TWiV 684 Persistence of SARS-CoV-2 immune memory

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 22 November 2020

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

[music]

VR: From MicrobeTV, this is TWiV, This Week in Virology Episode 684, recorded on November 20th, 2020. 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, everybody.

VR: What’s happening, Daniel?

DG: Let me start off with my quotation and we’re going to get right into it. I think this is going to be the TWiV that people listen to, either right before Thanksgiving, or maybe people are going to be sitting around as a family, staring at something, listening to TWiV. Maybe they’ll be watching the YouTube, but first, my quotation, “Whatever words we utter, should be chosen with care, for people hear them and be influenced by them for good or ill.” I will let people sort out who actually said that. The reason I use this quotation right up front, I want to encourage everyone to listen to TWiV 683, where I think there’s a nice discussion about the two COVID-19 mRNA vaccines.

I’m going to shout out to Vincent and the crew, is that this is a period of time when a lot of people decide they’re experts on all things. They go out there and they tell us things. They talk about vaccines and they quote numbers, and the numbers are just a little bit off. Then they say things like, “Oh, yes. Vaccine trials will be wrapping up in two months, and then they’re just going to shut them down.” People are listening.

If you are an eminent person, if people are listening to you, I’m just going to say, “Please, little responsibility to the truth. Do your research, or if you really don’t have the time to do your research, and people are going to be listening, you get someone who has the time to do the research, has the expertise. People are listening, let’s not misinform them. This is a point in time when trust is really critical.”

As we get into the vaccines a little bit here in this clinical update, I’m going to mention that people want to know. They’re going to be making decisions about whether or not they’re comfortable moving forward with the vaccines. We as physicians, as scientists, I think it’s more important that we’re consistent, that we’re a source of accurate information than the politicians. Let’s be careful. Take this responsibility seriously. These are critical upcoming months. [laughs] I’m off my soapbox. It dropped out about three inches.

I will open again today with a thank you, for all the support, for the fundraising, give people little feedback on all the great work that’s being done. Last time, I mentioned Floating Doctors. And this time, just to let people know, the Foundation for International Medical Relief of Children, like many NGOs, is struggling during these tough times. Thanks to all the support of our listeners, people going to parasiteswithoutborders.com and donating. FIMRC has provided clinical services to over 17,000 patients.

They have facilitated nearly 5,000 virtual workshops, for program participants to connect via a whole bunch of media and WhatsApp, Zoom, Skype, socially distanced in-person things. They’ve helped to provide personal protective equipment and other essential donations for project sites around the world. Since May, FIMRC has hosted over 300 virtual volunteer participants, wide variety of programs throughout the world, so international medicine and global health community development. Thank you, for continuing to go there and supporting all this excellent work.

As people may remember, we are still in a middle of our MicrobeTV support fundraiser. I think we’re well on track to be able to give $40,000 to help further the work of MicrobeTV, so, please, keep going in there. Now I’m going to shout out to some of our listeners. I think it’s nice how many people listen to us around, and now I will say above the world. People should, well, I’m going to say, watch TWiV 682. I usually listen, but I have to say, it’s pretty cool to watch an astronaut floating in weightlessness, talking through a toothbrush, it looks like.

VR: It does.

[laughter]

DG: A lot of people thought she was a little braggy, with all that blonde hair floating around, those of us who are hair challenged. It’s nice to know that every Sunday, the listeners up on the International Space Station are tuning in to This Week in Virology. A shout out to Kate Rubins, Victor Glover, Sôichi Noguchi, Dr. Phyllis, his friends call him. The real Dr. Phil, Sergey Ryzhikov, Michael Hopkins, Shannon Walker, Sergey Kud-Sverchkov. Last but not at least, Baby Yoda, who we know is up there in space, floating around, listening as well with his big ears. Great work up there in space. I’m very excited to hear that you are listening to us up there.

A little bit of news in the local area, the New York City schools just closed the day that we’re recording this on November 19th, with the rising rates. All students are now learning remotely. This has created a little bit of controversy because I think the growing evidence that the schools are a very safe place for the children, but there’s an aspect to this, where there’s concerns from the Teacher Union. That seems to be what drove this. There was an agreement there. We crossed the 3% threshold.

