TWiV 793 COVID-19 Clinical Update #75

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 14 August 2021

pdf of this transcript available (link)

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


From MicrobeTV, this is TWiV, This Week in Virology, Episode 793, recorded on August 12, 2021. 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: I wanted to ask you, Daniel, “What do you think of the science behind the idea that the FDA is going to allow people, transplant patients, to get a third dose? Does that make sense?”

DG: We don’t really have the science yet. I mean, that’s one of those tough things. I feel like I’m channeling Rich Condit when I say sometimes public health decisions are being made in front of the data– with the expectation. I have to say, in all the other vaccines, if someone got vaccinated, to even Hepatitis B, when I get checked, “Oh, you don’t have antibodies, let’s give you an extra dose.” Then if I get antibodies, great. If I don’t, they say, “All right, we gave you three. Good luck with that.”

We have a history of this. We have an idea that there’s something nice and protective about having those antibody levels. If clinicians want to do this, it’s good that it’s already and– I think, I don’t know if you know this Vincent, but the CDC estimates that over a million individuals in the U.S. have already gotten the third dose.

VR: Wow.

DG: Yes, isn’t that interesting? I don’t know if you’ve ever been on the highway and noticed that there’s a speed limit, but people are going faster than the speed limit.


VR: Of course.

DG: By doing this, a couple of things will happen. One is we’re going to get data on adverse reactions because we do want to know, “Is it safe if we start doing this?” We think it is. We think right. We’re waiting for the science. Then, also, we’ll start to get not just what do those antibodies do, but we’ll start to get some experience as far as may be efficacy in this patient population.

Yes, there’s no compelling data as we’ve talked about that says this has to happen, but this is one of the three top things that people want to talk about. Kids in schools, masks, and—w]What about boosters? I’m not opposed to it. It’s definitely– The wheels are rolling forward. We’ll see what happens.

All right, let me start with my quotation, and then we’ll get to the thick of it. “When you get into a tight place and everything goes against you, till it seems as though you could not hang on for a minute longer, never give up then, for that is just the place and time when the tide will turn.” That’s by Harriet Elisabeth Beecher Stowe from Oldtown Folks in 1869. I don’t know, personally, I think in the last couple of weeks here, I’ve felt a little bit frustrated by what’s happening. We are 20 months into this pandemic. What I like to say is, “A single point does not make a line.” Early on, we were just so hungry for knowledge– one study would come out. We have 20 months. We are building a line, one dot off in left field doesn’t suddenly mean that everything we’ve learned to date is wrong.

I was on a call the other day and someone was just talking about one study where people using the at-home-over-the-counter tests had a really poor sensitivity. One of the physicians on the call was like, “I’m never doing antigen tests anymore. I’m switching over.” I’m like, “Stop, it’s one study. Look at the context, one point does not make a line. We are building knowledge here and we’ve learned a lot over time.”

What are we seeing all across the country? We’re seeing rising case rates. I’m seeing more folks here in the hospital. One of the things also, one of the most dangerous words that a physician can ever say in my experience, the strangest three words is that with high vaccination rates, we expect a certain percent of the people who test positive. Then, even a certain percent of folks that end up in the hospital– two have been vaccinated before. This is, I thought, something we had learned from our vaccine adverse event reporting. What we’re looking for is, are we seeing more than what we expect?

If you see a patient who was vaccinated, who has a positive PCR, we expect that. The higher the percent of people in your population that are vaccinated, the higher percent you expect those to be positive. At some point in a perfect world, 100% of people that test positive would be vaccinated because 100% of people in your population would be vaccinated, but as I like to say, in that scenario instead of 300, 400 people dying a day, you’d have 300 or 400 people dying a year. Just keep perspective.

In the United States, thousands of people die every single day. You know what? If you’re in an area where 80% of your population is vaccinated, 80% of people that die every day have been vaccinated. Don’t let the math, don’t let the experience, don’t let the headlines frighten you from the effective tools, and understanding that we’ve developed over 20 months. I was looking for Vincent’s reaction to that, but all right.

VR: Sounds good to me. I like it.

