TWiV 783 COVID-19 Clinical Update #72

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 23 July 2021

pdf of this transcript available (link)

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

[music]

From MicrobeTV, this is TWiV, This Week in Virology, Episode 783, recorded on June 22nd, 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: Daniel, I noticed that the U.S. vaccination is just approaching 50% for fully-vaccinated. That doesn’t seem like a lot, does it?

DG: No, no. [laughs] That was my ‘Anthony Fauci’ where I put my hand up and shake my head. I was listening to another podcast the other day. It’s one that Andy Slavitt does. He was interviewing somebody from Facebook and they were talking about the fact that 65% of the mis and disinformation regarding vaccines comes from 12 individuals. 12 individuals! They just pumped the stuff out. They get banned from Twitter, but then they’re still on Facebook. Yes, this active disinformation is killing people. I was on a call with UnitedHealth Group, the Optum, one of the higher groups. There was a lot of pessimism about the people that aren’t going to get vaccinated, are just not going to get vaccinated.

I don’t think that’s true. These individuals are still spending an incredible amount of time, millions of dollars, to introduce fear, to just make stuff up about the vaccines. One of the comments, I think it was a Kaiser survey where they asked people and four out of five people who are not vaccinated believe something about the vaccine that’s not true. They were told something. They were misinformed. We really have to make a difference here. A lot of it, how do you get someone who’s not vaccinated to get vaccinated? Number one is, you listen. You stop, you take a deep breath, you listen. What are your concerns? You don’t ridicule them.

A lot of times they’ve been told something by someone and it’s just not true. I think we need to have patience. We need to have humility. We need to reach out to these individuals because I think that if they actually knew the facts, a large number of people would come to the conclusion that it’s not so important to be part of a tribe that you’re going to put the lives of yourself and your loved ones at risk by choosing to get COVID as opposed to choosing a much safer option, which is the vaccines.

VR: What is the motivation of these 12 individuals who spread misinformation?

DG: I’m speculating, of course. We do know that there’s a big financial incentive. There’s a lot of power that comes along with stirring up the masses. I think it was disturbing to find out what happened in France, where scientists were actually taking money to sign letters. It’s really, at some point, you can’t have a price. Your price has to be truth and honesty. I think these individuals need to look in the mirror and ask, “Is that blood money worth it?” Are you willing to take this money? Because this is not honest, scientific discussion. This is pure blatant misinformation, and it’s just wrong.

[laughter]                                            

I don’t think that’s political. I feel like that’s just honesty, but anyway, so let’s start off with two quotes from a rather impressive woman. I’m going to give the quotes, then we’ll be at our four second pause while people see if they can remember who said these things. “The work of today is the history of tomorrow, and we are its makers.” The second quotation, “To be inspired is great, but to inspire is an honor.”

VR: Juliette Gordon Low.

DG: I am impressed. You don’t even have daughters. [laughs] Yes, that was Juliette Gordon Low, the founder of the Girl Scouts of America.

VR: I do have a daughter.

DG: You do have a daughter?

VR: Yes.

[laughter]

VR: That’s why I know.

DG: Did you see, there was a pause there, everyone. [laughs] It took Vincent a moment to remember that he had a daughter.

VR: Yes, I just listened to you.

[laughter]

DG: I was like, wait a second. [laughs] Yes, Juliette Gordon Low was the founder of Girl Scouts of America, really a tremendous organization and a really inspiring woman. I don’t know if people were aware, but the Girl Scouts of America actually did get the vote out. Now, I know there’s discussions about getting the vaccine out, having Girl Scouts trying to help with these efforts. I have two daughters. I know that right away without a pause, Vincent.

[laughter]

They both actually went all the way through, became these gold star at the end. They did their Gold Awards. Actually, the last actually, Eloise’s Gold Award was the service dog project and raising a service dog, doing the puppy rearing, and then doing information sessions about it. Tremendous organization, tremendous woman. I think right now, when we look at these individuals that are not vaccinated, who is the most influential person? It’s your friend, it’s your family. Reach out to your friends and family, reach out to people you care about. Have honest, respectful discussions about the vaccines. We can make a difference. We can get over this hump.

