TWiV 667 Building a better virus trap

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 27 September 2020

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


VR: From MicrobeTV, this is TWiV, This Week in Virology, Episode 667, recorded on September 25th, 2020. I’m Vincent Racaniello, and you’re listening to the podcast all about viruses. Joining me today from New York State, Daniel Griffin.

Daniel Griffin: Hello, everyone. Hope you’re doing well.

VR: How are you doing, Daniel?

DG: I’m doing all right, actually. This thing is still dragging on and sucking the life out of a lot of us right now. I just told Vincent some hopefully entertaining story, so he’s going to be all cheerful people are going to be like, “I thought he was grumpy, but no.”


VR: I’m only grumpy when it’s necessary. Right, Daniel?

DG: [laughs] Sounds good. I’ve always found you very pleasant.

VR: Thank you.

DG: Let’s start off with a quotation. This is a quotation by Ruth Bader Ginsburg, “Fight for the things that you care about, but do it in a way that will lead others to join you.” I’m hoping that we can all keep working together here. I plan to make a point today to really, as I talk about each thing, I want to make sure I give all the different people credit because I’m not doing this by myself. This is thanks to you, Vincent, thanks to the other people on TWiV. Really thanks to everyone who’s been emailing, calling, Skyping, Zooming, meeting in-person. A little less in-person now than back early on.

I really think that the progress that we’re able to make is because a lot of people are working together. I quote Charles Darwin, maybe some people have heard about him.

VR: [laughs].

DG: Maybe some of our listeners, maybe we have an audience that’s heard of Charles Darwin, “In the long history of humankind and animal kind too, those who learned to collaborate and improvise most effectively have prevailed.” There certainly are some people who just opted out during this pandemic, didn’t want to communicate for whatever reason. Most people just to be positive, they’ve really risen to this challenge, been incredibly generous with their time and energy. As mentioned, these weekly updates are not just my own, they’re really the conversations, the contributions of all these people, tremendous people, that I try to bring to TWiV each week.

VR: Daniel, are the numbers still rising in the New York area, or are they flat?

DG: We do a lot of tests in the New York area, we do about 80,000 tests a day.

VR: Wow.

DG: We’re sitting here right about this 1% positivity rate.

VR: Daniel, the 80,000 tests, were they symptomatic people?

DG: No, it’s a mix. We’ve really embraced, in the New York area, the screening approach, so a lot of people are getting screened. We’re still seeing the patients come in the hospital, so I’m going to talk a little bit about that. This is a nice segue because I always like to keep a human face on the numbers. People hear 80,000 tests, they hear another 800 new diagnoses per day in New York on average.

Again, it’s not just about the numbers. I think we quoted Taylor Swift at one point, right? These are individuals. This is someone’s mother, someone’s sister, someone’s brother, someone’s daughter, someone’s friend. For starters, let’s bring people up to speed with some good news. My work colleague who’s been in the intensive care unit now for over two months, we are expecting her to be able to go home tomorrow.

VR: Wait a minute, you said last time that she couldn’t get off oxygen?

DG: Yes, she’s going to go home on oxygen. In a sense, when you asked me how I’m doing, we’ve changed the bar of what makes us happy. I was talking to her today. I’m always flattered when she speaks Spanish with me because usually, she speaks English, which I guess is a reflection on the level of my Spanish –


BG: Because I think it might be exhausting to her to have to speak Spanish with me and so today she spoke a little Spanish, which I think meant she was doing better. I don’t think it reflects on my improvement. If anything, my ability to speak Spanish has deteriorated. She was saying she was a little bit worried about going home, needing to be on the oxygen. This will be tough. She still has a long road for recovery, but it’s a huge milestone. Looking forward to her hopefully getting there. This will be released on Sunday, but here we are recording Thursday. I’m hoping Friday right before the weekend, she goes home.

VR: Great.

