TWiV 735 COVID-19 Clinical Update #55

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 26 March 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 735, recorded on March 25th, 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: How’s it going this week, Daniel?

DG: We are sitting on this plateau that we seem unable to get off of. As quickly as we vaccinate, everything opens back up. It’s a constant battle and I have to say, that’s the good news, right? Because around the world, the numbers seem to be increasing. Here we are a year into this and– over a year into this and we are not where we need to be. Let’s be honest, I was listening to another podcast, Vincent. I was cheating on you, right? Listening to other people’s podcasts. It’s okay. It was actually Anthony Fauci was talking. It was 1984 and he was saying, “We have the virus, we know the sequence. I expect to get back to you within the year with a cure and a vaccine.” It was like 16 plus …. 37 years ago.

VR: Wow.

DG: This is miraculous, right? That we went in less than a year from a sequence to a vaccine.

VR: It is.

DG: But it’s not miraculous. This is science. This is all that, I say basic science that we spent all this money investing in. My quotation, “Every great dream begins with a dreamer. Always remember, you have within you the strength, the patience, and the passion to reach for the stars, to change the world,” and that was Harriet Tubman. I think maybe that’s sort of appropriate with what we were just saying. This really has been tremendous over the last year to go from identifying that some people are dying from a strange illness, unidentified to understanding the etiology to a really impressive vaccine.

We haven’t done quite so well in other measures as far as therapeutics, but the vaccine has really been quite impressive. I’ll make sure I spend a little time talking about that today, but my rule is: never miss an opportunity to vaccinate, never miss an opportunity to test, never waste a vaccine dose. I’m going to entitle today’s episode, School Shots and Cocktails. I’m not sure how schools fit in with the shots and cocktails, but the shots and cocktails is what I call the Irish method for ending the pandemic.

There have been a few ID Society, IDSA, ID Society of America updates. I’m going to pepper those in as we get there, but there also were some nice reports from the CDC on schools.

In our section, Children and COVID, let’s start there. I mentioned last week that I was not particularly impressed with the Massachusetts study. That was the three versus six foot study that was not even quite observational, but I did intimate that there was good data out there and that we had the suggestion that we would be getting more of it, and the CDC delivered on their promise.

The MMWR “COVID-19 in Primary and Secondary School Settings During the First Semester of School Reopening in Florida,” August through December 2020. This was a report looking at close to three million registered students that were enrolled in approximately 6,800 public, charter, and private K through 12 schools ranging from a small size, maybe 707 to over 300,000 students per school district. Most of these schools had actually resumed in-person instruction sometime during August of 2020 except for those in two of the largest school districts, Broward and Miami-Dade, which began remote learning in August, but did not resume in-person instruction until October 9th and then November 10th, respectively.

Statewide, as of September 24th, almost half, 45% of registered students received full-time in-person instruction. Really the question here was how did that go? To assess the occurrence of COVID-19 in the Florida schools after resumption of in-person instruction, the CDC and the Florida Department of Health reviewed school-related cases and outbreaks during August through December of 2020. The county health department staff members conducted case investigations and contact tracing for all COVID-19 cases. This was, I have to say, there was a lot of rigor here. They were really looking into this and they found that fewer than 1% of registered students were identified as having school-related COVID-19.

Significant findings were that most of the identified cases in this age group were not school exposure-related and I know I’ve brought this up on some talks. Parents get upset when I suggest that perhaps the children are safer in the schools than sometimes they are at home, but it’s not a parenting comment. It’s that your child is home all day, socially isolated, there’s a tendency for the kids then to get together after that period of remote learning. One of the comments here is that masks being mandated was associated with less transmission and that was a p-value of less than 0.01.

The other thing that was a predictor was community case rates. Once community case rates started to go up, this was associated with a higher risk and that had an even more significant p-value of less than 0.01. There was another study and actually, there have been a few, but just to highlight another one, “Low SARS-CoV-2 Transmission in Elementary Schools,” Salt Lake County, Utah, December 3rd, 2020-January 31st, 2021. Here, there were very similar findings including low school-associated transmission with high mask adherence and classroom seat separation of three feet apart.

