TWiV 787 COVID-19 Clinical Update #73

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 31 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]

VR: From MicrobeTV, this is TWiV, This Week in Virology, Episode 787, recorded on 29th July 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: Well, you got the 787, Daniel.

DG: [laughs] Okay. In the show notes, there’s a nice picture of a large aircraft.

VR: Have you ever flown one of those 787s?

DG: I don’t think so. Actually, no I haven’t. I’ve been on some of the bigger Airbuses but never the 787s.

VR: I only flew one once to Singapore from San Francisco in December 2019. It’s a very comfortable plane, very nice. Unfortunately–

DG: You were in one of those private little suits, right?

VR: No. I was back in coach, but it’s an 18-hour flight so it was a bit rough. [laughs]

DG: Wow, yes, that’s a long flight.

VR: It’s a long flight. You take a nap, you wake up, and you think, “I must be there,” and you’ve got another 16 hours to go. Are you wearing a mask, Daniel?

DG: At the moment, no, but I never stopped wearing masks when I went to the gym or when I went to the grocery store or other places. We’re going to be touching on that, so let’s get going. All right, start off with my quotation. “I would rather have questions that can’t be answered than answers that can’t be questioned.” That’s by Richard Feynman– so anyone who just listened to TWiV 786. Rich Condit, I’d give him a little credit to Rich Condit, who I think is also a fan of Richard Feynman.

Actually, yes, on some aside, sometimes I’ll tell a side story about the connection with Richard Feynman, but I think that this is what science is about. Science is about asking questions, trying to get answered. There shouldn’t be dogma. People shouldn’t be afraid to ask questions, to try to discover things. Actually, just talking to Dickson Despommier earlier today, I’m seeing a little bit of a rise in the hate mail I’ve been receiving recently.

[laughter]

DG: I did an article in El Washington Post where I bemoaned that we didn’t have better therapies and, of course, I got lots of emails about, “What are you talking about, Dr. Griffin?” Then all the less than pleasant adjectives; crimes against humanity, other things in all caps about, “If only everyone in the world had access to ivermectin and HCQ, we would all be fine.” [clears throat] Don’t worry, I’ll make sure I mention ivermectin. I won’t let an episode go by without that.

What is the big thing that happened this week? The CDC updated their guidelines and boy, did this really get a lot of people confused/angry, so we’ll spend a little time going through that. What exactly did they say? What did they post? Then we’ll speculate or discuss a little bit on what is behind this. I actually thought this was pretty reasonable on the surface. I feel like this should have been something that came out before they dropped the mask mandate, just to give a little context about public health because that’s really what this is.

What the CDC posted, “Until vaccination coverage is high and community transmission is low, public health practitioners as well as schools, businesses, institutions, and organizations need to regularly assess the need for preventive strategies to avoid stressing healthcare capacities and imperiling adequate care for both COVID-19 and other non-COVID-19 conditions.” That’s just reasonable.

Then the CDC recommended five critical factors that should inform local decision-making. One, you should keep an eye on the level of SARS-CoV-2 community transmission. Two, you should keep an eye on your health system capacity. Three, you need to keep an eye on COVID-19 vaccination coverage. Four, look at capacity for early detection of increases in COVID-19 cases, and number five, you need to be aware of which populations are at an increased risk for severe outcomes from COVID-19.

A little criticism to the CDC, it would’ve been nice to have this outfront when they said a little while back that they felt like things were at a level where it was appropriate to get the masks off, but here’s what the CDC went on to say, and this is when people got upset. “Among strategies to prevent COVID-19, CDC recommends all unvaccinated persons wear masks in public-indoor settings.” Okay, so far, so good.

“Based on emerging evidence on the delta variant, the CDC also recommends that fully-vaccinated persons wear masks in public-indoor settings in areas of substantial or high transmission. Fully-vaccinated persons might consider wearing a mask in public-indoor setting regardless of transmission level or if they or someone in their household is immunocompromised or is at an increased risk of severe disease or if someone in their household is unvaccinated, including children aged less than 12.” Vincent, do you have any thoughts? [chuckles]

VR: Yes, I do. They shouldn’t have relaxed the masking back in April because vaccine coverage was less than it is now, so I don’t see why they have to go back. However, what does the delta variant have to do any different from any other variant? The vaccines prevent severe diseases as you have said, with any variant, so why this concern about the delta variant? Do they have some data which drives that decision?

