TWiV 918 COVID-19 Clinical Update #123

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 16 July 2022

pdf of this transcript available (link)

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 918, recorded on July 14, 2022. 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: Daniel, I can’t believe it, the headlines are screaming. Scientists are concerned about BA.5, the worst SARS-CoV-2 ever. I can’t believe this is still happening, Daniel.

DG: Here we are at Clinical Update 123. Yes, it is. It is not over. Let’s get into it because, as always, we have a lot to cover. I’ll start with my quotation, and I’m sure I will mispronounce this gentleman’s last name but, “The folly of mistaking a paradox for a discovery, a metaphor for a proof, a torrent of verbiage for a spring of capital truths and oneself for an oracle is inborn in us.” Paul Valéry.

I just thought that that was a nice reminder, as we’re two-plus years into the pandemic, about the eloquence-based medicine that I mentioned early on. Just because someone makes a nice cartoon and shares along with a few anecdotes on social media or another platform, it does not magically become true. Science is not about what feels true. It is about what the data shows to be true. No data, no science. I figured you would be on board with those comments, Vincent.

VR: I like that. I like it very much. I also think that another way of putting that is just because there are a lot of subjects in a study doesn’t mean that it’s universal.

DG: [laughs] That’s true. All right. On our clinical update, I just want to get monkeypox out of the way, remind people of the history. This actually started as a way to keep clinicians up to date in the early days of COVID. I have to say I’m now getting a similar number of frantic calls and texts about the monkeypox. Just a brief start here before we get back to COVID. The MMWR early release, “Rapid Diagnostic Testing for Response to the Monkeypox Outbreak – Laboratory Response Network, United States, May 17-June 30, 2022.”

As a part of public health preparedness for infectious disease threats, the CDC collaborates with other U.S. public health officials to ensure that the Laboratory Response Network, LRN, has diagnostic tools to detect pathogens. In this report, we hear that during May 17 through June 30, 2022, the LRN laboratories tested over 2,000 specimens from patients with suspected monkeypox. Among these, 36% were positive. Reminds me of the early days. When 36% of specimens are positive, we are not testing enough. I will say that this has gotten better. We no longer need to audition.

The Department of Health and Human Services through the CDC began shipping Orthopoxvirus tests to five commercial laboratory companies, including the nation’s largest reference labs, to quickly increase the monkeypox testing capacity. These companies include Aegis Sciences, Labcorp, Mayo Clinic, Quest Diagnostics, and Sonic Healthcare, I’ve never heard of them, but OK. This is just a basic. If you’re sending it to Labcorp, the code is 140230. Google the other codes. Just a quick little getting to the weeds to help with– actually multiple texts and calls I got today.

If a clinician is concerned, go right ahead, send off your usual HSV-1, HSV-2, and VZV swab. Send those off in the universal viral transport media, but also, vigorously swab the base of the lesion. If it’s a vesicle, you want to open it. I will point out, those of you starting to see these, these are not as wimpy shallow as those typical HSV. You may need to be a little more vigorous to really get the fluid. Then you’re going to take that swab that you have vigorously done. You’re going to put it into a sterile container. A lot of us are at this point just using those urine cups.

You’re going to go ahead and get a second one, the same. Break those sticks if you need to, to be able to close those containers, and do it in a way that you don’t snap it up into your face, by the way. Close those samples nice and tightly. These are dry. These swabs are going to be sterile polyester, rayon, or Dacron, just not cotton. You’re going to submit the two swabs. Turnaround time, two to three days from specimen pickup. If you’re concerned, go ahead, have that person isolate. Err on the side of precaution. Then if it turns out it’s positive, then work with your local ID doc.

VR: Daniel, just a note, 11,000 cases. Now we have exceeded the total number of cases for SARS-CoV-1, which is about 8,000.