DG: My other patient, the one who attended the wake, who lost her husband, by the time this drops, she will be home as well. That’s some nice things. Unfortunately, as some people recover, others fill their spots. My partner Anuja Lee just admitted a man who he attended a wedding, and he is not the only one who ended up sick after that wedding.

VR: These are the things we know transmit infection. People should know this.

DG: Yes. Who’s having weddings with guests? Just exclamation mark, question mark. Maybe Skype weddings. The two people getting married, yes, they’re getting married but I’m not sure you need to bring guests together because this is a tragedy. There’s individuals in the hospital, other people in the hospital. A couple more people I admitted, one was a woman who I actually just admitted her this morning actually, she came over through the night. Her daughter was sick down in Virginia. She was there with her daughter, and then they figured out the diagnosis the daughter had was COVID, so now the mom is in our intensive care unit on high flow oxygen. Not so great.

Another, I just admitted a non-union sparky. I wonder if our listeners know what a sparky is. My goal in life was not to become a clinician, I was forced into this by my controlling parents. I wanted to be a plumber or an electrician. The electrician slang is a sparky. Then I felt like you had to concentrate and pay attention too much to be a sparky, so I was thinking maybe a plumber?

VR: Is there a name for a plumber?

DG: Yes. [laughs] I’m not using that on the air, we might have some younger people listening. It’s not complimentary.

VR: Got it.

DG: People can email in and then we can read that in privacy. This 92-year-old gentleman is a World War II veteran. We’re talking this morning about first he was in the European Theater, then he was actually in the Japanese Theater, so the Pacific Theater. Spent some time in the Philippines preparing for the invasion of Japan that never came, fortunately. He actually started to get sick on Friday. Sunday he was getting sick enough that he was admitted. I initially saw him Monday. At that point, wasn’t requiring any oxygen. I think it’s always good to walk through because it helps us how much have we learned.

Then on Wednesday, day five of illness, he actually started to require oxygen, which is a little bit early. Normally, we say it’s during the second week. What we’ve learned is the earlier in the course of illness that a person starts to acquire oxygen, the worse their prognosis. He starts to require oxygen, initially early on so we started Remdesivir, it does something. Also, start him on steroids, so we have that mortality benefit. Particularly at him, he’s a 92-year-old, he’s a male, he’s got hypertension, he’s getting sick early on in a disease. His neutrophil-to-lymphocyte ratio was rising today, so there’s probably a benefit there. He’s on anticoagulation, and we’ll see how he does.

Today, I’m going to talk a little bit about some of the new data about tocilizumab, and whether or not this gentleman will be a candidate for that. We’re still seeing the cases, we’re still doing the best to try to keep these people with us, getting them out the other end. Remember, I’m really good at good news. This is going to be the episode that people refer to as maybe when Daniel’s wife calls him a bucket of sunshine, there’s no sarcasm, that maybe it is sincere. I actually have some good news. Saturday, September 19th, we set a record in the United States. One million tests, one million COVID-19 diagnostic. Not serology, but diagnostic tests in a single day.

I wanted to just say that it looks like testing as an approach is really being embraced. This week I was on a call with Chris Said and Phoebe Olhava. I don’t know if you know Chris Said, but he’s the one who set up, the whole of the Michael Mina website, and we were all on a call with the Heritage Foundation. Basically, we’re wanting to talk about the possibility of using rapid testing, we call them lick-a-sticks. The idea of using rapid frequent testing to open schools and businesses in a safe way. There’s reason to be optimistic. This is a lot of really bright people who are thinking, “Hey, this is something that really might be an approach that makes a difference.”

What I thought was nice in this conversation was that there’s a lot of modeling out there where people say, “I have this model,” and they suggest it worked. It was nice that I was actually able to bring up some real-life experiences, things that we’ve been doing at our different organizations, and say, “This is actual, we’ve been doing it and it works.” I’m working on a number of papers right now. One of them is with Scott Shimotsu, Ariel Johnson, and Ethan Berke. We’re writing this up for Emerging Infectious Diseases where we looked at twice-weekly testing in a long-term care facility in Pennsylvania.

