TWiV 912 COVID-19 Update #120

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 25 June 2022

Pdf of this transcript available (link)

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


From MicrobeTV, this is TWiV, This Week in Virology,Episode 912, recorded on June 23, 2022. I’m Vincent Racaniello. You’re listening to the podcast all about viruses. Joining me today from New York, Daniel Griffin.

Daniel Griffin: Hello, everyone.

VR: Speaking of viruses, Daniel, we have SARS-CoV-2, we have monkeypox, and now they find poliovirus in the sewers in the UK.

DG: I heard about that.

VR: It’s vaccine-derived poliovirus, which is interesting because they don’t use OPV any longer in the UK. It must have been imported from another country and apparently, it’s doing some local transmission because that’s what would get it in the sewer, not just one person. Interesting. Viruses in the news, right?

DG: Yes. Who would’ve thought you needed to know about viruses?

VR: Exactly, right.

DG: I realized I always start with,  “we got a lot to cover today.” People are like, “He always has a lot to cover today,” but we have a lot to cover today as always. I will start with my quotation:  “When men are most sure and arrogant, they are commonly most mistaken, giving views to passion without that proper deliberation, which alone can secure them from the grosses absurdities.” Maybe as we go forward, people will figure out why that quotation came to mind. Let’s start with an update. Where are we? I think it’s been a little while since I shared the numbers.

I know everyone has decided the pandemic is over, but I just want to point this out, as we all decide this pandemic is over and Omicron is just a mild upper respiratory virus, we are still seeing about 2,000 deaths a week here in the U.S. That adds up to over 100,000 people a year dying of COVID, despite vaccines, effective therapeutics, and great access to testing. Keep that in mind. I know everyone wants to move on, and this is human nature, but just we can keep in mind what’s still going on.

One of the things I will start about, how can we keep having all these infections? Hasn’t everyone been infected? Aren’t we running out of people? Isn’t that part of those equations? The article, “Outcomes of SARS-CoV-2 Reinfection,” was posted as a preprint, is currently under review, and this is coming from the U.S. Department of Veterans Affairs again. They built this cohort of people, where they looked at those with just first infection, and that’s 257,427. Then, they’re going to compare those, this database to those who have had reinfections, and so two or more infections, and then they’re going to have a noninfected control group.

Here’s really this question is, what outcomes are we concerned about? Because there is this idea, I think a lot of people have, that if I survived my first infection, that I’m really going to be just fine this second time, there really shouldn’t be any problem. Reinfections, that the popular wisdom is that reinfections are mild, nothing to worry about, nothing to see here. Well, here’s the data and I’m going to go through some of this and I’m going to put a link in our show notes.

Compared to first infections, those with reinfection exhibited increased risk of death, all-cause mortality, and that hazard ratio was greater than 2, increased risk of ending up in the hospital, threefold, people getting two infections versus one, pulmonary issues, and these are all hazard ratios, 2.5, cardiovascular issues, 2.4; coagulation hematological disorders over 2; fatigue, over 2; GI issues, 1.7; kidney disorders, mental health, diabetes, musculoskeletal, neurological disorders, all elevated.

I just want to point out this popular wisdom, so to speak, that if you did OK the first time that all’s going to be good going into the future is not really being borne out when we’re following the numbers.

VR: Daniel, is this dependent on vaccination, not vaccination, or they don’t know in these people?

DG: I would hope, and actually this is why we continue to recommend that people get vaccinated. That vaccination would reduce these risks and it certainly does.

VR: What do you think are the underlying mechanisms for why second and so forth infections cause these issues, do you have any thoughts?

DG: It is tough because one of the things we do point out is the first time around, we lost a million of the most vulnerable Americans. Every time you get an infection, different variants, you’ve now survived, so there’s been a certain you’re now a bit older, maybe you developed other health problems and we certainly see that. Maybe you went into the first infection. Now you’re going into second infection, you have a new diagnosis of diabetes, you have some residual pulmonary issues.