What about the hospitals here in the New York area? We are seeing increasing numbers of admissions. I mentioned last time and I think someone was like, “Oh my gosh, Dr. Griffin, what’s going on? You’re upset that one of your patients went on a ventilator?” Well, I was concerned, because I was concerned that this was the direction we were heading now. Multiple numbers of my patients are on ventilators. Since we last recorded, a number of my patients have died. I’m feeling a lot of déjà vu here. We’re back in March with the numbers rising, the hospital’s filling.

We had an issue today where we’re trying to move a patient and it was, “Dr. Griffin, we don’t have any open room.” We’re starting to have issues, really, with hospital ward capacity. We have room in the ICU. I think this is consistent. We have a bit of success here with changing this from an ICU to more of a hospital ward and even outpatient disease. Today was a bit crummy because another one of, I will say, our own, another one of my colleagues ended up getting admitted, not just to the hospital, but one of the people I work with is now in the ICU.

Not great, keep safe, keep respecting the virus. Let’s start off with the pre-exposure period. People are getting ready for the Thanksgiving holidays or asking for a lot of advice about what to do. I think it’s pretty clear a lot of people are embracing the testing paradigm. What’s a little unfortunate is here we are in November 2020, many months after the onset, we still don’t have the testing capacity to handle the demand. People are trying to do the right thing. They’re trying to get tested. They’re trying to do what they can to make things safe because a lot of people really do not want to spend the holidays alone.

They also don’t want to let the ones they love spend another holiday alone. The Columbia epidemiologist, Jeff Shaman, I think he’s been on TWiV. He and I have emailed back and forth a bit. He is a coronavirus expert, was a coronavirus expert before the pandemic. He’s not one of these Johnny-come-latelies. He actually put out an estimate based upon what we know. He was estimating, and this is a man I tend to trust, that 3.6 million people in America are currently infected and shedding enough virus to be contagious.

We’re talking about more than 1% of the US population is potentially infectious. We’re looking at only about a 10% drop in the amount of Thanksgiving travel this year, in the midst of a pandemic, relative to last year. People can start doing the math here. If you’re thinking about your group sizes, if you’re thinking about indoor versus outdoor venues, exposing yourself to people outside of that pandemic social cohort that you’ve been maintaining perhaps.

I worry a lot about bubble touching, bubble popping, and just remember knowing is not doing. We know what we’re supposed to do, try to be safe. There’s light at the end of this tunnel. For all our listeners hang in there for a few more months, as I think I can honestly say, we’re close to things getting better. On that note, a bunch of what I’m going to say, really good news. What did I promise last week? I promised we would talk about Moderna.

VR: That’s right, you did.

DG: Are you sure, that’s what I try to do.

VR: We said it was going to drop and it dropped on Monday. Didn’t it?

DG: [laughs] What was it like? Six or seven in the morning, and it was bright and early.

VR: Yes.

DG: We do have some exciting news about the Moderna vaccine interim analysis. I have to say, one of the ideal aspects, I think, of TWiV, is that even in my clinical updates, it’s not a one-person show. When I present my updates, we have Vincent ready to keep me honest, as I mentioned, which is really critical when you hear someone asking and answering their own questions. The nice thing here as I talked about vaccines, Vincent will jump in, if he ever feels like I’m stretching the truth, getting the numbers wrong, et cetera.

The plan going into the Moderna trials was that Moderna would do interim analyses at 53 and 106 infections. Their trial is called The COVE Trial. Those have these wonderful catchy names, the Coronavirus Efficacy and Safety Trial. I’ll say that it’s a lot easier to do the analysis here because it was a one-to-one split. They were very clear that it was a one-to-one split. You can basically say 30,000 participants in the US, 15,000 got the vaccine 15,000 got the placebo. They completed this enrollment back in October 22nd, or back on October 22nd, 2020. That was the start of the clock, from a safety point of view.

This trial had a very diverse population, not just a bunch of middle-aged white guys, so that was important. Actually, we’ll get to Pfizer because they jumped and say, “Oh, we have diverse people too.” Now this interim analysis, again, what we were going to do 53 they blew right by that. Again, this is the silver lining of the mushroom cloud of just letting the virus rage through our society. They were already up to 95 cases.