This was an area, Chester County, where the other facilities were seeing an average of 15.8 infections per facility. With our twice-weekly testing, we saw only two infections in that facility in this period of time. Pretty dramatic. This is a very vulnerable population. in the words of Peter Hotez, “COVID is the angel of death for people in nursing homes.” This is saving lives. This isn’t just reducing infections, this isn’t just about numbers, it’s actually about saving life. Testing, forget about just models, there’s real-life experience that it works. We talked a little bit on this call with the Heritage Foundation about the success we’ve had with the National Hockey League.

I was like, “I know the Islanders are not in the finals, but there are Stanley Cup Finals.” I credit Dr. Elliot Pellman who got me involved and actually listened to my advice when I had my zero-tolerance testing ideas and got the NHL to listen as well. I think that’s a success. We actually had an NHL season, we had an NHL Stanley Cup. This was all built on testing individuals, keeping infection from spreading through the league.

VR: How frequent was the NHL testing?

DG: It was very interesting because we did the bubble paradigm. Before a person could enter the bubble, what we did is you had to be tested, you had to be quarantined for 14 days, then you had to be tested again. Then anytime there was any concern at all, we were doing saliva testing. There was rapid resulting testing.

VR: The idea would be you get a test, if you’re negative, you still could have been infected early on so you just wait to make sure it’s not incubating, 14 days maximum. If you’re still negative, then you’re negative, right?

DG: Exactly. I’m going to talk a little bit about that quarantine. That’s important to have that in the model. A negative test today doesn’t predict the future, right?

VR: Yes.

DG: It’s like a pregnancy test. You can’t have a pregnancy test the morning after and think that now you’re fine. It takes time for things to develop. We also talked on this call about all the success we’ve had working with Bonnie Simmons, Adam Fiterstein, Z Baker using testing to open up the entertainment industry. When you guys are watching, and girls, everyone is watching all the productions by Lionsgate and Netflix, and Amazon Prime. We have these different industries are up and running and filming and creating content. There’s been a lot of success here.

We’re working on this much-promised online testing calculator, where people are going to be able to go online, put in your prevalence, whatever sensitivity of the test, the specificity, the frequency you’re looking at. I’m working on this with Natalie Sheils and Ethan Berke again, Caleb Kennedy, Greg Lyng. This, hopefully, we’re going to submit to the New England Journal next week. Then people will be able to look at their situation and say, “What makes sense for us as far as frequency? What makes sense for us as far as which test we might be using?” It really gives you a chance to run the scenarios and decide what’s best for you.

It’s exciting. I think this really enforces that testing works, testing can allow us to open stuff up. The big thing I said to the Heritage Foundation, you talk to a big business and you say, “Oh, it’s $100 a test.” That doesn’t work for a school. We need affordable, inexpensive tests. I think everyone’s getting behind this. I shouldn’t say everyone, lots and lots of people are getting behind this. I think there’s tremendous reason to be optimistic here. Let’s talk about this little issue about the specifics of quarantined and isolation. I just got an email to address this today.

What do you do? The CDC now has clarified, they listened to TWiV and they said, “Okay, we’ll fix that little error on our website that was confusing to people.” They now clarify it. Very simply, they say anyone who has been within 6 feet of an infected person for at least 15 minutes should get a test. This works well if you can create a visual in your head because there’s going to be a little subtleties here because the question is, when do you do that test and how many tests do you do? They were going to talk about the incubation that Vincent brought up. It takes from 2 to 14 days from exposure to when a person gets sick if they’re going to actually end up being an infected symptomatic person.

