TWiV 775 COVID-19 Clinical Update #69

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 3 July 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 775, recorded on July 1st 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, President Biden said by July 4th, we’d have 70% of the U.S. immunized. Has that been achieved?

DG: No, we’re not, not quite there. We’re falling a little short, and it’s regional, we’re falling short in different regions. You can look at a map and you can see where those regions are and you really just look at the incidents of COVID-19 and you know those are the areas with low vaccination uptake. Yes, we didn’t quite hit there, we’re doing decent. Could be worse.

VR: Could be worse. Could be better, right?

DG: It could definitely be better. I’m sorry that it’s not better. Yes, I had a woman I saw just yesterday, Haitian descent had moved to the United States when she was younger. She ended up in the ER and was talking to her a little bit about why she had not gotten vaccinated and there’s a lot of this misinformation. She had been told that there was bad stuff in the vaccines and in 15 years we would all be dead. It’s hard to fight against that because apparently, we have to wait 15 years to see, but no, here’s a woman who’s sick. I think we talked about my partner’s sister-in-law who died leaving behind children.

Yes, unfortunately, this misinformation is not innocent. It results in people getting sick, people dying. A lot has happened this week. I have to say, to Vincent and to our listeners, right after I record one episode, I start taking notes for the next one. I see an interesting article that came out. Sometimes I get to the end of the article and I realize I don’t like that, delete that, something more interesting comes up.

I keep thinking, boy, eventually, like the fire hose of information will settle down and we’ll go to this month in clinical updates, but there just seems– there’s so much information. Let’s jump right into it. My quotation, “Courage is not the absence of fear, but rather the assessment that something else is more important than fear.” Actually, Peter Hotez tweeted that out. That’s FDR. I think he tweeted it out. My heart and sympathy goes out to so many science educators like yourself, Vincent, like Peter, who are just trying to spread knowledge, to educate, and there’s really a bit of a backlash, which is more than vile at times. I know this is really tough, so I applaud the courage of all the people that continue to educate despite that backlash.

I will say, before I get into my episode, I really love the TWiV Episode 773 with Laurie Garrett. Certainly no shrinking violet– brought lots of passion. I love her books. It’s summertime, people go to the beach, they read books, they go to the lake, they have some time sitting on the back porch. These are great, great books and very, very timely, well written. All right, let me start, and I’m actually going to touch on a few controversial topics. This week, there was a guest essay, “Human Behavior During the Pandemic Is More Important Than Any Covid Variant.” I don’t know if people ran across this, but this was written by a Dr. Rosenfeld and Dr. Racaniello. Yes, same Amy and Vincent that our listeners might know.

The article really does an excellent job of making the point that I’ll be touching on today. Ultimately, a virus has a genetic sequence that changes and these changes, they can be neutral, they can be favorable. They’re usually unfavorable in terms of viral fitness, and this is my request to the audience and the media to start using the word fitness rather than transmissibility. This viral fitness is really the same Darwinian concept that underlies the whole survival of the fittest that many of us learned about, if we were allowed to be taught that in our schools, and reproduction is a chance for an organism to end up with improved fitness.

We have certainly given SARS‐CoV‐2 the opportunity to reproduce. It’s not surprising that we are seeing that the Delta variant– that there’s evidence to suggest that it has improved fitness that it’s going to have the ability to outcompete other viruses. I know I drive some of even the other ID docs a little bit crazy and focus on, let’s say things that are true, let’s use the right terminology, but I’m going to push on that. Let’s just spend a little time here before I get into other bits in the literature, but take some time and read that article. Vincent, hopefully, will post it up on the Parasites Without Borders website, but let’s go through this together.

What factors can improve a virus’ or a variant’s fitness? What changes would be favorable? I’m going to try to avoid anthropomorphism, I think I’m going to succeed, so everyone can listen and comment if they catch me, but a virus can change in a way that increases the duration of viral shedding. A person could perhaps shed virus for a longer period of time before they became symptomatic. Maybe they can continue to shed viable infectious viruses for a longer period post-symptom onset, and this might involve some changes that impact the interaction with the immune system.

A virus can mutate in a way that increases the level of this infectious virus shedding, a person could perhaps shed virus at a higher level. We’ve talked about CT values, even more than that, we’ve talked about how you don’t just need a lot of RNA, but you actually need viable virus. A little harder to look at that. A virus could change in a way that allows for infection of the next host with a lower inoculum, and people have talked about maybe improved affinity to the receptor.

