TWiV 744 COVID-19 Clinical Update #58

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 17 April 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 744, recorded on April 15th 2021. I’m Vincent Racaniello. You’re listening to the podcast all about viruses. Joining me today from New York, Daniel Griffin.

DG: Hello, everyone.

VR: This is clinical update number 58. Have things gotten better since last week, Daniel?

DG: I’m not going to say that they have. I will start off with a quotation that is in line with that. “When things are going well, something will go wrong. When things just can’t get any worse, they will. Anytime things appear to be going better, you have overlooked something.” That is the immortal words of Richard Feynman.

VR: Excellent. That’s perfect for this week, isn’t it?

DG: [laughs] Yes. I don’t know if people have a chance to read but he’s written a few books. One of them, Surely You Must be Joking, is one of my favorites. This has been a very tough week, so never miss an opportunity to vaccinate, never miss an opportunity to test, never waste a vaccine dose. Let me start off with my update. We’ve got a lot of stuff that happened this last week so we have a lot to cover.

This week, there was some attention given to Lost on the Front Line which has been a 12-month investigation by The Guardian, KHN (Kaiser Health News), to track healthcare worker deaths during the pandemic. I found that reading the article, this was titled, “12 Months of Trauma: More than 3,600 U.S. Health Workers Died in COVID’s First Year.” It was a very emotional experience for me to read this through.

I focus on the science, what we can learn from this experience, what we have learned about how to treat this horrible disease, but all the work we still need to do. I think to take stock of what we’ve really been through is upsetting. As I recount, thousands of healthcare workers that have died over the last year, these are my colleagues. Many of these individuals I’ve known, trained with. There were some key findings that were here in this publication, just a few of them.

One, more than half of those who died were younger than 60. I think that that is something. The general population, the median age of people who died from COVID is in the 70s, but in the healthcare worker population, it was younger. The other, nurses and support staff died in far higher numbers than physicians. There’s an equity issue here where the physicians were either better able to, or better helped to, keep themselves safe.

As I think a lot of people know, if they’ve ever been in a hospital, ever interacted with healthcare, it’s the nurses, it’s the assistants, it’s the aides who are really in there hands-on. One of the other, twice as many healthcare workers died in nursing homes as in the hospitals. This is something of a particularly sensitive issue for me because of all the controversies about the nursing homes and the fact that a lot of those workers, where I have to say, blamed, “Oh, those hard-working health workers brought it into the nursing homes.” It’s really tragic just how many of my colleagues have died through the last year.

The last week, I was talking with one of my partners, Anuja Lee, who is now the associate chief of the Division of Infectious Disease for ProHealth New York, just about how fondly I remember all the support and recognition we received from our communities during these difficult times, the free food, the evening vigils, the plaque cards, some of those are still up. Just to let everyone know, this has really meant a tremendous amount. Things continue to be tough, but I have to say, all the support has really meant something. Thank you.

In addition to all my colleagues that died directly from COVID, I suspect many of our listeners aren’t aware of how many. Well, more than one of my colleagues, you may even know in local community circles here, just found this whole tragedy too much and actually took their own lives during these dark times. This continues to be a difficult time. We are on a plateau with far too many people getting infected, far too many people dying.

Here in the U.S., we’re on a plateau. When we look beyond our borders and we don’t have to look very far, we can see those numbers. We’re now seeing counted over five million new cases a week and the death toll just keeps climbing. We are nowhere near mission accomplished here.

On that happy note, children and COVID and masks I’m going to throw in here. Perhaps, I’ll be remembered for a few things after this settles down. One of them trying to point out early on the tragedy of Long COVID and not to dismiss these individuals that this was real. I think the other is for repeatedly my attempts to point out that children, I believe, are at lower risk but they’re not at no risk.

