TWiV 795 COVID-19 Clinical Update #76

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 21 August 2021

pdf of this transcript available (link)

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

[music]

From MicrobeTV, this is TWiV, This Week in Virology, Episode 790, recorded on August 19th, 2021. I’m Vincent Racaniello and you’re listening to the podcast all about viruses. Joining me today from New York, Daniel Griffin.

Daniel Griffin: Hello, everyone.

VR: Hey Daniel, what do you think about boosters? Are you going to talk about that today?

[chuckles]

DG: I’m sure that will come up, that an episode will not go by without discussing that hot topic.

VR: Every week there’s a hot topic, right?

DG: I keep thinking that there’s going to be some point in time when it just settles down and I have nothing to say and I look forward to that point in time. We’re not there yet.

VR: No. This is update number 76.

DG: Yes. Maybe at update 100, we will reach that point. Maybe that’s optimism. When we get to clinical update 100, we’ll see if I was optimistic or not.

VR: Yes, right.

DG: All right, well, let’s get fired up because we got a lot to do today, and I’ll start with my quotation. “There is only one sin, and that is theft. When you tell a lie, you steal someone’s right to the truth.” I don’t know if I’m going to pronounce this correctly, but this is by the author of The Kite Runner, Khaled Hosseini. Maybe our writers can let us know if I pronounce that correctly.

Actually, I’m a great fan of this man’s work, his books, and this has really been a tough week, particularly in Afghanistan, seeing what’s happening there so my heart goes out to all those individuals. Now, I’d like to say a single point does not make a line, so I’m going to keep building on the knowledge we have, but people know that, here in the U.S., things are not going well in a lot of parts of the country.

Let’s start off with children, children may be at low risk, but they are not at no risk. And I’ve added to this wearing a mask is less traumatic for a child than being hospitalized. I think we’re all aware that there’s actually been some rather odd behavior around this respiratory contagion and children and we got the article, “Association of Age and Pediatric Household Transmission of SARS-CoV-2 Infection,” published in JAMA Pediatrics addressing some of the questions around children of various ages and transmission.

I must say when I brought up this study, my wife was like, “Well, I could tell you what it’s going to show.” She was right spot on [chuckles]. This was a cohort study where the authors looked at 6,280 households that had pediatric indexed cases, and of these, well, about a quarter, 1,717 households so 27% experienced secondary transmission. Just to give you a sense, this is a household with a child with COVID, and about a quarter of them, despite doing whatever precautions, still had secondary transmission.

The authors reported that children aged zero to three, so they’re going to break this down by different age groups– and this could be the question, “Who’s going to be the highest rate of transmitting?” They’re going to use aged 14 to 17 as our reference, our adolescents 14 to 17, and then we’re going to compare different age children to those folks. Looking at the zero to three years, these individuals, the youngest, had the highest odds of transmitting SARS-CoV-2 to the household. Context, their odds ratio relative to the 14 to 17 was 1.43.

This association was similarly observed in sensitivity looking at secondary cases and so basically going through the older the kids were when you got to four to eight, you had a slightly lower, was 1.4, when you got up to the 9 to 13, when you got up to these older– The highest transmission was in the youngest individual. There’s been this odd idea that I think our listeners are probably aware of, this odd idea that somehow children can’t get COVID and that they can’t transmit the virus. This is just basically letting us know that, yes, if children do get infected, they can transmit it in the household context.

Now, I’m going to move on to our testing transmission area, and I’d like to just remind people, I was on The Brian Lehrer Show a couple of days ago, and there was a whole question about rapid antigen testing, “Are we done with that?” And just another study to remind people of how useful rapid resulting tests can be.

This was the report, “Use of Rapid Antigen Testing for SARS-CoV-2 in Remote Communities Looking in the Yukon-Kuskokwim Delta Region of Alaska,” and they looked at the period of time from September 15th to March 1st, 2021. Here, no surprise, the authors reported that the introduction of rapid point-of-care antigen testing in this region was followed by more than a three-fold reduction in daily SARS-CoV-2 case rates.