Based upon this, in the people that got the vaccine, there were only, let’s say, only five cases of COVID-19, and they were all mild. All the other cases of COVID were in the people who were placebo, who didn’t get a vaccine. For the people with vaccine, no severe COVID in any of the 15,000 vaccinated individuals. Now in the placebo group, there were 90 cases of COVID and 11 of these cases were characterized as severe. The primary endpoint was cases, secondary endpoint was the severe cases. The math here is really easy, basically, you come up with about a 95% efficacy for preventing a case, and 100% efficacious for severe disease as their secondary endpoint so far.

For vaccines, this is pretty amazing. The full Phase 3 COVE study data will be submitted to peer-reviewed publication, that’s not just the FDA, but the rest of us will get a chance to really get through this. Based upon their interim safety and efficacy data, Moderna basically went public. They intend to submit an application for an EUA with the FDA with three-letter acronyms, in the coming weeks. They anticipate basically, by the time this goes forward, they’ll have the final safety and efficacy data with that median duration of, at least, two months.

Pretty exciting stuff, I think. Everyone keeps asking and I’ll throw this in and they say, “Dr. Griffin, are you ready to get the vaccine? Would you get this vaccine?” I am going to answer that question. We also got a little more information about the Pfizer vaccine. As I mentioned, there was an excellent discussion on both of these on the TWiV right before this for those of you who want to listen to a lot longer discussion. Pfizer actually on November 18th, this is the 19th when Vince and I are recording this. Just yesterday, Pfizer and BioNTech announced that after conducting the final efficacy analysis on their ongoing Phase 3 study, their vaccine candidate met all the study’s primary efficacy endpoints.

They were reporting a vaccine efficacy rate of 95%. This has pretty good confidence margins. We’ll see the actual data as mentioned. That was their primary objective. Then they talked a little bit about secondary objective. They also told us a little bit about the fact that they had a fairly diverse population in here. They do comment that the efficacy was consistent across age, gender, race, and different ethnic demographics. If you looked at older adults, I’ve been told never to say, I guess elderly, but older adults, those mature and full of wisdom, that in these individuals 65 years of age and over, the efficacy was 94% in preventing a case of COVID-19.

VR: Daniel, can I ask you a question?

DG: Yes.

VR: Is this the end of the cases and all those thousands of people or do we expect there to be more infections as we proceed in both the vaccine and placebo groups?

DG: That is an excellent question. Someone is giving a talk recently, like, “Yes, hit two months we’re all good. They’ll shut down the trial.” They’re not shutting down the trials. These trials are going to continue. At some point, there will be a point where potentially the placebo group is given access to vaccination. As we talked about, there’s a prioritization to vaccinating individuals. Even once the vaccinations are widespread, this study will continue for a minimum of two years.

We’re going to continue to learn about the Pfizer and the Moderna vaccines out for a minimum of two years. Then even when the formal studies end, there are post-marketing analyses, what we call Phase 4 studies that are going to continue. They really continue indefinitely at any point. If you start to see something you’re concerned about is reported, it’s studied, it’s analyzed.

VR: Presumably we’ll see some of those, you mentioned that both companies are going to publish these final endpoints, which is just a hundred some patients. What if there are many, many more infections, will we see those data at some point, you think?

DG: We will actually, so this is just the data that is important or relevant or going to be in the EUA submissions, but that’s not FDA approval yet. For full FDA approval, they’re going to have to keep moving forward. We’ll get EUA, that’ll be something that affects us now, but, no, I think, eventually everything we’re hearing so far is optimistic, these are eventually going to likely get full FDA approval.

VR: Presumably, the EUA will be like the [Eli] Lilly Monoclonal EUA that you talked about last time, it will be for at-risk populations, right?

DG: Yes, there’ll be qualifications on the EUA. This isn’t, “Just give it to everyone,” this is not, “Give it to children.” Let’s be clear that there have been a lot of children. I’ll answer that question. I said upfront, people say, “Are you ready to get the vaccine, Dr. Griffin?” Not quite yet, we don’t have to make that decision quite yet. No one feels like someone’s going to come knocking on your door this evening and tell you, “Make your decision now.”