DG: Yes, it’s amazing. If you’ve been following here in New York, the monkeypox trackers are a little behind, but about double the number of cases we have right now in the Tri-state area from just a week before. What, I’m just to give people an update from on the ground. This is people we’re talking about, a particular population, but I have to say if you only test one population, you only see it in one population. This is something that contact can be involved with the spread. This does not need to be any sort of sexual intimacy to spread. We’re probably just starting to appreciate how many monkeypox infections are out there.

Back to COVID. I just enjoyed this research letter. I think I was actually shocked. I was just going through it a little as we were having some technical difficulties. The research letter, “Leading Causes of Death in the U.S. During the COVID-19 Pandemic, March 2020 to October 2021.” This was published in JAMA Internal Medicine. Here, the authors determine the five leading causes of death by year and age group, and compared this period, March to December 2020 with the period, January to October 2021. I’m going to just walk through the figure, and I’m going to focus on the January to October 2021, because there’s a lot of data. Actually, go ahead and access this article. I’ll recommend that.

Let’s look at the different ages. Where does COVID-19 figure in here? We’ve got the younger folks, 25 to 34, and that’s Panel A. If we look January to October, we’ve got starting off with assaults and then suicide. No, actually, sorry. Is that accidents? Then suicide, then assault. I think I’m going colorblind. Then, boom, COVID comes as number four cause of death in the 25 to 34 right after accidents, suicide and assault, so number one outside that. Then we move up to the 45 to 54. I’m in that age range right now as we record. I will not be when this episode drops on Saturday. My birthday is Friday, July 15th.

VR: Happy birthday.

DG: Thank you. January through October 2021, number one: COVID-19. The number one cause of death for this period in people my age. Shocking, I have to say. I was served a double take there. Was trying to figure out maybe the colors were off. Now we move into those people a little bit older and wiser. There’s actually a gap here, the 55 to 64. Now we move to Panel C aged 65 to 74, January through October 2021. Cancer now becomes number one. Heart disease becomes number two. COVID drops to number three right behind those two. Just really, I think, shocking, just the impact where COVID sits among these risks of causes of death.

VR: Daniel, I’m shocked at the impact of accidents in the younger ages.

DG: [laughs] Are you now?

VR: It’s far more than anything else. Especially young people, 25 to 54, the accidents are pretty high. They’re over 20,000 in that period. Good for them, older people seem to have less accidents.

[laughter]

Folks, be careful.

DG: [laughs] As I say at the end of every show, be safe out there.

VR: Not listening to you, Daniel.

DG: Not listening. Right about here, I wanted to jump in. What we heard from the FDA, I’m going to quote for the FDA directly here, “We have advised manufacturers seeking to update their COVID-19 vaccines that they should develop modified vaccines that add an Omicron BA.4/5 spike protein components to the current vaccine composition to create two component bivalent booster vaccine so that the modified vaccines can potentially be used starting in early to mid-fall 2022.” What’s the story? What’s the story with BA 5. I see Vincent shaking his head.

VR: Daniel, Paul Offit didn’t like the data they had on BA.1, BA.2, and they have no data on .4 or .5 with respect to a booster. It’s crazy.

DG: We’re going to get back to that, because I thought that that was– Everyone, you got to listen to episode. Don’t worry, I’m going to tell you to do it again. First, I just wanted to just give people a little bit of a, we’ll say a primer, so the paper. This is a little bit dated, but it’s not really dated. The “Antibody Evasion by SARS-CoV-2, Omicron Subvariants, BA.2.12.1, BA.4, and BA.5.” This was published in Nature. They reported that the Omicron subvariant, BA.2.12.1- remember we were complaining about the Greek alphabet and how hard naming was? We’re back to hard naming again- Is only 1.8-fold, more resistant to sera from vaccinated and boosted individuals from BA.2.