There was a research letter that was published in JAMA, Characteristics and disease severity of U.S. children and adolescents diagnosed with COVID-19. Now, the authors here were affiliated with the COVID-19 response team at the CDC. The Epidemic Intelligence Service, Center for Surveillance Epidemiology and Laboratory Sciences, also at the CDC, and the commissioned core U.S. Public Health Service in Rockland, Maryland.

A couple things that this article pointed out. One was that more than two million pediatric COVID-19 cases were reported in the United States in 2020. They say, although approximately half of pediatric patients with COVID-19 experience mild disease, some children require admission to intensive care units or require the use of invasive mechanical ventilation. What they did here is they conducted a cohort study to try to estimate adjusted associations between demographics, clinical characteristics, and severe COVID-19 among hospitalized pediatric patients.

We just go through a little bit of what they present to us, but I’m going to give the caveats as well. They evaluated a cohort of 20,714 pediatric patients with COVID-19. Pretty evenly split, about 52.9% were girls. The other half, males, so we have a split here. They reported that of these individuals, 11.7% were hospitalized and of those hospitalized, about a third had severe COVID with management in the ICU, so a lot of caveats here.

I think that we can say a couple things from the study. One, this seems consistent with the experience shared among my pediatric colleagues, is that if a person under the age of 18 ends up in the hospital, as we saw this cohort, a quarter to a third of them will be taken care of in the ICU. One of the things the authors even said is it isn’t even necessarily the same level of severity we might see an adult that prompts that, but we have a heightened level of concern for our younger individuals.

One of the things that is tough, I don’t think we really have a good sense, and I’ve touched on this before, about how many kids with COVID actually go undiagnosed. We never find all the asymptomatic kids and we certainly never find the untested symptomatic kids. I don’t think we have a true denominator here.

The one thing I’m going to say, I like to be honest on this, when I see, “11.7% of kids that get COVID end up in the hospital,” I don’t think that really is consistent with our experience. I think 11.7% of this cohort ended up in the hospital. That is true but I’m not sure this is representative of the entire pediatric cohort. I think if that was actually happening, our pediatric hospitals would not be as quiet as they were during the pandemic to date. That may be different in different countries.

Some positive news on the vaccine front, don’t worry I’ll get to the negative, Pfizer-BioNTech did announce that they are requesting expansion of their EUA to include individuals aged 12, 13, 14, and 15. I discussed a week ago, when we recorded the last TWiV, that this was impending. Once that was announced, the clock would start with a minimum of 15 days from the announcement. We’re moving into that.

We’re hoping that in May, we’re going to see Pfizer expanded down to age 12. Also, still on the children in COVID, I’ve been getting a lot of communications about this. I think many people are comfortable with the idea that schools can be safely opened, but I’m getting a lot of questions about something I brought up on the last TWiV. There is this disconnect between, “it’s safe for the kids to sit three feet apart with masks on” and, at the same point, the CDC considering being within less than six feet, so at three feet, regardless of masks being an exposure.

Where are we with– as of March 21st, 2021 CDC Public Health Guidance for Community-Related Exposure definitions and guidance. As per the CDC, individuals who have had close contact within six feet for a total of 15 minutes or more exposed to– We pause there for a second. The CDC is still using that 15 minutes. I know a lot of times, you see the 10 minutes thrown out there. I’m scouring through the CDC website. Fifteen minutes seems to be what the CDC is still putting up there.

Exposed to whom? To a person with COVID-19 who either has symptoms or in a period two days before symptom onset until they meet the criteria for discontinuing isolation. That is either 10 days or there’s the test-out ending isolation option. The other is a person who has tested positive for COVID-19 but has not had any symptoms. Again, you’re going to do the same thing. You’re going to use that as your start date. The exposure is any time two days prior to that positive test or until they meet the criteria for ending the isolation.