I actually just recently had a gentleman, it was about a month prior, he had his first infection. He did fine, he survived it in the outpatient setting, about 30 days later with this whole discussion, he was testing positive again. Was it really lingering residual RNA? We did a quantitative PCR. It was in the 20s. He actually progressed to become hypoxic this second time. I’m not sure I have all the answers, but we’re certainly seeing this disturbing situation. Children. [crosstalk]

VR: I’m sorry. One more thing. Do you see this with influenza or any other respiratory infections?

DG: It’s really interesting. It may have to do with the fact that we have so many circulating variants. Early on in the COVID pandemic, people would get COVID, three months would go by, we really were protected citizen for that period of time, but now we’re seeing actually some pretty frequent reinfections as early I was describing a month there, one or two months, as we’re describing here people with four infections in just this two-year period. We didn’t really see much of that. We don’t really see much of that with the flu. Usually, you get your one influenza year, we certainly see some reinfection, but it tends to be less common.

Children, and this is changed, I will stay. Children are at risk of COVID, I think I’ve been saying that for a long time now. I want people to remember back in the early days when everyone was fighting to be first in line to get vaccinated. Everyone was trying to claim their job was essential, we had the unions pressuring the politicians, we had some large healthcare systems that shall not be named, where they were sneaking shots to the ex-wives of administrators and in risking financial penalties.

Nowadays, it looks like just about anybody who wants to can get vaccinated, even the littlest children. First, I want to give some perspective, and this is really the David Hume quote at the top. Don’t just throw out your thought, your blanket thought on vaccinating children. Let’s talk a little bit about when I say children are at risk from COVID what are we talking about. As of June 9, 2022, we have had over 43,000 children hospitalized and over 1,000 children have died from COVID.

It was not just the flu, that is extraordinary number. For the less compassionate out there, because I know what everyone thinks, one-third of all these kids hospitalized appeared completely healthy prior to being hospitalized with COVID-19. For all the age groups under 18, COVID is one of the top four or five causes of death for this last year. Now, with SARS-CoV-2 virus here to stay, the choice is either to protect our children or let them get infected without this protection, and let them have that risk of death, hospitalization, or long-term impacts of COVID.

We also have all the horrible social and mental health impacts that are much harder to quantify. I want to put this, so we think about death, we think about hospitalization, but one of the other things that is really out there as I’ll say a specter is Long COVID. Do kids get Long COVID, and I want to bring all up before we mention where we are with vaccines. This was a last-minute add-on article, “Long COVID Symptoms in SARS-CoV-2-Positive Children Aged 0–14 Years and Matched Controls in Denmark (LongCOVIDKidsDK).”

This is a national cross-sectional study that was just published in The Lancet Child & Adolescent Health. These are the results of a nationwide cross-sectional study that included children with a confirmed SARS-CoV-2-positive PCR tests, these are the cases, and then we have matched controls from Danish National Registers. Previously, four weeks has been used as the definition of Long COVID. This is an update, people are not following this. As of October, 2021, a new case definition from the WHO defines Long COVID to be symptoms lasting eight weeks or longer. This is a more rigorous. Actually, I agree with this. Four weeks is soft, eight weeks, that’s a long time to still be having issues, and that’s what they’re using in this study. There were 38,152 in the case group of this study compared to 147,212 in the control group. What they’re trying to do here is subtract out the background. They saw Long COVID across all age groups. Let me just go through each age group with the percent estimated to have Long COVID once they did the background subtraction. Zero to 3 years age group. This is that under 4 that we’re going to mention are now going to be eligible for vaccination.

Eight weeks out, 13% still had symptoms; 4 to 11, 4.4%; 12 to 14, 4.7%. I’m actually going to click on my link here because I wanted to go to Figure 2 to actually just talk a little bit about the actual. What are these symptoms? I think this is really important. We’re going to have a link to this in our show notes and I’m going to encourage everyone to go to Figure 2 of this publication. Let’s first look at those youngest of these children.

The youngest children, and this is that zero to 3 years, this is where we’re seeing stomach aches, we’re seeing fatigue, we’re seeing pain in the joints, we’re seeing mood swings, we’re seeing fevers, we’re seeing ongoing cough. Then as we move forward, we actually get into our more typical symptoms that we’re used to seeing. I’m going to encourage everyone to look at this. These are young children under 4, 13% of them were still having issues. If you look at the ones that separate, these kids are continuing at eight weeks still to have a cough, still to have fever, still to have a lot of these issues.