This gets back to something we’ve been talking about for well over a year now. It’s that one of the great things about these point-of-care antigen tests is you get a result right away, you can quickly remove an infected person from the transmission cycle. Where, particularly, you look at an area like remote Alaska, to get a return PCR results can actually take a significant amount of time, and during that time, that individual can continue to transmit the virus.

We still have, on Parasites Without Borders, that calculator where you can look at different sensitivities, different approaches. And one of the things I was talking about, is a lot of people have started to say this is not true, but they do say it that, “Oh, these rapid antigen tests, they don’t work for the delta variant.” Remember, the delta variant has some changes in the spike protein, still, plenty of nuclear capsid is being produced. That’s the protein we’re picking up with these tests.

Are they 100% sensitive? No, but are they 80% or 90% sensitive when properly done? Yes. Four to five times you’re catching that person right away in 15 minutes. If you’re still concerned, you can still send-off that secondary test, so it makes a lot of sense. If they’re positive, great, you can immediately intervene. If they’re negative and it doesn’t make sense or you want to have a higher sensitivity, you can always add a PCR on top of rapid testing.

Now in the MMWR, I’m sure Vincent is going to jump in on this one, “Shedding of Infectious SARS-Cov-2 Despite Vaccination when the Delta Variant is Prevalent,” Wisconsin, July 2021, was posted as a preprint. Now, it was told to me, and I didn’t actually see this initially, but this was tweeted my way, that initially this was posted with the “b-word.”

They updated it because they knew that we would find that “b-word” offensive, and they decided to use a much more appropriate term, just “infectious cases in vaccinated individuals.” I have that on unreliable authority. I probably should’ve asked one of the authors when I was emailing with them, but in this report, in this preprint, using PCR cycle threshold, Ct, data, they actually went ahead and they looked at can we actually culture virus from these individuals?

They report that yes, in the majority of individuals with Ct values less than 25, whether vaccinated or unvaccinated, they were able to actually culture virus so they did this in Vero cells. They report in figure two that they were able to see cytopathic effects after five days of replication in the Vero E6 TMPRSS2 cells, but we don’t get any quantification. And that’s really what I was hoping because really the question is, “Does this add anything?”

We know that vaccinated people can get infected, we know that vaccinated people can transmit, so we already knew going into this that there had to be a replication-competent virus there. The real question is, “Do those Ct values mean the same thing in a vaccinated and unvaccinated person at one point in time?” Because we do know that Ct value drops more quickly in vaccinated individuals. I reached out to Dave O’Connor, who actually was on TWiV 260 with Thomas Friedrich.

I don’t know, I’ll call them your colleagues. I don’t know if you guys are friends. And I really wanted to know a couple of things. Hopefully, we can start using the terminology “viral RNA load” instead of “viral load” because we don’t know if this is a virus, we know it’s RNA load, but I still really want to know the quantification. Vincent, I thought you would have comments on this paper.

VR: I think this is almost criminal to publish because as you say, they simply take the nasal fringe wash and throw it on cells and culture, and they get infection. There could be one PFU in the vaccine sample and many more in the unvaccinated sample. Does the author– say our data substantiate the idea that vaccinated individuals who become infected with delta may have the potential to transmit? Actually, it doesn’t substantiate it at all. It makes no conclusions possible. I’m really surprised that they’re trying to publish this and the problem, Daniel, is it’s a nuance that mass media is not going to pick up and that’s a problem.

DG: We’ve entered this different world. The world of preprints. I did reach out to Dave O’Connor. He emailed me back that they are actually are in the process of looking at the quantification of the cytopathic effects and that’s really what you need. By the time it gets published, we’ll have that, the only problem, and I agree with you in the preprint world, and I’ve been glad the media hasn’t jumped too much on this. This quickly becomes confirmation of this idea that vaccinated people are driving the pandemic, that vaccines are failing. None of that is true.