The two issues here, the first one I pointed out, 10 minutes versus 15 minutes. The CDC is still using the 15 minutes, but then there was a note. There was a note right below this and it says, “Note. This exposure, this is irrespective of whether the person has COVID-19 or the contact was wearing a mask or whether the contact was wearing respiratory, personal protective equipment, PPE.” Wait. Do masks work? We were just told that three feet of distance with everyone wearing masks in schools is minimal risk. Here, it comes down to the issue. Should the CDC update guidance for what is considered a school exposure and what ends up triggering quarantine?

I will say one of the schools in our area, not right here in Port Washington, but one of our local schools has been in contact with the local community of health, local Department of Health, and they’ve actually updated their local guidance and said, “No. If we’re going to allow these schools to open under these circumstances, if everyone’s wearing masks three feet apart with enforced mask wearing, if that’s really being held to, can you consider that a trigger for quarantine?” I think this is an important issue, if being three feet apart, less than six feet, wearing masks indoors at a school should count as an exposure.

This is actually an interesting issue because for healthcare workers, we actually have slightly different rules. For healthcare workers, there’s the idea that we know how to properly wear masks. There is some concern that, at least part of the CDC up until now, that people don’t really either know how to wear a mask properly or the mask that they are wearing are not proper masks. I understand the concern that people don’t wear their masks properly and the masks are different quality. I do want to point out, Dr. Fauci, we all see him on TV, we see our president, they’re not wearing medical masks. They’re wearing cloth masks.

I think it’s critical for messaging that we get on the same page with regard to are masks effective or not, but maybe we haven’t been doing enough education about how to wear those masks properly. I’m actually going to take a moment here. This will be my public service announcement on how do you wear your mask properly. I’m basically going to be sharing helpful CDC advice on how to improve how your mask protects you and others. I’m going to hit eight points here.

One, make sure your mask fits snugly across your face. You should be breathing through your mask and not around it and please cover your nose. In my mind, if your nose is sticking out, you’re not actually wearing a mask. For those people watching, I have a couple of masks here to demonstrate. I’m going to demonstrate that now. If you’re listening, I’ll describe it for you. I’m going to put a mask on that will fit snugly against my face.

I think people who are watching can see. Actually, I want to thank one of our listeners who I believe– this is handmade in Thailand. It’s not important that your mask is completely symmetrical, right? It’s not important, right? I always get in trouble with that, trying to get my mask symmetrical. It has to fit. You want to use a nose piece if you can. That’s number three. Choose a mask with layers. I’m going to take this off now.

You don’t want to have just one thin piece of fabric. You want to have layers. Also, some of these will actually have the ability to put a filter in there. Three, choose a mask with a nose wire to improve the fit and bend that wire over your nose to fit close to your face. Four, check your mask to make sure you feel warm air coming through the mask, not out the sides, the top or the bottom. Five, if you have facial hair, we’re not sure how effective masks are. Trim that beard if you can, consider double masking, consider shaving. Six, do not pull your mask down or out of the way to speak.

I want to use that as an example. Again, I saw this and I see this all the time. People put their mask on and then they want to speak. They either pull it away from their mouth or they pull it down to speak. I think while we may have witnessed one of our elected officials, he needed to cough or sneeze, he pulled off his mask, coughed into his hands, sneezed into his hands. I’m not sure where he wiped them. You do not take the mask off to cough or sneeze or talk. You want to have it on specifically at those times. Also, don’t take it off to yell at the athletes. That’s another one I see.

Also, teachers, you do not take it off to have your students better understand what you have to tell them. Seven, do not wear masks with one-way valves, they only protect you and not others. You are sending a very negative message. Eight, do wash your hands immediately after removing a mask. Remember, this is supposed to protect you. If it’s actually protected you, it is now potentially dirty. Take it off by the loops and then try to avoid contaminating your hands. We also have some do-nots from the CDC. Do not wear two disposable masks at the same time.

If you’re wearing those blown masks which are that charged fiber, these have been studied one mask at a time, not two. This also applies to the issue of KN95 or N95s. We are currently recommending not to cover those with a surgical mask. I have to say for my medical colleagues, we got quite used to the fact that we were using surgical masks to protect and preserve our N95. I know some of my colleagues still feel a little bit odd about that.

