parasites Without Borders. Click to donate.

VR: Daniel, have you heard that the FDA today modified the EUA for Paxlovid? You don’t need a positive test any longer to get a prescription.

DG: You don’t actually even have to have COVID. [laughs]

VR: Right, so you can now take it with you on your trip, right?

DG: Yes, people have been doing that. I think you and I are aware of that. People have been doing that ahead of time. Just sort of, “Here’s your Paxlovid,” it’s sitting on shelves, probably do not need to be quite as restricted. It does bother me. This whole idea that, “Is it going to become over-the-counter next?” This is a medicine that has different drug-drug interactions. You really want to make sure you’re only giving it to people that actually have COVID. You want to know about kidney function. There’s a lot of challenges here.

VR: When you go for your prescription, if you’re COVID-negative, you just want to get some Paxlovid, are they going to check your kidney functions, if you have any other drugs that would have a problem interacting?

DG: Someone is still going to have to write that prescription. That person is going to be responsible for making judgments and educating the person. Now, you’ve got that Paxlovid in your pocket or purse, so to speak, I like the alliteration there. Do you take the full dose? Do you take the renally-adjusted dose? What do you do with your other medicines? Yes, I think this is going to be a little bit of a challenge.

VR: All right, it’s time for your questions for Daniel. You can send them to Kevin writes, and this is perfect, “Wondering your thoughts about testing kids for COVID. Recently, my 8-year-old had fever, sore throat, vomiting, had COVID antigen tests lying around. Tested him, he was positive. Told the school out until next week, can’t get childcare as he’s COVID-positive. Wife thinks it’s unethical to send his 5-year-old brother to school. Negative antigen test.

“For all other febrile illnesses, it seems fever-free for 24 hours and feeling better is the standard to go back to school, except COVID. Obviously, we’re not testing for RSV, flu, paraflu at home, but seems like fever-free 24 hours and back to school for those. Do we really know of the infectivity after fever-free vaccine kids? Maybe I’m thinking this wrong, but should I’ve even tested them? I feel dumb testing them. I’m guessing people just don’t test their febrile or vaccinated kids because they thought through the apparent penalty of the knowledge. Thanks for any thoughts.”

DG: This is a great email, so thanks for sending it because this is an important topic. When you penalize people for testing, that’s what for a lot of people they’re viewing. This is a penalty, right? You’ve never forced my child to miss out on their educational opportunities when they had flu or RSV. Even for strep throat, what is it like? You’ve been on the medicine for 24 hours. This stuff just was made up over time.

It’s a lot harder to transmit strep throat, so I’m not even sure how long they need to stay out of school as long as people are washing hands. This came up today and people are very emotional about this, right? Parents are very emotional because they’re saying, “My kid is missing out on educational opportunities if my child misses five days of school.” That’s a problem for them. Also, how do you hold down a job when you’re missing five days of school for that first child and then what are you doing with that second child?

Are they staying home because they might convert at any point? Are you doing antigen tests every day? Those are going to not be so affordable soon. You’re going to spend, what? For 10 days, you’re going to spend $100 every time one child gets sick. If you’ve got one of these good Irish families like I grew up with, where there’s a lot of kids in the house who might need testing, and then what are you going to do as far as the other side?

This is what people get emotional about is, what if you’re immunocompromised? What if you’ve been taught the last three years to really be frightened of COVID-19? What if you don’t have access to a provider who’s going to get you on medicine? This is really a challenge. I’m not sure that the guidance that was put out in the early days of 2020 is going to withstand the future.

VR: Carol writes, “I recently came across some studies suggesting that nitric oxide nasal spray was somewhat effective in reducing the duration of nasal virus shedding in patients with mild COVID and the claim that an observational study suggested it may prevent infection. Can you comment on these studies?”

DG: Yes, so there were some studies that were done. Some of them were published in some decent journals and peer-reviewed and looked interesting, I know, at the time having looked over these. It even helped. I think it was Utah. They were recruiting for one of these studies. I actually have a background in nitric oxide research. Yes, it’s interesting stuff. Again, it’s going to need some more studies to determine. The idea here is that nitric oxide is a generalist when it comes to immunity against viruses inducing different pathways. We’ll have to see. It is interesting but, yes, still in the preliminary state.

VR: David writes, “I just tested positive, started Paxlovid. My wife was last boosted in October. When should she get another booster? She’s over 65. I would expect to have good protection for several months after my infection.”

DG: Yes, so you’re actually hitting on a question here that everyone was asking, right? Let’s see. It’s October. Say October, November, December, January, we’re four months out. The FDA was talking about the data where it takes two to four weeks to peak and then about four months of protection. This concept of boosting, are we saying, “OK, maybe we’re good for now because levels are dropping or are there certain populations where they’re willing, they’re interested where it might make sense to boost a little more often?”

As Vincent and I have talked about, I’m not sure there was great uptake with the booster this fall. I’m not sure how great the uptake is going to be when we start recommending or if anyone starts recommending more than once a year, but we still don’t have a great answer to this. We still don’t have a recommendation for another of the new boosters.

VR: Certainly should have a plan, right, Daniel?

DG: Well, that’s the big thing. Everyone who’s high risk should have that. If you end up like this gentleman testing positive, get on the antiviral. I think maybe one of the things that is encouraging is when we talk about the bivalent boosting. We’re talking about a boost above a relatively-sustained protection against severe disease and hospitalization.

VR: Russ writes, “A situation I have been seeing more often recently is symptomatic patients refusing to be tested for COVID-19. It is also seemingly more common for medical providers in my area to not test for COVID-19 even in patients who are clearly symptomatic early in the disease and not up to date on vaccinations. I can’t think of a number of negative consequences of people not knowing if they have COVID-19. Will you please address the reasons why you think that it’s important to continue testing for COVID-19?”

DG: I think our first emailer got to this. Some people view that COVID test as potentially something that is going to penalize them, they’re going to be punished for. Now, we found out you have COVID, so you’re not going to get five days of work. You’re going to miss five days of school. You’re going to have to isolate because you’re infected and then wear a mask for another six days, six through 10 after that.

A lot of people have gotten to the point where they’ve been either previously infected, previously infected and vaccinated, where they are not necessarily going to be a candidate for medicine. They’re just asking, “Why am I doing this? Because I’m going to have a negative consequence.” Why do we care? Well, we care for a couple of reasons. One, I’m going to say just sort of that altruism thing, is people with COVID can give it to other people.

They can get those other people sick. Those other people can end up in the hospital. Those other people can actually end up dying or ending up with Long COVID, which, for some people, might be worse than death, to be honest. The other is if you’re an individual who might benefit from early therapy. Because if you wait until it’s too late, if you wait to see how you do and you’re not doing so well, you’ve missed your window of opportunity.

VR: Daniel, someone mentioned on the live stream tonight that a study out of Australia said if you give antivirals a day after symptom onset, they’re better, more effective than five days. Do you think that makes sense?

DG: The initial data that we got on Paxlovid, for instance, the first three days, was better than Day 4 or Day 5. Really interesting because I know someone was, “Oh, maybe you should wait. Let that immune system start to respond before you start about -” No, the sooner you start the antiviral, that’s the science.

VR: That makes sense because, at the beginning, there’s less virus, so it’s easier for the antiviral to take hold, right? That’s TWiV weekly clinical update with Dr. Daniel Griffin. Thank you, Daniel.

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


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