TWiV 790 COVID-19 Clinical Update #74

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 8 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 790, recorded on August 5th, 2021. 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: You got another good number, 790, Daniel.

DG: [laughs] It is a good number.

VR: Do you feel lucky? You’re going to get 800, do you think?

DG: I was actually noticing that we are driving towards Episode 800. Amazing how much content has been produced.

VR: Yes, that’s thanks to COVID for sure. Otherwise, we’d be far behind. Speaking of COVID, what are you seeing in your hospital? Do you have a high burden of cases?

DG: I would say, “No.” We are seeing some. We’re seeing, in all honesty, what we expected when the vaccines came out, and when we started seeing real-world efficacy on them. We are certainly seeing an increasing number of people that test positive in the communities, that show up at our urgent cares. But the number of individuals in the hospital is actually relatively low. Just to give perspective, say the Northwell system, 22 hospitals, largest healthcare system in New York, back during the early peek, over 4,000 patients in the hospital at any given time. We’re maybe 150 in all the hospitals. That puts it in low numbers. We’re certainly seeing them. We’re not flooding the ICUs. We’re not flooding the floors.

Really, what I think that reflects, as we look around the country, is a high vaccine uptake in our local area. All right, so first, I’m going to start with a correction. I really enjoyed the quotation when I heard Rich Condit say it. It turns out, last week’s quotation was actually not said by Richard Feynman. I actually went back and listened to the interview itself. What did he actually say if you listen? He said, “You see, one thing is, I can live with doubt and uncertainty and not knowing. I think it’s much more interesting to live not knowing than to have answers, which might be wrong.” Mostly to try to be a stickler for the truth. I appreciate that being pointed out.

Let me start with my quotation this week, which I do believe was actually said by this individual. “Being defeated is often a temporary condition. Giving up is what makes it permanent.” That’s by Marilyn vos Savant. I think that we are having a tough time across the country, around the world, but this is our fight to lose. We can still get ahead of this, we can still make a difference. We have learned a tremendous amount. We have incredible tools. Where are we at the moment, if you follow the dashboard, some of us still check the dashboards on a regular basis. I like Worldometer. I like their curves and their daily counts.

If you look at August 4th, I think I had predicted last month that we would be over 100,000 new cases per day. On August 4th, we had 112,279 new cases and 656 deaths– just that one day. I’m trying to figure out if people have just become numb, or there’s some emotional fatigue. I think a lot of it is this emotional fatigue. People really just want this to be over. As my grandmother used to say, “If wishes were horses, beggars would ride.” Wish away. You have to actually act to make this change. The case fatality rate, if you look at the millions of people in the United States that have had confirmed COVID-19, it’s right at 2%.

1 in 50 people with a confirmed case of COVID here in the U.S. have died during the acute period. As we start our discussion, Vincent, this is quite different than the about one in a million risk if a person is vaccinated. What I like to say is, if everyone in the country was vaccinated, we’d maybe see 300 to 400 deaths a year, instead of 600 deaths a day with our vaccine uptake challenges.

VR: Do you think that we will ever get to a point where most people are vaccinated in the U.S.?

DG: We’re already there, if you use the word “most”. Over 70% of individuals eligible have started the vaccine process. Over 50% of eligible individuals are fully-vaccinated. There’s all this talk about, “Oh, vaccine hesitancy.” If you start doing the numbers, you realize it’s the tyranny of the minority. The majority of the eligible people are doing their part, getting vaccinated, helping us get to a point where we can move forward. I’m actually quite optimistic. Some people– I have a lot of conversations– they’re waiting for full licensure. They keep saying, “It’s not fully-approved. When it is, I will get vaccinated.” I believe some of them, not all of them.

When all of the military personnel are vaccinated, after a while– people look at this. I was doing a Medscape interview the other day, an educational thing. I compared this to polio. People were like, “Oh, back when polio, everyone was just rushing to get vaccines.” That’s not actually true. It took five years to get to over 90% with the polio vaccines once they were fully-licensed. We are at 70%, starting the process, at seven months. That’s pretty good. We keep this up three more months, we’ll be at 100%. Well, maybe not, but I’m optimistic. [laughs]

VR: Okay, good.

DG: What about you, Vincent, are you optimistic?

VR: No, I think we were stuck at about half a million doses a day, way down from over a million. Only now because there have been huge uptakes in the South, in the Midwest, then now it’s gone back up to 750,000 a day. If that continues, that’s good, but it’s going to take a while for us. I’m not optimistic because I think too many people have issues with the vaccine. I hear that perhaps by Labor Day, we’ll have full licensure for Pfizer. Is that true, is that what you’re hearing?