All right, the pre-exposure period. On April 13th, we saw the article, Physical inactivity is associated with a higher risk for severe COVID-19 outcomes: a study in 48,440 adult patients. This was published in the British Journal of Sports Medicine, this might be a surprise, that exercising might have some health benefits. I’m going to go out on a limb here. What did these individuals find?

They found for those individuals who were consistently inactive that they had a greater risk of hospitalization. These are individuals diagnosed with COVID-19 who were consistently inactive. Their odds ratio of hospitalization was 2.26. Their admission to the ICU was 1.73, increased odds ratio, and their chance of death was 2.49. Almost twice as likely to die if they were diagnosed with COVID-19, ended up in the hospital. Basically, people who are consistently inactive have a higher risk, at least per this study.

Out on a limb, perhaps people should exercise, one more reason. Now, we need a randomized control trial where half the people exercise and the other half serves as the control to really determining if exercise is a good thing. I’m a little worried if we do this as a blind study, people are going to end up hurting themselves. Somehow we have to have people exercising, not exercising, not aware of which group they’re in, and not wearing blindfolds testing.

I think we’re seeing an interesting pattern here in our primary care and urgent cares where people are post-vaccination. They have what seems like mild symptoms after a good COVID exposure, but yet, their antigen tests negative. We may be seeing some of that effect of the vaccine below the radar of even getting positive testing. When we have more information, I’ll make sure I share that.

Active vaccination. Everyone’s probably waiting for this. I expect all our listeners are familiar with the J&J vaccine pause here in the U.S. Let me just give everyone an update. I had the opportunity to be on the call today where we got a rundown on what we know today. This is hot off the press.

There were six reports to the vaccine adverse event reporting system between March 19th and April 12th of women between the ages of 18 and 48 having a rare clotting complication. These individuals had cavernous sinus thrombosis. This is a clotting of the vein complex inside your brain. Think about your few inches behind your eyeballs there. They had platelet counts less than 150,000 per millimeter cubed. I do want to point out, by comparison, we have seen zero reports of this cavernous sinus thrombosis with thrombocytopenia in the 182 million doses of mRNA vaccines given in the United States.

I know there’s a little bit of, “Oh, this is just something,” but no. This looks like it is not a problem with the mRNA vaccine. I want to make that really clear. Onset for these individuals, it was six to 13 days after vaccination. This follows the timing. That’s when we start to see the IgG or the immunoglobulin start to come up, not necessarily just IgG. They were all Caucasian females. Three out of the six were obese. Half were obese, half were not. There were no known coagulation disorders in this group of six women. Initially, headache was reported in five of the six.

The last person did not have a headache initially, but a headache soon developed. Their initial presentation was back pain. Now, half of the patients had clotting in other areas. Lower extremities, the portal vein, pulmonary artery. This is going to be relevant as we go forward, they’re able to test for something .. an antibody against platelet factor 4. Of the five that they were able to test, all of these antibody tests were positive. One individual died. Two of them recovered and were discharged from the hospital. At the time of the report that I got today, half of them were still in the hospital.

A couple of the conclusions, the rate of this CVST does appear to be higher than would be expected for this observation period and in this particular demographic. I will also point out that, in the Phase III trial, there was a 25-year-old man who also developed CVST. He also had positive anti-PF4 antibodies. We still have a significant number of individuals that were just recently vaccinated. They haven’t passed through this, say, six to 13 days after vaccination so we won’t reach that until April 25th. At that point, we’ll have a true number on what is the number of these events that are happening after vaccination.

There’s a lot of speculation. I think there’s growing evidence that this may be a similar phenomenon to what we are seeing as a rare issue with the AstraZeneca vaccine. There are a couple of publications in the New England Journal of Medicine that shed some light on what might be happening there. By comparison, I’ll try to get a connection here. The original article, Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination was published.