Hundreds of people do not need to keep dying every day in the U.S. Thousands of people do not need to keep dying around the world every day. We have safe, incredibly effective vaccines. Let me update on what’s going on. People know the trends are not great. We went from a cruise ship of people dying per day in America down to a jumbo jet crashing every day, as far as numbers of people dying. That’s not great. The numbers are going up, but I will say at least in our local area, when we are seeing vaccinated people get infected, it’s mild. It’s very rare for them to end up in the hospital. It’s incredibly rare for them to die.

We’re going from a 1 in 30 chance of death in an unvaccinated to a 1 in 1 million. We’re going to talk a little bit about kids here in a moment. There’s a lot of fear still in the media about this. The fear should be driving people to vaccination, but once you’re vaccinated, that is a very good place to be. One of my friends and colleagues actually wrote a paper, maybe a couple of papers in the last year, Denise Brennan-Rider. She’s an Irish-Canadian. She’s also a mother and she was sharing with me recently, just some of the struggles that she’s been going through as a mom with issues with access to vaccination and concerns that her children have.

We need to balance. As I talk about kids, I always say, “Kids are at low risk, but they’re not at no risk.” There is a balance here with all the fear. The vaccines continue to work even when we hear about these new variants. They continue to be very effective at preventing serious disease, preventing hospitalization. We would love if they were 100% for our herd immunity aspect, but that’s only a small part of the story, and that should be balanced with all the fear that we see in the media. I just want to start with that. Let’s get right on to kids. I’m going to talk about long COVID in kids because I think this is part of the metric, part of the equation that people are not considering.

I actually had a gentleman email me directly earlier today and I was really taken aback because his daughter’s pediatrician, she’s an eligible adolescent, daughter’s pediatrician was not really in favor of vaccination and had not recommended vaccination. I was a bit shocked. I know sometimes people say, “Only a few hundred children have died while we shut down everything. Only several thousand children ended up in the hospital.” What about kids that got COVID? How are they doing two, three months down the road? Is long COVID a significant issue in children?

We just saw the study, “Long-Term Symptoms After SARS-CoV-2 Infection in Children and Adolescents,” published in JAMA, the Journal of the American Medical Association. The authors addressed a significant issue that we really need to know about when we’re looking at return to school this fall. We have a lot of people saying, “Ah, get the kids back in school, not a big issue if kids get COVID. I don’t want my kid wearing a mask or anyone else.” We know about deaths, we know about hospitalizations. What about long COVID? This was a longitudinal cohort study investigating SARS-CoV-2 seroprevalence in 55 randomly selected schools in areas in Switzerland.

They chose a linguistically and ethnically diverse population of 1.5 million residents in both urban and rural settings. We’re getting a nice cross section here. The investigators collected blood for serological analysis and then used questionnaires to assess the symptoms. They compared children who tested positive for SARS-CoV-2 with those who tested negative during a period, October-November 2020. Ultimately, over 1,355 children were included in the analysis. What did they find?

They found that the most frequently reported symptoms lasting more than 12 weeks– I just want to repeat that, 12 weeks. Three months after these children had been infected with COVID, 3% of them were still reporting that significant fatigue, 2% were still reporting difficulty concentrating, another 2% were reporting an increased need for sleep. Now, there are background rates, we assess these symptoms. Just think about asking 1,000 kids and there is a background rate. Overall, what they were seeing is about 4% of the serology-positive children were still having symptoms three months later. That’s 1 in 25 kids who gets COVID is still having issues three months later, symptoms consistent with long COVID.