DG: That is the circulating rumor. I suspect September to be a good month. I suspect that in September, we will have full licensure of Pfizer. We’ll have expansion down to six and up. I really think that’s going to be helpful because I think a lot of individuals would like access, but they would like access to a licensed vaccine. Hopefully, FDA will acknowledge this. All right, well, I’d like to start off with a couple of stories. Just actually two individuals I saw today who did maybe not get optimal care. I want to point out that I’m actually seeing the majority of patients in our area really get good care. These are the outliers that, hopefully, are examples for everyone. Learning lessons, we’ll say.

One was a woman in her 20s, the other was a man in his 30s, both unvaccinated. The woman in her 20s, we’ll start with her. She wasn’t feeling well for about three days, typical viral syndrome. What was going through the back of her head, we can imagine. She went to an urgent care where the provider suggested that she get a COVID test. She started to cry, she explains to me that she gets very emotional when she’s sick. The provider did not want her to cry. He said, “Oh, don’t worry, you don’t need a COVID test. Go home, take some ibuprofen, Tylenol.” By the next day, she was starting to feel like maybe that was not the best shared decision and went to a different urgent care the next day.

This time, she shared with me that the provider spent a little more time, connected with her, encouraged her to get tested, and yes, the test was positive. She had COVID. Now the provider said to her, “Listen, you’re in the first week, sounds to me pretty good so far. We can treat this symptomatically. We’re going to follow, and see how you do. If you start to have issues during the second week, then we might suggest some other things.” Little miss on this is this young lady had a BMI of greater than 30, so it would have been nice for her to get the monoclonals. Instead, I met this young lady today in the emergency room, hypoxic, and so she’s been admitted to the hospital.

Second individual, a man in his 30s. This, we got a little more learning lessons here. This individual went also to– I remember this because he said what I said was really entertaining. He said, “I went to a city MD. I thought there’d be MDs there, but there weren’t.” [laughs] He was seen by a non-MD, whatever provider level, I’m not sure. Again, he was feeling ill, he had decided not to get vaccinated, a decision he was regretting as we spoke. When he was seen, he was about three or four days into his illness. For his viral illness, has confirmed COVID, he was given steroids and antibiotics.

Now, fortunately, as he told me, he decided after taking a few of the steroids, that he wasn’t happy continuing and did not continue with the steroids. He did take the antibiotics, which as we know from a lot of evidence, is not really ideal, but now he’s coming in during the second week. Actually, unfortunately, this gentleman, he’s actually escalated despite starting steroids to a higher amount of oxygen. We had to add tocilizumab to his management. He’s in the hospital, he’s passed really that acute window where we consider him death-severe.

He’s getting oxygen, steroids, tocilizumab, anticoagulation, and we’re going to follow and, hopefully, this gentleman doesn’t progress to mechanical ventilation or death. Again, two misses on the monoclonals, and I’m going to keep hammering on the monoclonals because really, if you look at the studies, 70% to 80% reduction in people progressing if they get them in that first week. A BMI higher than 25 is really quite widespread in our population. Both these individuals had BMIs greater than 30, and if you look at the studies, no deaths in the arms that got monoclonals. Even if there is some degree of progression, people tend to do much better if you can get things in during that window.

All right, children and COVID. As I like to say, “Children may be at low risk, but they are not at no risk.” The media, I think, has done a good job lately of pointing out that we are seeing rising rates of infections and hospitalizations in children. Our listeners are likely aware that the more children that get infected, a percentage of these children will end up hospitalized, a percentage of these will go on to develop long COVID. The number of cases in children actually doubled this week compared to the prior week, to over 70,000 infections in children. Some really heartbreaking stories, a description of two children that died over the weekend at the Children’s Hospital in Memphis, Tennessee.

One child was so ill that by the time the decision was made to send him to the hospital, he actually died en route to the hospital. Just a reminder, children can die from COVID. Children can end up in the hospital. Children can get long COVID. As we plan for full in-person schools, we really need to move past the myths about children, base our decisions on the science, work with the facts. Children may be at lower risk for many of these complications, but they are at-risk. As Nelson Mandela said, I believe he actually said this, “There can be no keener revelation of a society’s soul than the way in which it treats its children.”