The authors report that of the 11 original patients, nine were women, median age of 36 and a range of 22 to 49 years of age. Beginning five to 16 days after vaccination, the patients presented with one or more thrombotic events with the exception of one patient who actually presented with a fatal intracranial hemorrhage. Of the patients with one or more thrombotic events, nine had cerebral venous thrombosis, three had splenic vein thrombosis, three had pulmonary embolism, four had other thrombosis, and of these patients, six died, five patients had disseminated intravascular coagulation.

Now, the authors used a standard ELISA to detect these platelet-activating antibodies against PF4 and a modified PF4-enhanced platelet activation test to detect platelet-activating antibodies under various reaction conditions. Included in this testing were samples from patients who had blood samples referred for investigation of these vaccine-associated thrombotic events with 28 testing positive on a screen. The author suggest that we refer to this as vaccine-induced immune thrombotic thrombocytopenia, so VITT, V-I-T-T.

Same edition, there was a brief report, very similar name, Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination, and they really came to the same conclusion. What is going on here? What is this PF4? PF4 is platelet factor 4, also known as chemokine CXCL4. It’s a protein that’s found in the alpha granules of platelets. It’s involved in the clotting cascade.

We see a very similar phenomenon rarely with a medicine we use called heparin. It’s very similar. You may have heard the term HIT or heparin-induced thrombocytopenia. What we’re seeing here is really a consumption of our platelets followed by bleeding in one instance, but in most cases, clotting. We do feel, I have to say, there is a smoking gun here. It looks like there is a connection. We will see the true numbers right now. We’re talking about one in a million. AstraZeneca is about one in 600,000. As we go forward, we’ll have to see what the numbers are now.

Does it make sense for them to have pause from a scientific point of view? Yes. If we are able to pause for another week or so, we will actually have that 13 days after the last J&J was given in the U.S. We’ll be able to see if there’s any more of these events and then we can revisit this. On the call today, they actually talked about several options here. One was to just put this in context and say the rate is, let’s say, one in 500,000, whatever they want to say, there may be the ability to say this is isolated to individuals under the age of 50. This may be isolated to women.

There may be discussions about what do we do with the vaccine relative to restricting or targeting certain populations. I think it’s the right thing to do and I think it’s also reassuring to see what a robust adverse event reporting system we had. I think we had an email where someone asked like, “How many people need to die before we’ll find out about it?” I think the answer, as I said, was one and that’s what it was here. We had a connection here. One person has died in the entire country. This has been stopped until we clarify the issue.

Now, people are a little concerned. We’re in the middle of a pandemic here. Are we stopping our vaccination efforts? I want to give some reassurance to our listeners. If you look at the number of vaccines that have been given so far, this makes up a small part of the number of vaccines. As I mentioned, we have given almost 200 million doses of the Pfizer and the Moderna vaccine, we have given less than seven million of the J&J vaccine. Going forward, if anything, we have a vaccine glut. We’re actually getting looks from around the world, “What are you doing with all those vaccines?”

We expect that we will have the ability by May 31st to have enough vaccines to fully vaccinate 260 million Americans even without J&J being an option. This was something that we could really do without making any huge sacrifice or impact on our ongoing really robust vaccination efforts. As we learn more, I think by next week, we might have a little more information, the following week, we should have all the information and know where we’re headed with this challenge.

Passive vaccination. Actually, some good news here. We are really moving forward with monoclonal cocktails. As about a week ago, the NIH, the National Institute of Health, is now recommending that monoclonals are part of the treatment. They are now part of the NIH’s COVID-19 treatment guidelines. They are saying, for mild to moderate COVID-19 who are at risk of worsening disease, they should be treated with monoclonal antibody cocktail. That’s a pretty strong statement.