Lower inoculum resulting in infection. A virus can change in a way that modifies its tropism for lower down in the airways, potentially increased in the degree to which it’s contained in smaller droplets. That’s been discussed on a prior TWiV— or maybe it can modify its tropism to start involving more of the upper airways, more runny, drippy noses, maybe more sneezing. A virus can change in a way, and I’m going to focus on this, where it can allow it to reinfect previously infected people. People that thought they had natural protection, maybe had natural protection against one of the early variants, but perhaps now changes maybe that sweet spot in the receptor-binding domain– changes enough that those natural antibodies no longer target as well. Maybe the T cells aren’t up to the challenge or a virus might change in a certain way that decreases its susceptibility to antiviral medications or vaccination.

I think that these are all reasonable. I think that I’m going to keep asking people, and I think it’s for the media, the virus is becoming more fit. We have a fitness increase in the variants. I think that’s exciting, people can read that I think. Now we do have concerns with the Delta variant that in addition to reinfecting the previously infected, there’s evidence such as the report from Scotland that I discussed last time that the Delta variant may be associated with an increased risk of hospitalization, death, and seems to be infecting younger individuals. Let’s just go through a few of these, but what I’m going to do is jump to the escape from vaccines and therapeutics. Let’s get some science here, so I’m just not another person with two thumbs and an opinion.

We got new information from Moderna in the form of the press release, “Moderna Provides a Clinical Update on the Neutralizing Activity of its COVID-19 Vaccine on Emerging Variants, Including the Delta Variant First Identified in India.” They also released the data as a preprint. Let’s jump to the preprint. Right to the preprint, “Serum Neutralizing Activity of mRNA-1273 Against SARS‐CoV‐2 Variants.” This is the Moderna vaccine. The authors reported that Sera from participants immunized on a prime-boost schedule, first shot then four weeks later with Moderna get the second shot, had neutralizing activity against several SARS‐CoV‐2 variants, including variants of concern and variants of interest and this was compared to the D614G so the wild type SARS‐CoV‐2 as a reference.

They showed that there were minimal effects on neutralization against– and we are going to go with the Greek here, against the alpha variant only a 1.2-fold reduction. The other VOCs, they looked at beta, gamma, delta and you saw between a 2.1 and an 8.4-fold reduction. What they were describing as small reduction, but little detail here. The participants were immunized. The Sera was collected seven days post-boost.

They only analyzed eight participants and these assays were done using pseudovirus, not real stuff in a BSL-3. Just to put that in context, “What about other vaccines comparison?” We have data from the UK suggesting that their Pfizer-BioNTech vaccine was 88% effective against symptomatic disease from the delta variant two weeks after the second dose compared to 93% effective against the alpha variant. Two doses of the AstraZeneca not as impressive, 60% effective against symptomatic disease from the delta variant compared to 66% compared to the alpha variant.

Both vaccines, I think people may know this, were only about 33% effective after just one dose, which is where many of us peg natural infection. The J&J efficacy is largely unknown. I know I get a lot of questions here like, “Now that we have the delta variant, what’s the role of J&J?” I have to say here, in the U.S., we are fortunate the vast majority of our vaccination campaign has utilized the mRNAs in Moderna and Pfizer vaccines. We are seeing the real-world data from Pfizer-BioNTech and now we are getting a little more data on Moderna as well.

All right, children, COVID, and mental health. I am gonna lump it all in there. As I like to say, children are at low risk, but they are not at no risk. I had a great conversation, it was actually yesterday, with Dr. Melissa Stockwell. She’s one of the few experts in pediatric COVID and she’s right there, right here at Columbia University Medical Center. It was really an interesting conversation we had. I have been working at the UnitedHealth Group level to try to identify referral centers for individuals with difficulty and one of the biggest challenges is finding centers that have an experience and a focus on children.

We were discussing a bit of her experience regarding long COVID in children and her suggestion was that we may have underestimated how much long COVID is impacting children and she says she’s starting to see in the recent few weeks here, as the children leave school, try to get out there and exercise and get involved in activities, a lot more parents are noticing that their children are struggling. We had a little conversation how much of that is post-acute sequelae of COVID versus post-acute sequelae of a pandemic.