As we open the schools, let’s think about the safety, let’s think about what we can do to make it safe to get education. One of the things that I recently heard, which I agree with, is that wearing a mask is much less traumatic for a child than being hospitalized, infecting their loved ones, seeing the loved ones get sick or die, or developing an illness in them that can last for months or even a lifetime.

All right, this is going to be the meat of something. I’ll say here, the pre-exposure period, transmission, testing, never miss an opportunity to test. This is actually a publication that was discussed on the last TWiV. I deep-dive into this, and I think I’m going to recommend to everyone– Well, finish listening to me first, but then go back and listen to the last TWiV. The publication, “Outbreak of SARS-CoV-2 Infections, Including COVID-19 Vaccine Breakthrough Infections, Associated with Large Public Gatherings,” Barnstable County, Massachusetts, July 2021. This came out as an early release in the MMWR. I would like it if they would stop using the ‘B-word.’ I think spending a little time reviewing this in detail is important because I think that misinterpretations of this, I will say, have frightened a number of individuals.

It’s impacted this perception about the role of vaccinated persons in this pandemic. Now, this was a solid group of authors affiliated with the Massachusetts Department of Public Health, the CDC COVID-19 Response Team, the Broad Institute in Cambridge, Massachusetts, Barnstable County Department of Health and Environment in Massachusetts, and the Community Tracing Collaborative (CTC) of Commonwealth of Massachusetts. What was this MMWR report discussing?

Well, the authors reported on 469 cases. It’s not really a research study, it’s a report. It was a report on 469 cases of COVID-19 associated with multiple summer events and large public gatherings in a town in Barnstable County, Massachusetts during July 2021. Now, they did some sequencing on the specimens from 133 of the patients, and they identified the delta variant as responsible for 90% of the cases. The big issue here is a number of the individuals were fully-vaccinated either with the two-dose mRNA vaccine or the J&J vaccine and had to have that 14-day period.

I’m not going to talk about what percent of the vaccinated persons ended up infected. I think that a nice deep dive is, the more and more people who are vaccinated, the more percent of the people who end up with an infection will be vaccinated. I think that’s a math thing, but I will point out that one of the interpretations of this report is that only 1% of the vaccinated individuals required hospitalizations and there were no deaths among the vaccinated people. You can do the math on this. Unvaccinated, we see about a 20%, and we would expect to see at least 1 or 2 deaths, maybe more, about that’s a 2% case fatality rate.

Now, the unvaccinated did not fare as well, and as pointed out, one of the unvaccinated individuals, they’re 123, so 1%, one of them did die. Unfortunately, we’re seeing that unvaccinated people still are at significant risk. Now, what were the details of this? Because I think there is some important information here. The persons that had COVID-19 in this report, they reported that they had attended densely-packed indoor and outdoor events at venues that included bars, restaurants, guest houses, and rental homes. I’m going to say, “So far, so good. Not so far, so good.” I think we’ve been told those are high-risk venues.

These are vaccinated individuals with a decreased risk of infection, decreased risk of death and hospitalization, but they are putting themselves in harm’s way. For the people that got vaccinated, it had been about three months since they completed their vaccinations, a median of 86 days. As we’ve discussed repeatedly, we are expected to see a drop in the level of the antibodies, a drop in the protection against infection, and localized mucosal replication with transmission, but continued protection against moderate and severe disease, which was demonstrated here.

This is what we saw; no deaths, only a 1% hospitalization rate, instead of that 2% deaths and 20% hospitalization rate that we’ve consistently seen in the unvaccinated. Then, things get a little bit messy here. They report that they had cycle threshold values, Ct values. Now we have pretty sophisticated listeners here. They actually say– when we in this report, when we looked at those Ct values, they didn’t go to the subtlety, but I think we can here. The RNA copy numbers at the initial testing that they had were similar between the vaccinated and unvaccinated individuals.

Now, our listeners are very familiar, I think, with this topic and we’ve repeatedly returned to this over the last, I’m going to say, now 19 months. The Ct value, the cycle threshold, is the number of cycles we have to run in the PCR machine prior to detecting the RNA in the sample. The less RNA, the more amplification to get to a level of detection. The more RNA, the sooner the signals detect it. Now, we did have information, a correlation between the RNA copy number for the ancestral and alpha variants of COVID and contact tracing, as well as some virus culture data, our plaque-forming units, PFUs, that’s what PFU stands for– for the TWiV listeners. But we still don’t have this information for the delta variant.