I feel bad. I feel like we fall down on the job here sometimes. I have a couple of instances. This happened, I have a gentleman right now in the ICU who will probably die. The situation here, he and his wife were diagnosed. They were offered monoclonals maybe not as persuasively as it should have been. The wife said certainly. Two days later, she was fine, symptoms resolved. The husband is now in the ICU on the ventilator, week three. I don’t think he’s going to make it.

That’s the second of those stories in just a few weeks here that I’ve experienced where a married couple are offered therapy. The wife, maybe women are smarter than men, just throwing that out there, say yes. The men decide they’re going to just see how it goes. It doesn’t always go well.

What are the news? We’ve got a few more Phase III trial results. Phase III treatment trial in recently infected asymptomatic patients showed Regeneron-COV, this is casirivimab with imdevimab, significantly reduced progression to symptomatic COVID-19. This was another Phase III trial. It enrolled 204 individuals with any COVID-19 symptoms who tested positive for SARS-CoV-2 but did not have antibodies at baseline. They were randomized to either receive the Regeneron cocktail or placebo. They reported that they reduced the overall risk of progression by 31% with a p-value of 0.038.

They also go on to report that the total number of weeks that patients experience symptoms was decreased by 45% with the cocktail and the viral burden was reduced by more than 90%. While not included in the initial analysis plan, they also found that zero of the patients that got the cocktail compared to six placebo patients ended up in the hospital or visited the ER during this 29-day efficacy assessment period. From a safety standpoint, there were no issues.

We also have a Phase III prevention trial. I think this is huge. There was an article recently looking at people with immune compromise, saying, “What about these people? What if they can’t actually respond well to a vaccine? Is there any way to passively protect them from the virus?” There was a Phase III prevention trial showing 81% reduced risk of asymptomatic SARS-CoV-2 infections with subcutaneous administration of the Regeneron cocktail.

This prevention trial was a double-blind, placebo-controlled trial assessing the effect of the Regeneron cocktail on uninfected individuals without SARS-CoV-2 antibodies or any symptoms who lived in the same household as an individual who tested positive for SARS-CoV-2 within a period of four days prior to enrollment. They enrolled 1,505 individuals, pretty much split one to one, getting the cocktail versus placebo and then they followed them out.

Remember, this is a subcutaneous injection. This doesn’t have to be IV. It’s another way of improving access. They reported 72% protection against symptomatic infections in the first week and 93% in subsequent weeks, p-values with about three zeros each after the decimal.

They also reported, I think this is important, an impact on severity of disease. For those who did go on to get infected, on average, the individuals who were treated with the cocktails experienced asymptomatic infection. Their symptoms resolved in about a week compared to the placebo group who were sick on average for three weeks. The infected individuals also cleared the virus faster so there was a significant reduction in the days with a high viral load by 90%.

Again, from a safety point of view, there are no concerns here. What’s the future with monoclonals? A couple things to say here. Is there really this invariant region and we can just target that if the spike could be set forever? Can we make this perfect monoclonal and just sit on our laurels? I’m not sure that that’s true. I’m not sure that there is a part of the spike protein that does not vary.

I was emailing with David Ho today who does not believe that there’s actually a part of the spike that cannot, will not change. I think that this is going to be an ongoing challenge. I’ve been reaching out and communicating with my colleagues at UnitedHealth Group about how important it is that we have regional guidance, regional access to the monoclonal cocktails, the monoclonal therapies that work the best in a given region based upon which variants are circulating and what resistance patterns they might have to the different monoclonals.

What’s the best thing we can do to stay ahead of the virus? It’s to reduce the opportunity of the virus to replicate and change, which means mitigation, means vaccination. Period of detectable viral replication, right? This is when that person comes in positive. Just a little touch on here, because I’m going to close with some discussion of anticoagulation. At this point in time, we’re basically saying we have no compelling evidence that starting people on aspirin, starting people on anticoagulation is helpful. The first week of illness is the time for monitoring and monoclonals.