DG: Right to children, COVID, and mental health. I think people are learning and now there’s a big discussion about what’s going on, but as I’ve said for a long time, children may be at low risk, but they are not at no risk. If this pandemic just affected children, I think we would all be frightened and treating it differently, but everyone compares the children to the 65, the 70, the 85 years. You know what? It’s not as bad. It is bad in children as we’re seeing and now the discussion is, “Is it bad because the delta variant is specifically targeting children? Is it more virulent?”

People don’t want to go back and say, “I was wrong. Right now the virus is affecting children in a significant way.” You don’t have to be wrong, just focus on the moment. We are now seeing about 100,000 cases per week in children here in the U.S. What does that mean? It means some deaths as per the American Academy of Pediatrics, about 0.03%, that’s a small percent, or less of all child COVID-19 cases have resulted in death to date. A small percentage of a large number starts to add up. This is certainly better than the 2% case fatality rate that we currently have in the U.S. for all age groups.

The other estimate is, and this is a wide -0.1% to 1.9% of all child COVID-19 cases resulted in hospitalization and part of that has to do with the demographics of your region. This is a wide range and it’s 1 in 1,000 in the optimistic low to 1 in 50 in the less optimistic. Somewhere in the 1 in 100 kids who get COVID might end up in the hospital. Think about this. Think about a school, think about a high school. Think about 1,000 kids, 2,000 kids if COVID runs through there in an unvaccinated population. That’s a lot of kids ending up in the hospital.

Now, the last that we really don’t know about is the percentage of children that get PASC or post-acute sequelae of SARS-CoV-2 or what a lot of groups refer to as long COVID. That’s still unclear in children. Low estimates put that about 1 in 50. Other estimates are saying this may be as high as 1 in 5. It may be more similar to what we see in adults and as the children become older, we may see that.

All this information, getting all this pinned down, is really critical as parents grapple with decisions around vaccination, all the other COVID mitigation measures. There are vocal anti-masking groups that actually are showing up at school board meetings. I have to actually say I was disturbed by hearing this. There’s an organized movement in that direction. I’ll talk a little bit about this, but a lot of the issues with masks are protecting our children, protecting our teachers, protecting our school staff, but also keeping those kids in school so they’re not always out quarantining for the next round. We’ll get back to that.

VR: Daniel, what do you think of the California decision to have all school teachers and kids vaccinated and masked?

DG: It makes sense. I do think, as we’ve talked several times, there’s the tyranny of the minority. There’s really a small vocal group that has been opposing good public health measures over time. All the other vaccinations have been mandatory. It made good sense public health-wise. Yes, I think it makes a lot of sense. I would feel so much more secure knowing my children were going to an environment for learning where it was as safe as possible for them. I think we have a responsibility as citizens. People say, “My choice to vaccinate, why is that any of your business?” It’s the drunk driving analogy. You drive drunk down the road, it’s not your freedom. You live in a society. Just like with this virus, you can kill people if you infect them with the virus. I’m pro-vaccine just in case people were wondering about that. [laughs]

Now, in the transmission testing section, never miss an opportunity to test. We are doing better. The number of tests over the last week has actually risen about 50% from 600,000 to 900,000 tests a day. That’s nice to see. Now, this was a peer-reviewed paper published as a rapid communication in Eurosurveillance. Actually, this was discussed, Vincent, you brought this up at the tail end of the last TWiV.

The study was, “Vaccine effectiveness against SARS-CoV-2 transmission and infections among household and other close contacts of confirmed cases,” the Netherlands, February 2 May 2021. Now, this paper really addresses the hot topic of the impact of vaccination on transmission, and I think provides some reassuring clarity. Let me start by saying as a qualifier, the variant that we’re discussing here is the alpha variant or Pango lineage B.1.1.7. That was dominant in the time of this study. I like to say, we need to keep repeating these studies as we have new variants to make sure that things are consistent.

This was a very robust data set. This was 253,168 contacts of 113,582 index cases. These are big numbers. This is not a few hundred people got sick in P-town. There were two important findings. Let me break this down. The first was, if the infected person had been fully-vaccinated, how much did this protect the household contacts? This is saying, “If I’m vaccinated, does that protect others?” The authors found a vaccine effectiveness against transmission of 71%. That’s big because people want to say, “Why do you care if I’m vaccinated?” This is some data. I care because if you’re vaccinated, your chance of giving it to me has been reduced by 71% in this big, robust study.