I know here in– I have to say right here in the North Shore of Long Island, our schools are getting ready to open up for full in-person next month in April. They’re looking at the three feet and as I mentioned, the three feet is something that’s really required for getting people back to full in-person school. Very few parts of our country have the real estate, the size, the space to do six-foot spacing and the data I suggested last time is you get about 80% of the benefit at three feet, you get down to a 90% reduction by six feet, but you get most of that bang for the buck in the first three feet.

You couple that with masks, you couple that with upgraded ventilation systems, you add testing, and I think that this again, this is something that can be done at low risk. We’re getting more data. This is a science-driven recommendation.

Testing, the CDC updated its guidance on testing. I know there’s been a lot of focus on vaccines and we’ve forgotten about our poor tests, but there are key points in the updated recommendations. One, they said persons with signs or symptoms of COVID-19 should have diagnostic testing. I know there’s a tendency to give out the presumptive diagnosis, but we really want to confirm these. The CDC is really saying, get people tested, document what’s going on here. Rapid point of care, serial screening can identify asymptomatic cases and helped interrupt SARS-CoV-2 transmission.

They’re going to say this is especially important when community risk or transmission levels are substantial or high and this sort of goes into that frequency and rapid results are really critical. What gets us into trouble are these resulting delays. They’re really having the CDC coming out here, really endorsing the use of rapid point-of-care tests. These are being used still by clinicians across the board and then making a judgment. If it’s positive and it makes sense, great. If it’s negative and doesn’t make sense, looking at PCR, looking at making decisions about isolation and quarantining, et cetera.

The selection and interpretation of SARS-CoV-2 tests should be based on the context in which they are being used, including the prevalence of SARS-CoV-2 and the population being tested. Testing gets a little sophisticated as we’ve talked about. There are negative and positive predictive values which are maybe more important than sensitivity and specificity as sensitivity and specificity need to be brought into the context of prevalence which ultimately tells you when a test is positive or negative. How confident can you be in that result?

Then this, I think, is really important. I get this question quite a lot. It’s nice to get the CDC putting up something on this. Prior receipt of an mRNA COVID-19 vaccine will not affect the results of SARS-CoV-2 viral tests, right? A lot of people ask, they say, “I’ve been vaccinated. Can I even look at the test results?” Yes, you can. You can still count on these. I will say that there is now about $10 billion available for K through 12 schools to expand the coronavirus screening of staff and students. I think this was a quote, but this funding could be used for schools to offer rapid antigen tests that generate results in 15 minutes, allowing schools to quickly respond when students or staff test positive for the virus.

Finally, our article, “Identifying optimal COVID-19 testing strategies for schools and businesses, balancing testing frequency, individual test technology, and cost,” was published. It was actually– it was interesting, under embargo until about 2:00 p.m. today, so I couldn’t talk about this until, well, a few hours before Vincent and I recorded this, but now it’s fair game once this gets dropped. This article is an open-access article in PLOS ONE, and what we’re doing is trying to create paradigms, some sort of guidance on how people can use testing in the school, and actually really any opening plan that they might have.

I’ve been getting a lot of questions, and it really goes back to the variant thing and the question I’ve gotten lately is whether a person infected with a variant will still have a positive COVID PCR. I’ll cover this here in the testing section, and when I get this question, I usually say yes, but then I walk through the technology of the tests, and I point out that many of the COVID PCR tests, which really should be SARS-CoV-2 PCR tests, go to Quest or Labcorp. The Quest PCR primers target nucleocapsid. The Labcorp PCR test has one primer set targeting nucleocapsid and another targeting the RNA-dependent RNA preliminaries sequence. Therefore, a change in the sequence of the spike protein should not impact this test.