Some people go through that period, they never show any symptoms but they still might be infected. That’s what I talked about with the Hockey League. When someone at day 14, I feel great. They may be asymptomatic, you let them into your pod, into your school, into your hockey bubble, and the world falls apart. How do you address this? Quarantine is 14 days. We’re going to talk about isolation, which is different, so quarantine. When might you do that first test? You really don’t want to do it any sooner than day 3. Sooner than day 3, a very limited number of people will have become positive by then.

Day 3 is a reasonable first day. Day seven is another that’s going to actually pick up most people by then. Day 10 is reasonable, but you really want another at day 14 to know that this person – What is it called? Ducked the thing, missed the gun, whatever the expression, but got through this without getting infected. Why are we doing a few tests in here? Because then there’s the other issue of isolation, what happens when that test turns positive? Let’s say you get tested on day seven and the test is positive. Now what you need to do is you need to isolate and that’s a little bit different.

Isolation is you isolate for 10 days from the time you test positive for a virus or the time you have onset of symptoms. Then at the end of 10 days, you have to be without fever, your symptoms have to be getting better, and this has to be without taking medication. You’re taking Tylenol and that is why the fever’s gone. Hopefully, this clarifies testing approaches for folks. Testing is good, we all like it. [chuckles] Some treatment and drug updates. By the time our episode dropped on Sunday, I think everyone knew about the monoclonal antibodies, so that was good. I was a little worried I was jumping the gun on that and sharing confidential information, which I try not to.

Actually, I’m not good at keeping secrets. We were talking about that at the hospital today, and they’re like, “Dan, there’s a show, Curb Your Enthusiasm, you should be on it.” [laughs] The monoclonal antibody stuff is exciting that that’s out there. We keep talking about but you got to go to an urgent care and someone’s got to be intravenous, but some of the monoclonal antibody therapies –

I don’t know people listening have osteoporosis or know someone with osteoporosis but previously, I did consulting, I’m going to say. Amgen was involved in the development of denosumab or Prolia, which is a monoclonal antibody but it’s just subcutaneous. You can just inject yourself, and there are millions of people that do this. This could be you go somewhere, you get your diagnosis, and then the pharmacy delivers it to your house or you pick it up and just an injection under the skin. This is another way. These therapies are not cheap, they cost hundreds of dollars. If you can really keep people out of the hospital, that saves tens of thousands of dollars and lives.

VR: That would have to be tested, though, of course, to make sure for SARS-CoV-2, it does work.

DG: Yes. I’m not saying don’t use denosumab.


VR: Yes, of course.

DG: These monoclonal antibodies that are now being tested by Regeneron and Eli Lilly, and Amgen, we’re actually looking and not all of them are IV. Some of the preparations could just be injected under the skin. These are all in Phase II and Phase III trials.

VR: How long will they last, Daniel? Two weeks or so?

DG: It’s interesting. You only need them to last a short period of time. When you develop these antibodies, basically, if you think of them as a Y, that stock part thing of it as a slingshot, the part you hold in your hand, by modifying that stock part, you can modify their half-life. It’s perfect to have a half-life of about two weeks. I guess if you thought about it going into the season before you have vaccines, you could give yourself one that lasted six months like the denosumab one so to be protected for the season.

Hopefully, I’m thinking by that period of time, the vaccines will be giving us a little more efficacy data. Stay tuned for these. We still have Remdesivir as I mentioned. I’ve been getting a lot of questions about vitamin D. Stay tuned, we’ll talk about that next time.

VR: We’ve also got a bunch for you, they want a discussion of it.

DG: We’ll have a discussion, I promise. Tune in next week because I’ve actually been doing a little bit of work in the vitamin D area as well. We’ll share some of that next week.

VR: Do you take vitamin D, Daniel?

DG: I do actually.

VR: I do as well.

DG: 50,000 units once a week.

VR: 50,000 a week, that’s a lot.

DG: Yes.

VR: If you took 1,000 a day, that would be 250% of the daily minimum requirement.

DG: Yes.

VR: You’re okay?