We still don’t have this information for the person. I saw a wonderful tweet meme where it was Bart from the Simpsons writing on the board over and over again, “RNA copy number is not viral load. Ct value is not viral load.” I don’t want anyone to make that “rookie mistake.” Those Ct values do not necessarily tell us that vaccinated persons are carrying “tremendous amounts of virus in their noses.” They have a high RNA copy number, we’re going to get to some data in a moment to show that that is actually short-lived relative to an individual who is unvaccinated.

As we’ve discussed with a previous study, we’re not sure that this is actual virus or just a bunch of RNA and that the virus has been neutralized by the immune response. I think that we need that science before we jump to scary conclusions. What are my takeaways from this study? I’m going to come away with four. One, persons attending densely-packed indoor and outdoor events at venues that include bars, restaurants, guest houses, and rental homes are at risk of infection with SARS-CoV-2, the virus that causes COVID-19, even if vaccinated. Just in case people didn’t get this, vaccinated people can get infected with SARS-CoV-2, vaccinated persons can transmit.

This study didn’t look at that. They did not look at secondary attack rates from vaccinated individuals. This study did not tell us about any transmission being done by vaccinated individuals. I think that’s key. Two, in real-world situations, even months after completing vaccination, our current COVID-19 vaccines continue to offer protection against moderate and severe disease. In this study, only 1% of these individuals involved in these high-risk behaviors with really significant exposure went on to require hospitalization– and no deaths. Three, we see again that vaccinated persons can get infected and we know from other studies that vaccinated persons can transmit to others.

As I mentioned, this study does not look at secondary attack rates or transmission, and I don’t think you want to walk away from this with that conclusion or suggestion. Four, we need to repeat our case contact studies, our tracing studies, our viral culture studies with each new variant and in both vaccinated and unvaccinated persons to understand the kinetics and their correlation with shedding of infectious replication-competent virus. I’m actually going to talk a little bit about a study that’s starting to move in that direction. All right, so I’m going to move forward to our next study.

This one I really like. That suggests that maybe I didn’t like the other one so much. [laughs] This was a free print and when I was listening to TWiV 779, I guess it was, and Brianne was talking about the biological and serological kinetics and talking about the red and the green curve, I was yelling at my radio, “Brianne, it’s the Singapore study. It’s the Singapore study.” This is the Singapore study, which is great. “Virological and serological kinetics of SARS-CoV-2 Delta variant vaccine-breakthrough infections: a multi-center cohort study.” This was posted as a preprint, so it’s still going to go through peer review. We’ll still get some more input.

I really like this because we’re starting to get the important information about the kinetics of the RNA copy number in both vaccinated and unvaccinated persons infected with the delta variant. Now, we’ve heard before, and this will challenge us, that individuals with the delta variant have a thousand times more virus in their upper airways. This study, here, where we’re seeing kinetics does not support that contention. The authors conducted a multi-center, retrospective, cohort study of patients in Singapore and compared the clinical features, virological, and serological kinetics. Anti-capsid, anti-spike, surrogate, virus neutralization titers between fully-vaccinated and unvaccinated individuals.

A couple of things I will say. One is, the odds of severe COVID-19 requiring oxygen supplementation was significantly lower following vaccination, about a 93% reduction with a P value of 0.001. No deaths in the vaccinated group. Now, the PCR cycle threshold, Ct values, the RNA copy number was initially similar between vaccinated and unvaccinated groups at diagnosis, but decreased much faster in vaccinated individuals. If you look at the levels we’re seeing here, we’re seeing Ct values at about 20 early on, at about day one or two of illness.

That is a very similar number to what we saw with the other variants. We’re not seeing support for this contention that it’s 1,000 times higher, but then, what I think is great, and I am going to say, “People, go out there. This is not behind a paywall.” Hopefully, we’ll post this up on Parasites Without Borders, our COVID weekly updates. If you look at this idea, one, we do not know if this is replication-competent infectious virus. We’re looking at RNA, but that RNA level starts to really fall off the cliff at about day five or six, where the unvaccinated, really, it’s like a slide where you’re not going to get much speed.

It just really continues to very slowly go down where we’re seeing the individuals who are vaccinated really clear this RNA. This would be for me, the idea that, okay, that first number may be high, but vaccinated individuals, even if you’re just looking at RNA levels, are quickly reducing that. A shorter period of time at these high RNA levels, really evidence for me that being around vaccinated people, even if they’re exposed to an infected with SARS-CoV-2, is safer for me as an individual. We still need more data, we still need the viral culture data to make sense of what these RNA copy numbers mean.