There will be more on this as we go forward but just to keep this in mind, a lot of these younger individuals still do not have the opportunity to get vaccinated and certain parts of our country still have, actually, unacceptably high infection rates. As I mentioned, mental health, the pandemic has had a significant impact on mental health. I discussed the issue in adolescent girls, actually. A significant increase in them ending up in the emergency room.

We had an MMWR early release from the CDC, “Symptoms of Depression, Anxiety, Post-Traumatic Stress Disorder, and Suicidal Ideation Among State, Tribal, Local, and Territorial Public Health Workers During the COVID-19 Pandemic,” United States March-April of 2021. Now, the authors reported they looked at 26,174 public health workers. 53% reported symptoms of at least one mental health condition in the two weeks prior to the survey. Symptoms were most prevalent among those who were unable to take time off or who were working greater than or equal to 41 hours per week. The majority of public health workers surveyed were reporting mental health issues.

The reported symptoms; depression 32%, anxiety 30%, PTSD 37%, suicidal ideation was as high as 8.4%. The highest prevalence of a mental health condition was among respondents aged less than or equal to 29 and among transgender and non-binary persons of all ages. The authors do comment that findings of this report have certain limitations. I thought the most important that they mentioned was that the participants were surveyed only about symptoms experienced in the two weeks preceding the survey.

It doesn’t reflect all the stress and all the difficulties over the last 18 months, sort of a snapshot here but an incredibly troubling snapshot. I think this reinforces what we are seeing, all across the healthcare sector. We are seeing individuals struggling with mental health challenges due to stress, financial and security loss. I mean, a lot of people have lost loved ones, jobs, other things and I really appreciated a piece by my friend, Lucy McBride, published in The Atlantic, I need to subscribe, “By Now Burn Out Is a Given.” Just discussing how we are seeing this in so many healthcare providers. But we are in no special class, we are seeing this all across our society, so mental health is health.

All right, I always like to say testing, never miss an opportunity to test. We still need to keep doing testing and, particularly with the suggestion that we may now see presentations that are less typical than we’re used to. I had an individual today who went to an urgent care center with the chief complaint of, “I think I have sinusitis. I am feeling all that fullness in my sinuses.” Tested positive for COVID, ended up in the emergency room, we confirmed that that was COVID. This gentleman is now hypoxic in the hospital and really, the presentation was sinusitis, which quickly then evolved into hypoxemia and pulmonary involvement.

All right, active vaccination, never miss an opportunity to vaccinate and vaccination is how this pandemic ends. Lots here this week. The article, “Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection,” was posted as a preprint by a number of authors and the Oxford COVID Vaccine Trial Group.

Data from a randomized efficacy trial of the ChAdOx1 AstraZeneca vaccine in the UK were analyzed to determine antibody levels associated with protection against SARS-CoV-2. Drum roll here, we all wanna know this, “Like can I get a blood test? Can I find out? Am I protected?” So, they looked at any spike and anti-receptor binding domain IgG by multiplex immunoassay, they used pseudovirus, and live neutralizing. They used the word ‘live’ in this virology paper, say active neutralizing anybody at 28 days after the second dose and they looked at infected and non-infected vaccine recipients.

They reported that higher levels of all immune markers correlated with a reduced risk of symptomatic infection, but antibody responses did not correlate with overall protection against asymptomatic infection. The authors reported that they had data for anti-spike and anti-receptor binding domain IgG from 1,318 individuals, they had 163 cases, 1,155 non-cases. Interesting, but still very preliminary, and not sure we have all the answers. This data is only for the AstraZeneca vaccine. It only looked at responses in a predominantly Caucasian population in the UK when only the alpha variant was circulating and has noted no correlation was seen with higher levels of antibodies and protection against asymptomatic infections. And we do know that we can get transmission with asymptomatic infection.

All right, now people that, unfortunately, have to tolerate me in-person or on regular basis, have probably grown tired of, I always find a way to insert the word ‘heterologous’ into conversations. One of my favorite words. But we now have a study published in The Lancet about heterologous vaccinations– mix and match. See, heterologous is so much easier to say. “Immunogenicity and reactogenicity of BNT162b2 booster in ChAdOx1-S-primed participants (CombiVacS): a multicentre, open-label, randomised, controlled, phase 2 trial.”