DG: I don’t get out a lot. I don’t get a lot of sun. I don’t know if you’ve noticed. [laughs]

VR: I don’t either. Most of us are not. I was on a call with a doctor last week who treats CFS patients and she said we should all be taking vitamin D because most of us are indoors now.

DG: Yes. I said I was going to talk about vitamin D, but apparently, we’re going to talk a little bit. I always tell my patients, “Listen, you don’t really need to take supplements. You can get all the vitamin D you need from the sun. You just need 15 minutes of full-body exposure to the sun at the equator and you need the skin of an 18-year-old.” I just don’t see why you can’t do that.

VR: No problem.

DG: [laughs]

Vincent: Let’s talk about next week. I’m sorry to –

DG: No, that’s okay. I enjoyed talking about vitamin D. We’re going to get back to vitamin D, a teaser there. The cytokine storm phase, we had some interesting developments, is a bit in the press because finally, we’re actually getting to see some data. The ACTEMRA trial on tocilizumab is finally out there so we can actually see what the data is and judge for ourselves. A couple of interesting things. I’ve talked in the past about our experience seemed to be that people that had a background of steroids who then got tocilizumab did better than people who got just tocilizumab, this is an IL-6 receptor inhibitor, all by itself.

In the ACTEMRA trial, they weren’t quite as strict, and so some people got steroids as well. People who didn’t get tocilizumab were much more unlikely to end up getting steroids. In this trial, they had an eight-day shorter hospital stay, so eight days shorter time to hospital discharge. That was p-value less than 0.05. If they ended up in the ICU, an almost six days shorter stay. A big thing that was picked up in this study and another was the impact on reducing your chance of ending up on a ventilator. In this study, there was a 24% reduction in people ending up on a ventilator. That was nice.

There was no increase in infections, there was no increase in mortality. I know a lot of people had fears about that early on. Then there’s a second trial where we got a little bit of information, the EMPACTA trial. This is where they actually did a really good job of enrolling a more diverse population than a lot of our studies have had. In this population, patients who got tocilizumab, or we’ll just call it toci, were 44% less likely to end up either on a ventilator or dying. Hazard ratio of 0.56 and, again, p-value less than 0.05. No increase in infections, no increase in mortality, no negative impacts. Boy, if you can reduce my chance of ending up on a ventilator by almost 50%, that’s encouraging.

VR: These patients received the drug in hospital once they were admitted, right?

DG: Yes. That seems to be the timing that makes a lot of sense. I just submitted a paper with Paul Marik, who was famous for vitamin C. He was bemoaning the fact that people have not really thought about the phases of the disease, the viral phase early on, the cytokine phase following that. It really makes sense to target therapies, to time your therapies based on what you’re trying to do. If an antiviral, you give it early, a monoclonal that’s going to neutralize the virus, you give it early. If you’re trying to target the cytokine storm, these are your sick hospitalized patients, it’s second, third week.

VR: Daniel, I was on a call with a Chief of ID at a hospital in Bergen County, you probably know him. He showed a slide with the four phases just like you do. He must have got it from you.

DG: [chuckles] He got it from all of us. I don’t want to take credit. We’ve all been sharing our experiences. The clotting phase, so this is all the clots that we worry about. The American Thoracic Society, American Society of Hematology broadly recommending that all patients be put on thromboprophylaxis. The ASH, American Society of Hematology, goes a little further and actually suggests that, in those hospitalized patients, it’s low molecular weight heparin, in particular, one to choose. I guess we’re still bemoaning as we meet that there aren’t as many randomized controlled trials. The data helping us in this area is still really low quality so it’s difficult.

It looks like there’s a trend towards improved mortality with anticoagulation, but this is not without risks. This is with major bleeding risks. Some people gastrointestinal bleeds. There is a present risk of bleeding into the cranium, which can be devastating. Again, a call to arms to get some randomized control trials and give us the information we need to make the right decisions by our patients. Tail phase. I think it’s now becoming more and more clear that many people are sick for months, and we’re really learning how to treat the symptoms.