I want people to think about this when you send kids back to school. Let’s say your child, let’s say you have a daughter, like Vincent now remembers, and she goes [chuckles] to class and there’s 25 kids in the class and we say, “Oh, you know what, not a big deal. We’ll just let them all get COVID. It’s not a big deal. 1 of those 25 kids is still going to be sick three months later.” I have to say, as a parent, that’s too high for me, 1 in 25. We look at the risks of vaccination. We’re talking about short-lived myocardial cardiac inflammation, maybe for a couple of days, that get better with over-the-counter medicine. Rates of maybe 1 in 100,000, 1 in 1,000,000, things like that versus 1 in 25 being sick for three months, having problems going to school.

I think when people talk about the risks in children, you can’t just look at deaths, you can’t just look at hospitalizations. It’s the same as adults. You’ve got to look at the whole picture. When someone has long COVID, that’s a disaster. That’s a tragedy in my book. Now, we did get some good news in the realm of pediatrics and this was, “What about those kids who had that multisystem inflammatory syndrome?” There was a publication in Pediatrics. That’s the official journal of the American Academy of Pediatrics, “Longitudinal Outcomes for Multisystem Inflammatory Syndrome in Children.”

The authors reported on all of the 45 children that had been admitted to Columbia Presbyterian Hospital. It’s about a block or two from where Vincent is sitting right now. They followed them, actually, out to four to nine months and they found that, basically, about a month, a lot of the inflammatory markers were going down. When they got far out, only one child was still having persistent mild dysfunction. One had mild mitral and tricuspid regurgitation, but in general, the kids were getting better. I think that’s reassuring. We don’t have longer term outcome, but the authors actually concluded the majority of children with MIS-C, so that’s multisystem inflammatory syndrome of children, present critically ill, but most inflammatory and cardiac manifestations go on to resolve in a period of months, so rapidly.

That’s nice to know. I know people have always asked what happened to these kids. Now, sticking with children here, the American Academy of Pediatrics came out with some recent guidance with a statement that got a bit of press. Some people are unhappy about it. Let me go through the high points of that statement because some people are asking, “How do we take this statement and mesh it with what we’re hearing from the CDC as we’re looking at school opening?” The first part is in line. American Academy of Pediatrics is saying, “All eligible individuals should receive the COVID-19 vaccine.”

That pediatrician, I’m not sure what professional organization he gets his guidance from, but the American Academy of Pediatrics is recommending that we go ahead and vaccinate all the eligible individuals. The other is, and this is the thing that was controversial, all students older than two years and all school staff should wear face masks at school unless medical or developmental conditions prohibit use. Why? They do– I think they knew that this would get some feedback, so they go ahead and they give us five reasons. The AAP recommends universal masking in school at this time for the following five reasons.

One, a significant portion of the student population is not eligible for vaccination. I think that’s something. Second, protection of unvaccinated students from COVID-19 and to reduce transmission. This is coupled with the fact that we do not have a system to monitor the vaccine status among the students, the teachers, and staff. I think we’ve all had that experience. You go into a supermarket in an area where maybe 50% of the people are vaccinated, but no one’s wearing a mask because people who are vaccinated don’t need to wear masks. Well, people who are unvaccinated have got the masks off too. They’re pointing that out.

There’s really no good system for knowing who’s vaccinated and enforcing masks only for the unvaccinated. Point three, this ties right in, potential difficulty in monitoring or enforcing mask policies for those who are not vaccinated. The ability of schools, and this is right and the same, to have consistent messaging expectations, enforcement, and compliance without needing to try to monitor vaccination status. Four, and this relates to the community, the biggest risk for a child is what’s going on in the community around the school. Schools are often safer than the environment around. The AAP says the possibility of low vaccination uptake within the surrounding school community. Then, finally, five, and this we’ll be touching on as we go further, continued concerns for variants that are more easily spread among children, adolescents, and adults. They’ve got their recommendation for face masks at school and they’ve got their explanation for why they’re saying that.