VR: I presume these are all unvaccinated kids, Daniel.

DG: Unfortunately, the situation, particularly in the youngest, is going to be unvaccinated. This is using emotion to hopefully sway people, and I do. I have compassion for adults with Long COVID and I definitely take care of a lot of individuals. Periodically, as I’ve shared, I’ve been asked to help with children and adolescents who continue to suffer with Long COVID. I’m sure I’ve shared the story of that teenage girl whose mother showed me videos of her dancing, who now has the intractable vomiting triggered by just having her sit up for more than 45 minutes.

With that as background, why am I so excited that we’re going to have access to vaccines for the youngest children? On June 18, we heard the CDC recommends COVID-19 vaccines for young children. The CDC director endorsed the Advisory Committee on Immunization Practices recommending all children 6 months through 5 years of age, adding this, should receive a COVID-19 vaccine. This eligibility expands access to vaccination to nearly 20 million additional children and means that all Americans age 6 months and older are now eligible for vaccination.

With our encouraging of women to be vaccinated, I’ll say pregnant individuals to be vaccinated during their pregnancy or before their pregnancy, we’re also hoping that we’re going to get that maternal transfer of protection even to those under 6 months of age.

VR: Daniel, this information that you just gave us, how does this jive with the surgeon general of Florida who said there is zero risk in children for COVID? This is a physician, I understand. How can a physician say that?

DG: Unfortunately, Vincent, and I think everyone is aware, people are willing to say things that are their own personal financial and political best interest as opposed to feeling like they need to respect the truth. That’s why it started off with this ahead of time, over a thousand children have died. That’s a risk. I don’t know how that can be interpreted anyway. Over 40,000 children have ended up in the hospital. They want to believe it’s fake news. They don’t want to believe what the truth is. There’s a special place in a fiery afterlife for such individuals.

I alluded to this a little bit. What about if a mother gets COVID-19 while she’s pregnant and is unvaccinated? We’ve been really pointing out that pregnant women enter a period where they are actually at about 20 times the risk of bad outcomes compared to women that are not pregnant at about the same age. What about their children? How do the children do when we look at them about a year out? The paper, “Neurodevelopmental Outcomes at 1 Year in Infants of Mothers Who Tested Positive for SARS-CoV-2 During Pregnancy.”

This was published in JAMA Network Open and these are the results of a cohort study of 7,772 infants delivered during the COVID-19 pandemic. In this cohort, 222 of the mothers had a positive SARS-CoV-2 preliminary chain reaction test during the pregnancy. Maternal SARS-CoV-2 positivity during pregnancy was associated with a greater rate of neurodevelopmental diagnosis. This was over a twofold increased odds ratio. There was an interesting comment by the authors and I’ll just read it.

“We observed neurodevelopmental diagnosis to be significantly more common among exposed offspring, particularly those exposed to third-trimester maternal infection. The majority of these diagnoses reflected developmental disorders of motor function or speech and language.” I was actually surprised that it was the third trimester, but this really builds on other studies, really reinforces our recommendation that women should not wait until after that pregnancy. They should get vaccinated before, during.

Really, if you’re giving advice to pregnant women, if you’re suggesting they delay that vaccination, that’s bad advice for the mother, that’s bad advice for the child. We are now where I like to say use tests intelligently. Remember, there’s more out there than just COVID. When someone comes in, think about COVID, think about influenza, think about RSV. Remember that incubation period is still two to 14 days. Most people are going to show up in that first week, but we still have people that turn positive after day 14.

Active vaccination. I really feel, and I’m going to be positive here, that we are getting to a new stage with regard to COVID-19 for everyone here in United States. The last few segments of our society that had been left out were the youngest individuals. We now have vaccine access for them. What about those immunocompromised, those with transplants The article, “Evaluating Clinical Effectiveness of SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients: A propensity Score Matched Analysis,” published in Transplant Infectious Disease.