If you’re listening to our podcast and you’re having symptoms and you’re being poorly treated by the medical profession, find a physician who takes this seriously because you can make a difference for these people. Whether it’s how you treat the headache or how you treat the cough or how you treat the insomnia or the rash or the mental health aspects, there’s a lot we can do. Don’t give up, find a doctor who can take care of you. Vaccines, this is pretty exciting stuff. This is my bucket of sunshine podcast intro. The public is getting a bit concerned about safety issues relative to the COVID-19 vaccines.

I’m going to promise, as I think a number of us have, that we’re going to just keep unbiased solid scientific information about what we know to help our listeners navigate these waters. This week, a fourth COVID-19 vaccine candidate went into Phase III or efficacy trials in the U.S. Johnson & Johnson announced the start of its Phase III trial. First doses were given this week. This drugmaker follows Pfizer and Moderna whose Phase III trials began in late July. AstraZeneca started its Phase III vaccine trial, but at least as we’re recording this when I last checked, still in a bit of a pause at least in the U.S. while they clarify the safety issues.

What is exciting about this Johnson & Johnson adenoviral COVID-19 vaccine, it has a couple of nice features. Pfizer and Moderna vaccines require two doses about a month apart. The Johnson & Johnson vaccine can be given as a single dose. There is a small subpart of the study where they’re going to look at second doses to see if that makes a difference. In general, this is a one-shot vaccine. In addition, the Johnson & Johnson vaccine only requires basic refrigeration. Pfizer’s vaccine has to be stored at minus 100 degrees Fahrenheit on the dark side of the moon or something, so there’s [chuckles] issues there. Moderna has to be in a freezer as well.

I know Dr. Anthony Fauci called the latest vaccine trial launch a very important advance. He’s a reserved guy so that’s huge. I should say, full disclosure, I’ve been talking for a while about my role at UnitedHealth Group. We’ve been working with Johnson & Johnson to create these readiness cohorts for this trial. We’ve been doing this for a while. Actually, it was back in March, I started working with this woman, Deneen Vojta, and she’s the Executive Vice President and Chief Medical Officer of Global Research and Development for UnitedHealth Group. She’s actually, I think, the main reason I got involved with UHG. They created a lot of these programs to help people who are trying to move things forward with COVID-19, I’ll say.

These readiness cohorts were created. People go to these websites, very nice website, maybe not as nice as MicrobeTV or Parasites Without Borders, but United In Research. People have been pre-enrolling for this vaccine trial. Really clever this thing is, now that it’s in Phase III trials and we need 60,000 people enrolled in this trial, this email blast goes out to all those people that have said they want to be considered. We look at areas that are considered hotspots. Then what people can do is if you’re in a hotspot, if you meet the criteria, we start with a narrower range of people. You’re bringing up United In Research there? [crosstalk]

VR: I’m looking at a site where you can go to see if you can get into a trial.

DG: If you go to United In Research, right at the top, you can actually pre-enroll. It should really just be enroll at this point. You can actually become a citizen scientist.

VR: I see, yes.

DG: These vaccines are not going to just give us efficacy data mysteriously. They’re going to take tens of thousands of, let’s say, brave committed individuals who are willing to get that vaccine, see what happens. We don’t know yet. Over the coming months as we see, unfortunately, unexpected rise in cases, we’ll see people who got the vaccine or the placebo, is there a protection? How much is that protection? Actually, the same, if you register to be a citizen scientist, we’ve got our serology tests there where we’re going to follow 5,000 people who have positive COVID tests, and see do those antibodies stay up?

If those antibodies stay up or go down, who might end up getting reinfected? Is there any ability for us to predict? I thank people like Deneen Vojta and Steve Catani, the Chief Scientific Officer at UHG, because we really need partners like this. We need a lot of people working together to get the vaccine trials, to get the research, to get the numbers, to get everyone together on this. I’m going to finish off on that note. Go to, become a citizen scientist, help us get past COVID-19 and get back to shaking hands and hugging and having big weddings.