We still have a little bit of time. We’re still going to get a little bit more information. I think that we’re almost there. Just keep your seatbelt on for a little bit longer. We have fantastic, amazing efficacy data and safety data. We haven’t heard of any kind of a negative signal. You know what? The FDA is going to check. This reminds me of Reagan, “We trust you but we’re going to verify, verified trust.” I trust Pfizer, I trust Moderna as far as I can verify that the data is really true.

That’s why we have an FDA. That’s why we publish things in peer-reviewed journals. That’s why we have scientists and physicians. A lot of people say, “Dr. Griffin, I’ll get the vaccine right after you get the vaccine.” I think a lot of people say that about Anthony Fauci, “I want to wait and see until he gets the vaccine.” I think at the end of the day, maybe Vince and I, we can get our vaccines together, and we’ll do a live Zoom that they can watch up in space.

VR: That’s cool.

[laughter]

DG: Actually, I’ll throw even here, by the end of the year, I anticipate we’re going to get updates on the Oxford and the Johnson & Johnson vaccines as well. A lot of really exciting positive things here. I’m going to get you engaged a little bit here, but there’s still a lot of fears and concerns that people are throwing my way. There’s a certain level of distrust, but I have to say it’s diminishing when people hear how potentially effective these vaccines are. I’ve gotten questions about, “What if you had Guillain-Barré syndrome in the past, should you consider getting vaccinated?” There’s concerns that the government is going to put luciferase or some genetic or nuclear tracking devices in these.

People don’t necessarily trust Big Pharma, just to be clear about that. This is again back to people like Vincent, it’s scientists, physicians, we really have to be consistent. We have to be careful about the message. We have to make sure that we tell people the truth. People like myself, physicians; we took an oath, not to Big Pharma, not to our employer, but to take care of our patients. We will continue to give you the truth here. The incubation period, the post-exposure period, “Oh my gosh, I’ve been exposed. I think I might have COVID-19. Maybe I didn’t behave myself.” Let’s not shame people. People do stuff. We’re human beings.

I’ll admit, I don’t always make the best decisions. Boy, when I was younger probably, I was famous for making bad decisions. We now have another tool in our testing kit, the little mini-home molecular test by Lucira got authorized and reportedly going to sell these units for a little less than $50 a piece. We’ve actually been keeping our eye on this, because this is something where I think I mentioned one of the UnitedHealth Group, Well At Home programs where we’re setting up a system to be able to test then protect our older, wiser Medicare advantage members. Actually, we’re already talking to Lucira and we’re waiting for this approval process.

This is a little, it’s really cool actually, people should go on the website, Google Lucira COVID Test. It’s this little battery-powered isothermal amplification. It’s layout is a little loop-mediated. You put the batteries in. You swab your nose. A physician’s watching you over the video chat for basically about 30 seconds, making sure you actually swab your nose properly. You’d be surprised [laughs] that people swab their nose properly. They put in the little vial. They push this down, 30 minutes later, you basically get a green or red light. It’s actually pretty cool I have to say. It’s as sensitive as an Abbott ID Now. This is very sensitive technology. It’s a great additional test to have.

We also heard I guess, this is very positive. This is my bucket full of sunshine TWiV. We also heard that the US government is sending over 7 million Abbott Rapid antigen BinaxNow COVID test to the states this week. Millions really embracing this and the timing is right on for the holidays. A lot of these tests, actually over 400,000 of these, are going to assisted living communities. We’re really trying to target these to higher-risk individuals. I think it’s really important because we’re starting to see delays with our PCR tests. We’re seeing delays of three or more days that really just started to ramp up here in the New York area. I can confirm this personally.

Quest sent out a communication confirming this as well. The nursing homes actually share their data on resulting delays with the government. They’re saying as well, the same three to four days, and this was a few days ago. If you look around in the New York area, you see people lining up outside the urgent cares in 27 degree and windy weather to get COVID tests. The demand for testing is an issue putting a lot more emphasis on the rapid resulting test. You send out a PCR and I think I mentioned Black Friday, you find out on Black Friday that you went to Thanksgiving dinner shedding virus, not great to be using a test with a resulting delay that doesn’t tell you till after the fact.