In addition to the logic here, this has actually been studied and both Quest and Labcorp have come out saying that, “Yes, this understanding translates into reality and that these tests continue to be sensitive and specific despite changes in the sequence of the spike protein.” As I said, the test still gives you a positive result, even if your infection is with a variant, but it does not tell you whether this positive result is detecting that you have or do not have a variant, and unfortunately, we still are doing very limited amounts of sequencing, so we don’t quite have the robust surveillance that actually is probably important for monoclonals when we get there.

Active vaccination. I’ve got a few questions I get hit with, so I’m going to put them out here. “Can a person get COVID after the vaccine?” The answer is, yes, but it is much less likely, and when they do, they tend to do much better. We actually have some pretty robust data, really suggesting that the vaccines are impacting not only symptomatic but also asymptomatic, certainly severe or critical disease.

“If I had COVID, how long should I wait to get my vaccine?” The CDC and I were on the same page on this. We recommend no minimal interval. As soon as you feel well, go get that vaccine. We don’t want to go out during the first 10 days, right? You’re in isolation, but as soon as that isolation ends, as soon as you start feeling better, get yourself scheduled, get out there.

“If I get COVID after my first shot, should I still get my second shot?” Again, this goes back to the same thing. As soon as you feel better, you can go ahead and get that second dose. Wait your 10 days of isolation, so you’re not going to the vaccine center getting everyone sick and infected. Most of the sites have a “Manage my Appointment” feature online, so you could actually go in and push that off a little if you’re in 10-day isolation, if your symptoms mean that there’s going to be a little bit of a delay here.

“If I had Long COVID or had COVID before, should I get that second shot of the two-shot vaccines?” This can get a little complicated, but I’m going to say we do recommend two shots for everyone. Of note, we’re hearing more reports. I’m going to cover one here today, that improvement in Long COVID often doesn’t come until after that second shot. Certainly, if someone has an anaphylactic or an autoimmune or concerting reaction, then whether or not you get a second shot should be a decision made in consultation with a specialist, but in general, the answer is, get that second shot.

“Do vaccines prevent asymptomatic SARS-CoV-2 infection?” I’ll say here, although we have good data vaccines prevent symptomatic and severe COVID and what’s really going to be ending this pandemic, is really going to depend a large part on the impact on asymptomatic infection and transmission. As we know that about 50% of the transmission is probably done by either pre- or asymptomatic individuals. We are getting more information suggesting that it prevents asymptomatic infection as well.

We have another paper here, “Impact of the COVID-19 Vaccine on Asymptomatic Infection Among Patients Undergoing Pre-Procedural COVID-19 Molecular Screening.” This was published in CID and goes right at that issue. These are asymptomatic individuals who are being tested as a pre-procedural screen.

This group conducted a retrospective cohort study of consecutive, asymptomatic adult patients (n = 39,156). This was done within a large healthcare system here in the United States. They underwent over 48,000 pre-procedural SARS-CoV-2 molecular screening tests December 17 through February 8, 2021. They compared individuals who had received at least one dose of the mRNA COVID-19 vaccine versus those that had not, and they looked at the relative risk of a positive SARS-CoV-2 molecular test among these asymptomatic persons, and then they adjusted the relative risk.

They found that compared to unvaccinated individuals, the risk of asymptomatic SARS-CoV-2 detection was lower among those greater than 10 days after the first dose, their relative risk was 0.21. I think this is critical here. This is suggesting almost an 80% reduction in the risk of an asymptomatic infection, which is interesting. How do we define infection if you’ve gotten infected but no symptoms? Also, we are seeing, as we translate this, we have vaccinated millions of individuals, which means an 80% reduction means we are still seeing lots of people who are PCR positive after their vaccines, and as I mentioned before, the experience we’re seeing is they tend to do quite well, and I think the science and experience support that. Now, I’ve mentioned briefly on the last TWiV, this observation that we’re seeing this. It’s just to sort of give you the real world mixed with what we’re seeing in the literature.