If they have a specific high-risk feature, then of course, always use your judgment and the latest clinical data to recommend for your patients. The early inflammatory phase, remember that 94% is what we’re worried about so, ideally, we’ve got a lot of pulse oximeters out there in the community. Remember, steroids are not during the first week, it’s during that second week if needed. I am going to comment here. Where are we with anticoagulation? Should they end up in the hospital? We are universally recommending anticoagulation.

I’m going to skip here to the tail end because we’re running long. I apologize. I just wanted to revisit the post discharge anticoagulation guidelines because they have evolved over time. Currently, as per the NIH treatment guidelines, prophylaxis after hospital discharge is not recommended for patients with COVID-19. There’s currently no ASH guidelines addressing this issue. There will be, we’re working on them.

I think the consensus has been, as we look at the data, this population is not necessarily at a higher risk of post-discharge clotting complications than your general medical patient, so use the same post-discharge anticoagulation guidance you normally would. Person has cancer, person has a clotting propensity, person has another indication, go ahead and use anticoagulation. If they just came in the hospital for their five days of remdesivir, for their 10 days of steroids, it may be that offering anticoagulation, the DOACs, the Eliquis, the Xarelto that may be doing more harm than good.

All right, I will conclude there. Again, I want to thank everyone. We’re just a couple weeks here left in our American Society of Tropical Medicine fundraiser, so take a deep breath, go to parasiteswithoutborders.com. Click that donate button because we are going to, I’m not going to say we’re hoping, I say we are going to support the American Society of Tropical Medicine in creating three annual meeting travel awards to bring early career women from economically-challenged parts of the world to the annual meeting this fall, really help do something to push their career forward and undo and address a lot of the inequities that are here. Thank you very much again.

VR: Time for a couple of questions for Daniel. You can send them to daniel@microbe.tv. The first is from Jay. “My daughter has celiac disease, irritable bowel, lactose intolerance, and has migraines. We were so happy when she managed to get the J&J vaccine. She suffered only mild chills. About to switch birth control for one that has no estrogen but what does one need to be aware of for symptoms?”

DG: That’s actually interesting. I’m not sure where exactly the question is going but I’ll go with it anyway. My daughter actually sent me a graphic looking at the risk of clotting complications with different therapies. One of the things in there was birth control. Birth control can actually increase a woman’s risk of having clotting issues. We definitely strongly recommend women on oral contraceptive pills, do not smoke. Smoking is another issue.

If we’re concerned here about the J&J complications, I will be reassuring. We’re looking at this being less than the risk of getting struck by lightning, certainly much safer than driving to and from a vaccine appointment. Everyone, it looks like, either acutely came in with a severe headache or soon thereafter, developed headache. We’re advising people after the J&J vaccine across the board, if you develop a severe headache, if you have trouble breathing, if you have abdominal pain, then get evaluated.

We can actually do blood work. We can sort out whether or not this is a significant concern. I know we had a ton of individuals. The ERs over the last couple days worried about these issues. Again, this is very rare so I really want to reinforce that. There’s no recommended treatment at this point. We’re not recommending putting everyone on aspirin or anticoagulation. With an event as rare as this seems to be, we’re more likely to do harm than anything beneficial.

VR: All right. Mary writes, “In a recent clinical update, you said if a school plan results in lots of potential exposure, then the plan is not a good one. The school needs a better plan. I’m a high school teacher. We have been doing cohorted hybrid days since September. We’re being forced to come back full in-person in a few weeks. Instead of 12 kids in a room with six-foot distancing, we’ll now have 25 to 28 kids in a room with three foot.

The CDC guidelines say anyone within six feet for more than 15 minutes would be considered a close contact, would have to quarantine. In that case, a single positive student in six classes throughout the day could yield as many as 36 contacts in the building. Given the limitations of space in our building and the CDC guidelines on close contacts, I don’t see how there could be a return to a school plan that does not result in a lot of potential exposures. Do you have any advice on this?”