Now we’ll move into that period of detectable viral replication, which moves right into the viral symptom phase. We talked last time about the Eli Lilly Monoclonals. This is exciting, and actually, people are very excited about this. The government purchased 300,000 doses. Well, that’s enough for about a week, so [laugh] not a lot when you look at the criteria. The way this is being distributed is to the hospitals via the same remdesivir network. This is going to acute care hospitals. They’re trying to figure out how do you distribute this outpatient medicine under an EUA? For a lot of them, this is reinventing the wheel.

As I mentioned, the hospitals are starting to fill with all these COVID patients. This means tying up an ER bed, if you do it that way, for an hour of the infusion, two hours as you observe them – all the sort of front and rear time. There are some of the local hospitals looking at setting up tents in the local areas to try to create these outpatient Bamlanivimab Access Centers. The first vials have actually arrived. Some of our hospitals actually have vials on-hand. We’re already talking about this, just to really go through the specifics because this is important. This is clinicians listening. I know you’re getting deluged with these questions.

Here’s what you need to know. A person is diagnosed with COVID-19 and there’s a couple of questions that are critical in what you do. The first thing you want to know is when did you get sick? Where are you in the course of disease? For this therapeutic, for antiviral therapeutics in general, you want to be in that first 7 to 10 days. Earlier the better. You’re not requiring oxygen. You’re not admitted to the hospital. This is an outpatient medication. I think this is true. We’ll move into remdesivir after. Then there’s a bunch of criteria: Are you over the age of 65 or older? Do you have one of these risks we discussed? Are you maybe a little bit younger, but then you have hypertension?

There is actually a whole list and it’s freely accessible on the web. I actually printed it out for our docs today. It’s a checklist. This is an outpatient medicine. In the same phase, I’m actually going to move into remdesivir. It was a New York Times article this week and Vincent shared it with me. It was really just like, “Are we that excited about remdesivir?” I think here I’m going to say timing we think matters. Here, I’ll say this with a bit of caution. I’m going to suggest that early administration of remdesivir seems to make a difference, seems to be reinforced by our clinical experience.

I say that, but again, the word of caution, I always say the plural of anecdote is not data. People who are getting remdesivir, who have a lot of risk factors, who we expect to do poorly, they seem to be doing better than expected. Remdesivir given in the first 10 days, maybe it does make a difference. Once you get past day 14, once they’re in the ICU, once they’re on the ventilator, probably more harm than good. That’s one thing.

The next thing you want to know, because this comes up actually multiple times every day for me now, is, “Is this patient a candidate for remdesivir? Are they within 10 days from the onset of illness? Are they not on high flow oxygen or on the ventilator? Is there glomerular filtration rate, is their kidney function good enough?” The GFR, glomerular filtration rate, needs to be better than 30. Then we also look at liver tests, the AST, the ALT, these need to be less than three times upper limit of normal, because this can have liver toxicity.

Those are the big things. You’re within the viral replication window. The kidney and the liver can handle it. I think with increasing supplies, now we’re seeing, I’ll say, a fair amount of remdesivir being used. Is it a miracle drug? No. Does it make a difference? Maybe. Do we need better therapeutics? I think a solid resounding, yes, we really do. Any comments there Vincent, before I move on?

VR: It’s very expensive and you’re not clear if it works. I think that was the point of the article, right?

DG: Yes. It’s $3,000 for a five-day course. We say from the data that, “Oh, it keeps people . . . it shortens your hospital stay by about three days.” I don’t know if it does because sometimes people come in with what seems like a very mild case and we keep him in the hospital for five days to get all that remdesivir.

[chuckles]

I have a patient who seems pretty mild and he could start on remdesivir and he’s got another dose tomorrow and that’s why he’s still in the hospital waiting for his last remdesivir. I’m not sure. It’s the $3,000 a dose. It’s not water. It’s not cheap. It has toxicity. I think, again, this is not for everyone. If you’re past day 10 really think about, “Am I going to just keep spending all these resources while people are on food lines and so?” Now the early inflammatory phase, we still have steroids.

Also, [laugh] this is that critical time for starting anticoagulation. I really enjoyed the most recent TWiV. It drops for me Thursday morning and I get to listen to it before I get to pre-record my front-end part of TWiV. There was a whole discussion about autoantibodies that seem to trigger the anticoagulation or the coagulation cascade here. Maybe this reminds people of our early TWiVs when we were talking about how I purchased all the Russell’s Vipers in the world. I don’t know if you remember that?