I also want to thank everyone. This will be our last episode where we’re going to be asking for support for Floating Doctors. I think we’re going to make our goal of being able to give them $40,000, which is really critical. People, go to, donate. This is a tremendous organization, these people down in Panama are really having a tough time with limited access to medical care, but also just basic food and everything else. Thank you to all our listeners who keep being so generous.

VR: I started to fill out the form at United In Research.

DG: Oh, this is great.

VR: I did and I got to the point where they don’t like my password. I have to work on that after we record, because now I have a few questions for you.

DG: Oh, do you want to tell me what your password? I could help you. No.


VR: It wasn’t long enough. They want me to put more things, so I have to wait. I have a few questions for you. This is from Steven Ripple, DOMD. In TWiV 665, an important topic was almost brought up, but not fully-discussed. That is if one is in a SARS-COVID-2 vaccine trial, and six months to a year into the trial, someone’s vaccine is released. Should that person be allowed to know if they are in the placebo part by simply asking?

This is a serious bioethics issue that I know many would appreciate hearing the opinion from each of TWiV regulars, as well as Daniel Griffin, to each person answering individually. As that individual would like to know, so I can make the necessary choices as to remaining an unprotected person or receiving protection.

DG: These are different times. I think we talked about this last time. What was unprecedented was the word that we’ve been using way too often in the last six months. This is a unique situation where we’re going to start to have efficacy data here in the next few months actually for a number of these vaccines. An interesting thing then is it’s going to make it harder for, if you’re a vaccine, isn’t the Johnson & Johnson, if it isn’t the Moderna, Pfizer or AstraZeneca and data company that there’s efficacy here, and you’re in the placebo group, you’re going to start to wonder, “Can I get access to something that works because I got placebo?” and placebo is just not going to protect you from COVID.

The other issue is what about the other vaccines? Are we going to put all our eggs in one basket because we don’t know how effective? If a vaccine is 52% effective at preventing you from getting ill, going to the doctor or a hospital, that’s really not good enough, we need more. I don’t know how each different company is going to select to do this. It’s pretty easy to figure out if you were in the placebo trial. I hate to say, you just go get a serology test and you’re going to know. There really isn’t a way to tell people that they can’t sort this out. I hope people are not doing that because then that might affect their behavior.

People might feel like, “Oh, I’ve got the vaccine, so now I’m going to go to that bar because I feel protected.” Then it’ll look like the vaccine doesn’t work because there’s different exposures. This is a great question, this is uncharted waters, it’s going to be difficult because this will only affect efficacy data. We’re going to have that pretty soon, I think. It’s not going to affect safety data because the people who are in the arm that got the vaccine, those are the ones where we’re going to be looking at risk.

It’s going to be a little bit difficult because we usually compare. We say, “These people got the vaccine, these people didn’t. What was the difference in serious adverse effects between the two groups?” You’re still going to be able to see, do we see transverse myelitis? Do we see MS? Do we see whatever above what we would expect people to normally get? This will muddy those waters.

VR: My opinion is that if you want to do a proper double-blinded trial, you can’t tell people what they got. It’s not an ethics issue because that’s what you sign up for when you sign up for a vaccine trial. You’re saying, “I accept this.” If you don’t, don’t sign up for the trial. That’s what I think.

DG: I think to get back to the concept, it’s like when people go to United In Research, they become a citizen scientist. We’re all in this together, it’s a community thing and a lot of us are making different sacrifices. The people that are going to make this sacrifice and allow us to have the science to know which vaccines are effective, which are safe? In the next six months, you’re going to have some efficacy data but it’s all you’d have is some. You’re not going to know the long-term protection.