Here’s really looking at that question of how effective are vaccines in these folks who got solid organ transplants. These are the results of a retrospective cohort study, where they’re looking at the SARS-CoV-2 infection rates between those folks that have received two doses of mRNA or one dose of the J&J vaccine, and those that are not fully vaccinated. Those partially vaccinated, those are unvaccinated. I do want to point out here that this is two doses and we’re now up to recommending four doses in these individuals of the mRNA vaccines. We’re really not doing much of the J&J. Keep that in mind.

I’m just going to hit on, what were the high points that they saw? All the COVID-19-related deaths in this study were in unvaccinated patients. No deaths in the vaccinated patients. Some hospitalizations may have been prevented with the use of monoclonal antibodies in the outpatient setting. Three patients in the fully vaccinated, nine in the not fully vaccinated group received monoclonal antibodies, avoided hospitalization. It could have been worse. Our transplant colleagues really seem to love those monoclonals and I understand why.

There’s a lot of drug-drug potential interactions that we can have with Paxlovid, very limited access to remdesivir. There’s really a population that is still getting a lot of monoclonal antibody therapy. Just a bit from the conclusion, I like to keep reinforcing this, with regard to measuring the humoral immune response to COVID-19 vaccination and infection, a reminder, validated cutoffs for many of the wide array of available antibody assay is still being investigated, making it difficult to interpret the meaning of a given antibody test.

Our results, which show protection from infection, severe critical disease, hospitalization, and death among fully vaccinated solid organ transplant recipients, suggest that measurement of antibodies should not be the sole surrogate marker for vaccine effectiveness.

VR: Gee, who’s been saying that for two years now?

DG: I hate to say it is painful, but at some of the cancer centers of excellence throughout this country, we still have people making believe they’re immunologists and not giving patients the protection they need based on some antibody tests that they – Remember, this is that same population where we’re discussing Evusheld giving that passive antibodies to people who are concerned may not be able to produce those effective neutralizing antibodies. The article, we’re back to Syrian hamsters, I know that that’s a favorite of Vincent. I’m sure Vincent has a pet Syrian hamster.

“Therapeutic Efficacy of Monoclonal Antibodies and Antivirals Against SARS-CoV-2 Omicron BA.1 in Syrian Hamsters,” published in Nature Microbiology. A note for authors of these types of papers, you need something right up front to keep track of what monoclonal antibodies you’re talking about, this is like War and Peace. I’m like, “Let me take their conclusion of the FDA-approved therapeutic monoclonal antibodies.” That is REGN10987/REGN10933, COV2-2196/COV2-2130, and S309. I don’t think people know what you’re talking about. Let me translate this.

They’re looking at the Regeneron cocktail, they’re looking at Evusheld, and they’re looking at S309 an antibody made by Abcam that’s supposed to be variant resistant. They only found that Evusheld efficiently inhibited BA.1 replication in the lungs of hamsters. My translation, I’m just going to say that one more time, they tested the Regeneron cocktail sub-variant resistant, supposedly variant resistant monoclonal from Abcam and Evusheld and found in this animal monoclonal that Evusheld and only Evusheld worked of the monoclonals they tested.

I would have liked if they had tested bebtelovimab but we didn’t quite get that. Now, we are cutting to the time when a person has detectable virus, when a person develops symptoms, when a person first develops COVID-19. I’m actually going to share a little bit of a story and I want everyone to think, what would you as a TWiV listener have done in this situation. There’s a gentleman, ends up in an emergency room, having chest pain, known history of coronary artery disease, blockages of the blood vessels supplying the heart muscle.

In the emergency room, they’re evaluated, they are allowed to be discharged, they are seen by their cardiologists, risk stratification, other things. A period of time later, they end up admitted to the hospital with an acute cardiac event. They spend a period of time in the hospital, they’re getting ready to leave but now they start to develop some mild upper respiratory symptoms. They are found to be COVID-19 positive. What should they do in this high-risk elderly individual who just suffered an acute coronary event?

We’re going to go through our options and then I’m going to tell you what happened. Number one, this person is in the hospital but they are not admitted for moderate to severe or severe to critical COVID-19. They could have been given Paxlovid with an 89% to 88% reduction in progression if given in the first three to five days, but this individual was on statins, and a number of other medications, so there may have been a reason to move on to the next in our list. The next would be remdesivir.