The question of, “Are vaccines safe in patients with Long COVID? A prospective observational study.” This was posted as a preprint by a group out of the UK, and this is looking at that issue of vaccine impact on Long COVID. You can see here they’re really going into this with the question of, “Is it going to be safe? Are they going to be okay? Will there be harm?” This group looked at patients that had COVID-19 severe enough to require hospitalization who then went on to develop Long COVID. That’s a minority. Most people with Long COVID never were sick enough to end up in the hospital.

They looked prospectively at 44 vaccinated participants and 22 matched unvaccinated participants and assessed them at a median of 32 days post vaccination. These were mostly people with severe or highly symptomatic Long COVID about eight months after acute infection. They reported that 23.2% reported an increase in symptom resolution versus 15.4% in the unvaccinated with a p-value of 0.035 in just the small sample size. They reported no obvious difference in response between mRNA vaccination versus adenoviral vector vaccination.

It’s nice to actually start to have some science here instead of lots of building anecdotes. This is encouraging and does seem in line what we’ve been hearing from patients, physicians, or post-COVID recovery clinics and support groups. But still a few caveats, right? This study only looked at post first dose improvement, so I wouldn’t hang my hat on the percent reporting improvement. As we’re hearing, as I mentioned before that some do not report improvement until after their second dose or farther out with the one dose J&J vaccine. This is also a small sample size with really short follow-up. We do not know much about the long-term as far as the durability of this reported improvement, but this study does support the safety of vaccination for people even with severe Long COVID and here is this suggestion of possible benefit.

AstraZeneca vaccine, the white elephant in the vaccine room, we got a press release reporting the results of the AstraZeneca U.S. phase III trial demonstrating statistically significant vaccine efficacy of 79% at preventing symptomatic COVID-19 and 100% efficacy at preventing severe disease and hospitalization. A lot of people got really excited. Anthony Fauci said, “This is fantastic but maybe not.” I’d like in this just– someone’s getting measured and you notice they’re standing on their tippy-toes. It may be 76% of preventing symptomatic, but we heard, I think, some disturbing news that maybe they had cherry-picked, maybe they had not presented the most up-to-date data. It’s a little disturbing because the thing we really care about, “Is this a vaccine that keeps people from dying, from ending up in the hospital?” That data has continued to be very clear. This other sort of competitive number, what’s the number for mild disease whether it’s 76, whether it’s 79, would have been better if this data had been presented better.

It’s unfortunate here because this is really a great vaccine from a physician’s standpoint. This is easy to use, it can be stored, transported, handled at normal refrigeration conditions for about six months. Doesn’t need any kind of preparation before you administer, so it’s a much easier vaccine for us. As we heard, the Data Safety Monitoring Board notified everyone that this data was not quite the data that we wanted it to be. I will return to the AstraZeneca vaccine when all the information is available for the FDA review and we have a chance to go through the data.

Just want to sort of remind everyone here, we’re not just, “Oh, call it a vaccine and we’re pro.” We’re going to be honest. When something like this happens, we’re going to share that, as I’m doing here now.

Passive vaccination. This is the monoclonal antibodies. Really good uptake of the monoclonal antibiotic cocktails and we continue to see excellent results. This is now part of the IDSA guidelines. What exactly do their guidelines say?

They advocate for the use of bamlanivimab and etesevimab together in outpatients with mild to moderate disease who are at high risk for progression to severe disease and say that casirivimab/imdevimab may have a similar clinical benefit but the data are currently limited. Well, I have to say, in the days of COVID, the concept of living guidelines is presented with lots of challenges as we live in the days of the fire hose of information. This week, Tuesday, March 23rd, Regeneron released the data from their phase III trial as promised.