DG: Yes, some special super double secret information?

VR: [laughs]

DG: Do you remember back in December when you and I talked about how everyone in the UK, in December– Boris Johnson decided that we could take December off from the pandemic and everyone could go to the pubs, the taverns, and have a good old time? Then suddenly, the alpha variant came along and changed everything. I think the variants are becoming a bit of a scapegoat.

We saw a huge surge after July 4th. We saw a lot of people indoors transmitting and I think there’s a couple of things in here that we’ve talked about that maybe we need to reinforce. One is that unvaccinated people can get infected and transmit to others. I think we all know that. The other is, vaccinated people can get infected and transmit to others. Particularly symptomatic vaccinated people.

I think we have growing data that the further we get out from those jabs, the higher the risk is for people to get mild symptomatic cases of COVID-19 despite vaccination and spread it to others, so I’m not sure that throwing the delta variant in here really tells us very much. There is this buzz that there’s some PCR data out there about PCR levels being similar, RNA amplification levels being similar.

We’re going to talk about that when we get to testing, but I think, Vincent, you and I are on the same page. What is more significant, behavior or a few substitutions in the spike protein? I think its behavior and dropping the mass mandate was a little bit premature. We’ve got to reinforce that. As my mom was saying about a bulletproof vest, “I don’t understand how you think that’s going to protect you when your head is sticking out.”

[laughter]

DG: Children, COVID, and mental health, right? There’s a lot of concern about vaccinations and the fact that some of our children are not going to be eligible when the schools open. There is significant concern about what we can do to make those schools safer, so I’m going to start off by discussing an MMWR, Morbidity and Mortality Weekly Report. An early release came out, “SARS-CoV-2 Infection in Public School District Employees Following a District-Wide Vaccination Program,” Philadelphia County, Pennsylvania, March 21-April 23, 2021.

This is the concept that if the school employees, if teachers are all vaccinated, does this create a safer environment for the children? Will this prevent those employees, staff from becoming infected, potentially spreading it to the children? This addressed that question of whether promoting vaccination amongst school staff members could potentially make our schools safer. The School District of Philadelphia reopened for in-school instruction, the week of March 21st, 2021.

That’s a number of months back, so we’re going to see data from the spring. They required weekly testing for SARS-CoV-2, the virus that causes COVID-19, for all employees returning to in-school responsibilities. The resumption of in-school instruction followed a mass vaccination program using the Pfizer-BioNTech two-dose mRNA vaccine offered under a partnership between the Philadelphia Department of Public Health and Children’s Hospital of Philadelphia, CHOP, to all the 22,808 School District of Philadelphia employees.

Now, this was a mandatory testing program, provided an opportunity to assess the percentage of positive BinaxNOW, point-of-care antigen tests identified among school staff members, based upon their self-reported vaccination status. We’re going to be able to see vaccinated, nonvaccinated, and what happened as far as positive tests.

They found a 95% reduction in the percentage of positive SARS-CoV-2 test results among persons who had reported receipt of two doses of the vaccine compared with those who had not been vaccinated. They concluded that vaccination of school staff members is a potential important strategy to maximize the safety of indoor in-person education of K-12 students this fall.

I have to say, this is actually pretty interesting. This is not looking at protection against hospitalization or severe disease. This is looking at the vaccines ability to prevent people from even testing positive. I’m looking at Vincent to see if he has a comment.

VR: I think it’s kind of contradictory to what we’ve been hearing lately. Out of Israel, people are getting infected after vaccination. I think my view is that the further you get out from the second dose, your antibodies level drop, you’re more likely to get infected. This was probably done early on, and that’s why the infection was prevented, but it’s a good indicator that [laughs] they should vaccinate everybody in schools, right?