Three days, they’re already there in the hospital, they could have given that first dose and either kept them for a couple more days or had them come back for a couple more days, but 87% reduction in progression and that would have not had the concerns with drug-drug interactions. We still could have done bebtelovimab and then a low-hanging fruit molnupiravir. Let’s go through our list and let’s find out what happened to this individual. I’m going to start with the preprint to now-published article in the wink of an eye – I didn’t know you could get things published this quickly, but I am impressed.

Remember that article we discussed as a preprint, “Rebound Phenomenon After Nirmatrelvir/Ritonavir Treatment of Coronavirus Disease 2019 in High-Risk Persons?” It is now published in Clinical Infectious Diseases. Just to basically remind people who may or may not have listened last time. In this cohort, 93% fully vaccinated, treated with Paxlovid for COVID, only two patients, 0.4% required hospitalization by day 30. These were for reasons unrelated to the rebound, zero deaths in this high-risk cohort that were treated with Paxlovid. Only four, imagine that only four. Not every single physician I know who wants to be in The New York Times.

Only four patients, less than 1% experienced rebound of symptoms which were generally mild at a median of nine days after treatment and all resolved without additional COVID-19 directed therapy. They actually have a really nice description, you can look at each of the four rebounders because everyone has their theory. I’m going to point this out, two of them were started on therapy on day one, the other two were started on day three, no obvious pattern there. I do worry that there’s this perception or confirmation bias out there, everyone is looking to have this experience.

I was talking with my friend Stefan Muehlbauer, the head of the ER at one of our local hospitals about this, and it really is one of these things. Everyone is convinced that COVID is a five-day illness. When they have any symptoms during that second week if they took Paxlovid, they’re quite upset about it. I just want to point that out. This is what I think is a really critical article, and boy, I think I’ve actually mentioned this article about 10 times just today. This is an MMWR early release, “Hospitalization and Emergency Department Encounters for COVID-19 After Paxlovid Treatment, California, December 2021-May 2022.”

This just reinforces. as we’ve been saying, what Paxlovid actually does. We have no compelling data on Paxlovid but making you feel better much more quickly, shortening your period of infectiousness, or preventing Long COVID, but we do have compelling evidence in people at high risk that this reduces their chance of hospitalization or death. In this report, COVID-19-related hospital admissions and emergency department encounters occurring five to 15 days after Paxlovid treatment were described using data from a large integrated healthcare system.

That’s the California Kaiser Permanente Southern California. Reports of such hospitalization or ED encounters occurred infrequently, representing less than 1% of Paxlovid-treated patients over the study period. Just reinforcing that when administered at an early stage treatment, Paxlovid prevents COVID-19-related hospitalizations among persons with mild to moderate COVID who are at risk of progression to severe disease. We mentioned remdesivir with that 87%, we mentioned bebtelovimab, and the fact that we do not have great efficacy data there, we’re optimistic that it works.

We have molnupiravir as number four. Let’s get back to our individual. The decision was made not to give him Paxlovid. The decision was actually made to give him no therapies. He was discharged from the hospital, readmitted a week later, and a week after that he died. As I made a comment to our group this morning, that was a missed opportunity. We had the opportunity to reduce the chance of that outcome by 90%. Let’s not be that person, let’s not wait, let’s not say it’s mild. Mild means you’re in the first week, severe and critical is what happens that second week if you miss the opportunity.

Moving on to the early inflammatory phase, and I continue to reinforce here, once we miss that opportunity in that first week and they end up in the hospital, we have some tools but limited impact. We have steroids, we have anticoagulation, pulmonary support, maybe remdesivir if we’re still early enough, tocilizumab. Really, at this point, we’re chipping away those dramatic powerful tools, we’ve lost our window. The tail-phase Long COVID, post-COVID, actually hitting this twice because we hit this up front talking about children, but the article, “Risk of Long COVID Associated with Delta Versus Omicron Variants of SARS-CoV-2,”was published in The Lancet.