We need contact tracing to look more at the secondary attack rate, and I want to say, the information I’ve seen so far on delta does not suggest to me a higher secondary attack rate. We may have a shorter replication cycle. Okay, four days later you’ve infected those two to three other people. Eight days later, you’ve infected another two to three people, per two to three people. It may appear from the epidemiology to have a higher reproductive number, but I think that the secondary attack rate, so far we’re not seeing that this is “as contagious as chickenpox.” We’re just seeing a faster spread.

I have to say, this is stuff we’re working on, and my friend, Dr. Yuan-Po Tu, up at the Everett Clinic in Washington, is collaborating with the University of Washington with their BSL Virology Center. We’re, actually, going to, hopefully, get some really good information what do those Ct values mean, what do they mean as far as plaque-forming units, viral culture, etc.? Because, I think, this is really important for those public health recommendations. I do not think the sky is falling. I still feel much safer around vaccinated individuals.

All right, exciting news this week on passive immunization. Monoclonal antibodies as post-exposure prevention. The REGEN-COV monoclonal antibody cocktail got expansion of their EUA to include post-exposure prophylaxis for individuals who are either, one, not fully-vaccinated, or two, are not expected to mount an adequate immune response to complete SARS-CoV-2 vaccination.

For example, a person who has an immunocompromising condition, who’s on immunocompromising medications, if they come in and say, “I was exposed to an individual. I made a mistake, I had an exposure,” these individuals, if they’re considered high risk for progression, can go ahead and actually be treated with the Regeneron-COV2 cocktail. They go on, give a little more information– I do think that this is really critical. We’ve been talking a lot, and we’ll get back to this, about that third dose, boosters, here in the United States when half the world hasn’t had firsts.

We do not know, in all honesty, what that third dose offers as far as protection for our individuals with immunocompromising conditions, but we do have really good data– I’m about to present it– on what happens when you post-exposure prophylaxis individuals with the monoclonals. I want people to think this is a big changer in treatment, a big expansion. What is the science behind this expansion? There was a paper, we’ve talked about this information previously, but now the paper, “Subcutaneous REGEN-COV Antibody Combination to Prevent COVID-19,” was published in the New England Journal of Medicine.

This study, individuals– I say individuals because they’re not necessarily patients yet, they haven’t been infected. They’ve just been exposed. They were randomly assigned in a 1:1 ratio within 96 hours after a household contact received a diagnosis of SARS-CoV-2 infection. They actually were treated with a subcutaneous injection versus placebo. Again, we don’t need to necessarily have that IV, we could do this as a subcutaneous, so increase our access. The primary efficacy endpoint was the development of symptomatic SARS-CoV-2 infection through Day 28, and what did they find?

Well, symptomatic SARS-CoV-2 infection developed in 11 of the 753 participants in the treatment group, 1.5%, but in 7.8% in the placebo group. This was a P-value of 0.01. By weeks 2 to 14, a total of 2 of the 753 participants in the Regeneron-COV group, 0.3% and 27 of the 752 participants in the placebo group, 3.6% had symptomatic SARS-CoV-2. We saw a relative risk reduction of 92.6 among the symptomatic infected participants. The median time to resolution of symptoms was two weeks shorter than in the individuals that were treated.

The duration of– I’m going to translate high viral load into high RNA levels, greater than 10 to the fourth copies per milliliter was shorter, 0.4 versus 1.3, so about a week shorter there. That is now out in the New England Journal of Medicine. A couple of times this last week, I’ve run into this and been a little bit shocked. The “in my experience” from the physicians saying, “I haven’t really had great experience with those monoclonals, but in my experience, the remdesivir has been working really well.” Yes.

VR: Daniel, how can they do the control group? Isn’t that withholding standard of care in the control group if you know they’re exposed?

DG: This was, actually, the study that gave the indication– Prior to this, exposed individuals, there was no treatment option. Now we know that if you’re exposed and you’re a high-risk individual, you can go ahead, get this antibody combination, and for about three months, have this passive antibody protection. Now, can you do a placebo control trial in the future? Actually, the monoclonals, it’s a problem, they can’t– It’s actually considered that effective, which throws a little bit of a wrench in the system. Why are they not FDA-approved if they’re considered so potent, so valuable, so impactful? So if the FDA is listening . . .