The second question is whether the vaccine worked if the exposed household members were also vaccinated. That’s, “What about the people around me?” Remember, this is a high exposure setting. This is household context. You’re in a residence with these people without great air exchange. If you’re going to get it, this is really your tempting fate. The adjusted vaccine effectiveness for fully-vaccinated household context of a confirmed case was 75%. Actually comment, as I said, a point does not define a line. This number is very consistent with other studies.

If a person is vaccinated, they’re doing themselves a service. They’re also doing the community a service. It’s just another study building the case that COVID vaccines not only protect the vaccinee, but also offer protection for those around us. This is this concept of ring vaccination, where we encourage vulnerable individuals to ring themselves with vaccinated friends, family, and step a little bit back from those who are unvaccinated, particularly if you’re a higher risk individual.

Now, I want to build the story here because I’m really going to keep pushing with my idea or, I should say, that the science suggests that vaccinated people are at lower risk of infection, so they’re less likely to get infected. I know we say that’s not what we’re so excited about, but that’s great. Vaccinated people can transmit if they get infected, but we think that they transmit less. I ran a numbers game. Let’s say you say the vaccine, and these are numbers from our science, make you about 90% less likely to get infected. You drop down to 10%. Then, on this study, you say you’re less likely to transmit to others by about 70%. We’ve already dropped down to three. Then, if those around us are also vaccinated, you drop that number by another 75%, so you’re down to about 2%.

I think that we have a growing amount of evidence at each step of the game that vaccination is really a positive thing for you to do for yourself, for your loved ones, for your community. All right, this is a preprint that Amy Rosenfeld shared with me, “Modeling the effectiveness and social costs of daily lateral flow antigen test versus quarantine in preventing onward transmission of COVID-19 from traced context.” This goes back to the rapid frequent, the lick-a-stick model. The idea that frequency is really important and, even with the loss of sensitivity, frequent testing is critical relative to the resulting delays.

Now, this is a huge problem, I think, that a lot of people have experienced; having a contact, being called, being told you have to quarantine for this, as my wife says, “Excessive period of time.” A lot of that excessive period of time has been 10 or 14 days depending upon CDC versus local rules. They point out in this paper that quarantine requirements are unpopular and also associated with low adherence. Again, think about when you’re on the highway, all those people violating the speed limit.

What the authors did here was they developed an integrated model. This is a model, this is not real-world testing yet, of COVID-19 transmission dynamics and compare the strategies of quarantine and daily contact testing. They’re trying to reduce transmission here. They’re also trying to model the social-economic costs associated with the days of quarantine, the impact of self-isolation. Specifically, in this study, they compared a 10-day quarantine to 7 days of self-testing, using rapid lateral flow antigen tests starting three days after exposure to a case. That’s looking at the viral dynamics, that’s when we usually start seeing people get to the point where they can be contagious.

Now, the paper is really a lot of fun. Maybe this weekend, when you’ve got some extra time, it’s fun to go through all the modeling because they ask all the questions; “What if people don’t follow the rules, incomplete adherence to quarantine, incomplete adherence to the daily testing?” They did find that in this model, again, that daily contact testing with rapid tests can reduce transmission from contacts with similar effectiveness and a much lower social-economic cost compared to these 10-day quarantines. Especially, when you move this into a highly-vaccinated population, where really a lot of this is happening without much benefit.

The findings they report were robust against a spectrum of scenarios with varying assumptions on the speed of contact tracing, different sensitivities to the lateral flow tests, different adherence, different uptake to testing, but really, at the end, daily tests could really allow for a rapid and really nice way of capturing people who are infected without really asking people to do things that they’re ultimately not going to do.

Get back just a little because this then, I think, gets us into a question I’ve been asked a lot. Beyond schools and all the things around there, what are the CDC current CDC guidance for people who are vaccinated and unvaccinated post-exposure? What are they supposed to be doing? On July 27th when the CDC updated its guidance for vaccinated people, they made a little bit of a change, they added a recommendation for fully-vaccinated people who come into close contact, which I’ll talk about, with someone with suspected or confirmed COVID-19.

What they suggested now as an update is that instead of just watch and see how you do and only get a test if you have symptoms, they said, “If you’ve been vaccinated and you had close contact, you should be tested three to five days after exposure and”– I know people caught this– “you should be wearing a mask in public-indoor settings for 14 days or until you receive a negative test result.”