Now, pre-exposure testing. Testing, never miss an opportunity to test. Now, I know when I talked about some of the other guidance, part of the school reopening guidance is having testing strategies. I’m excited that we have some data now to understand what’s going on potentially with transmission with the delta variant.

What is going on? Is it spreading faster? What are the kinetics here? What’s happening? We got an interesting publication, “Viral infection and transmission in a large well-traced outbreak caused by the Delta SARS-CoV-2 variant.” This was published by a group that was looking at cases in China. Now, I’ve talked a bit about how sloppy the word ‘transmissible’ is and that when we hear that a certain variant is becoming dominant, we really need to understand the mechanism behind this variance fitness advantage. I think that this paper was a step in the right direction. Did we get any answers? The authors investigated data from quarantine subjects in this delta variant outbreak and compared it to previous 2020 epidemic outbreaks caused by earlier variants.

A couple questions that they tried to address. One, is there a shorter reproductive time? Let me explain a little bit about what I mean by that. You get exposed to someone who has SARS-CoV-2 infection, who has COVID-19, who is contagious, you have your exposure event. Now, what is the time from exposure till you test positive or till you test positive and have enough virus that you can transmit it to the next individual? This is the time for infection to becoming PCR positive and being able to give the virus to the next person, a nuance of that.

Now, their results showed that the time interval from exposure to first PCR positivity in the quarantine population was four days versus six days. Six days was what we saw back in 2020, and now we’re seeing four days. That’s an interesting issue. I’m going to talk a little bit about whether our experience meshes with this. The other thing that they saw, and I think this needs to be taken in context, that first positive test that they were seeing was 1,000 times higher as far as the RNA copy number. What we think we’re seeing here is from zero, at day four, people are already PCR positive, but they’re already at a level of virus that makes them contagious.

Now, when we talked about day six turning PCR positive, usually at day six, they were PCR positive but at a high Ct value, so a high cycle threshold, low level of virus, not quite transmitting. You could pull them out before they spread it to the next person. Usually, it was day seven that they were contagious. Instead of seven days from exposure to spreading to the next person, this may be shortened to only four days. We’re thinking that there is a more rapid rise from negative to infectious. People have looked at that thousand times higher, and I want to point out, that’s just looking at the first positive test. That’s not the peak.

We don’t have the area under the curve. We did not follow these people every single day to see whether there’s been a change in the duration at high levels, the area under the curve, the period that they might become infectious. I’ve been asking, “Does this really mesh with our experience?” One of the things our listeners may know is we do these large screening programs for the movie industry where we test thousands of people every night with the idea that we’re going to catch them early when they first get positive and then we’ve got this day before they become infectious.

Someone tests positive on a Wednesday night, usually it’s a high Ct value. We say, “That’s great.” We grab you, we pull you out. We’ve been doing this for over a year without having any issues. What we’re now seeing, unfortunately, is we’re seeing a lot of people testing positive. The concern is when they test positive that night, they may have already been infectious in the latter half of the day. When we’re talking to our out-patient providers, when someone says, “Boy, I felt crummy for about a day, so I decided to finally get tested.” Now you get them a PCR test, there’s a 36-hour resulting delay.

You call them and you say, “John, your test is positive. We got to figure out who you may have had exposed.” When you test those people that they’ve exposed, those people are already positive and they’re already positive at high levels. This data is meshing with our experience and as you can imagine, this really challenges our TETRAS, our contact tracing paradigm. If by the time you tell someone that they’re PCR-positive, everyone they’ve exposed is also already PCR-positive at a contagious level, it’s already spread to the next tier, and it’s a dominoes-type phenomenon. This is one paper. This is meshing with our experience, but we need more data to help us with this because this is a problem.

If it is a shorter incubation time, a shorter time of exposure to spreading, that could explain a lot of what we’re seeing. It also is really relevant to how we’re going to address this.

VR: If I may–

DG: Jump in. I was hoping that my dramatic pause would get you pulled in, Vincent.