DG: Yes, and I actually think that’s important. This is the nice thing– I think about the TWiV audience, our TWiV audience, we are educating up. We’re good with nuance here in this TWiV world. As you point out, Vincent, this was done right after vaccination. This is people with the really high antibody levels, mucosal surfaces.

This is that window, we’ll talk about how long that window is in a science paper later, where that vaccine not only protects you against severe disease, but is giving you this herd immunity impact actually blocking infection and transmission. All right, let’s go, something I was just reading today. I read the Texas papers. I don’t know if you read the Houston papers there, the Houston Press.

In the Houston Press, maybe Rich Condit, I don’t know, he’s down there in Austin, maybe Houston is close enough,h but this was in the Houston Press, out of all the kids who show up to Texas Children’s– concern that they may have COVID. Roughly 10% of the children who tested positive required hospitalizations, and roughly a third of those ended up requiring critical care.

Now, this is concerning on the surface, but what exactly does it mean? I want to make a couple comments. One, it does point out that children can get sick with COVID. Children can end up in the hospital, but this is a select population. These are children who are symptomatic. When a child’s brought to the hospital, there’s usually an impression by the parent or the provider, that this is a child with a more serious manifestation.

Historically, those numbers have been down around 1% or less, so we’ll keep an eye on this. I think I would be shocked and frightened and bewildered if really 10% of children end up requiring hospitalization with COVID. I did not think SARS-CoV-2 has changed its biology enough to affect that, but we will see. But it is important to realize that kids can get COVID, kids can end up in the hospital, kids can end up on ventilators, kids can have adverse impacts.

Testing, just a brief reminder or primer, because we’re going to be hearing now about CT values. I think that’s great. The conversation is getting a little more sophisticated, but you don’t want to have just a little bit of knowledge or enough knowledge to make you dangerous. Let’s talk a little bit about the really two large category of tests that we use. We use PCR or molecular amplification tests. These amplify RNA and give us RNA copy numbers when we look at that CT value or cycle threshold.

This is a test for RNA. It’s not actually a viral load. It does not give us number of infectious virions. I think that’s really critical because we’re going to talk a little bit later on perhaps about, “Does an RNA copy number in a vaccinated person mean the same thing as an RNA copy number in a person who is unvaccinated? Who is not potentially destroying or neutralizing those varions?”

The other test that we use quite often, and hopefully more and more, is the antigen test– that BinaxNOW that we talked about. A couple other ones, the BD Veritor, Quidel Sofia. The antigen tests are not looking for RNA, they are looking for proteins, and particularly the immunodominant protein, the nuclear capsid proteins. These tests require that that protein is produced and present in sufficient quantities.

Now, we know at the front end of infection, we start to see those antigen tests turn positive in an unvaccinated person when the RNA copy number gets above 50,000 and then the same number as it drops off the tail several days later. Remember, that information, and we’re going to hit some studies here, come from the unvaccinated viral kinetics. Antigen tests, historically, have correlated very well with individuals being infectious.

Active vaccination, never miss an opportunity to vaccinate and vaccination is how this pandemic ends. I don’t know if people remember or know the When Harry Met Sally movie. I don’t know, Vincent, if that’s a favorite of yours. [laughs]

VR: Not a favorite, but I’ve heard of it.

DG: [laughs] Okay, well, I will recommend re-watching it. We all need a little break. This is a movie with Billy Crystal and Meg Ryan. There’s this restaurant scene where Sally, played by Meg Ryan, is ordering and she says to the waiter, “Waiter, I’ll begin with a house salad, but I don’t want the regular dressing. I’ll have the balsamic vinegar and oil, but on the side. And then the salmon with the mustard sauce, but I want that mustard sauce on the side.” I remember as a child thinking, “Can you do that?”

[laughter]

DG: “Don’t you just take what’s on the menu?” I feel like we’re seeing with the COVID vaccines a little bit of what I’ll call the Harry Met Sally phenomenon. We have these well-studied vaccines, dosing regimens, but people want to order something not on the well-studied menu, like, “Maybe I’ll just take one of those mRNA vaccine doses and maybe I want to change the interval of what’s being done or what’s being recommended.”