However, the BA.4/5 is 4.2-fold more resistant. They talk about changes at spike residue L452. I’m not going to go into a lot here, but just also to put people onto another, we’ll have links in the notes about the article, “Broadly Neutralizing Antibodies Against Emerging SARS-CoV-2 Variants,” published in Frontiers in Immunology. There’s a nice Figure 3. When they start talking about Class 1, Class 2, Class 3, Class 4 antibodies, this is just a nice reference for our listeners to go to so they can feel like they understand all the jargon. I do want to just remind, and I think, Vincent, you mentioned this here too, this is not over.

Over 2,000 people here in the U.S. are still dying each week from COVID, we’re still looking at an average of greater than 100,000 per year. We put this into perspective with regard to risks of death. This question keeps coming up, who are those people? Who are the people that are still dying from COVID? To reinforce, it is the unvaccinated, it is the elderly, and it is the immune compromised. I’m going to discuss the MMWR, “Factors Associated with Severe Outcomes Among Immunocompromised Adults Hospitalized for COVID-19, COVID-NET, 10 states, March, 2020-February, 2022.”

Among adults hospitalized for COVID-19, and maybe we’ll have a little discussion about hospitalized with hospitalized for, 12.2% were immunocompromised. Once hospitalized, immunocompromised patients with COVID-19 had increased odds of ICU admission, in-hospital death, irrespective of vaccine status compared with non-immunocompromised patients. This is the part that I really like. I’m not quoting directly, but a little bit of paraphrasing, given the increased odds of severe COVID-19 outcomes among immunocompromised patients, multi-layered preventative strategies for immunocompromised patients are critical to preventing hospitalization for COVID-19 and subsequent severe outcomes.

These strategies include implementing non-pharmaceutical interventions, ensuring that immunocompromised persons and their close contacts are up to date with COVID-19 vaccination, effective pre-exposure prophylactic therapeutics such as Evusheld, early testing such as at-home tests, early disease treatments such as antiviral medication. We keep hammering this home. These immunocompromised individuals should not be dying at these rates. We need to really double down on vaccination, but we also need an action plan for early treatment, and Evusheld, 85% reduction in even a symptomatic case, if added on top of these other measures. Let’s not leave this sitting on shelves.

VR: Daniel, is Evusheld effective against BA.4 or BA.5.

DG: We do have data, and it looks like it’s effective against BA.4 and BA.5. Very reassuring. Definitely get that question a lot, so thank you for asking. I also wanted to discuss the article. I know Paul Offit made a reference, and I actually got some questions directed to me, “What does Paul mean by that?” The article, “A More Accurate Measurement of the Burden of COVID-19 Hospitalization,” published in Open Forum Infectious Disease. It’s a very short article, but raises a really important distinction regarding the three distinct categories of patients hospitalized with COVID-19.

One, we’ve got the classic COVID-19 hospitalization that most people think about when a patient tests positive, it’s the second week, they’re admitted for pulmonary support with hypoxemia, they’re in the early inflammatory phase or, per WHO definition, have critical or severe COVID. This is very different from the mild or moderate COVID-19 with normal oxygen saturation. This is when patients might get hospitalized during that first week because they’re dehydrated, maybe they’re confused, maybe they’re not just doing well at home.

Then we have the third distinct group with a positive COVID-19 test, but no symptoms at all. That’s the true getting hospitalized with, and not for, COVID. There’s really three categories here. Unfortunately, these patients all get the same diagnosis code, and that’s U07.1. That’s laboratory-confirmed COVID-19, but these are very different hospitalizations. As these authors point out, patients hospitalized for severe COVID-19 due to Omicron with hypoxemia had a mortality of about 14%. It’s really not much different than early on. Just think about that.

Those with mild or non-hypoxic COVID-19 still were at some increased risk, but the mortality here was about 3.5%. I have a suggestion, a very simple fix is to add diagnosis codes. You can go ahead and retain that 07.1 for the classic COVID-19 with oxygen saturations less than 94% with confirmed COVID. Fine to keep that U07.2 that no one actually uses when the diagnosis is made clinically and you just can’t confirm it. We can go ahead and add a new U07.3 for symptomatic COVID with oxygen saturations greater than 94%, and U07.4 for asymptomatic with only a positive test for COVID-19.