I feel like these guidelines need to be rapidly updated. These results from Regeneron were from a phase III randomized control trial looking at treatment in infected non-hospitalized patients, 4,567 in this trial. They met the primary endpoint of showing that the REGEN-COV, this is the Regeneron cocktail with the casirivimab and imdevimab, significantly reduces the risk of hospitalization or death by 70% with the low dose, 71% with the higher dose compared to placebo. The p-values for high and low dose were either 0.0024 or less than 0.0001. No safety issues were observed.

I think the data is becoming really compelling for the impact of this approach, the monoclonal cocktail approach. What was really interesting, I have to say, in this press release– I’m looking forward to the published data– is they actually provided a table of neutralization data looking at several variants from different regions of the world. They tested key substitutions and actually showed that this therapy based on this data would continue to be effective. We’ve moved to cocktails, I think as I mentioned, across the country. Vaccine shots and monoclonal cocktails for everyone.

The early inflammatory phase. We have a little bit of information here. There was a paper, “Aspirin use is associated with decreased mechanical ventilation, intensive care unit admission and in-hospital mortality in hospitalized patients with coronavirus disease,2019.” This was published in the Journal of Anesthesia and Analgesia. This was a retrospective observational cohort study. We got to put that in that context. They looked at COVID-19 patients admitted to multiple hospitals in the United States between March and July of 2020. The authors looked back through the medical records, basically identifying who was on aspirin, who wasn’t on aspirin, and then they tried to adjust.

I want to point out, this was not a randomized blinded prospective trial. They ultimately looked at 412 patients, 314 (about 76%) not getting aspirin, 98 patients (or about 24%) did get aspirin. They reported seeing that the patients getting aspirin were less likely to end up needing to be transferred to the ICU, less likely to end up needing mechanical ventilation, and less likely to die while in the hospital. They did not report any significant increase in bleeding complications.

Just to put this in context, this is not a prospective randomized control trial but sort of interesting attention on the possible role of aspirin. Here again, in this section, the early inflammatory phase, the IDSA has updated its guidelines and is now recommending that tocilizumab should be used in hospitalized patients who are sick enough to have progressive severe or critical COVID-19. Of note is that this is an add-on to steroid therapy.

We actually have a bunch today on the Long COVID, the post-acute sequelae COVID-19. There was a really nice review, “Post-acute COVID-19 Syndrome,” that was published in Nature Medicine. There really was so much here that I’m going to actually say, people should sit down, read this once, twice, three times. They have a really nice box summary of the post-acute COVID-19 issues by organ system. They go through all the pulmonary issues, hematological, cardiovascular, neuropsychiatric, renal, endocrine, GI, dermatologic, and then even have a little section on the MIS-C. This is excellent.

I think as we’re working with these patients in our Long COVID or post-acute COVID recovery centers, this is actually a helpful paper for realizing that it actually takes a team to help these individuals. The neurologist might jump in with a lot of the severe headaches, which seem like vascular migraine type. Pulmonary is critical cardiology. There’s a lot of complexity here.

We also saw “COVID-19 Survivors’ Reports of the Timing, Duration, and Health Impacts of Post-Acute Sequelae of SARS-CoV-2 PASC Infection” was posted as a preprint. This was a very interesting paper in that the participants in this study are members of Long COVID support groups. I actually say– I think this represents an exciting development whereby citizen scientists are working together with data and other scientists to try to understand the challenges, the needs, and characteristics of these people suffering from Long COVID or what’s now termed post-acute sequelae of SARS-CoV-2.

Very interesting and consistent with my experience are the described stages or waves of this post-acute COVID experience. With this early wave, with neurological and cardiovascular manifestations, then a second wave with skin manifestations such as COVID toes, hair loss, and then this final wave of symptoms during which the fatigue just continues to be ongoing. I think that this is sort of nice for clinicians who are taking care of these patients to see how the patients are describing this experience.

I think it helps for the patients as well to speak to a clinician that has had the ability to understand this. There’s a lot of validation for the patients here when you can sort of be almost anticipating where they are in this process and what the challenges might be at that time. There certainly are limitations here. One is that this was predominantly white women since the participants come from online support groups. There’s a certain amount of selection, so this isn’t a random sample.