We just had this article, it’s original article, “Effectiveness of Covid-19 Vaccines against the B.1.617.2 Delta variant,” so you get the different nomenclature there in the New England Journal of Medicine. The authors used a case-control design to estimate the effectiveness of vaccination against symptomatic disease caused by the Delta variant comparing this to the Alpha variant over the period that the Delta variant began circulating.

Variants were identified with sequencing of the (S) or the spike gene. Data on all symptomatic sequence cases in England were used to estimate the proportion of cases with either variant according to the patient’s vaccination status. They found that the effectiveness of just that one dose was notably lower among persons with the Delta variant, only 30.7%. With the Alpha variant, 48.7%.

They report the results were pretty similar for both vaccines after just that first dose. Now, when you went to two doses of the mRNA, Pfizer-BioNTech vaccine, 93.7%, with the Alpha variant, 88%, with the Delta variant. Now the ChAdOx1, the AstraZeneca vaccine, the effectiveness of two doses was 74.5% with the Alpha variant, 67% with the Delta variant.

I just want to point out, because I know there’s a lot of discussion now about maybe we should wait, maybe we should change the interval for that second vaccine dose. I just want to point out that after just that first dose, you’re looking at only about a 30% protection against the Delta variant, which is what is circulating. Do you want to sit around there at 30.7% protection hoping that if you wait a few extra weeks, you’re going to somehow tweak that 88% second dose impact a little higher?

I’m going to say, “Don’t be Sally, just go ahead and get that second dose when recommended.” Now, we still keep having questions about the third dose, the booster dose. We had another paper and this was, “Antibody Response After a Third Dose of the mRNA-1273 SARS-CoV-2 Vaccine in Kidney Transplant Recipients With Minimal Serological Response to Two Doses,” published in JAMA. That’s the Moderna vaccine, Moderna mRNA vaccine, that we’re talking about. The findings were very similar to other investigations that we discussed with low responders getting some increase in antibody response with a third dose, and about 49% of kidney transplant recipients, who did not respond having detectable antibody levels after two doses, did after a third dose in the case of Moderna mRNA vaccine.

I will point out, “They did not assess the T cell responses. Now, this ties in to what’s happening to these people, are they getting sick? What is the story? In the journal Kidney International, unfortunately, behind a paywall, the article, “Occurrence of Severe COVID-19 in Vaccinated Transplant Patients,” was published. Here, the authors describe 55 solid organ transplant recipients, 52 kidney, 3 simultaneous kidney-pancreas, who went on to develop COVID-19 after receiving two doses of mRNA-based vaccines. Of these 55 patients, 27% required hospitalization for oxygen therapy.

It’s a little bit higher than we would think in our generalized unvaccinated population. Of these, six were admitted to the ICU, three ended up dying. They had information on 25 patients with available data on the anti-SARS-CoV-2 antibodies, between the second dose and the onset of the COVID-19 symptoms. 24, so about half, had negative serology. One was positive, but had weak antibodies. Just little bit of information we’re getting here trying to figure out what to do with this group.

I will just say, currently, we have not started to recommend booster or third doses. We are studying this. We are trying to get a sense of what might happen in the future. I’m going to call this next paper the optimistic one. I think we need a little optimistic paper here. The paper, “Protection Afforded by the BNT162b2 and mRNA-1273 COVID-19 Vaccines in Fully-Vaccinated Cohorts With and Without Prior Infections.” This was posted as a preprint.

We get a lot of questions about this. The authors assessed the effect of prior infection in Qatar, Q-A-T-A-R, where the Alpha and Beta variants were dominant during this period of time. They used two national retrospective-matched cohorts studies. One for the Pfizer-BioNTech vaccine, one for the Moderna mRNA vaccine. They reported that the incident rates of infection among the Pfizer vaccinated persons with and without prior infection were respectively 1.6 or 11 per 10,000 person-weeks.

They looked at this and people with the Moderna vaccine, 1.55 versus 1.83 per 10,000 person-weeks. They actually found that prior infection enhanced protection of those that received– the Pfizer-vaccinated, but they really didn’t see a difference here with the Moderna-vaccinated. Actually, saw pretty low rates with Moderna-vaccinated individuals whether or not they had pre-existing infection. Interesting.