Just throwing that out there, because I think we need to know, these distinctions are critical for therapeutic recommendations, just so people know when steroids, when not steroids, when antiviral, when not antiviral. Do we fully anticoagulate a person who is completely asymptomatic and just has a positive test, but is admitted for a different reason? I think making these distinctions is really critical.

 Children, COVID, and other vulnerable populations. We now have vaccines for kids all the way down to 6 months. I know, Paul Offit really, I think expressed the importance of this as a vulnerable population, the youngest kids.

The article, “Parental COVID-19 Vaccine Hesitancy in Diverse Communities, a National Survey,” was published in Academic Pediatrics, the official journal of the Academic Pediatric Association. These investigators found that overall 23% of parents in this survey stated that they plan to, or have already vaccinated their children. 23%, about a quarter. 30% said they would not vaccinate their children. 25% reported they were unsure. Of the parents who said they would not vaccinate their children, the majority stated it was due to insufficient research, and over half of parents stated that they would follow their child’s healthcare provider recommendations.

I think that this is really critical. Have those conversations, most parents are saying they would defer, they would trust their child’s healthcare provider. Even if you start that discussion about vaccines, have that discussion. I’ve seen this even personally that once you start talking and explaining, a lot of people are willing, interested in vaccination.

Testing, as I like to say, use tests intelligently. Remember, there’s more out there, not just COVID. Now we have saliva, molecular testing for low resource settings. It’s the paper, “Evaluating Saliva Sampling with Reverse Transcription Loop-Mediated Isothermal Amplification to Improve Access to SARS-CoV-2 Diagnosis in Low Resource Settings.”

This was published in the journal of the American Society of Tropical Medicine and Hygiene. Here, the authors used fresh saliva, and testing with a color metric, loop-mediated isothermal amplification. It’s interesting and all, but I must say that we’re actually seeing, I thought, equivalent or better results with our current rapid antigen test. I’m optimistic about this technology for the future. I’ll just throw that out there. Active vaccination, hot off the press.

After two years of development, Novavax has finally overcome manufacturing problems. Advisors to the Centers for Disease Control and Prevention will meet next week to discuss who should get the Novavax vaccine. I have to say, I have a list of patients who are vaccine hesitant, and are just waiting for this vaccine as it perceived to be a more traditional vaccine with a protein made in moth cells and Matrix-M adjuvant from bark of the soapbark tree. [chuckles] I see you shaking your head. You don’t perceive this as a more natural, holistic alternative to those cutting-edge mRNA vaccines?

VR: No. I don’t think it’s a traditional vaccine. The only one that’s really similar is Shingrix, which is a glycoprotein made in insect cells, and adjuvanted, but that’s just one, so I wouldn’t say it’s traditional. If they’re going to get vaccinated, it’s great.

DG: If they’re going to get vaccinated, let’s call it traditional. I do think there are millions of individuals out there who are comfortable going this route, so it’s great to have that option. Here’s where I do my plug, and I tell everyone to listen to TWiV 917 with Paul Offit. We’ll put a link in our show notes. When I give people the synopsis of the episode and I talk about the fact that Paul said, “You know what? This is great, but can you show us the data on BA.4 and BA.5? Because that BA.1 isn’t circulating anymore?” everyone was like, “Did he have to ask?” [chuckles] I thought that was great.

What we were hearing from that, and you can’t put it all, a whole 60-minute interview with Paul into just this little brief here, but really talking about the fact that we want the data. We don’t want to make recommendations. We don’t want our vaccine experts making recommendations just based upon encouragement, optimism. We need the science. We need the data. We did get a little bit, and I’ll just barely touch on the press release that we got from Moderna where they tell us, BA.4/5 geometric mean fold rise from pre-booster levels was 6.3-fold for the new mRNA-1273.214, and 3.5-fold for the mRNA-1273.