I don’t know if I’ve seen anyone do that last part. Now, for unvaccinated people, it’s still the same. As per the CDC, stay home for 14 days after your last contact with the person who has COVID-19, watch for fever 100.4°F or higher, cough, shortness of breath, or any other symptoms of COVID-19 and if possible, stay away from people you live with, especially people who are at higher risk. Now, 14 days, 10 days, the CDC defines close contact as being within six-feet of an infected person for a cumulative total of 15 minutes or more over a 24-hour period.

Five minutes here, five minutes here, five minutes there, but each state and local DOH actually has slightly different guidance. In a lot of areas, instead of 14, it’s just a 10-day isolation for the infected, a 10-day quarantine for the exposed. This is going to be an issue as we open schools. If your children are vaccinated and they’re at school and there’s no masks, then potentially there’s just one testing. But if they’re asymptomatic, they can keep going to school, but now the CDC is going to say, “Throw a mask on those folks if they weren’t wearing one already.” The unvaccinated, they’re out for 10 days every time one of those exposure happens.

A lot of times when I talk to schools, I say, “Even if you don’t care about the kids and protecting them from infection, I’m sure you’re really annoyed making all those phone calls.” Think about the logistics and the impact and the interruptions by not having masks in those settings, particularly if don’t have 100% vaccination in your student and teacher staff populations.

Active vaccination. Never miss an opportunity to vaccinate. Vaccination is how this pandemic ends. There’s a lot of questions about elapsing, waning immunity. Everyone’s curious about boosters. There was preprint, “Elapsed time since BNT162b2 vaccine and risk of SARS-CoV-2 infection in a large cohort.” That’s the Pfizer BioNTech vaccine. This was posted as a preprint. It was a very large cohort. The authors reported on 33,993 fully-vaccinated adults who received an RT-PCR test for SARS-CoV-2 during the study period. They compared individuals with a positive test. Less than 146 days, you say the first five or six months after vaccine, to those with a positive test greater than or equal to 146 days since vaccine. We’ll say five, six months after the vaccine.

Now, this was this data that made everyone say, “Oh, my Gosh, the vaccines are losing their efficacy.” Now, they found that during that first period of time, during the first five or six months, about 1.1% tested positive. This then rose to a striking 2.4% after day 145. Now, a statistician tells us that this is significantly different, but I’m thinking a 1.3% increase is actually reassuring. Only 1.3% increase after five, six months.

I want to take Vincent’s take on this because this is this compelling data that the vaccines are losing efficacy statistically significant, and we must go ahead and get boosters. Vincent, do you have a take on this?

VR: All right, several takes. First of all, they were never tested to prevent infection. They were tested to prevent disease, and they still do. Secondly, if you did this with any other human viral vaccine, you would find that people get infected, and so I don’t know why this needs to be done for SARS-CoV-2 vaccines. It makes no sense. What do we care about, as you have said, preventing disease? Not getting infected?

DG: I found, actually, reassuring data. I was not sure what to make of this. Actually, right on the tail of this was the announcement from Moderna that the “Moderna COVID-19 Vaccine mRNA-1273: Final blinded analysis of Phase 3 COVE study shows 93% efficacy; Efficacy remains durable through six months after second dose.” Then, they went on to say, “We think you’ll need boosters.”


I couldn’t understand where that last little headline comment came from, because, what I think, both of these studies showed– Even to just nitpick a little on the BNT, the Pfizer one, is this is PCR testing. This isn’t necessarily someone who has symptomatic COVID. This isn’t necessarily someone who gets sick with COVID. We really don’t even know what’s the implication here. People say, “I don’t want to get a positive test at all.” What about long COVID in an asymptomatic-infected vaccinated person? I think we’re going to need actually answers to that rather than speculation. Again, there’s a big equity issue here as I try to bring up over and over again. Half the world hasn’t even gotten a first dose, and we’re ready for our boosters.

I guess there are vaccines sitting on shelves that are going bad and, as my mother told me as a child, she likes to be quoted, “You eat everything that’s on your plate, Daniel. Children are starving in China.” I was trying to figure out how my finishing or not finishing was going to reduce hunger challenges in other parts of the world. Let’s move on, but I think it’s important.