Now, hot off the press. Amy just sent me this and so I sent her back and said, “Hey, this is already on the block to discuss.” This was an article in the journal Science. “Immune Correlates of Protection of the mRNA-1273 Vaccine Against SARS-CoV-2 in Nonhuman Primates.” This is the Moderna mRNA vaccine. I liked it, but I just want to change the title. If we change the title, I think we’re all really good here. This is really, “Immune Correlates of Decreased Viral Replication,” and the authors even have a section heading entitled, “Antibody Responses Correlate with Protection against SARS-CoV-2 Replication.”

The authors do demonstrate that the levels of the anti-S antibody and neutralizing activity correlate with reduction in viral replication in bronchoalveolar lavages. That’s when you put a tube down, you put in saline, you wash it out, you pull it back out, and nasal swabs following SARS-CoV-2 challenge in vaccinated animals. There’s a lot in this paper, but they do also go on to show, I think this is interesting, that lower antibody levels were needed for reduction of viral replication down in the lower airways compared to the upper airways.

They also reported dose-dependent response, and this actually correlated with the S-specific T follicular helper cells that activate the B cells to secrete IgG, and the canonical cytokine IL-2 was also correlated with dose. I think this goes with the discussion, Vincent, that you and I were having earlier, that high antibody levels may have some impact on the ability of the virus to replicate in our airways, particularly the upper airways. This is not really a correlate of protection, it’s a correlate of reduction in SARS-CoV-2 replication.

VR: It’s not a real-world thing. We want to know, in people, what protects you against severe disease, right? This doesn’t tell us that, unfortunately.

DG: Yes. I think it is and I’ll say, it would be great if we have vaccines that had high degrees of sterilizing immunity. If once you were vaccinated, you could not be infected, you could not transmit, you would be a dead-end if you’re exposed. I think that was actually discussed on 786 TWiV. That, we’re not even sure how many of those vaccines really are out there. Whether or not the HPV or the measles even do that, but, yes, this is going to be a challenge if we’re looking for “herd or community immunity.” How much can the vaccines really play a part in that? Unless you’re getting vaccinated every three months or something, sort of along those lines.

The period of detectable viral replication, what I’d like to say is the time for monitoring and monoclonal is not the time for antibiotics. Remember, this is a virus. We have antivirals. No, not so many great choices here in the COVID world. We have antibacterial that target bacteria. We have antiparasitic drugs that target parasites. This is a virus, so do we think that antiviral antibiotics, antibacterial agents will work? A lot of physicians seem to feel that, a lot of patients feel that, but we have to have another paper that tells us, “Yes, water is wet. Fire is hot.” This was The Lancet Respiratory Medicine publication, “Doxycycline for Community Treatment of Suspected COVID-19 in People at High-Risk of Adverse Outcomes in the UK.” This is the PRINCIPLE study, a randomized, controlled, open-label, adaptive platform trial.

The background here is that doxycycline is often used for treating COVID-19 respiratory symptoms in the community despite an absence of evidence from clinical trials to support this use. There’s a lot of hand-waving about it interfering with the virus and in vitro assays, and having anti-inflammatory immune-modulating effects, etc. This data comes from this trial, the PRINCIPLE, and was performed in primary care centers in the UK. 2,689 participants were enrolled and randomized.

The authors found that in patients with suspected COVID-19 in the community in the UK who were at high-risk for adverse outcomes, treatment with doxycycline was not associated with any clinically meaningful reductions in time to recovery, hospital admissions, or deaths related to COVID-19, and should not be used in the routine treatment for COVID-19. I will comment that there were 780 folks in the doxycycline group, 978 in the control group. There were five deaths in the doxycycline group, only two in control, so that’s more than double. I do not think that doxycycline is something we should be using for COVID-19 and the science does not support it. What do we end up with? An unnecessary intervention and an increase in antibiotic resistance.