We are still seeing vaccines are incredibly effective and we’ll get into that as we discuss boosters when we get into active vaccinations. All right. I will return to this paper, I hope when we have some quantification data there, but the sky has not fallen. On the 12th day of August 2021, the FDA said, “Let there be boosters.” They went ahead, the U.S. FDA amended the emergency use authorization for both the Pfizer-BioNTech COVID-19 vaccine and the Moderna COVID-19 vaccine to allow for an additional dose in certain individuals.

Now, what did I like about this announcement? What I liked, Vincent and listeners, is that when they did this, they threw a line in where they said it is recommended that immunocompromised individuals discuss monoclonal antibody treatment options with their healthcare provider, should they contract or be exposed to COVID-19. We do have great science that an individual who gets infected, who is at high-risk, if they get the monoclonal antibodies, that this really is associated with a reduction in their chance of a bad outcome.

Do we know whether or not a third dose of vaccine will give them benefit? I’m going to say, as we move forward, I’m going to return and again say that we are still lacking that data. Yes, we can get some antibody levels a bit higher, but what does that really translate into? Who are these individuals who are now eligible? Many of the states have already jumped on– As of Monday, this has been happening in several states. The CDC is recommending that moderately to severe immunocompromised people can receive an additional dose.

This includes, I’m going to give the six categories, one, been receiving active cancer treatment for tumors or cancers of the blood. Two, received an organ transplant and are taking medicine to suppress the immune system. Three, received a stem cell transplant within the last two years, or are taking medicine to suppress the immune system. Four, moderately or severe primary immunodeficiency. They give some examples; advanced or untreated HIV or active treatment with high-dose corticosteroids or other drugs that may suppress your immune system.

Now we do hear that on the 20th of September, that week, boosters are going to be rolled out to the entire population that’s eligible in the U.S. If you look at these six categories, this is actually a very small subset. This is not, “I’m 65 and overweight.” This is not, “I have multiple medical comorbidities.” These are really severely, moderately to severely immunocompromised people that have been added now. Then again, the suggestion is that the third week of September, this will roll out to a larger population. Don’t worry, I’m going to hit some of the studies that supposedly support this concept.

Lots of vaccine mandates in April. There was a new vaccine mandate for New York State. This came out on, I say April, but it’s actually August 16th. I’m going to own up to that. All healthcare workers in New York State will be required to be vaccinated by Monday, September 27th. This will include staff at hospitals, long-term care facilities, nursing homes, adult care, and any other congregate care settings. There will be certain vaccinations limited for religious and medical reasons.

Remember, those medical reasons are incredibly limited. Basically, it’s a person who had an adverse reaction to this vaccine or one of the components of this vaccine. It’s not, “I have lupus.” It’s not, “I have high blood pressure.” It’s not, “I’m allergic to bees or talcum powder.” The medical exceptions are very narrow. I know there’s already a lot of people running out to see if their family doctor will write them a note. Those notes really are not going to mean much unless you have had an anaphylactic serious reaction to a component in these vaccines.

What about vaccines and variants? Who’s to blame? That’s what we like to do as a society. Along the lines of “no one is safe until anyone is safe,” there was a preprint that I found rather interesting, and this was, “Full vaccination suppresses SARS-CoV-2 delta variant mutation frequency.” And it wasn’t frequency, full vaccination suppresses SARS-CoV-2 delta variant mutation frequency. Now the authors analyzed SARS-CoV-2 delta variant sequences from Australia, France, Germany, Indonesia, India, Ireland, Israel, Italy, Japan, Mexico, Netherlands, Norway, Portugal, Singapore, Spain, Switzerland, Sweden, Turkey, the U.S., and the UK.

There was a lot of data. This all came from the global initiative on sharing all influenza data. This is the GISAID, G-I-S-A-I-D, and they had a number of different variant sequences. They did, I don’t know if anyone’s familiar with the Tahema D test. I looked that up. This was new to me, but really I thought it was interesting. In figure one, they show a mutational frequency, on the Y-axis they show the fully vaccinated rate, really areas with high mutational frequency had low fully vaccinated rates. Areas with low mutational frequency had lower fully vaccinated rates.