VR: Just two things. First, the shorter serial interval, that’s what this is, that could account for a more rapid spread, but it doesn’t mean the virus is more transmissible intrinsically. It just reproduces faster and therefore can go from one host to another quicker, and as you said, the people are infectious sooner, and that can result in more people being infected as a consequence. That’s possible, but I would say it’s not intrinsic greater transmissibility of the virus. I agree we need more data on that. The other issue is that PCR, a ‘thousand times’, that might not be infectious virus. I think, at some point, people need to do infectious virus measurements.

We have to stop depending on PCR because I can imagine a variant throws off more mRNAs and that’s going to show up positive in the PCR, but it’s not infectious virus. Nobody has done that for any of the variants yet. I’m a little bit frustrated at that.

DG: Yes, I know. I share your frustration and I think that this is really -from my point– You can’t just use the word ‘transmissible.’ You’ll say, “What are you talking about?” If it’s a shorter incubation period, so many of our rules about when you contact trace, how long a person– We need to know the kinetics of infectious, viable virus for all the variants. We need to keep doing the research. We can’t say, “Oh, we’ve got this for the–” because this is a problem. I think also people have probably seen the Olympics when people are “testing positive.” What does that mean? Are they having a low level of RNA positivity? Do they actually have viable, infectious virus?

Do we need to pull Olympic athletes who’ve been vaccinated and are young and healthy out for 10 days because that’s what we did a year ago? We can’t be sloppy with our language because it matters. It affects– It affects what we do. It affects people.

Active vaccination. Never miss an opportunity to vaccinate. Vaccination is how this pandemic ends, and no one is safe until we are all safe. I know I get a lot of questions. Actually, it seems like I got a lot more this week and I’m not sure if it’s that we’re hitting a particular population, but they want to know, “If I had COVID-19 before, if I had a natural infection, do I really need to get vaccinated? Maybe I’m just okay.”

I’m just going to take a little aside to, I think, all the clinicians that are getting these questions. I’m going to answer it for all of you. We do have information on this topic in three forms. This is, “I had COVID-19. Do I need to get vaccinated?” One, we have a number of the serology and T cell studies. There was that nice paper in Cell that we discussed back in June, “Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum,” because people really are now asking about the delta variant. We’ve talked a little bit about neutralizing ability of convalescent plasma. We also had “Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization” published in Nature. And that was just this month. Both papers suggesting convalescent plasma was about four times less potent against the Delta variant.

We’ve discussed many times, we don’t really know what that translates into. We really think that T cells are important. We have some information on T cells in the paper, “Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection.” This is by Shane Crotty and Alessandro Sette’s group. This was in Science. Here, there’s a couple of things that we saw. I’m going to throw in words like only to emphasize things. Only 70% of individuals possessed detectable CD8+ T cell memory at one month after infection that declined to 50% by 6-8 months after infection.

Not great, but CD4+ T cell memory, 93% of subjects had detectable SARS-CoV-2 memory at a month after infection, and this remained high for 6-8 months. We also see T follicular helper cells being maintained. We’re getting mixed here. Now, we did have the preprint, also by these same gentlemen, “Low-dose mRNA-1273 COVID-19 vaccine generates durable T cell memory and antibodies enhanced by pre-existing crossreactive T cells memory,” where they report that spike, CD8+ T cells were generated in 88% of subjects with equivalent percentages of CD8+ T cell memory responders at six months post-vaccine.

You’re seeing here that there looks like when we’re looking at these lab-based studies of B cells, T cells, and serology, vaccines do look like they’re a little bit better and we have good data on the efficacy. We also have the reinfection studies, that’s where the rubber meets the road. What happens when people have had natural infection and now they’re exposed again? I think we discussed before the SIREN Study out of England and that was “SARS-CoV-2 infection rates of antibody-positive compared with antibody-negative health-care workers in England: a large, multicentre, prospective cohort study (SIREN).”