This is the science, and I think it’s open to interpretation. A big recurrent theme is this issue that, “If I already had COVID, do I need to get a vaccine? Do I need to get a dose?” We discussed some of this evidence previously. I think the MMWR early release, “Reduced Risk of Reinfection with SARS-CoV-2 After COVID-19 Vaccination” – Kentucky, May-June 2021 really addresses this issue, the issue of benefits of vaccination for those previously infected with COVID-19.

Here, the authors reported on 246 case patients who met eligibility requirements and were successfully matched by age, sex, and date of initial infection with 492 controls. What they’re really asking here is if you had COVID before, is there a benefit to being vaccinated? I want to be clear, this is not saying natural infection versus vaccine. This is specifically asking for those people, if you had natural infection, is there a benefit to getting the vaccine?

They found that the people who were unvaccinated, who were just riding on their natural immunity, that they were more than twice, they were 2.34 times more likely to get a second infection than those folks that went ahead and got the benefit of a vaccine. When they did just one shot in these people instead of the two shots, they did not see a statistically-significant benefit. Reinforcing that, there is a benefit in people with previous infection and you should go ahead and get the two shots.

Forget about those studies that show you a really high antibody levels. This is real-world efficacy data, which is really what we want. We don’t want correlates, particularly, the correlates that have not been shown to correlate. We want real data, and that’s what this is. I will say a couple of things. This is not as big a number as we would like. We’d like more statistical power. I want to keep seeing studies like this, but I think this is just more evidence, more points in the line, supporting the recommendation that previously-infected individuals get vaccinated, and that they get vaccinated with the full two-dose series.

The period of detectable viral replication; the viral symptom phase, this is when people often end up in the hospital. The first seven days, when hopefully you’re going to do everything you can to keep them out. This is, I’d like to say, the time for monitoring and monoclonals. When these people show up at the hospital, hopefully they’re not being admitted. Hopefully, this is the time for giving them the monoclonals. We keep getting a number of missed opportunities and this still pains me. I hear multiple stories every week often with the, “In my experience,” thrown in there. This is the time. Don’t miss those opportunities. These monoclonals are the most effective antiviral therapy that we have, but there’s a window that closes.

Now, we move into the early inflammatory phase. This is when people start to get hypoxic. When they start to have that early inflammatory reaction. This is often when people end up in the hospital or even in the ICU. We’ve talked about steroids at this point, oxygen support, but an important topic is anticoagulation to prevent thrombotic complications. It’s universally recommended that hospitalized patients are treated to prevent the clots, but we continue to look at, “What is the right dose?” And we finally have the peer-reviewed publication, “Therapeutic Anticoagulation with Heparin in Critically Ill Patients with COVID-19,” from the REMAP-CAP, ACTIV-4a, and ATTACC Investigators.

We’ve talked a little bit about this data before. These are where a number of investigators, a number of trials, were brought together. They coordinated and here, we have the results of the open-label, adaptive, multiplatform, randomized clinical trials, looking at critically ill patients with severe COVID-19 and asking whether or not they should be on prophylactic or full-therapeutic-dose anticoagulation.

We have data here on the primary outcome for over 1,000, so 1,098 patients, split pretty much one-to-one, so 534 assigned to therapeutic-dose anticoagulation and 564 prophylaxis. The median value for organ-free support days was not different, so the overall impact on morbidity was not different. The percent of patients who survived to hospital discharge similar between the two groups.

Major bleeding, however, was significantly increased; 3.8% in the high-dose therapeutic-dose and 2.3% in the usual care. In critically ill patients, this support wasn’t the same for a while here. Prophylactic dosing is as good as full-therapeutic dosing without the increased risk of bleeding that you get with the full dosing. Remember, this is not the time for antibiotics.

I haven’t talked about this in a while, but I just want to hit on this. What a horrible disease. This is a late four-to-five week manifestation often in individuals who had a mild or asymptomatic initial infection with SARS-CoV-2, COVID-19 disease. About four to five weeks later, they can have this massive inflammatory reaction. Just when people think they’re worried about vaccination and side effects just see one individual with MIS-A, losing fingers, losing hands, losing feet. Really what a horrible disease, strokes, permanent neurological damage. This continues to be something we see, continues to be a challenge. Just keeping that on people’s radar. Another thing that we do not want to have happen. Yes, sometimes these people live, so that counts as a save, but pretty horrible to be saved without fingers, hands, feet.