This makes biological sense. The more you give the virus a chance to replicate you would expect higher mutational frequencies. I don’t want people to run out and start yelling at the unvaccinated people claiming that they are a menace to society based on this one paper, but it is an interesting report. Vincent’s got his hand up. Jump in Vincent.

VR: It’s actually an incorrect interpretation. The mutation frequency is not affected because the mutation frequency of the virus is a constant. What is affected is selection out of that pool of variants of ones with changes, depending on the factors that they look at in this paper vaccination in this point. It’s not correct that vaccination suppresses the mutation frequency, it suppresses the number of changes that you see ending up in spike as a result of selection. Does it make sense?

DG: Yes, it makes a lot of sense because this is really not looking at really the mutational frequency as far as occurring. It’s looking at sort of an end product.

VR: Exactly. Yes. I’m sorry to keep interrupting.

DG: No, no, I think that that’s helpful.

VR: Because I’ve gotten a lot of questions from people, how the mutation frequencies… No, no, no, no, no. It’s not.

DG: Maybe we could, this is you get to roll the dice less still going to get the same number of– All right, now boosters, and I know this is the only reason Vincent is here today because he wants to know–

VR: No, no, no. I’m here every week for the same reason.

[chuckles]

DG: This is the special secret data that we were not allowed to know about, but now is being shared with us. There were several reports that came out. One came out in the MMWR, “Effectiveness of Pfizer-BioNTech and Moderna Vaccines in Preventing SARS-CoV-2 Infection Among Nursing Home Residents Before and During Widespread Circulation of the SARS-CoV-2 B.1.617.2 (Delta) Variant” – National Healthcare Safety Network, March 1-August 1, 2021. This is an MMWR early release and it’s interesting. I had a discussion with one of my colleagues about what were MMWR early releases before the pandemic? Really, was there many people other than me and my infectious disease colleagues that looked at these? Now, they’ve become primetime. They’re being asked to be something they weren’t before this.

We’ll get into that whole idea of asking something to be something that was not asked to be before. But in this weekly report, they looked at data that was reported to CMS Centers for Medicaid and Medicare-certified skilled nursing facilities or nursing homes. This was the National Healthcare Safety Network and analyzed to evaluate, this is interesting, the effectiveness of full vaccination with any of the two currently authorized mRNA COVID-19 vaccines on effectiveness against infection. This is where we’re suddenly asking vaccines to do something quite different.

Using 17,407 weekly reports from almost 4,000 facilities from the pre-delta period, adjusted effectiveness against infection for any mRNA vaccine, was reported to be 74.7%. They then followed it up with this intermediate period where they reported it was 67.5% and then they looked at 85,593 weekly reports from 14,917 facilities during the period when the delta variant was becoming prevalent, and here they reported an adjusted effectiveness against infection of 53%. They say this was similar for Pfizer BioNTech and Moderna. The point I want to make, and I’m, Vince and I’m sure you’ll jump in on this. I’m already prompting you to do that– is I was asked by someone today said, “I was watching a Fox News report and they’re saying, ‘Oh, these, these vaccines look at this. If you had a vaccine that was as crummy as this, what would you do?’”

I wanted to point– well, I did point out to this gentleman, we are suddenly asking the vaccine to do something that the vaccines were not necessarily designed to do. We designed these vaccines– Vaccines traditionally have protected us against disease, against serious diseases, ending up in the hospital or dying. Suddenly these vaccines have such a new superpower. They are actually protecting people. They are effective against infection. This is tremendous and continues to be tremendous. I don’t walk away with this being worried. Now, maybe we’re saying we want them to do this new superpower even better. We’re asking, “If we give the third dose, can we do even better effectiveness against infection?” But this is not failure. This is actually vaccines with a new superpower being asked to do even more. Vincent, I don’t know if you had a comment.