Here, this was The Lancet, suggesting a median duration effect of seven months at about 83% from prior infection with the same variant, raises concerns. Then we have this growing experience. What are we seeing as clinicians? We are seeing our own growing experience of people who were infected early in the pandemic, a year or more ago, now coming in testing PCR-positive, having symptoms, and some of them not doing well. I think I may have shared the experience of a young woman who had long COVID after first infection, did not get a vaccine, and a couple of weeks ago, she started to get ill again, and again had a second infection.

I think now people ask, “Oh, can you test to see if it’s the delta variant?” It’s almost 90% of the sequences we’re now seeing across the country are delta variant. I think that the data may not be as compelling as some of the anti-vaccinators or the hesitant might want to be. We have really good, compelling data on the safety and efficacy of vaccines. We are, across the board, recommending that all people get vaccinated even if they have prior infection.

Now, the period of detectable viral replication. This is going to be an exciting part. I’m looking for some emails. We had some very disturbing news. This is the time for monitoring in monoclonals, not the time for antibiotics. There was a bit of drama because a preprint that had been posted suggesting that a randomized control trial demonstrated a 90% reduction in mortality and substantial in ivermectin-treated patients may have been something that never happened. A London medical student named Jack Lawrence was the “Woodward and Bernstein” in this story, if people remember all the president’s men.

He was investigating this preprint. He discovered initially that the introductory section of the document appeared to have been almost entirely plagiarized and then run through a thesaurus program. It appears that the authors, they pulled entire paragraphs out of press releases and websites about ivermectin. Then they changed these key words. The data appears to have been completely falsified, the tables in the article mathematically impossible. Apparently, the study never happened. They just invented the study, invented the data, put it out there, really just a case of scientific fraud.

This data was part of a lot of these meta-analysis where people were saying, “Ivermectin, it looks so promising. It’s a crime to humanity that we’re not using it when there’s this study with a 90% mortality reduction.” My hope is that all the people that have braced ivermectin and are using it based on this data will rethink their position and embrace the importance of honest scientific investigation. Now, if someone is passionate about ivermectin and they want to know, don’t just make up data, don’t just invent a study and put a preprint. Right now, we’ve talked a little bit about this, “ACTIV-6: COVID-19 Study of Repurposed Medications” is recruiting to properly study ivermectin, fluvoxamine, and fluticasone.

If you’re passionate, if you’re excited about ivermectin, either enroll, direct your patients this way. We need good science, don’t just make up science. Little more information on the reliability of point-of-care rapid testing with the Abbott BinaxNOW with the publication of “Multidisciplinary assessment of the Abbott BinaxNOW SARS-CoV-2 point-of-care antigen test in the context of emerging viral variants and self-administration.” It was published in Nature Scientific Reports. A lot of people, I get at least every day, “Hey, do our tests still work against the delta variant?”

I’ve talked a little bit about how it may go from this low level to high levels in hours instead of the day plus. The authors here looked at the BinaxNOW, they looked at the Quidel Sofia 2 SARS test, they looked at the BD Veritor. They were all 100% concordant with the RT-PCR with Ct values of less than 20. Then they started to lose sensitivity at higher Ct values or we translate that into lower RNA levels. Just a reminder, Ct stands for cycle threshold. This is how many times you’ve got to run that PCR or that amplification before you get a positive signal. The higher the number of cycles, the lower amount of RNA that you started with.

As Vincent likes to point out, that’s just RNA. That doesn’t necessarily tell us about infectious virus. I think there’s a correlation more in time than levels. That’s important. What about this? I get calls all the time. Is there one rapid test better than the other? There are a lot of publications that come out. It seems every time a publication comes out, I get a question. Just to give some context here, there are over 300 COVID-19 tests and collection kits authorized by the FDA, over 200 molecular tests. We have 11 antigen tests. What about this? The specificity, people say, “Oh, well, not only are they less sensitive, but they’re less specific. If I get a positive on an antigen, I don’t trust it as much.”