That’s the new Omicron booster versus the tried-and-true vaccine. 6.3 versus 3.5. They report consistent results for all the different subgroups. There’s good and good here. The good is, wow, and we’re getting a free lunch here. Another dose of that original is giving us a 3.5-fold increase in those neutralizing antibodies. The new one is giving us a 6.3-fold. That’s some of the data that I know Paul was asking for. Pretty nice that we’re starting to get the data. No efficacy data, just antibody levels.

Passive vaccination. I need to keep reminding folks about Evusheld. Remember, these are for folks who have mild to severe, not necessarily severe. Moderate to severe immune compromised due to a medical condition or receipt of immunosuppressive medication or treatments, and may not mount an adequate immune response to COVID-19 vaccine, or for whom an individual cannot get that vaccine. Really need to start getting better access to this. You don’t test the antibody levels, you don’t deprive that vulnerable immunocompromised individual from this protection.

Here, I feel like my head might explode, but I’m going to continue through this next section. I feel like I have to keep reminding people the early viral upper respiratory non-hypoxic phase. This is that early mild to moderate phase of COVID. Number one, Paxlovid, almost a 90% reduction in progression. You don’t wait and see. This is based upon risk factors. I think it is odd that I’m part of a profession that celebrates its own obsolescence, but per the FDA news release, “The U.S. FDA Revised the EUA for Paxlovid to Authorize State-Licensed Pharmacists to Prescribe Paxlovid to Eligible Patients, with Certain Limitations to Ensure Appropriate Patient Assessment and Prescribing of Paxlovid.

I’m hoping this really helps with getting this medication out there. Number two, remdesivir. Remember, the order changed, this is number two now. Not a lot of great access here, so we do need to do more to improve that. Remember, this is the one that we can do all the way down to 28 days of age. Number three, not number one, but number there, monoclonal therapy, bebtelovimab. Think about that. If you’re sending your patient for treatment, or you’re thinking about treating, monoclonals have dropped to number three.

There definitely are certain areas where I know a lot of my colleagues are more comfortable. A lot of drug-drug interactions, particularly in some of our transplant patients who were concerned. We have remdesivir. We have bebtelovimab, and last and least, molnupiravir. I do, and this is the part where my head was going to explode this week, we do want to avoid doing harmful things. Just yesterday, I asked Lawrence Shulman if he would just repeat to all the physicians that listen to our weekly call, please don’t give steroids during that first week, it is harmful.

I do another talk to another group every Wednesday, a little bit after noon just reinforcing that. That afternoon, one of the clinicians listening to my 1:30 talk went ahead and started their high-risk patient on steroids, because the sore throat was just so uncomfortable. No wonder I have no hair. I feel like I just need to keep repeating this, so I will. Critical during this first week of viral replication, is not harming our patients with ages that increase the risk for progression to severe or critical COVID and death, or result in patients not accessing effective therapy.

There are interventions that fail to provide benefit, and cause societal harms, such as an increase as we’re seeing an antimicrobial resistance with all those unnecessary antibiotics that we are using, that people are using to treat a viral illness. Antibacterial agents have been extensively studied. They do not show benefit. Number two, steroids given during the first week of illness when a patient is in the early viral upper respiratory non-hypoxic phase with oxygen saturations greater than 94% can be harmful, and are associated with an increased risk of progression to severe and critical COVID.

An increased risk of ending up in the hospital, an increased incidence of cardiac events, pulmonary emboli, and mortality. I think the only good takeaway, that clinician said that because they had listened to me, instead of giving the full Medrol Dosepak, they only gave one day of steroids. People get that? No steroids. [chuckles] Now we get into the early inflammatory lower respiratory hypoxic phase. The oxygen sat drops below 94%. Now is when you think about steroids. Right patient, right dose, anticoagulation, again, adjusted for the particular patient.