VR: Well, the problem here is that, as you say, they’re looking at infection, and the infection efficacy declines because serum antibody declines after vaccination or infection. It always does. It’s not surprising. For other vaccines, we never really looked at infection. We just looked at disease and that’s how these vaccines were tested. They do note this analysis assessed VE against infection without being able to distinguish between asymptomatic and symptomatic presentations. Additional evaluations are needed to understand protection against disease and nursing home residents. That’s the key. I bet it’s not declining as you’re probably going to tell us from some other studies that came out in the same issue.

[laughter]

DG: Let’s hit this. A couple of others, which I think are reassuring because there were a couple of other releases. One was “New COVID-19 Cases and Hospitalizations Among Adults, by Vaccination Status” – New York, May 3-July 25, 2021. This is looking at real-world effectiveness in the general population here in New York. These authors linked to information from four large databases to construct a surveillance-based cohort of adults aged greater than or equal to 18 years residing in New York. They found that new COVID-19 hospitalizations were 0.17 per hundred thousand person-days in the fully vaccinated compared with 2.03 per hundred thousand person-days among the unvaccinated.

They concluded that the overall age-adjusted vaccine effectiveness against hospitalization in New York had remained relatively stable, 91.9 to 95.3%. I have to say, this is what the vaccines were designed to do. They continue to be highly-effective in preventing hospitalization greater than 90% for fully vaccinated New York residents. Even during a period when the prevalence of the delta variant increased from less than 2% to greater than 80%. When so many of the non-pharmaceutical prevention strategies, the societal public health restrictions, were eased. Getting rid of the mask-wearing, cranking those restaurants back up to 100% capacity, and the like, and a hand is up from Vincent Racaniello.

VR: In the same period when the hospitalization, V-against hospitalization was steady, the VE against infection went from 90% to 80%, it declines. It just goes to show a decline in preventing infection doesn’t matter. [chuckles] They know how to do it in New York State. Maybe you were involved with this because it’s done right.

[laughter]

DG: Now along these same reassuring lines, I’m going to give you a third. Hopefully, people are going to walk away– Dr. Griffin, you started forlorn, but now you’re giving us good news. “Sustained Effectiveness of Pfizer-BioNTech and Moderna Vaccines Against COVID-19 Associated Hospitalizations Among Adults.” This is United States, March-July 2021. This is not just in New York, but here the investigators found again, the vaccine effectiveness was 86% two to 12 weeks after vaccination, 84% at 13 to 24 weeks. Really, the vaccine effective was sustained among groups at risk for severe COVID-19.

Sort of a second study looking at a different population continuing to have some– really reassuring. Here’s the big question, “Where’s the science? Why are we giving everyone third doses? Are we just going to bump antibody levels? Do we really have evidence that this will translate into a real-world benefit?” Keeping people out of hospitals, keeping people from dying, keeping people from getting sick, keeping people from ending up with long COVID, that’s data we still need.

VR: So booster or not Daniel? [laughs]

DG: Vincent, I actually had a sleepless night about this the other day, because it came to me sort of this issue of, I say, “Oh, Dr. Griffin, you’re eligible for a third shot. Do you want one?” There really is this sort of embarrassing equity issue. I feel like I’m at the family table and Uncle John just showed up and he hasn’t gotten the first portion and they want to know if I want to get thirds. I actually have to say, I feel a bit embarrassed about the global vaccination rollout. This whole concept that without data like, well, what benefit are we really getting, particularly when it rolls out as someone?

I like to think of myself as young and healthy. Do I really need that third shot? If it’s going to go in the trash, if they’re like, “Hey Dr. Griffin, we had a no-show and we’re not sure what to do with this.” Okay. That’s a different scenario, but the idea that we’re going to keep buying hundreds of millions of vaccines, that we’re not going to somehow modify our bureaucracy and share, we’re in a global pandemic it’s time for the bureaucracy to add and people to be a little more reasonable.

VR: Can I ask you, Daniel, though, let’s say we did give a third dose. I presume within eight months, the levels of antibodies are going to weigh in again. Are we going to give a dose every eight months? Is that the plan?