All right, tail phase. Now, our listeners have probably picked up on my view and I was putting a little bit of it there, that there’s a lot more to COVID and numbers than cases, whether you live or die. What do we really need to know when we see these increasing case numbers? One, asymptomatic and only picked up– I’m breaking this down into our six groups. The asymptomatic cases, they’re only picked up by screening or serology testing. Important to know what percent of those, 100,000 approaching 200,000 cases a day fall into that. Two, symptomatic, but never severe enough to seek medical care. Three symptomatic, but are requiring some level of outpatient care. Four, severe enough to require hospitalization.

We hear about that, but that’s quite different than one, two, and three. These are people that have a level of oxygen support in the two to six liters by nasal cannula. Then we have group five. This is not only severe enough to require hospitalization, but we start requiring a level of oxygen support of greater than that six liters by nasal cannula. These are individuals on Venturi mask, non-rebreather, high-flow nasal cannula, CPAP, or BiPAP.

Six, that last group, severe enough that they’re not only requiring hospitalization, but may end up being treated with mechanical ventilation. Even ECMO, extracorporeal membrane oxygenation. As we hear numbers, we do not have this granularity that people ask about. We also, that’s just the acute, because we want to know also what happens four to six weeks later, the impact of the post-acute sequelae.

Hopefully, we’re going to get a little more data, but we did have another paper right here that we’re going to close with. This was the, “Six-Month Outcomes in Patients Hospitalized with Severe COVID-19,” published in the Journal of General Internal Medicine. Here, the authors were reporting on those level five and six. These are severe patients, greater than 18 years of age, hospitalized for COVID-19. This was at a single health system. These were individuals who required a minimum of six liters of oxygen. It’s six liters or higher including high-flow ventilation.

They basically looked at these individuals who were discharged alive, because a chunk of these individuals did die, about a quarter. Those that were still alive, they looked at six months after hospital discharge, the majority of patients with this level of severity reported that their health had not returned to normal. They continued to be ill. I think it’s really important to look at that as well.

All right, let me close by saying, we still have a lot of problems around the world. No one is safe until everyone is safe. I have yet to see really significant progress, globally, on getting those vaccine access issues addressed. Along those same lines, and I want to thank everyone who continues to support us through the months of August, September, October, all donations made to Parasites Without Borders will be doubled. Hopefully, we’re going to be able to give them up to $40,000. Floating Doctors, which is really a fantastic group that I’ve worked with through the years. They’re down in Panama, and they really need your support. Issues with COVID are not just directly COVID-related. A lot of these individuals are starving in these isolated remote areas. Please help us help them.

VR: Time for some questions for Daniel. You can send yours to Kimberly has a question about vaccines and effects on fertility. “I, personally, have come to the conclusion that COVID vaccines posed no known fertility risk, but a few young women amongst my acquaintances have heard things or read something which made them question the matter. I am pro-immunization, but I also believe each person should make their own informed decisions. Do you know of any studies which focus on women from vaccine trials who went on to become pregnant or who experienced fertility issues? I would appreciate anything you could point to me that is scientifically sound on this issue.”

DG: No, this is great and I’m glad you’re bringing it up. Because, I will say, and I’m going to say the anti-vax powerhouse of misinformation, always goes after this issue because it’s very frightening. They use the, “You don’t know 15, 20 years from now.” The thing about vaccines is all the vaccine adverse events that we have ever seen in decades of using vaccines, they show up in the first six weeks, they show up early. We are well past the first six weeks. Not only have the studies continued to look at this, not only have we tracked this in over a hundred million individuals here in the U.S., but hundreds of millions of people throughout the world, there’s no scientific basis, and there’s no evidence to support any adverse issue on fertility.

Now, I will say the other side is getting COVID-19 is not great if you’re looking at going ahead, getting pregnant, having a family. At this point, COVID-19, this disease, is here to stay. Your choices between rolling the dice every day until finally that one day when you get COVID-19, or going out and getting that vaccine, which is incredibly safe and effective for pregnant women, or women wanting to get pregnant, or women who have been pregnant, I’m going to say across the whole board.