I’m going to say that if you get a positive test, the specificity of antigen test is generally as high as our nucleic acid amplification test. Which means that a positive test on an antigen test is as reliable as a positive test on a PCR. There’s a lot of experience, but just remember, your prevalence of infection in the community is going to help you interpret whether that positive test makes sense or not. Now, what about sensitivity? Really straight forward. This is related to the amount of antigen that is present. If it’s the first couple days, that one to three days that corresponds with the Ct value of less than 20, as pointed out, we’re getting sensitivities. We’re getting concordance right up there at about 100%.

Once you get out to day seven, day eight when that RNA level is dropping, when you’re not really having much the way of antigen, these tests are going to turn negative. They’re actually helpful when you think about what it’s testing for. These are great at picking up that infectious period of time. They correspond with the infectious period of time. PCRs can sometimes stay positive for weeks, for months. There was a really nice, I’m going to say Cochrane Review, which they keep updating. “Rapid, point-of-care antigen and molecular-based tests for diagnosis of SARS-CoV-2.” This is a 409-page document.

Nice light read. And it goes through different tests, their sensitivity, and specificity at different Ct levels. It’s an excellent document. Don’t let that latest publication shake your Earth. Go ahead, look at this accumulation of data. Rapid point-of-care antigen tests have a role. That testing delay is leaving someone who’s potentially infectious wondering around spreading it to others. Another article, it describes that water is wet, [chuckles] as Mark Crislip says. This is how antibacterial therapy is not helpful for the treatment of a virus. This is the article, “Effect of Oral Azithromycin vs Placebo on COVID-19 Symptoms in Outpatients With SARS-CoV-2 Infection, A Randomized Clinical Trial,” published in JAMA.

I think this is interesting. Some people think that, “Maybe the azithromycin will make my patient feel a little bit better.” It does not. You’re just inducing antibacterial resistance. They did not see that antibiotics help viral infections.

We’re getting near the end. Long COVID. I mentioned last time that post-acute COVID syndrome, apparently when you’re on a call with CDC, they don’t like the phrase long COVID. They feel happier when you say PACS, but I like long COVID because I think it actually points to something within the larger world of PACS, of post-acute COVID syndromes.

What about the rest of the world? We talked about the U.S. and the UK. We did see the article, “Post-Discharge Symptoms Among Hospitalized COVID-19 Patients In Nigeria: A Single-Center Study,” published in the American Journal of Tropical Medicine and Hygiene. Basically, what they were pointing out is, this was a small study, but the majority of their discharged patients were actually having symptoms continuing for months after discharge. I know a lot of people were very focused on the U.S., but outside the U.S., things continue to be really difficult.

There was a nice paper, “COVID-19 Therapeutics for Low- and Middle-Income Countries: A Review of Candidate Agents with Potential for Near-Term Use and Impact.” This was actually, I think, what you would expect. You’ve got to think about the resources in the area relative– injectable tools, expensive therapies are not going to be able to play as a bigger part in this area. There was actually a nice article, “COVID-19 in Africa: a lesson in solidarity,”published in The Lancet. Actually, my friend Dr. Titus Divali from Malawi brought this to my attention. Just pointing out, you can’t just send vaccines to these countries. The same complexity applies there.

You’ve got to have needles, you’ve got to have syringes, you’ve got to have trained people, and you actually have vaccine hesitancy and an interest in education in these areas. Just like you do in the United States, in Western Europe, in many parts of the world. To get those vaccines into arms is going to require a pretty large effort. I actually made Vincent record this a little earlier today because I’m going to be talking with the Bill & Melinda Gates Foundation COVID-19 Task Force later to talk a little bit about these challenges. As I like to say, “We are not safe until everyone is safe.”

To conclude on that note, just a couple of weeks left here for our campaign to support the Foundation for International Medical Relief of Children. Go to Parasites Without Borders before the end of July, we will double your donation. We’re going to try to get up to a level where we can double that $20,000 and give a full $40,000 to support Foundation for International Medical Relief of Children’s efforts throughout the world.