All right, active vaccination. Never miss an opportunity to vaccinate, vaccination is how this pandemic ends. We keep getting more information comparing natural infection, induced immunity compared to vaccine-induced protection. Another article, “Neutralizing antibodies against SARS-CoV-2 variants induced by natural infection or vaccination: a systematic review and pooled meta-analysis.” This is pulling a lot of things together. When we pull these 106 articles together, basically, we’re seeing that the beta, the gamma, and delta significantly escaped natural infection-mediated neutralization.

Neutralizing antibody levels induced by mRNA vaccines were, in general, at least the same level or higher. Just more and more data suggesting that vaccination is really the way to go. Don’t take a chance, I have certainly seen plenty of re-infections and it’s really at about six months when we start to see, at 180 days when we start to see the reinfections rise, but I’ve seen it as early as three months. Once you’ve had SARS-CoV-2, once you’ve had COVID-19, you really don’t want a second infection.

All right, as I said early on, the viral replication or viral symptom phase. What I like to say, “The time for monitoring and monoclonals and not the time for antibiotics.” Well, monoclonals are not just for this phase anymore, it can now be moved up to prophylaxis as well. Remember, they are out there and we need to keep using them. They shouldn’t sit on shelves.

Okay, the early inflammatory phase. This is that time when everyone ends up in the hospital and gets the remdesivir. Well, let’s talk a little bit about that. To be clear, the data on remdesivir has never been very persuasive and the FDA approval was based on the idea that this drug, remdesivir, could reduce hospital stays. Not mortality, not morbidity, but that it would reduce the amount of time people ended up in the hospital. Well, the article, “Association of Remdesivir Treatment With Survival and Length of Hospital Stay Among U.S. Veterans Hospitalized with COVID-19,” really supports what I am seeing, what is being seen across the country. That remdesivir may be associated with unnecessary and prolonged hospital stays. What did we see here?

This was a cohort study of 2,344 U.S. veterans hospitalized with COVID-19. The investigators reported that remdesivir was not associated with improved 30-day survival, but was associated with a significant increase in median time to hospital discharge. The findings suggested that routine use of remdesivir may be associated with increased use of hospital beds, but not with any improvements. I think this is really relevant in many areas of the country where we hear about rising hospitalizations, and it’s worth asking if all these people are really benefiting from these five-day remdesivir stays at $3,000 per course of remdesivir– the huge costs associated with hospitalizations, the filling of those hospital beds.

A lot of these individuals really, to be honest, the data would suggest could be treated quite well at home with oxygen, oral steroids– keeping these beds open for people who really need them. People who are going to have an escalation of oxygen requirements, and, actually, all the other individuals who need the services of our acute care facilities.

All right, the tail phase, long COVID. We keep getting confirmation of the significant risks of developing long COVID. This is a real thing. The article, “Postacute Sequelae of SARS-CoV-2 Infection and Impact on Quality of Life 1-6 Months After Illness and Association With Initial Symptom Severity,” was published in Open Forum Infectious Diseases.

The authors reported that among 290 patients discharged from an outpatient telemedicine program– we’re starting to get information on individuals who did not require hospitalization; 39.7%, almost 40%, reported persistent symptoms, including fatigue, dyspnea on exertion, mental fog, among others. Fatigue was 20%, dyspnea was 14%, mental fog was 13.5%, and 40% of individuals who were treated in this outpatient program had symptoms that continued. Long COVID is real. Unfortunately, I’m hearing reports that we may have even underestimated the incidence in adolescents and younger children. That will be critical, keep an eye on those numbers as we see more children getting infected.

All right, what’s going on in the rest of the world outside the high-income, in the low- and middle-income countries? As I like to say, “No one is safe until everyone is safe.” Just a little musing on third doses versus first doses. As we’re seeing, there’s already a code here in the U.S. They’re getting ready to allow us to give third doses. There’s a little bit of a dialogue and Jen Psaki was talking about the U.S. perception on this. I do not know the right answer, I’m just going to put this out there. Her presentation was that our ability to give third doses here in the U.S. will not necessarily impact our ability to provide first doses in many other parts of the world.

I think that’s really important when we make these decisions, to realize that there is an equity aspect and there’s a science aspect. Now that we have the potential to use our monoclonals for those individuals who did not respond to just two doses, I think it’s important that we balance those in our decisions. Whether that’s true or not, I think it’s important to know whether or not that’s true.

VR: What’s the science behind a third dose, Daniel?