The very interesting feature that we should bring up, this concept that I know I mentioned before about antibody-dependent enhancement. I encourage people to sign up for our serology study because what we want to figure out is maybe you have a certain level of antibodies and it’s protective. When you get to a low level of the antibodies, we’ve seen this in dengue, for instance, they have the potential to make you sicker than if you never got a vaccine to begin with.

We really need people to stay committed to these trials so that we can figure that out. The last thing we want to find is, oh, that vaccine that looked like it gave you a really good three months protection is the one that if you don’t get it every six months, you’re going to get really sick. I think as we mentioned before, this whole butterfly effect, you can’t just be mixing and matching. We need this data. It’s really important.

VR: The next question we got from several people. This is from Evan, “Daniel Griffin talked today about the possibility that masks might be more effective than a minimally effective vaccine based on the estimated 50% to 75% effectiveness of masks versus a nominal 50% threshold for vaccine approval. I think Daniel may have underplayed this difference. An important distinction is that masks, like physical distancing, are effective at preventing infection, while the primary endpoint for vaccine approval has been repeatedly described as prevention of disease. This means that masks could be significantly more effective at actually reducing virus prevalence in the population.”

DG: I think Anthony Fauci recently came out saying that he thought that even once we have vaccines, masks don’t go away. For a while, these may be complementary approaches.

VR: I agree.

DG: No, I appreciate this.

VR: It’s a good point though. It is a good point. We have a quote sent in from [Winston] Churchill. “Our peoples would rather know the truth, somber though it may be,” addressed to Congress December 26th, 1941. Do you like that, Daniel?

DG: I like that. I think that’s great. Hopefully, that’s what we’re giving, we’re giving the truth. I think people need a place where they can go and know that they’re going to get the truth, they’re going to get what the science says, not what we would like the science to say.

VR: One more from Liz. “Question for Dr. Griffin. This may seem a stupid question, but should people with genetic thrombophilia consider themselves in a high-risk group with respect to COVID-19 complications? With all the talk of blood clots, that seems like a given but I haven’t found much discussion of this or any studies about it. Do you know of any?”

DG: I mentioned this briefly. It is really somewhat painful how limited the data is at this point about what to do about the clotting complications. We don’t have much guidance here. This is just thinking things through and trying to figure it out. I would think if you have a disturbance in your coagulation system, that theoretically puts you at increased risk but we don’t know. This is where we are trying to extrapolate from what we know. but we’re extrapolating out into a data-free zone.

VR: I don’t understand. Do these people with genetic thrombophilia have clotting issues?

DG: Thrombophilia, the love of clotting, these are people who are more likely to clot just even at baseline.

VR: Got it.

DG: This reminds me of my dad, always says when I can’t understand, he’s like, “Oh, just think about what it means in Hebrew.” I’m like, “Yes, it’s great, dad. I don’t speak Hebrew.”


DG: Here I was just thinking about what it means in Latin. [laughs]

VR: Got it.

DG: I think in Philly people are familiar with that. If these people are going into that baseline increased risk, then you would worry that something that is triggering activation of that system is going to put them at higher risk than someone without a disturbance in the system.

VR: If you had a patient come in with COVID-19 and a thrombophilia, you would make sure they had treatment for that, right?

DG: Yes. Across the board. As I mentioned, it’s generally recommended that people are put on some sort of prophylaxis. Just the issue with anti-coagulation, is it at just this low prophylaxis dose? Do you put it at a full dose? At this point, we have evidence that there’s a mortality reduction to these different approaches but you really have to individualize it because there’s a risk. This is not without a risk. A person like this, you’re going to figure this into your calculation of whether or not they should be at low dose or higher dose.

VR: That’s our weekly COVID-19 clinical report from Dr. Daniel Griffin. Thank you, Daniel.

DG: All right. Thank you so much. Everyone, thank you for listening and supporting all the stuff that we do.

[00:42:40] [END OF AUDIO]

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