DG: That sounds like the current plan. That sounds like where we’re headed. Maybe we’ll do it every six because who can keep track of every eight. I don’t understand the– to bounce back to Afghanistan, what’s the end game? What are we doing? Where are we going with this? Are we going to just keep every six months? After a while, you’re going to have to start wondering what’s the safety profile if we keep doing this every six months, every eight months?

VR: With the influenza vaccine, it doesn’t even work well when you have to get everyone back every year for a new shot. The uptake is very low. I think it’s a public health problem.

DG: From a public health problem, what is fueling this pandemic? People failing to get a third shot? It’s people failing to get the first two.

VR: Exactly. I think we should push to get people vaccinated, not to give those who already got vaccinated a third shot. That’s crazy. Oh, well.

DG: All right.

[laughter]

The period of detectable viral replication, the viral symptom phase. This is that first week for most people, it’s when people start to feel crummy, maybe they had an exposure. What I like to say is, “The time for monitoring and monoclonals, not the time for antibiotics.” We’ve had a lot of enthusiasm about convalescent plasma and the article, “Early Convalescent Plasma for High-Risk Outpatients with COVID-19,” was published this week in The New England Journal of Medicine. This is the SIREN C3PO study. There were 511 patients enrolled in the trial, 257 in the convalescent plasma group, 254 in the placebo group. The median age was 54. Median symptom duration was four days. They’re doing it the right way. The mean titer of SARS-CoV-2 neutralizing antibodies was 1:641.

High-titer neutralizing antibodies given early, disease progression occurred pretty much the same about 30% in people in the convalescent plasma group and in the placebo group. Now, five patients in the convalescent plasma group died, only one in the placebo group. Outcomes regarding worst illness severity, hospital free days, really similar in the two groups. Just another study, “Early administration of high-titer convalescent plasma for the treatment of COVID-19 obtained from blood donors who recovered from coronavirus disease,” 2019– was not helpful. I want to leave that there. I know there’s a lot of enthusiasm. We’ve done a lot of the science, and the science does not support this intervention.

Now, I am going to try to keep this short today. We have a few emails, so I’m going to wrap up here. Just with really a couple of concluding thoughts. One is as I continue to say, and we bounced into this, no one is safe until everyone is safe. We really need to figure out what’s going on with the global vaccination approach because it is falling flat. We are going to continue, during the months of August, September, and October, to support Floating Doctors and we’re hoping to give them a donation up to $40,000 to support their work down in Panama. We were able to get that support out to FIMRC and got a nice thank you photo from my friends in Uganda where there is not a lot of vaccines, where there’s not a discussion of third doses. I want to thank all of our listeners for continuing to support us, continuing to go to Parasites Without Borders to donate, and to help us with this work.

VR: Dan, you mentioned the Afghanistan situation. I assume nobody’s getting vaccinated there these days, right?

DG: Yes, it is a problem. It’s a problem. Yes.

VR: People are concerned about getting out, right?

DG: Yes, I mean, it’s really a humanitarian disaster we have right now and vaccinations are certainly not part of that.

VR: Yes. Time for some email questions for Daniel. You can send yours to daniel@microbe.tv. We have one from Pare who writes, “My daughter is a kidney transplant recipient and has recently been through lymphoma and barely has any B cells, thanks to rituximab. She’s, however, in intravenous IG therapy and I’m wondering, would that now confer some level of immunity against COVID? I found a few papers commenting that there are common COVID antibodies in common IVIG, but I haven’t been able to find any information about if they confer any level of real-life protection. I guess in an ideal world, she would be a recipient of monoclonal antibodies, but unfortunately, we don’t live in the U.S. and they’re not available where we live.”

DG: Yes. Just to give our listeners maybe a little bit of background. The whole concept here is this is an individual who cannot make their own immunoglobulins, their own antibodies. The IVIG treatments, periodically you’re giving this individual donated immunoglobulins from other individuals. Now, if those other individuals perhaps have been vaccinated, and we’re starting to see this now, that people who are donating IVIG have been vaccinated and in that IVIG are actually some of these protective antibodies generated by vaccination or maybe prior infection. That’s helpful.