VR: Margaret is in Sydney where they have a delta outbreak and insufficient vaccines despite a younger population desperate for them. “We’re scared of AstraZeneca side effects. Until we get some Moderna or more Pfizer, is there a strategy for avoiding infection by using an antiviral nasal spray, which claims to be effective against delta for several hours?”

DG: This is, again, we’re 20 months into this. We do not have any really compelling evidence that there’s some magic intra-nasal antiviral. If there was, someone would be making a lot of money, probably more than whoever this one person probably is out there right now, but no, there’s no compelling evidence of which I’m aware that really would encourage me or have me encourage you to recommend that.

VR: Dominic is writing from Malaysia, currently experiencing a multi-month failure of a lockdown and still rising cases. He’s got a new job where he has the opportunity to design the office space. COVID, as we know will likely be with us for a long time—“I feel it would be good to take a proactive approach to designing in as much ventilation and filtration in the office itself, but I’m not sure where to start. Are there any resources you would recommend regarding office ventilation and filtration?”

DG: Yes, this is a great question. Just a shout out to the last TWiV with Jeff Shaman where they were talking about the epidemiology and the transmission. Maybe in the future we’ll have a ventilation specialist on. A lot of what has gotten us into trouble with this pandemic is each different discipline has their own words. We use them very specifically and we get very upset when someone else uses the word inappropriately. When we’ve talked about, “What we can do to protect individuals in indoor settings?” We’ve talked about some of the studies, some of them done in schools. Where if you space people apart, three-feet, you’re going to get about this 80% reduction, six-feet, you get about a 90% reduction, not 100% reduction. If you have more air exchanges, and one of the recent sort of cheap tricks that people are doing to this carbon– Is it carbon monoxide or carbon dioxide monitors?

VR: Carbon monoxide.

DG: I have an actual buddy, Seth Cirker, who’s– He’s one of those brilliant types that you hate to be around because you feel stupid, but, yes, there are different things. There’s a lot of information. What you really want in that setting, vaccinated people if you can do that. You’re going to talk about masks or not based upon vaccination status and transmission level. Then a big thing is air changes and a “poor man’s approach” to that are these monitors. Maybe not such a “poor man’s approach.” Yes, you’re thinking of all the right things.

VR: Finally, Ellen is a relatively healthy 76-year-old, second Pfizer six months ago, taking a short flight next week, and wondering “Whether I should one, get a COVID test say four to five days afterwards. Two, try for a booster of Pfizer, or perhaps even better adenovector. Even if I did this, I think it would be too late for the trip or try to get a monoclonal infusion just to be on the safe side as long as they’re sitting around unused.”


DG: Okay. Let’s go through these different things. What are the scientifically based recommendations? There are two types of masks that I like to roughly break them down in two. There’s masks that are good source control. I was explaining to one of the nurses why he needs to get these masks that don’t weigh as much because the ones that he’s wearing keep falling down off his nose and I want them on his nose because that’s source control and that protects me.

Meanwhile, I was sitting there in an N95, which protects me, so that’s personal protective equipment. Think about that on the airplane. Think about wearing either an N95 or the KN95 to protect yourself. Hopefully, you’re picking an airline where everyone around you is wearing at least source control masks. We’ve talked a little bit about the data at six months. Don’t feel like you fell off a cliff with the protection there, unless you have some immune issue that would make it seem like you would not be responding appropriately to the vaccine.

What we do have here in the U.S. is an expansion of the EUA for the monoclonal. If you fell into that category where you had a hematological malignancy or you are on immuno-suppressive medicines, and we didn’t really think that the vaccine was going to work in you, and then you had a high-risk exposure, we would talk about the monoclonals. I’m not sure you need to worry quite as much as you’re worrying here.

VR: You think Ellen doesn’t need to get tested when she comes back?

DG: No, the testing, yes. You want to be testing before, you want to test afterwards. If you test afterwards and you’re positive and you develop any symptoms at all, you’re going to want to go and get those monoclonals. If the doctor or someone doesn’t want to give them to you, you keep trying. You be that self-advocate and make sure that you get that treatment.

VR: That’s COVID 19 Clinical Update, Number 75 with Dr. Daniel Griffin. Thank you, Daniel.

DG: Oh, a pleasure as always. Everyone, including you Vincent, be safe.


[00:41:52] [END OF AUDIO]

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