One of the things I was going to say, I’ve heard several times where clinicians look at people with Long COVID, they say, “You know what, these people are doing much better than the average ICU survivor. If I was in the ICU and survived, I’d rather have Long COVID than something else.” What I’d like to point out here, and this was very clear from the paper, is that 84% of these people who are doing so well compared to someone who spent a month in the ICU, never were even hospitalized.

A lot of these individuals started off with a mild or even asymptomatic acute COVID and here they are many, many months later looking a little bit better than someone who was in the ICU for sepsis or something else. Also, another paper, “Persistent Neurological Symptoms and Cognitive Dysfunction in Non-hospitalized COVID-19 Long-haulers.” This was published in the Annals of Clinical and Translational Neurology.

They reported the results from this, was a prospective study of 100 consecutive patients, SARS-CoV-2 laboratory positive and then they had a 50 laboratory negative control group. These individuals presented to a neuro COVID-19 clinic. Due to early pandemic testing limitations, patients were included if they were never hospitalized for pneumonia or hypoxemia and had neurological symptoms lasting over six weeks. This is sort of a snapshot of those people who never ended up in the hospital but had a neurological issue that required attention. They reported that the main neurological manifestations were, I think this will sound familiar to people– brain fog was reported 81%, that feeling that you just can’t think clearly, 68% were reporting headaches. As I’ve mentioned, a lot of these headaches actually seem like the intractable vascular migraine severe headaches. Numbness and tingling 60%, dysgeusia 59%, anosmia 55%, myalgias 55%, and the overwhelming 85% had this ongoing fatigue. They exhibited impaired quality of life in cognitive and fatigue domains, and the patient performed worse on attention and working memory cognitive tests compared to that control population and demographically matched U.S. population. I think this points out what’s really upsetting to a lot of us, just how many of these patients are continuing to suffer.

Let me close on there. Leave a little time for emails but just ask everyone for their continued support, and thank you so much for all the support we’re continuing to get. We are going to continue to support the American Society of Tropical Medicine and Hygiene. It looks like we’re going to succeed in being able to donate enough money for three travel awards, bringing early-career women from low-income parts of the world to come to the fall annual American Society of Tropical Medicine meeting. Thank you for continuing to support our work.

VR: Okay, it’s time for some email. You can send yours to daniel@microbe.tv. The first is from John Mascola, who is the director of the Vaccine Research Center at NIH. John writes, “I love TWiV. I listen every week. As an ID doc that does mostly research, I also appreciate the COVID clinical updates, so glad to help out Dr. Dan Griffin regarding one question that is in my wheelhouse, where he did not know the answer, immunogenicity of COVID vaccines in older subjects. There are published data showing mRNA is similarly immunogenic across age groups, so good news.” John provides a link for that. It’ll be in the show notes.

DG: Thank you, John. I think this is great. I mean, this just reinforces that this is not actually just a one-man show. I get a lot of support from my colleagues, and I love this. I love getting emails, and you can send them either directly to me, or this is even better, send them to daniel@microbe.tv. And yes, this is great. There’s a lot of information. Thank you so much, John, for sending this in.

VR: Yes, if you send them to daniel@microbe.tv, then many more people will get the answer rather than just you, and that’s better.

DG: Yes. That makes my life easier. Send them to daniel@microbe.tv.

VR: Paul, in the University of Manchester in the UK wants to know if you can comment on the AstraZeneca vaccine, specifically the clotting issues, and wonders if he should be taking aspirin around the time of vaccination.

DG: Yes. I actually appreciate the fact that you wrote this in. If you look at the data here, it looks like the incidence what 30 in about that many million people vaccinated, one in a million, which is actually not higher than we see as a background in the population almost seems lower, to be honest. I think that we’ve come down with not thinking that there’s any kind of clotting complication associated with the vaccine, but I don’t think the AstraZeneca has done such a great job of instilling confidence. I will weigh in– as I do not think this is an issue. I’m not going to recommend taking aspirin around the vaccine. I actually think this vaccine is effective. I think it’s safe, but it just maybe wasn’t quite as effective with a few percentage points off of what they were trying to suggest.