The authors reported on this randomized control trial on adults aged 18 to 60 vaccinated with a single dose of the ChAdOx1-S AstraZeneca vaccine 8 to 12 weeks before screening, no history of prior infection. Then the participants were randomly assigned to either get the Pfizer-BioNTech vaccine via a single intramuscular injection or just to continue observation, a control group.

The primary outcome was 14-day immunogenicity, measured by immunoassays for SARS-CoV-2 spike protein and receptor binding domain. Here again, we’re measuring antibody levels. We just got a little bit of sense that maybe there’s some correlation we might have there. 676 individuals were enrolled, randomly assigned to either intervention at five university hospitals in Spain. This was done in Spain.

In the intervention group, the receptor-binding domain antibodies increased from 71.46 up to 7,756.68 as far as the IgG against trimeric spike protein, this increased from 98.4 to 3,684.87. Reactions were mild to moderate. Some injection site pain, some induration. About 44% of the people said they developed a headache, about 43% felt the muscle aches. No serious adverse events, but basically they were showing that we were seeing a significant rise in antibody levels using this mix and match or heterologous vaccine approach.

I know we get a lot of questions because in certain parts of the world AstraZeneca was rolled out and then they pulled it back and then people are getting other vaccines. What I don’t know if I can comment on here is this is just getting one dose of the mRNA vaccine. The current recommendation is still let’s say you come to the U.S. and you’ve only had one AstraZeneca vaccine, we recommend just restarting and doing two shots of the mRNA. This is the kind of data that might factor into those recommendations.

Now if a person had COVID-19 previously, should they get one or two doses of a two-dose vaccine? Certainly controversial, the report, “Prior SARS-CoV-2 infection rescues B and T cell responses to variants after first vaccine dose,” was published in Science. We’ve been hearing a lot about this issue. It may be helpful in many areas of the world that already have significant number of prior infections, more limited numbers of available vaccine doses, to know can we take people who had COVID before and just give them one vaccine.

Do we need to use two, twice the resources? The authors analyzed T and B cell responses after first-dose vaccination with the Pfizer-BioNTech mRNA vaccine in healthcare workers. They followed them longitudinally, these were people that had previous infection. After one dose, individuals with prior infection showed enhanced T cell immunity, antibody-secreting memory B cell response and neutralizing antibodies against the variants. I think that all this is interesting and, to be honest, does build on what we know. This is actually, I’ll say, a rather dense interesting paper. Perhaps on Immune, some immunologists will do a deeper dive into this. I’m not sure this is so far, or at the point, where this is practice-changing information, but we are learning more.

This may also impact the WHO forecast that certain vulnerable high-risk individuals may need yearly COVID shots– vaccines. There won’t be COVID in the shots, there will be vaccine in those shots. If richer countries feel they need boosters for some of their citizens, then this again will affect equity issue. I do want to remind all the listeners how effective these vaccines are, even in people with negative serology tests. I don’t want everyone to run out and get those serology tests. In the last month, there have been more than 18,000 deaths from COVID here in the U.S. Over 99% of those were unvaccinated individuals.

In the New England Journal of Medicine, we saw “Effect of Vaccination on Household Transmission of SARS-CoV-2 in England.” This is really, I think, addresses the critical issue of ‘Community Immunity’ that comes up all the time. If I’ve been vaccinated, can I transmit the virus to other people? This really is critical because the whole concept of ‘Community Immunity’ relies on vaccines interrupting transmission. This is that question, “Is there free lunch for the unvaccinated?” The authors analyze data from the Household Transmission Evaluation Dataset (HOSTED), which is information on all laboratory-confirmed cases of COVID-19 in England. As you can imagine, it’s a very large data set. Between January 4th and February 28th, 2021, there were 960,765 household contacts of unvaccinated index patients and there were 96,898 secondary cases of COVID-19.

The authors compared the risk of secondary infection defined as a positive SARS-CoV-2 test 2 to 14 days after the positive test for the index case. Among unvaccinated household contexts of vaccinated persons with the risk among unvaccinated household contacts of unvaccinated persons with infection. They reported, drumroll, that vaccination was associated with a 40% to 50% reduction in transmission of SARS-CoV-2. Now, there’s a couple of things I will say there. One is, they are through their contact tracing confirming that vaccinated people who get infected can still transmit it to other individuals. I was a little underwhelmed. I guess 40% to 50% reduction in transmission, I had hoped for better. That is not as much as I would like, but remember this is only the second step in the process.