I don’t think we’ll end up doing large-scale studies, but a lot of the mechanism here just makes sense. The next thing that would make the most sense is these are individuals who, if they were in the right setting, could receive monoclonal antibodies. That’s being studied here in the U.S. That’s an expensive option, but IVIG is not cheap. Yes, I think you’re thinking this through properly.

VR: Gene from London, by the way, discovered you from your appearance on The Brian Lehrer Show podcast, Daniel. That’s great. She says, “I never use the ‘B-word’ or the words ‘viral load.’ I distinguish infection from disease.” We’re teaching them, Daniel. That’s great. We did make a mistake, and it’s actually my fault, and several people have pointed this out. I’d like to say it’s carbon dioxide that we need to measure for indoor air quality relating to COVID and I had said carbon monoxide. Of course, carbon monoxide would also be a serious concern for air quality.

I’ve implemented CO2 monitoring in my office as a proxy for understanding ventilation levels. It’s part of our layered mitigations, which include vaccination, masking, hand and respiratory hygiene, reminding people to stay home if unwell. That was my mistake because you had said, “What are those monitors?” And I said, “Carbon monoxide.” And a bunch of people wrote in to say, “No, no, no. It’s carbon dioxide for that.”

DG: Yes, I don’t know if you noticed, Vincent, from there on out I just kept referring them as the monitors and not correcting you.

VR: Yes, because that was– Well, you can correct me. It’s no problem. I’ve got many people.

DG: I like when our listeners write in. All right.

VR: The last one is Thomas, who’s up in Alberta, Canada. “I would like your thoughts on the anticoagulation issue you spoke about in the last clinical update where the one arm of the paper in New England Journal for critically ill patients showed no benefit with therapeutic anticoagulation, but the other arm, which wasn’t highlighted in the update, of non-critically ill patients, which would be a large proportion of hospitalized patients, did see benefit with therapeutic doses of LMWH. What is the standard of care for non-critical COVID-19 hospitalized patients in your community as it relates to anticoagulation certainly?”

DG: Certainly. The LMWH, that’s low molecular weight heparin or Enoxaparin, is kind of the common one that we use. There’s a balance here. If you do nothing, people who have COVID-19 are at a higher risk of developing clotting complications both venous and arterial. I said on the American Society of Hematology guideline panel, where we keep reviewing all the literature here, I like to think that our treatment is up with the literature and the baseline recommendation. Across the board, is anyone with COVID-19 who requires hospitalization and the associated immobility put on prophylactic dosing anticoagulation?

If you escalate that, okay, maybe you’re going to have a reduction in the amount of clotting complications. But it is looking, particularly as this study pointed out, in critically ill patients that you’re going to increase your risk of major bleeding. Now, what is major bleeding? That’s tough. Is it a gastrointestinal bleed with about a 20% to 30% risk of death? Is it an intracranial bleed with the associated neurological impact? Is it a retroperitoneal bleed that we can transfuse through? That’s really the balance here. Our standard is everyone who comes in prophylactic dosing anticoagulation, vigilance to make sure that they don’t have a clotting complication and then case-by-case basis considering, “Is there a reason to escalate in this individual?”

VR: Daniel, what’s on your bow tie today? I can’t quite see it.

DG: Today is clostridium difficile.

VR: Wow.

DG: It’s a gram-negative. This is that antibiotic-associated diarrhea from people using too many antibiotics.

VR: I’m very happy that your bow ties represent all microbes.

DG: I try to be an equal opportunity bow tie pathogen wearer.

VR: That’s COVID-19 clinical update number 76 with Dr. Daniel Griffin. Thank you, Daniel.

DG: Oh, thank you, and everyone, including you, Vincent, be safe.

[music]

[00:37:00] [END OF AUDIO]

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