DG: Yes, we don’t have any. [laughs] I should say the lack of science behind the third dose. It’d be nice to have that science before we started giving people third doses, so yes, good call, Vincent. Let me close by thanking all our supporters, and I want to say thanks to an anonymous donor right there under the wire at the end of last month. We were pushed right up to our goal. We were able to provide full support for FIMRC. We cut them a check for $40,000 to help them with their efforts. They’re starting to do some overseas, some in-person traveling starting to return.

I was going to wear my Rotary Club International Polio bow tie, which I will remember to do, but just the whole point is that we can’t do this without your support. Thank you for your continued support and we are now moving on starting this month. August, September, October, all donations made to Parasites Without Borders will support Floating Doctors, so go to parasiteswithoutborders.com, click the “Donate” button, and help us support all the work that we do as well as Floating Doctors.

VR: Great, congratulations, FIMRC. It’s wonderful.

DG: That is fantastic.

VR: Time for some questions for Daniel. You can send yours to Daniel@microbe.tv. Jason is going to have a catered party in a few weeks out on Long Island. Hey, Daniel, maybe you can go?

DG: I was waiting for the invite. Is there an invite in this email? Wait, let’s see how well they do to keep people safe.

VR: “130 or so guests. We have a handful of unvaccinated. I’m assuming we need masks for them and kids who aren’t vaccinated? Can they test out of a mask requirement? Would we do a rapid, or a PCR, or both, and how long before the party?”

DG: Well, what we try to talk about, let’s say I was in charge, I was your infection control officer, what would I recommend? The biggest thing I recommend, you’ve got over 100 people, this is a large gathering by any criteria. You really want to keep everyone outdoors. We’ve got the High holidays, the Jewish holidays, coming up in September. When I’m asked about that, I always say, “Let’s keep people outdoors.” One of the things we say about outdoors is, part of what’s safe about outdoors is that dilution, but also your ability to have a little bit of space. Let’s keep going with that, state that three or four feet apart outdoors, starting to keep things very safe.

You can do testing, but remember, no test is 100% and tests don’t predict the future. Those are important things. If someone had a test the day before, if they had a test that morning, the day before might be more sensitive test, but then again, the test doesn’t predict the future. They might have a point-of-care test. Again, not every test is 100% sensitive. As we’re learning, or as we’re communicating, as we’re trying to reinforce, even vaccinated people can get infected and spread.

Those would be my big things. Keep it outdoors, try to keep people spaced apart. Masks are great. You got over 100 people, someone showing up at your party infected with COVID, just with SARS-CoV-2, if you don’t want any transmission, if you’ve got vulnerable people there, really, encouraging masks is great, staying outdoors is great. People are going to have drinks, they’re going to eat food. Then you step aside. I always think of that as a time when my mask is off and I’m not going to be face-to-face with an individual. Remember, layered approaches increase safety. Nothing is 100% safe, so balance your risks and risk tolerance.

VR: Tom writes, “I know guidance from FDA and CDC at this point is that boosters are not needed to prevent disease. However, it seems like they could prevent infection, as a third dose appears to elevate neutralizing antibodies to a 100X if you take the Pfizer data at face value. Well, we don’t know if neutralizing antibodies are a correlate of protection from severe disease. It does seem to correlate with infection based on small data from an NEJM paper out of Israel. As a father of two young children, I’m finding it hard not to go and find a third dose. I’m not worried about myself, instead a mild case that allows me to transmit the virus to my children.”

I still may wear masks in areas where I can’t verify vaccination status, but I am worried this might not be enough. For instance, do we need to go back to the days of masking around everyone not in our immediate family, such as my parents and in-laws? To me, I would like to see boosters or an expansion of the vaccines to those less than 12. Not looking for you to comment on whether I should get a third dose, but rather, on how the FDA full-approval might change the ability of physicians to prescribe a third dose. Would full-approval allow doctors to write off-label prescriptions based on the needs and risks of their patients?”

DG: Well, I’m glad, Vincent, that you and I hit on this a little bit. The first thing we really need is the science. One of the aspects of vaccines, which is really not something we have a lot of great evidence for, or a lot of vaccines that have a track record for, is preventing infection. Vaccines are really good at preventing serious illness. We look at the injectable polio vaccine. “Does the injectable polio vaccine prevent infection, Vincent?” I’ll ask you. “No.” “Is it a crummy vaccine?” “No, it’s a great vaccine.” What we do not know and what people would like to know is, as we’ve seen, it does look like vaccinated people may be less likely to transmit to others.