The early inflammatory phase. This is when they show up in the hospital, still not much new here. We’re still steroids, tocilizumab if they progress to a higher oxygen need, prophylactic dose anticoagulation, in general, adjusted to a higher dose in specific situations. We are still waiting for more therapies both in the early viral phase as well as this phase. We’re hearing it may not be until October or November before we get small molecule inhibitors specifically targeting SARS-CoV-2. We’re still in July, so we still have a little bit more time to go.

All right, and to the end. The tail phase, the long COVID, or the post-acute COVID phase. Lately, we’ve been hearing a lot about the neurological impacts about acute COVID. Now, there was an article, The Lancet Child & Adolescent Health, the peer-reviewed article appeared in this journal. “Neurological Manifestations of SARS-CoV-2 Infection in Hospitalised Children and Adolescents in the UK: a prospective national cohort study.” The authors performed a prospective national cohort study in the UK looking at children adolescents age less than 18 admitted to hospitals with neurological or psychiatric disorders in whom they considered SARS-CoV-2 infection to be relevant to the presentation.

They identified 1,334 children and adolescents hospitalized with COVID-19 and reported a prevalence of 3.8% neurological psychiatric disorders following hospitalization for COVID-19. 3.8% of these adolescents and children that have been hospitalized for COVID-19 went on to have neurological or psychiatric disorders. That’s about 1 in 25. The diagnosis included seizures, encephalitis, that’s inflammation of the brain, Guillain-Barré, acute demyelinating syndromes, chorea, which is uncontrolled movement, psychosis, encephalopathy, transient ischemic attack, even one child had a stroke. You can just imagine how devastating. Again, I try to give people a balance here between the risks of COVID in children, should they require hospitalization, versus the risks associated with vaccination.

I think this helps to give us more information around the decision-making with regard to vaccination and mitigation strategies for children. We’re still working to get solid numbers, but the risk for children, death is rare. Hundreds of children have died of COVID here in the U.S. Hospitalization is uncommon, thousands have ended up in the hospital. I think in the UK, they already have over 1,000 hospitalizations in just July and long COVID seems to be a significant risk.

Now, this last article could be the last article we hit on, this was in the New England Journal of Medicine. “COVID-19 Breakthrough Infections in Vaccinated Healthcare Workers.” Now, the B-word is in the title, so I couldn’t leave that out. [laughs] The authors reported on infections in vaccinated healthcare workers and they looked at 1,497 fully-vaccinated healthcare workers for whom RT-PCR data was available. 39 SARS-CoV-2 infections was documented in this 1,497-person cohort. They calculate an infection rate of 0.4%, less than 0.5%. There were a few interesting findings.

They reported of these individuals, 74% of the case-patients had a high RNA level. I’m translating here because they call it viral load, but I’m going to say this is a CT value, this is an RNA copy number. 74% of the individuals had a CT value of less than 30 at some point during their infection. However, of these patients, only 59% had a positive concordant antigen rapid detection test. I think this is interesting, and I just want our listeners to think a little bit about what does a CT value means? We know the relationship between CT values or RNA copy numbers and infectiousness in unvaccinated people, but what does this mean in vaccinated individuals?

They also reported that neutralizing antibody titers in the case of patients during the peri infection period were lower than those in matched, uninfected controls. Not clear if that’s a marker for people with other risk issues or if that’s actually a causal connection. There is a figure three where that correlation, if you look at the figure, it’s not really that impressive, but I will leave it up to our readers to go ahead and take a look, this is not behind a paywall. They did report that most of the breakthrough cases were mild or asymptomatic, but, here, was a bit of why is this in the long COVID section.

Of the people that had symptomatic infections post-vaccination, and remember this was a small amount, this was less than 1%. 19% of those people that did have asymptomatic cases went on to have persistent symptoms for greater than six weeks. I’m sort of– put this in context– getting asymptomatic infection post-vaccine is very uncommon, but it does happen. But should you get that, it actually looks like a pretty similar rate of long COVID in these individuals, so pretty on-par with unvaccinated. What’s going on with the rest of the world? I think this is important for us to keep an eye on that. We continue to see rising case rates and deaths with much of the world still being a vaccine desert.