DG: This is an excellent question. I think hits right on what I talked about. A lot of parents have this as a disconnect. You just told me that, if the children are three feet apart and wearing masks, that is not a risky behavior. Yet, you’re telling me that if the kids are three feet apart and someone has COVID, if they’re both wearing masks, it doesn’t matter, it’s exposure. There is a disconnect here.

I know some local health departments have worked with the school and said, “No, this doesn’t make any sense.” This is a reaching out to the CDC. We need this guidance on a national level. I think it’s great now that the CDC is here back giving us really helpful guidance. I think it’s just a matter of getting the guidance updated to be consistent with what we now know. Mask wearing can be successfully enforced in schools if the kids are wearing masks.

If you, as a teacher, and the kids are wearing a mask and you’re keeping this separation, this is a very low-risk activity. Also, go and get vaccinated. That’s one of the biggest things we can do here. If you look at our high schools, a chunk of the kids are 16 and 17. The more people you get vaccinated, the better. Good ventilation systems. Three feet is going to give you that 80% reduction. You throw a mask on either side of that three feet. Yes, otherwise, I think your math is exactly what I worry about. One child, six different periods. Every time they’re sitting surrounded by eight kids. Next thing you know, everyone’s in quarantine. We were only in school for a day.

VR: One more from Ellen who talks about the discussion we had about pulling back on the IM injection for the vaccine. She has a question, which is, “What might be the consequences of inadvertent IV administration of the vaccine? Someone I know came to me with a concern that one of the vaccines he gave did in fact go IV, which he believes based on the feel of having hit a vessel followed by continuing to inject before his brain and muscles had time to react to this unexpected sensation.

I realized there is no data, but would appreciate thoughts on what would be theoretically expected in this case. The vaccine in question was mRNA. I suppose in either case we would have the recipe for spike protein, as I call it, within circulation. Would this lead to uptake and spike production within the vessels? If so, could this be related to rare clotting issues seen with AZ and now J&J? Would it move out of the bloodstream and be used in a similar but less localized way than in IM? Your insight is always much appreciated.”

DG: Yes, I am speculating here, but I will share my experience. I was doing a lot of vaccines this last week. We did over 300 last week. We actually did over 100 J&J just Friday, right before the pause was triggered. I always ask the people before I give them a shot, I say, “Oh, are you a bleeder?” One of my partners, Anuja Lee, who I mentioned earlier, she was like, “Why do you do that?” Some people, you give them a shot and they bleed.

The majority of the people we are giving these shots to, when you’re done, they don’t even need a Band-Aid. They’re fine. A certain percent of them will bleed. Sometimes it prompts them to let me know that they’re on a blood thinner or something like that. Sometimes you do the shot and, actually, they really start bleeding and you have to apply pressure and put a Band-Aid, which is not consistent with this concept that we have been told that the deltoid, there’s no blood vessels there, it’s very small capillaries.

There is some vascularity to a deltoid particularly in someone who’s maybe more active, et cetera. I don’t think we’re quite clear on what’s going on here. Significant bleeding sometimes in some of these individuals suggesting a larger vessel than we’ve been led to believe when we talk about pulling back the plunger. Let’s move on to the next level. The issues that we’re seeing do not appear to be that the vaccine is necessarily in the blood system. What we’re actually seeing is an immune response. We’re seeing six to 13 days later, we’re seeing antibody production.

These antibodies are against a certain target PF4, so platelet factor 4. I don’t necessarily think getting in the circulation explains it. If anything, a good, robust immune response is what explains this. I understand the concept of pulling back on the plunger, but I’m not sure I would understand the mechanism.

VR: That’s COVID-19 clinical update number 58 with Dr. Daniel Griffin. Thanks again, Daniel.

DG: Thank you so much. Everyone, be safe.

[00:45:08] [END OF AUDIO]