That’s one of the things that, actually, when we talk about, “Oh, healthcare workers should get vaccinated,” we’re not worried about protecting the healthcare workers from getting sick. We’re thinking the vaccines may somehow protect our patients. Before we start pushing third vaccines, we need the science. The science is something we can get, the experiments we can do, the contact tracing we can do. We need to do the studies. If you give individuals a shot at six months, if you give them a “booster,” does that really accomplish what we’re after? We still need the science.

I think that when we look at the amount of money we spend on so many different things, we need to spend the money on this. We need to do these studies. We need that information. We need to know, “What do the vaccines do as far as protection against severe disease?” We also need what they can do relative to transmission and even just infection. Right now, we’re just guessing, and as you point out, neutralizing antibodies are not a clear, reliable correlate of protection.

VR: Keels writes, “I’m a primary care doctor here in steamy Jacksonville, Florida. We’re having a terrible time with SARS-CoV-2 and COVID-19 disease here. What, if anything, is the role of UVC light to potentially sterilize the air? If UVC room light can be helpful, especially in places where mask mandates are prohibited, like our schools– or ignored, could UVC light be another mitigating measure? Expensive, probably impractical. I do wonder about long-term exposure, but at least it’s passive. What do you know, Daniel?”

DG: This is painful. I’m so sorry. If they find out that you are opening the windows or spending time outdoors or using UVC or any other measure to decrease your risk of getting infected, sick, or dying, you may end up in trouble in that state. It’s a little crazy to me. Anyway, back to the science. We actually discussed on some of the TWiVs, and there were, actually, some pretty good deep dives in some of my non-updates looking at UVC. This is definitely a modality that has been looked at and may play a role. I think there’s also a safety aspect here. Usually, not shining these in people, but there’s specific frequencies that you want to look at. I won’t go too into that.

Actually, maybe in our show notes, we can put the link to when there was a deep dive in some of the data here. As we like to say, this is something where, if you can do something about the quality of the air, that can actually decrease your risk. We’ve talked about a lot of these school studies when they’ve done things with improved ventilation, with open windows, all these different strategies are part of that multi-layered mitigation approach. Just don’t tell people why you’re doing it.

VR: Isn’t it crazy that they’re preventing you to wear a mask? What are they thinking?

DG: Next thing you know, they’re going to outlaw seat belts because it compromises freedom. There’ll be no airbags. I’m not sure what they’ve said.

VR: Good thing they can’t get near airplanes. Right, Daniel?

[laughter]

DG: Okay.

VR: All right, Jennifer has two questions. “First, with delta, do we have to change our masking? Do we need N95, K95s, or double masking with a surgical under a cloth mask? What are your thoughts on this?”

DG: Let’s be really clear about what the science is. The science is not that you walk past someone on the street– I was on a call yesterday and actually one of the questions was, “I heard that it only takes five seconds of exposure to get infected with the delta variant.” No, it does not. If you look at the secondary attack rate for the alpha and the delta, and there’s data out of the UK, it actually looks like, at one point, it was pretty similar. Actually, current data suggests it’s a lower secondary attack rate with delta. These studies are really hard because you have all the non-pharmaceutical interventions, the masking, the heightened awareness.

We have no compelling data, in all honesty, that the delta is going to spread, going to get through masks, things that we worry about. It does look like it spreads faster. It does look like there’s a quicker replication cycle from exposure to you being able to spread it to the next person. I do not think there’s any biology or any evidence that says you need to change your approaches. I still encourage people to think about masks, the surgical mask, as source control. When you’re coughing, sneezing, breathing, you are catching it. As far as you protecting yourself, the KN95s do a better job.

When I walk into a room with an individual who has COVID, I wear an N95 mask. When my family or I travel on a plane, we all wear the KN95 masks. A physician today walked into one of the rooms with two surgical masks, thinking that that was really a great way to protect against COVID. It’s not. Think about using the right mask in the right situation. I think it’s interesting that delta is the symbol for change, but delta has not changed everything. Our non-pharmaceutical interventions still work.

VR: Jennifer wants to know if the 15 minutes, six-feet recommendations have changed?

DG: In some places, they’ve been using 10 minutes for a while, but that’s been for a while. That has not really changed recently. It is interesting, I’ll tell you, in New York State, the exposure is 10 minutes within six-feet and they don’t care whether it’s indoor or outdoor, which doesn’t really sit with the science. That’s the deal.

VR: That’s COVID-19 clinical update number 74 with Dr. Daniel Griffin. Thank you, Daniel.

DG: Oh, thank you, and everyone be safe.

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