VR: Daniel, when I went to our new office this week, I walked in and the lady shouted, “Parasites is here.”

DG: [laughs] That’s great.

VR: Time for some questions for Daniel. You can send yours to daniel@microbe.tv. Kevin writes his favorite public speakers are Barack Obama and Dr. Daniel Griffin. Here’s a question about his grandfather’s immunization status. “In February, he got mRNA vaccine, four days later tested positive for COVID. Thanks to your advocacy, I got him monoclonal therapy. Infection passed. My grandfather had only mild disease. Following CDC recommendation, he waited three months before getting the second dose of the mRNA vaccine. Last time we checked, CDC recommendation for someone in the same circumstances does not need to restart the vaccine schedule.

However, we’re a little concerned that perhaps his first dose did not prime his immune system as well. What are your thoughts? We’d like to think he’s well immunized after natural infection and at least one good dose of mRNA vaccine, but we’re not completely confident.”

DG: This is a great question. I suspect we’re in a good situation here. There was a period of time, at least, where the immune system was learning from that first infection before the monoclonals jumped in there. That is the current recommendation. There’s a science and there’s an equity side to this, “Where should we be giving third doses to people when so much of the world hasn’t even had their first dose?” A situation like this, you’re probably in good shape. What we have sometimes done is, if there’s doses that might end up in the trash because we’ve had a no-show, an individual like this might look at the whole picture and try to make a decision there relative to that. This is the recommendation. We think that this individual is protected. Definitely a lot better protected than someone who has had no vaccination.

VR: Frank writes, “Why do you not mention the use of daily rapid tests at school as a high-quality method eliminating COVID without restricting socialization? A dollar per student per day is not a burden. If the answer is waiting for FDA approval and high volume manufacturing, we need to know that and put more pressure on representatives.”

DG: Actually, when I’ve talked about schools and campuses; rapid testing, actually testing, can be a really important part of your multi-layered approach to keeping the kids safe. One of the things I will throw in, I think this is important as a thought experiment, let’s say you’ve got all these layers of protection, you’re looking to try to get those masks off so those kids can be in-person, in school with masks off. Let’s say you have a breakdown and in that class of 25 individuals, you miss because of the sensitivity of the test. Someone comes in on a Monday, it’s negative. You test Tuesday, they’re positive.

You realize, “Okay. If everyone’s wearing masks, you may not have had an exposure event. You may have actually been able to avoid that. You may be able to move forward with only that one person coming out of the school. You got to balance this issue. Is wearing masks such a burden that you’re willing to take the risk of exposure events and all those implications, or are you okay wearing masks in certain settings, so should there be a failure of your layers, that you’re not pulling everyone out for the quarantine and everything that follows from that?

VR: Laura from New Mexico writes, “As COVID infections continue to rise, is it advisable for a fully-vaccinated person who ends up with an infection to get monoclonal antibody treatment? I live in a somewhat medically underserved area, keep notes on the recommended treatment approaches. Should I need to be an advocate for myself or a loved one? My immediate family and the majority of my regular contacts are fully-vaccinated, but I want to be prepared for the uptick in cases that is starting.”

DG: The role of monoclonals is not impacted by prior vaccination. If an individual who has risk factors for progressing to severe disease does test positive, go right ahead with the monoclonals. Remember, the vaccines are great, but nothing’s 100%. We have had a few hundred people, so it’s a one in a million chance of dying if you get COVID. We’ve also had some people, I hate to say, at least there are reports of individuals who got infected after the vaccine and ended up in the hospital or got long COVID. Go ahead, get the monoclonals. There’s no reason not to. They’re sitting on shelves. They’re paid for by the government, so go ahead.

VR: That’s COVID-19 clinical update number 72 with Dr. Daniel Griffin. Thank you, Daniel.

DG: Thank you. Everyone, be safe.

[music]

[00:45:10] [END OF AUDIO]

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