Now, these are the results of the case-control observational study where the authors set out to identify the relative odds of Long COVID, defined by the National Institute for Health and Care Excellence guidelines as having new or ongoing symptoms four weeks or more. This is four versus the eight at the WHO. I want everyone to walk away with the fact that the updated is going to be eight, this is using four. This is in the UK during the Omicron period compared with the Delta period. If we go out to eight, I am hoping that we’re going to see a little bit lower numbers here. They first identified 56,003 UK adults first testing positive between December 20 in 2021 and March 9, 2022. These were the Omicron cases and they’re saying that because about 70% of the UK cases at that time were attributable to Omicron. Now, they’re going to compare these to 41,361 UK adults testing positive between June 1, 2021, and November 27, 2021. Those will be our Delta cases where during this period about 70% were Deltas. We’ve got these numbers, we’ve got our most likely Omicron, our most likely Delta. Among the Omicron cases, 41.5% experienced Long COVID at this four-week cutoff. Among the Delta cases, 10.8% experienced Long COVID using that four-week cutoff.

For starters, this is interesting, where although you might see a lower percentage with the different variants. When you get the many, many more cases with Omicron, you actually can end up having more people with Long COVID. A lower percent of a bigger number can actually equal a bigger number. What about vaccination? Vince and I pasted in the figure, so we can look at it together and we will have a link so people actually can go to the show notes and be looking at these figures as we talk. This is the figure.

If the participants had their vaccine more than three months before and then got infected with Omicron, 2.8% had symptoms past 4 weeks, compared to people who got Delta less than 3 months post-vaccination with 8% having symptoms passed 4 weeks. I tried to translate this, the lower incidence of symptoms past 4 weeks was in those less than 60 greater than 6 months past a vaccine infected. Omicron, that was about 2% or 1 in 50, and then the highest group was those who were 60+ less than 3 months post-vaccine. With Delta, that was 10.4%.

We’re seeing this interesting relationship actually, which I’m hoping we could talk about. We were seeing a little bit of a difference with Delta versus Omicron. We were also seeing, as we got farther out from the vaccine, that there was less likelihood of developing symptoms past four weeks of Long COVID. I don’t know if you add any thoughts about the immunology there, Vincent.

VR: That is what stuck out at me that if you have less than three months between vaccination and your infection, you’re at higher risk, which is suggesting to me that you need to allow the immune response to mature a bit more before it fully protects you. That’s consistent across the 18 to 59 and the greater than 60-year-olds. Something in common is going there. The other thing that struck me is that for, three-to six months vaccine in this over 60 group, the error bars are huge, huge.

DG: They are, they really.

VR: I don’t think you can conclude anything from that, there’s too much noise. Part of the issue, as you know, Daniel, is how many symptoms does it take to – it just takes one to have, be defined as Long COVID, but some of these people have more and less. This is complicated. It’s not a straightforward analysis. I don’t know if you saw the commentary in Nature this week, the title was something like, why does every Long COVID study give you a different number? It can be 15% or 50%.

That’s because they’re all different, they’re all different populations, and they also say, which is really interesting, just because a study has a lot of people in it, it doesn’t mean it’s representative.

DG: We even touched a little bit, how do you define? Is it four weeks? Is it eight weeks? Is it a single symptom? Is it a constellation of symptoms? Then, even severity figures into all this. Still a lot to do, but even the most optimistic here we had, was people vaccinated six months letting it mature. We still were seeing 2% of people, 1 in 50, still having persistent symptoms four weeks afterwards, maybe if we go out to eight weeks, it’ll be a little bit better.

VR: Daniel, what do you think? Do we have data on the percentage of Long COVID that resolves at four weeks, eight weeks, 12 weeks, et cetera? What if you waited a year, what would the numbers go to? Would it not change or would it change?

DG: It’s tough because we have to then do this with variants, with vaccine. We  certainly see that numbers go down over time. This is one of those things where if you just continue to be supportive, not be dismissive, a certain percent of your patients are just going to get better over time. We really don’t know yet. Is there a percent of patients that just will not recover even given enough time?

I think we’ve talked a little bit about other post-infectious or post-viral symptoms like chikungunya, and that’s something where we have enough data to know what percent at one year, at two years, at three years still have that debilitating arthritic pain, for instance. We don’t have enough time, I don’t think we have enough data yet to really know.