VR: Yes. I do. I do.

DG: I purchased them because we actually use their dilute venom to do a test, a functional assay for the impact of these antiphospholipid autoantibodies. It actually can impact the choice of what agents we use. I think that it’s interesting to now see a little bit of science filling this out. I think this also brings me back to the responsibility issue I started with. I saw a paper recently. They were saying that “We’re looking at these COVID patients. They’re using these medicines to prevent clots, really not seeing any clots.”

My conclusion was, “Wow, yes, this is so much better than I described in the early days. People are having these massive clots and they were losing limbs and we’re really not seeing this.” Now their conclusion was, “Maybe clotting isn’t really an issue anymore? Maybe we just need to stop using all this anticoagulation now?” I’m shaking my head. Just people think it through, we saw a lot of clots. We saw a lot of people dying from these clots.

We now have effective ways of treating them. We now have really good guidelines from the American Thoracic Society. American Thoracic Society, Hematology, helping guide us. Don’t stop, don’t return us to these dark days when people were having pulmonary embolisms and strokes and losing fingers and limbs.

VR: They used a drug in this paper that you mentioned, Dipyridamole, which is an antithrombotic medication. They show that it attenuates the clotting that’s caused by the sero from these patients. Is this something that’s being looked into do you know?

DG: Dipyridamole, actually, one of the medications that we actually use in certain circumstances. It’s an FDA-approved drug that we use. Secondary infection phase, I want to just reinforce, I feel like I have to keep doing this, is the time when antibiotics are usually to be considered. I had a conversation just yesterday; actually, it was the day before yesterday. It’s a physician I respect and he was describing a patient who came in day six of disease, wasn’t interested in admission, got sent home on oxygen and antibiotics. I said, “Really why the antibiotics? Was there a chest X-ray? Was there some indication? Did you think there was a bacterial secondary infection going on?”

The quote was, ”Well, this probably will do no harm.” I have to say, I see so many ER patients who get that first dose of antibiotics of Ceftriaxone, Azithromycin, this standard American Thoracic Society guideline therapy for bacterial pneumonia. This is a viral process. We’re already seeing a lot of resistance issues. We’re headed towards this post-antibiotic apocalypse if people don’t refrain. Please, stop using inappropriate antibacterial agents. This is a virus. The secondary bacterial process. It’s rare. It’s 10% or less. When you see the infections, they tend not to be upfront in 90% of people. When you see them, they do not need one course of antibiotics.

They certainly don’t need three courses of antibiotics. If it’s week two, week three, maybe you’re concerned about a secondary infection then possible, but let’s try to use some judgment here. The algorithm for a viral illness should not include antibiotics uniformly. Now the hyperinflammatory phase. Actually, this is the last time I’m going to call it that. I get a little pressure from the consortium. They want me to rename this. I feel like this is the consensus cabal from that show The Blacklist. They want me to call it the multi-system inflammatory phase going forward. That’s fine. We’d see this in inpatients, but we also see it in outpatients.

This was initially described in the pediatric population. This tends to be the timing when we see the onset of that brain fog, which maybe people remember from some of the long haulers. A lot of people with COVID have neurological issues, but often at about week four or five. Actually, patients that I’m involved with their care just started going into this. I have several patients that have developed this. There is some growing evidence that this is antibody-mediated, makes sense with the timing may be due to self-targeting autoantibodies that impact brain function.

There was a nice paper in Nature. It’s actually a comment that brings together a lot of research and reports called, “Do Cross-Reactive Antibodies Cause Neuropathology in COVID-19?” They referenced some evidence, which supports our experience that often a short course of steroids at about this time, so Prednisone 40 milligrams once a day for 10 days, can often impact these symptoms. A thing to think about when you get into that phase, the tail phase. There was another paper published in the Annals of Internal Medicine, “Sixty-Day Outcomes Among Patients Hospitalized With COVID-19.” They looked at over a thousand COVID hospital survivors by 60 days, post-discharge.