The first step in the process is a vaccinated person has to get infected. We already have good information on symptomatic infection. We’re getting better information as time goes by on the decrease impact of any asymptomatic infection. Just to keep in mind, a vaccinated person is not 100% safe if they get infected with SARS-CoV-2. They are less likely, but not zero. Now, the next question I get all the time, how long will my vaccine-induced immunity protect me? Will I need a booster shot?

The article, “SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses,” was published in Nature. Again this is a rather deep, complex article. The flow cytometry for all the immunologists in the audience, they’re very nice. I’m sure they had to do a lot of flow cytometry to get such nice flow plots. What the researchers did here is they examined fine needle aspirates. Let me explain what that is. You take a small needle and you actually put it into a lymph node and then you draw back on a syringe, you’re actually obtaining cells.

They did this from 14 individuals from the draining axillary lymph node. You can think about you’re getting your vaccine in your deltoid, in your arm, and then they’re checking the lymph nodes under the arm, in the armpit. They identified germinal center B cells that bound S-protein in all participants sampled after primary immunization. They reported that high frequency of S-binding germinal center B cells and plasmablasts were sustained in these draining lymph nodes for at least 12 weeks after the booster immunization.

They suggested that these findings supported the idea that SARS-CoV-2 mRNA-based vaccination of humans might induce a persistent germinal center B cell response enabling the generation of robust humoral immunity that might be rather durable. This is interesting. It’s a cause for optimism, but we still need some more data before we hang our hat on this. Now, this was a late one coming in, but I think exciting. We saw the New England Journal of Medicine publication “Safety and Efficacy of NVX-CoV2373 COVID-19 Vaccine”– that’s the Novavax, the protein-based vaccine, as I like to say, the honest traditional vaccine that we’ve been using for many years for shingles vaccination, SHINGRIX, pertussis, hepatitis B.

Here, in the New England Journal of Medicine, we saw the peer-reviewed publication of the Phase III randomized, observer-blinded, placebo-controlled trial conducted at 33 sites in the UK, individuals adults ages 18 to 84 in a 1:1 ratio to receive two intramuscular immunizations or placebo administered 21 days apart. The primary efficacy end point was virologically confirmed mild, moderate, or severe SARS-CoV-2 infection with an onset of at least seven days after that second injection in participants who were serologically negative at baseline. These are people that had not been infected, were immunized. The two-dose Novavax vaccine conferred 89.7% protection against SARS-CoV-2 infection and showed high efficacy against the alpha variant. The incidence of serious adverse events was low.

Actually, I thought this was interesting. It was very hard for individuals to be able to tell whether or not they were in the placebo or the vaccine group. This has a lot less of that reactogenicity that we’ve grown accustomed to. We hear rumors that Novavax is going to be putting this forward to the FDA this quarter, the corporate approach to the world. This quarter will be, I guess, July, August, September. This will be an exciting addition. I think it will make a difference. There’s a lot of individuals that I talk to that are waiting for this vaccine. I think if we can give people options and that option then ends up with them vaccinated, I’m all for choices.

The period of detectable viral replication, that first week, that viral symptom phase, the time for monitoring and monoclonals, and as I like to say, where you get your test is where you should be able to get your monoclonals. U.S. health officials on Friday, February 25th paused the distribution of Eli Lilly’s COVID-19 antibody cocktail therapy with concerns about a lack of effectiveness against the beta and gamma corona variants. The FDA recommended use of the Regeneron cocktail and the Vir/GSK therapy instead of this combination therapy. All of the assays to date would suggest that those other monoclonal therapies continue to be effective.

Just some real world– the government has purchased a lot of the Regeneron cocktails. They’re out there sitting on shelves. I have not seen much uptake with the Vir/GSK yet. I’m still waiting to find out will the government purchase that, will that be something that health insurance companies are expected to reimburse? What are the on-the-ground issue differences? Regeneron is frozen, must be thawed. You can do IV or as we now know, sub-q with four injections. Then there’s a two-hour observation period. The Vir/GSK can be in the fridge. It can be a 30-minute infusion with a one-hour wait time. May have a certain role in that doctor’s office, that busy urgent care. Since a lot of people have decided not to get vaccinated, there will continue to be a first week of COVID.