I like to say, “No one is safe until everyone is safe.” And we are far from that at this point. Whether it’s to protect ourselves or through altruism, this pandemic does not end until we have widespread access and acceptance of vaccines. I want to thank everyone who’s continuing to go to parasiteswithoutborders.com, clicking on the “donate” button. This is going to drop the last day of July. We’re trying to make that $20,000 donation level, so that we can give a full $40,000 support to the Foundation for International Medical Relief of Children. They’ve actually started to open up some of their travel to some of their sites. Brighter days on the horizon, but this work is going to require funding and support. Please help us support FIMRC.

VR: Daniel, that last paper is of consequence to the CDC decision on masking, which is based on this PCR equivalence between Delta vaccinated and Delta unvaccinated– would suggest that that’s flawed in their case.

DG: Yes, I think that’s really a problem. One is it looks like the people who are vaccinated are very like less than 1% risk of even testing positive and then if they do test positive, you can’t just use CT values because you’re looking at RNA. It’s not viral load, and I hope that the CDC isn’t making that– Can we call it a rookie mistake? You need to ask, and I think the fact that we’re not picking up antigen, that we’re not seeing the protein production, does really suggest that maybe that RNA level is not correlating with infectious viru,s and we need a little more data.

VR: Yes, the other thing, Daniel, I was on a call yesterday from Mumbai and one of the women on the call said they have immunized 450 million people in India.

DG: Wow, that is impressive.

VR: Now, compared to the U.S., that’s very impressive.

[laughter]

DG: We’d be done if we had done that in the U.S.

VR: It’s not even half of their population, but she said, “In India, we don’t have a problem with people getting vaccinated.”

DG: Interesting. I think I shared this on This Week in Parasitism where I was talking about Ben LaBrot. We were in one of these little communities and we were talking to one of the women, a woman, about the fact that in the United States, we actually have people that do not want to vaccinate their children. She looked at us, a little confused, and she said, “But don’t your parents love their children in America? I don’t understand.”

VR: [laughs] Indeed. Okay, time for some email questions for Daniel. You can send yours to daniel@microbe.tv. The first is from Alan, a gastroenterologist in New York. “If a fully-vaccinated patient who was in a high-risk group, age over 65, or medical comorbidities developed an early COVID infection, would you recommend monoclonal antibody? Will the level of the patient’s COVID antibody obtained at the time of infection make a difference in deciding the treatment? I realize there may not be any randomized trials for this type of situation, however, clinicians frequently have to make decisions in the absence of good data or good studies.”

DG: Okay. This is an excellent question, and I’m going to break it down into two parts, so let’s say this is a person who’s been vaccinated. They’ve not been infected with COVID before they’re in that first week. And I’m going to throw the person who’s been infected before also vaccinated in that first week, we do recommend monoclonal antibody therapy in those individuals. Your prior vaccination status does not impact your eligibility or our recommendation for monoclonal antibody therapy.

Now, I will say, have we repeated the studies with vaccinated people to see if we’re still getting that 70% to 80% reduction in the progression. We have not, but we’re not excluding people who are vaccinated. The other little twist– so let’s say you’re not sure about the timing and this person has not been infected with SARS-CoV-2 before, you can check a nucleocapsid antibody test to see are you really catching them early before they start producing their own antibodies because that really is what we’ve seen as far as the benefit of monoclonals.

If you can give people the monoclonals prior to them developing their own antibodies, those are the patients that we see the most benefit. I just recently had a case where– it was really unclear to me– a person was cognitively not a 100% sound to me, like we were only two or three days in, we did a stat nucleocapsid antibody. It was negative and I went ahead and recommended monoclonals. No, we have not repeated the monoclonal studies in vaccinated people, but if they’ve broken through, gotten an asymptomatic case, I think it makes sense not only to reduce the hospitalization and death rate. We’re working on data because maybe it’s also going to impact their risk of long COVID.