Pulmonary support, maybe remdesivir for early enough. Maybe immune modulation with tocilizumab or baricitinib. Now, we got the article published, “Oral Sabizabulin for High-Risk, Hospitalized Adults with COVID-19: Interim Analysis.” I like saying that word actually. This was published in New England Journal of Medicine Evidence. These are the peer-reviewed, published results of the randomized multicenter placebo-controlled phase 3 clinical trial conducted with hospitalized patients, with moderate to severe COVID-19 who are at high-risk for acute respiratory distress syndrome and death.

Patients were randomly assigned 2:1 to 9 milligrams of oral sabizabulin or placebo daily up to 21 days. The primary endpoint was all-cause mortality up to day 60. A total of 204 patients were randomly assigned to treatment, 134 to sabizabulin, and 70 to placebo. Baseline characteristics were similar. Sabizabulin superiority was demonstrated by a planned interim analysis for the first 150 randomized patients. Sabizabulin treatment resulted in a 55.2% relative reduction in deaths compared with placebo. The mortality rate was 20.2% for sabizabulin, versus 45.1% for placebo.

For the key secondary endpoints, sabizabulin treatment resulted in a 43% relative reduction in ICU days, a 49% relative reduction in days on mechanical ventilation, a 26% relative reduction in days in the hospital versus placebo. Adverse and serious events were lower in the sabizabulin group compared with placebo. I did hear some criticism that the treatment and placebo arms were not well-matched.

I did not see that, but I’m going to just spend a little time going through the demographic and clinical characteristics of the patients. You can go through looking at age, looking at sex, looking at BMI, looking at comorbidities. Actually we’ll put a link to this article. I encourage people to go through this. It really actually looked like it was well-matched, and as mentioned, we’re seeing some pretty significant differences with some pretty impressive P-values.

VR: Daniel what’s the mechanism. Is it an anti-inflammatory?

DG: That’s what we think. It works on microtubule network. I don’t think we completely understand the mechanism at this point. It was originally repurposed from cancer therapeutics. That would be the way it would seem to be working.

VR: Because it’s given later when patients are hospitalized, or just before or so. It’s late to be an antiviral, right?

DG: I would agree. To see the results that we’re seeing, I don’t think it’s working as antiviral. I think this is another immune modulator. The secondary symptomatic phase, and then we move into the late phase. Paul Offit mentioned this observation, if I remember correctly. I will mention the article, “Lower Risk of Multisystem Inflammatory Syndrome in Children (MIS-C) with the Delta and Omicron Variants of SARS-CoV-2,” published in CID, Clinical Infectious Diseases.

Certainly lots of limitations, but these investigators reported that in Southeast England, MIS-C rates per confirmed SARS-CoV-2 infections in the 0-to-16-year-olds were 56% lower during pre-vaccine Delta, 66% lower during post-vaccine Delta and 95% lower during the Omicron period. Really, really encouraging if this data holds up. I think Paul mentioned that they were seeing less MIS-C down there in Philly.

The article, “Neurovascular Injury with Compliment Activation and Inflammation in COVID-19,” was published in Brain. I will start by saying, this is a very speculative paper looking at a particular subset of patients that died during the first wave of the pandemic. They died after a short duration of infection with minimal respiratory involvement. This is a very interesting group. The researchers looked at the brains and found platelet aggregates, microthrombi adherent to endothelial cells along vascular lumina. Immune complexes with activation of the classical compliment pathway were found on the endothelial cells and platelets.

Perivascular infiltrates consisted of predominantly macrophages, some CD8-positive T cells, only rare CD4-positive T cells and CD20-positive B cells. Astrogliosis was also prominent in the perivascular regions. Microglial nodules were predominant in the hindbrain. This was associated with focal neuronal loss and neuronal phages, the eating of the neurons. I do want to point out, this is a very distinct subset, not necessarily representative of much of what we’re seeing. I will wrap it up here with reminder, no one is safe until everyone is safe.