VR: People get very scared of Long COVID, but if you see 8%, that could change in six months, so don’t take these studies as gospel yet.

DG: I think actually, this is a tough issue because a lot of people are making decisions, risk assessments, and this concept that unless my risk is zero, I will stay locked in my home with an N95, and people would like better data on Long COVID to help them make decisions, what’s my age, what’s my vaccination status, what’s the circulating variant, what is my actual risk? Can I go out to a restaurant? Can I go to that birthday party? I think that is still the one thing hanging over us. By the way, if I get Long COVID, can there be some effective treatment?

This, I see as being one of those things that’s continued to challenge us as we try to move forward. As I always like to conclude, no one is safe until everyone is safe. There’s an entire world out there, and in many areas, we still do not have great access to vaccines or therapeutics. I want everyone to, I say, pause the recording right here, go to and click the Donate button, even every small amount helps us do the work we’re doing, but also we are continuing our fundraiser for Foundation for International Medical Relief of Children.

For the rest of June and all of July, donations made to Parasites Without Borders will be matched and doubled up to a potential donation of $40,000 to our clinic in Bududa, Uganda. It’s our clinic Foundation for International Medical Relief of Children, I think of it as our clinic. Really, this clinic is essential. Over 100 children, mothers, and fathers are cared for here. It’s a malaria-endemic, it’s a very limited resource area. If FIRMC can’t do its work, there’s over 100 individuals a day at risk of dying of succumbing to these illnesses.

VR: Time for your questions for Daniel. You can send yours to Carolina writes, “My Uncle Andy, 61, woke up Monday with a sore throat, tested positive for coronavirus. He has an international flight scheduled for Sunday and he’ll be abroad for a long time. Tonight, he’s going to receive Paxlovid, fully vaccinated, and in an at-risk age group. His primary concern is infecting others. How should he approach this delicate situation in terms of behavior and what should the family expect from doctor feedback at this point?”

DG: I’m doing the math in my head. If symptoms started Monday, so that’s day zero. Tuesday, Wednesday, Thursday, Friday, Saturday. Sunday is when he moves from isolation for the infected to precautions. I’m trying to figure out how this individual can be on an international flight, keep an N95 on the entire time, not infect those people around them. The shortening of the isolation to five days followed by precautions for a five was really an economic decision because people need to deliver food, they need to deliver healthcare, they need to drive the buses.

It wasn’t so that someone could jump on an international flight. I think you are putting people at risk. I don’t understand how you’re going to be on an international flight. It’s going to come off, you’re going to go to the bathroom, you’re going to drink something, you’re going to eat something. When you do that, you’re going to be spreading virus to those around you. That’s the reality. You are infectious in those six through 10 days.

VR: It’s important that you mentioned earlier on this episode that we don’t have any good data about how Paxlovid affects shedding, right?

DG: We don’t. We have no compelling data that this is not like getting those antibiotics and 48 hours later, you can share your toothbrush with your sibling. I’m sure you’re never supposed to do that. No, it there’s no compelling data that Paxlovid decreases your contagiousness to others.

VR: Sounds like if he’s going to be in Europe a long time, he should just delay his flight for a bit.

DG: That would be the responsible recommendation.

VR: Laurie writes, “We are a big busy pediatric office in San Francisco, we’re excited to finally offer COVID vaccines to our youngest patients. We’re barraged by questions. The most common is by far how long should we wait after our recent COVID infection to get the vaccine? Of course, everyone has their own story, but barring a compelling reason to vaccinate ASAP.

My understanding is that it’s best to wait two to three months after recent disease to vaccinate, the AAP is saying otherwise, pediatricians across the U.S. await your response with bated breath. We cannot reach a consensus on this one. We will be using Moderna, by the way. I’m curious what local peds are choosing back east.”

DG: I’m going to do it backwards. If you’re looking at the two choices, Pfizer versus Moderna, Moderna is the no-brainer because right the data was, you get that first vaccine, four weeks later, you get that second, at six weeks, you’ve basically achieved separation of the curves, you’re considered protected, you’re considered fully vaccinated. Pfizer really is a three-shot series, so first shot in June, second shot in July, and then five months later. That’s December, it’s Christmas time.