All right, early inflammatory phase. These are those individuals, the oxygen saturation drops below 94%. They end up in the hospital. We have steroids, we have oxygen, we have remdesivir monoclonals. If their antibody is still negative, the data we talked about from the Regeneron cocktail. June 24th, the FDA announced that they had issued an Emergency Use Authorization, an EUA, for the drug Tocilizumab for the treatment of hospitalized adults and patients who are receiving steroids, require supplemental oxygen but then progress.

The data supporting this EUA was based on four clinical trials. We’ve talked about, I think, most of these. They included one randomized, controlled, open-label, platform trial that was RECOVERY, and three randomized, double-blind, placebo-controlled trials; EMPACTA, COVACTA, and REMDACTA. While all the four clinical trials contributed, the most important as far numbers– potential benefit came from the RECOVERY and the EMPACTA trial.

Just to remind people of those trials, but to put this in context; a person ends up in the hospital, you’ve started remdesivir, you’re supporting them with oxygen. You’ve started steroids, their oxygen requirement increases. That’s where you think about Tocilizumab. The RECOVERY trial was the trial that looked at over 4,000 hospitalized patients with severe COVID-19. This study demonstrated a statistically-significant reduction in risk of death and time in the hospital. The EMPACTA trial, a smaller trial, 389 hospitalized patients also demonstrated benefit. A decreased risk for ending up on a ventilator and also a decreased risk of death, but to reinforce, timing really matters.

The benefit is only seen in those patients with an elevated inflammatory markers that progress to higher oxygen requirements despite steroids and there’s a time window. You want give this less than 48 hours after they escalate. If they escalate, they’re on a ventilator, you wait till day three. You may just be increasing their risk of opportunistic infections.

This has been long enough, but let’s finish with long COVID. There’s really a nice perspective in the New England Journal of Medicine and it was entitled “Confronting Our Next National Health Disaster – Long-Haul Covid.” The authors suggest that factoring in new infections in unvaccinated people, we can conservatively expect more than 15 million cases of long COVID resulting from this pandemic. Even though the data is still emerging. The average age of patients with long COVID is about 40, which means that the majority of these individuals are in their prime working years. They discuss that giving these demographics long COVID is likely to cast a long shadow on our healthcare system and the economic recovery that everyone is talking about. This is certainly something we’re continuing to see.

I’ll conclude there before we hit emails. Again, to remind everyone, we are continuing to support Foundation for International Medical Relief of Children. Drop what you’re doing. Pull up to the side of the road, go to parasiteswithoutborders.com and donate so that we can continue to help them and continue to provide this weekly COVID clinical update.

VR: Daniel, I just want to point out, that transmission trial in the UK, or the observational study, was only most of the people were only after one dose. So it could be better after two.

DG: That is encouraging.

VR: All right, time for some email. You can send yours to Daniel@microbe.tv. Mark writes, “I wanted to bring to your attention that there are an estimated 9 million Americans living abroad for work or retirement, where they’re temporary trapped. I’m based in Southeast Asia for work. I can return, but for many Americans, it’s too expensive or dangerous. The U.S. State Department has failed to respond to this group. Something that would be easy to address via the embassies and consulates. I’ve written to Dr. Francis Collins requesting this issue be raised. My question is, ‘If we can ship millions of vaccines to India, why can’t we also take care of at-risk Americans currently residing outside the U.S.?’ I’ve written to The New York Times and The Washington Post with no response. I would appreciate you raising the issue on TWiV and forwarding my message to those persons you believe could be helpful in moving this forward.”

DG: You make really good points here. We do know that the State Department has shipped vaccines to those embassies to vaccinate their staff. My brother-in-law is actually in the State Department stationed in Ukraine with his family Tim, Juliet, and their three kids. Actually, people may know my other connection to the State Department. My wife’s father was a U.S. Ambassador. He was career State Department. This is a tough situation. They have sent limited amounts of vaccines to vaccinate State Department personnel. They really haven’t expanded that out to the millions of expats that you describe. I’m not sure what the political thinking is behind that. These are American citizens. We’re supposed to be looking out for them. Right now, in the middle of a pandemic, looking out for someone is getting them access to a vaccine. We’ll, I guess our listeners can all hear this letter read on the air and hopefully something will happen.