VR: Anne is treating a patient, 77-year-old patient got her first vaccine on March 6th, and then she was found unresponsive and, finally, had a diagnosis of encephalopathy with possible seizure. Anne wants to know what to do. “The family’s quite apprehensive about the patient receiving the second vaccination, never has allergic reactions, only medical intolerance is myalgia on statin therapy. I’m inclined to have the patient receive the second vaccination, but wondered if you had a different response.”

DG: This is a tough one, I have to say. This falls into this category where I think this is going to have to be an individual decision where you look at the situation, and you’re going to have to try to parse out, do you think this encephalitis was a vaccine reaction? We certainly– I think I related the story of this. I had a gentleman who developed an autoimmune reaction. It was really a multi-inflammatory-type syndrome with his natural COVID infection. He had issues with his vision, diplopia. Then when he got his vaccine, he actually seemed to have recurrence and responded very quickly to steroids and IVIG. We talk about these are agents that have efficacy that have effects on the human body. I think that this is not going to be a very easy decision. Anne, I’m glad you’re making it and not me. I think you probably want to reach out to your local ID, your local allergy immunology. Really, make sure that we’re giving the best advice here. So, this is complicated.

VR: All right. The last one is from Anthony from Brown University Medical School, who is a family physician who encountered a scenario this week, confused about despite the benefit of your teaching, “I was involved in the care of an elderly woman who lives in the community but is homebound, has home health aides. Unfortunately, one of her aides tested positive for SARS‐CoV‐2 last week, on the day that this patient received her second mRNA vaccine. Four days later, the patient has now tested positive but is asymptomatic. She clearly meets criteria for eligibility for monoclonal antibody based on her age. The conundrum is she’s also probably derived some protection from developing COVID from her newly completed vaccine series, and there would be a theoretical concern about the passive immunization provided by monoclonal therapy, blunting her own immune response. We decided to get her treated, prioritizing short-term gains in a patient at risk. What would you say?”

DG: Yes, so I would treat in this case, and let me just run through my rule and the thinking. If someone meets criteria, as we’ve shared the data, these are really impressive tools, the monoclonal cocktails. You take an individual, and you look at this individual, and you say, “Okay, this is a person who is high risk for ending up in the hospital.” If they end up in the hospital, we know that people often don’t do very well. The monoclonals are really going to reduce that chance of progression. I actually expect someone who’s already had the benefit of the vaccination, the benefit of already starting up to have some sort of a T-cell response is going to do even better. That’s actually, I have to say what our experience has been.

What is really the downside? I’m going to ask that question. You give the person monoclonals. Okay, maybe that second dose of vaccine doesn’t work so well. In three months, you can probably go ahead and give that second dose again, basically say, “Okay, I sort of interfered with its ability to have efficacy,” and for that three months while you’re waiting, the person has these monoclonal antibodies at a very high level, they’re protected, they’re passively immunized. Basically, what you’re doing here is you’re instantly having this person immunized by sending them for monoclonals, rather than waiting for whatever days for this to happen.

I do not– we don’t in any of our programs– use prior vaccination as an exclusion criteria. If the person ends up getting infected, it’s either because it wasn’t enough time for them to get protection, but as we point out, we might do a study of 40,000 people where 20,000 get it, no one ends up in the hospital, but you translate that into the real world, where you are starting to give this to older individuals, maybe they have medical problems, maybe they have an issue bouncing that protective response, they end up infected with the virus. I would advise jumping in with these really highly effective therapies.

VR: That’s COVID-19 clinical update number 55 with Dr. Daniel Griffin. Thank you, Daniel.

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

[00:38:54] [END OF AUDIO]

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