I know a lot of our local pediatric practices are looking at Moderna. Now, it’s nice to have both options, I’ll be honest because as opposed to I guess when I’m not honest but [chuckles] Pfizer has less reactogenicity. A pediatrician might want to make that judgment call saying, “This is a mom, I see some vaccine hesitancy here. If her child has a fever which they might has some reactogenicity,” he may just said I’m throwing in the towel. It’s actually nice to have both options.

It’s a challenge I say that because you’re then making the judgment call that you can convince this family, this parent to go ahead with three shots versus just two. The other is, what about this issue? What about waiting? Early on, and I think we made this bed and now we’re trying not to sleep in it, is early on when we first had limited access to vaccines, there was this whole concept of waiting three months before you were vaccinated, after an acute infection with the ancestral virus.

You probably could get away with that because we were not seeing a lot of repeat infections, but now it’s very clear, we’re seeing second, third, fourth, fifth infections. Some of those infections as little as a month after the first. Particularly, in children, an Omicron infection, the data would not suggest that you have great protection from that. Really, I am on board lock step with the American Academy of Pediatrics. When the child is better, when a couple of weeks have gone by, let’s get up let’s start that vaccination series.

VR: Lou writes, “My mother’s 75 high BMI type 2 diabetes hypertension, has had four shots of Pfizer last one in February, next month, she’ll be coming to the U.S. to stay with her daughter and grandchildren for two months. My question, if she gets COVID, will she be able to have access to Paxlovid as a foreign visitor? Whom should she turn to? She’ll be in the New Canaan, Connecticut area.”

DG: I don’t see there being any issue. Paxlovid is not something that is supplied under your health insurance pharmaceutical benefits. It’s here in the U.S. Our government has supplied Paxlovid, our tax dollars at work, so I do not see why it would be an issue accessing Paxlovid.

VR: One more question from Lou, “In our circle, we come across a number of people, me included, who had symptoms but the antigen test did not turn positive till three to four days later after the worst of symptoms had resolved. In my mother’s case, this would be bad to miss the early window of opportunity for antiviral treatment. I thought the only thing we can do is if symptoms reappear do a daily antigen test, and if negative do a PCR, any other advice?”

DG: I think this gets to using your tests intelligently. The antigen tests have a lower sensitivity than the PCR, unless you’re willing to wait. We’ve talked about the studies where you do serial ones. Timing does matter, so if there’s concerns and one of the nice things that the antigen tests have done, is they’ve relieved the amount of pressure on our molecular testing. If you’re concerned, go to that urgent care, get that molecular test, if it’s positive then you’ve also connected with someone who hopefully can get you going on early treatment.

VR: Cliff writes, “I have a question regarding the timing of my grandson’s vaccination. During the second trimester of her pregnancy, my daughter got both doses of Moderna, a booster three months postpartum. The grandson was born August 2021 being breastfed. In May, the mother had COVID symptoms, had a positive RT-PCR, and during this time, her son 9 months old, had flu-like symptoms but did not test positive. With the availability of a vaccine for infants, should the boy receive the first dose now or wait three months until after the May episode to have him vaccinated?” This is a similar question.

DG: This is a similar question. To me, there’s no reason to wait. Go ahead, get that first shot, and we’ve actually talked about is that second shot should it be four weeks. If you delay it a little bit, that’s fine as well. I would start on that vaccination series, just really echoing what the American Academy of Pediatrics is recommending.

VR: He says, “How protective is mother’s milk, compared to vaccination, and will it decrease the effectiveness of the vaccine?”

DG: Yes, so the mother’s milk will not decrease the effectiveness of the vaccine. I don’t think we have any evidence or even mechanisms where we would worry about that. Even we’ve discussed some of the data on giving passive monoclonal antibodies to people, and then vaccinating really minimal effect there. I’m not concerned that the breastfeeding is going to have a negative impact on vaccines, the vaccines are more effective than breastfeeding. Do both.

VR: That’s COVID-19 clinical update number 120 with Dr. Daniel Griffin. Thank you, Daniel.

DG: Thank you. Everyone, be safe out there.


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