VR: Linda writes, “I wanted to understand the role of at-home rapid antigen tests for the vaccinated person following the exposure to a COVID-positive vaccinated individual. Currently, as I understand, New York rules no quarantine or testing is required for the vaccinated person that’s been exposed. I find that a tad concerning and wanted to protect my family. No one in a high-risk category and friends following such an exposure and so have been wearing a mask at home and limiting my exposures to others for what will be seven days, timing on my choice, based on my own review of the current debates.

I’m not sure what the magic number of days should be, particularly as I go on this frolic of my own, since no one is telling me I have to do anything other than wear masks indoors. I feel like there’s a role for the at-home antigen test in this setting, and consider doing it at days three then six. I just really don’t know what the reasonable approach is following close exposure to a COVID positive-vaccinated individual. Can you explain if the at-home antigen test plays a useful role in this context?”

DG: Yes, so this is a fantastic question. We have great listeners, or maybe Vincent just picks out the really great listener’s questions, but so we’ll give everyone credit here. We do know that a vaccinated person can develop an asymptomatic case of COVID-19 and can transmit to others, right? Not only is that well-described, but you know I’ve seen several cases myself. Can an asymptomatic, vaccinated person get enough virus that they’re going to transmit to someone else? A bit of uncertainty there. We could use some better data. The last study we talked about where these individuals who were fully-vaccinated, got infection, we’re talking about 0.2% actually had a positive antigen test.

We need a little more information here. If it turns out that vaccinated people only transmit, this is case control and tracking studies. If they only transmit with symptoms, that’s helpful. But I think if you try to be on the side of extra caution, you are vaccinated, you’ve had an exposure, you may be pre-symptomatic, right? Because you can’t get symptomatic, I think that the antigen test is a reasonable extra layer, so remember always looking at layers, looking at people’s different risk tolerances, and I think it can factor into that.

VR: Gabriel writes, “A friend of mine suffers from Bruton’s agammaglobulinemia and many medical doctors in Ecuador do not recommend any COVID vaccine for him. I’m a microbiologist, I’ve carried out research in immunology and though I understand that he can’t produce antibodies, the T cell responses should be fine, and I don’t see any risks of getting vaccinated. I would appreciate your opinion about whether he should receive vaccine, what kind of vaccine would be better?”

DG: I definitely would encourage vaccination. I think we’ve tried to reinforce several times that there’s more than one arm of the immune system. I’d say two, that’s a little simplistic, but there’s the B cell antibody production. We’re not going to get that with Bruton’s agammaglobulinemia, but we should be able to get a protective T cell response, and our data, our understanding of immunology, suggests that it’s that T cell response that is really critical in protection against severe disease hospitalization and death. I definitely would encourage vaccination. I would say whatever vaccine you can get access to, I would go ahead. Don’t be picky, don’t be Sally.

VR: The last is from Abby, which is really a comment, but we should read this, “Peds New York here. My daughter was 17 in early March 2020 when I brought COVID home from the peds clinic. She had mild illness, was a fit rugby player, still having GI issues, neurological symptoms, tachycardia, fatigue, brain fog, depression, couldn’t eat, lost 20 pounds. We need more parents to learn about long COVID. Many docs are saying it’s mild in kids and they are just as at fault not vaccinating their own kids. Millions of kids with this around the world.”

DG: Yes, Vincent, we keep seeing these scoreboards, dashboards, [Johns] Hopkins’ Worldometer. And they have a number of cases, they have hospitalizations, they have deaths, but what they are missing is long COVID. And I think that that’s a critical number as well, so when we see pretty soon over a hundred thousand cases a day here in the U.S. Welcome to August, I’m predicting. What percent of those individuals are going to continue to be ill? I think that’s really an important thing.

When you look at the kids, and you say, “Oh kids, well, we can see the deaths, we can see the hospitalizations, but what about the long term, greater than four weeks, greater than 12 weeks of long COVID?” I think stories like this, parents need to hear because parents are not necessarily swayed by scientific studies. They’re swayed by stories, by people sharing these experiences. As I brought out last time having conversations about vaccines, if your child has suffered, let’s share these stories, because we do not need even one more child suffering with long COVID.

VR: That’s COVID-19 clinical update number 73 with Dr. Daniel Griffin. Thank you, Daniel.

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

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