Just to give you the numbers, so about 7% of the hospitalized, floor patients went on to die during the next 60 days. A little over 10% of the ICU patients went on to die during the next 60 days. Over 15% of the patients discharged, went on to be rehospitalized. In their summary, they note that at 60 days, the majority of the people that survived, we had a chunk that died or were readmitted. Those that survived, the majority had ongoing morbidity. They had difficulty returning to normal activities. They had physical and emotional symptoms. A lot of them had financial challenge. They can’t work. Their resources were depleted.

They described that a lot of the people that survived are left only to have depleted savings and need to ration food, heat, housing, medications, and ongoing morbidity and suffering. The hospitals had these ceremonies. I don’t know if people saw these clap-outs where they would celebrate the discharge of patients with COVID. I think that many people were under and maybe still are under the illusion it’s a victory. They’re out the door. We saved them. It’s all better now. Just this week I was seeing my colleague that I’ve talked about previously on the show.

This was the individual that I worked with at the hospital, ended up admitted mid-July, was in the ICU for a couple of months, finally discharged in September. She’s slowly improving at home. As a milestone, she told me when I saw her on Tuesday, ”Dr. Griffin, today was exciting. This was the first day that I was able to go to the bathroom, get up out of my chair, go to the bathroom, get back in my chair, all by myself without assistance.” What are we six months after she got diagnosed with COVID? Six months and she just is well enough to go to and from the bathroom.

This is a vibrant woman that I have worked or had worked with for years struggling at home. Then I think the thing that broke my heart was she said, ”You know what, Dr. Griffin? You are the only doctor of all the doctors that took care of me in the hospital that still sees me and checks in to see how I’m doing.” The people, when they go home from there, it’s not to clap them out. Don’t forget about them. I think I really applaud you, Vincent, for putting on people to talk about long-term COVID. The fact that this is not just a two-week [virus], you live or die. A lot of people are still out there suffering and they need care and they need respect and they need affirmation.

When you discharge your patients, make sure someone’s going to see them, make sure someone’s going to see if they’re on their anticoagulation medicines, make sure someone’s going to check in and see how they’re doing. This is not just, ”Oh, we got to recondition you and get you back in shape.” There is a true aspect of COVID, a true tale that a lot of individuals suffer from. Now we’re seeing really solid high-level publications objectively demonstrating this. I did promise another thing and we’re getting near the end here. I promised an update on therapy for smell and taste issues.

Anyone out there who’s still having issues with smell and taste, been struggling with this. I was actually talking to the wife of one of my colleagues who had COVID still struggling with this. Basically talking to her about the fact that a lot of these patients have actually gone to ear, nose, and throat physicians, ENTs. Actually, they’ve looked up in the nose, in these areas, in the nasal passages, and really just fired up ongoing inflammation even months after they were infected with COVID. What I have done on a few patients is actually had them do the steroid nasal spray, two sprays each side, twice a day as well as a daily antihistamine.

Here, I’m going to say the plural of anecdote is, one more person with improved ability to taste and smell. I’m actually seeing a number of individuals who say it’s not like two days later, you’re all better, but improvement. People are starting to smell the cooking, smell of olive oil, starting to get a little bit of a return of taste. It seems that there’s an ongoing inflammation. I do not think there’s ongoing viral replication. I think it’s an ongoing inflammatory process. I’d be curious as we go forward, as I have more experience with this, how many people benefit from this approach to the smell and taste issues.

VR: Daniel, you’re getting infected by your colleagues. You said after infection with COVID.

DG: [chuckles] It’s terrible. Infection with SARS-CoV-2, the virus that causes COVID-19. [laughs]

VR: It’s so good that Daniel has a sense of humor.

[laughter]

DG: Let me close on that note. With the holidays coming up before we hit some emails, let me just say, be careful, make smart, safe decisions to keep yourself and your friends and family safe, and respect this virus.

VR: We have a couple of questions for you. Azeem is a physician at Queen’s University in Canada. He has a couple of questions. He wants to know first, considering that the vaccine target was 50% or more, and these recent numbers are 95%, how about using a single dose? We could do more people. Is there any data on that?

DG: When they went through the preliminary phase one and two, they were trying to determine the sense, you’re going to have to pull the lever or just basically go for it. They said, let’s go with the double shots. As I think was mentioned, so everyone go listen to the TWiV right before this. Pfizer and Moderna, they anticipate the ability to make billions of these. Sort of amazing how much RNA is required, kilograms, kilos. I don’t think there’s going to be an issue here. Also, we’ve already paid for it.