VR: Joy writes, “There’s an active clinical trial for use of monoclonals Leronlimab for treating long haulers. I signed up for it last January, but got reinfected again before the trial began. I think there are a couple of other trials being conducted since there are no treatment options for long COVID. I’m wondering, ‘Why are they not testing Regeneron, etc. for that purpose?’ As long haulers– know who we are. Sadly, many of us are being gaslit by the medical community. My doctor has known me for most of my life, and didn’t recognize this as a condition until recently, after more than a year.

I’m deeply saddened this isn’t getting enough attention. After 18 months, still no medical code. My doctor doesn’t even know how to refer me to a specialist for it. My insurance won’t cover the long-term effects. We’re being denied care because our doctors are unable to code for it. I was unable to get monoclonals after my most recent infection because my doctor didn’t know how to prescribe the infusion. Hope you can give us long haulers some hope and insight because the public health and medicine system is moving too slow.”

DG: Joy, it is moving too slow. I’m going to echo that. I mentioned last time and maybe you can write this down and tell your physician, but we were encouraged to currently use the code B94.8 to identify these individuals, and that is for sequelae of other specified infectious and parasitic diseases. I think this is always shocking to me. We’re hoping in October we’ll be using U09.9, but what are we supposed to do in the meantime? Reminding me of one of the discussions at one of the hospitals where they felt like one medicine was not really effective and they said, “We’re going to stop using it on Friday.” I’m like, “I’m going to stop using it today.” Why don’t we have a code and start using it today? Crazy as that seems. What I will say, and this is encouraging, is there’s a lot of money and there’s a lot of interest in trying to find treatments for you, for the people suffering with long COVID.

A big thing is we want to do it right. What did we learn over the last 18 months? We can spend a lot of money and do a lot of trials and find out nothing. It’s very easy to do a bad trial. That was actually what was triggering my conversation with Melissa Stockwell is there’s a lot of centers that are now in stage one phase and it’s going to then move into stage two, and there will be centers all around the country PASC, post-acute sequelae COVID, centers where patients will go for treatment.

They will also go for the opportunity to participate in research because we do not have a lot to offer. I think I’ve mentioned in the past, there was this suggestion that we would send people to these Centers of Excellence. It’s not a Center of Excellence until we can provide excellence and we’re not there yet. We don’t have a lot of answers. The research, the clinical trials that are all being set up, are going to give us those answers. Then, we will have Centers of Excellence. I want to say, I’m very optimistic, but yes, it is moving too slowly. If you have long COVID, it’s moving much too slowly.

VR: Tom writes, “My son will turn 12 early July, plans to get vaccinated on his birthday. During your show last week, you mentioned this study on college athletes and responded to a parent email about myocarditis pointing out that the long-term risk from natural infection is much greater than from vaccination. We’re also hearing some doctors saying that the first dose might be okay, but two for a child, too much, too risky. How much does the first dose of vaccine decrease the infection risk compared to the second dose? How much does the myocarditis risk from the vaccine increase between first and second dose? Are you recommending one dose or two for a 12-year-old male?”

DG: Yes. We are. I am recommending two doses of the mRNA vaccine for a 12-year-old. The reason we say that is all the evidence has suggested that this is a true prime-boost vaccination series. That initial vaccination gets us a little bit of T cell, a low level of antibodies. We’ve seen some of the data out of the UK, particularly against the delta variant, not a lot of protection. You get that second dose and you really get a boost. The antibodies really go up and the real-world data suggests that then you are protected. We see the myocarditis after that second dose, we now see that there is a certain connection here. It’s been pinned down and we have a sense of what the rate is, what to expect. If you want that protection against COVID-19, maybe for a lifetime in an adolescent, I encourage two shots.

VR: Lori writes, Lori is a Canadian working in Kazakhstan, they received two doses of Sputnik, but now when they come back to Canada, they’re not recognized. The vaccine is not recognized by Health Canada, so they have to be re-vaccinated. The question is, “We had two doses of Sputnik in May. Is two doses of another vaccine in July bad for the body?”

DG: I wouldn’t say bad for the body. You may experience some reactogenicity. I would expect that. We’re seeing lots of people in the situation you’re in in Canada and the United States, other places that have the same policy. Are you going to get a little bit of extra protection? Maybe. I think it’s fine to go ahead and I think it’s safe and will be effective.

VR: That’s COVID-19 clinical update number 69 with Dr. Daniel Griffin. Thank you, Daniel.

DG: Thank you, Vincent. Thank you everyone and be safe.

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[00:44:58] [END OF AUDIO]

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