We’ve already bought these vaccines. The plan is in place. I think we’re okay. Get that second shot. This isn’t something where you want to say, “Oh, I tried this, I tried that.” Let’s stick with the science. I’m going to encourage people if you get your first shot, a month later, get the second shot. As we go forward, we’re going to have a lot of questions about durability. How long are you protected? Things like that. I think it makes sense to stick with the program.

VR: He also wants to know if previous infection with SARS-CoV-2 changes the immunity associated with one or two doses of vaccines. Do we have that information or will we have it?

DG: Pfizer made a comment. We’ll see more data when it’s more than just a press release. They vaccinated individuals who had been sick, who had positive antibodies, and basically, it was all good. We don’t know the details of the antibody immunoglobulin kinetics. I love that word. We will get more information here, but still, the standard recommendation at this point is two doses. It doesn’t matter if you’re exposed before. How many millions of people in America have been infected already? We’ll be getting more interesting information as these individuals get vaccinated.

VR: That’s interesting you should say that because then finally he wants to know, what’s the seroprevalence in the US? He says, “We assume 10 infections for every case, meaning the US is quickly approaching 50% of people being infected.” Seems high to me, Daniel.

DG: Yes. I think people have made estimates in the 10% to 20% range. It’s hard to do the math on all this. You say, “Oh, but if I say 10 and this.” As we get a better diagnosing it, probably the number of infections relative to identified probably narrowing. I don’t think 50% of people have gotten infected already. I think it’s quite a bit lower. It’s probably the 10%, 20% range.          

VR: The number you quoted from Shaman is just the current number of infected people, right?

DG: Actually, the current number of infected people that are estimated to have a viral RNA copy number at an infectious level, 1.6 million people we think are currently walking around America, shedding virus. That’s a lot, right?

VR: Yes.

DG: It’s probably going to be more in the coming months till finally, we get to February, March, and start coming out the other side.

VR: Mark wants you to know Daniel. He donated to MicrobeTV via Parasites Without Borders. He said, “The best part that you should be hyping more on the donation receipt is the autograph of the fabulous Dr. Daniel Griffin. That alone may have been worth the donation.” [laughs]

DG: [laughs] All right. Everyone go to parasiteswithoutborders.com and you can get my signature, my autograph, and you can save that. One day, it’ll be worth the paper it’s printed on. [laughs]

VR: That’s great. He says, “Keep on keeping on as my mother always says.” All right, one more from Casey, from Winnipeg. He said, “You all deserve your daily TV show on a big TV network.” Well, we’d love to do that one day on our network, MicrobeTV. I have a question for Daniel Griffin about N95 masks. If you’re only issued one mask per 12-hour shift, what’s the best way to prevent contamination when you need to remove it for eating and drinking? It’s scary to see so many fellow healthcare workers contracting COVID despite their best efforts at wearing appropriate PPE.

DG: I think I started by relating that one of my colleagues just got admitted to the ICU today. This was an individual that I work with. It was an individual who decompensated rapidly, who needed to be intubated. He rushed into the room without his N95 because he had a surgical mask on. It was all emergent. I was talking to the residents. I was like, “You know what guys? What I do and you probably have noticed, I put my N95 on before I get out of my car. I drink my Soylent, it’s my morning breakfast drink. I drink a bunch of water. I put on my N95. I don’t take it off until I get back in the car.”

A bunch of us, if we need to eat something, we’ll leave the building; we’ll go eat in our car. There’s only a few months left. Maybe a year ago that seemed unreasonable. The whole idea of removing it for eating and drinking, you got to have a lot of trust in the facility that nobody has undetected COVID. That PCR didn’t miss it. Nobody is doing anything that’s aerosolizing. No one is vomiting. That’ll be my advice. That’s what I do. I’m hoping to make it out the other side, and the way I will have antibodies to SARS-CoV-2 [laughs] is because I got a vaccine.

VR: That’s our Weekly Clinical COVID-19 Report from Dr. Daniel Griffin. Thank you, Daniel.

DG: Thank you, everybody, and enjoy a safe, Happy Thanksgiving.

[00:45:27] [END OF AUDIO]

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