I feel like it’s the effort to get equal pay for men and women. They say that will happen in 200 years. Efforts to vaccinate the globe, apparently that’s many, many years ahead of us. We seem to have lost a lot of momentum here, and I am not happy with that. I do want people to pause the recording right here. Go to parasiteswithoutborders.com, click on the “Donate” button. Even a little bit, I love the small amount, so even a small amount helps with our work and also our continued foundation, International Medical Relief of Children fundraiser, to help keep the clinic in Uganda open.

VR: Time for questions for Daniel. You can send yours to daniel@microbe.tv. Sonia writes, “I’m a pediatrician in Wisconsin, and need to clarify about the interval because it seems like the recommendation has changed. Is it as soon as the isolation period is over, or is it three months from the start of symptoms? I see the CDC recommends three months, but wanted to make sure you concur.”

DG: It’s you have a choice. What does the CDC say? The most current CDC timing of COVID-19 vaccination after infection. Here’s what they say. People who’ve had COVID-19 should wait to receive any vaccine, including a COVID-19 vaccine, until after they recover and complete their isolation period. Space, and then they go on and say, additionally, people may consider delaying their next vaccine by three months from when their symptoms started, or if they had no symptoms when they first received a positive test.

They then go on to say, reinfection is less likely in the weeks to months after infection, but however, certain factors such as personal risk, the level of COVID-19 in your community, and the most common COVID 19 variant could be reasons that you want to go ahead and get that vaccine sooner than later. With the amount of SARS-CoV-2 going on, I think we’re getting that second part, bringing us full circle back to the first. When you’re done isolating, go out there, let’s get that vaccine. I hate to be the doctor who is having the call with the patient who got reinfected during that three-month period when we were waiting.

VR: Meredith writes, “Would age, history of serious pulmonary illness, and a congregate living situation qualify my 88-year-old dad for preexposure prophylaxis with Evusheld? He’s fully vaccinated, twice boosted, but spent months last winter getting through an RSV infection. In the past, he’s also had pneumonia serious enough to need intubation, mechanical ventilation.

His assisted living facility is dealing with yet another outbreak of SARS-CoV-2 infections. In the abstract, I know this is a fact-of-life thing at this point in the pandemic, but I’ve only got this one now fragile dad. If there’s a way to protect him with store-bought antibodies, I’d rather work on getting them now than waiting for a confirmed exposure.”

DG: I would talk to, have a conversation with your dad’s physician, get your dad involved. This is going to be one of those determinations your dad’s physician is going to have to make. Being in the congregate setting, the high exposure, that doesn’t necessarily fall under the Evusheld EUA. Once it’s licensed, there’s a little bit more freedom here. Currently, Evusheld is for those who are moderate to severe immune compromise. Listening to what you’re saying about your dad, that might be a judgment by his clinician. Does your dad have factors that qualify him for someone with moderate immune compromise? That would be the criteria.

VR: Joni writes, “I’m a primary care doc in Northwest Georgia. I recently recommended a patient of mine to look into Evusheld and discuss it with her rheumatologist because she has rheumatoid arthritis and is taking methotrexate. She messaged me this week stating that her rheumatologist told her she wasn’t a candidate for Evusheld because her dose of methotrexate is too low. Is this right? I didn’t know there was a dosing threshold for the immunocompromised. The patient decided to get a fourth booster shot instead.”

DG: I’m not aware that there’s a threshold here with methotrexate. This is good because it brings us right back to the same issue we talk about, moderate immune compromise. Someone on methotrexate with rheumatoid arthritis, would I consider them moderately immune compromise? Yes. I’m not sure I would – How low is this dose of methotrexate? This may be an issue where you just want to get a second opinion, someone commenting on this.

If the methotrexate is effective enough to reduce the immune response so that the rheumatoid arthritis is better, then this person is immunosuppressed, immunocompromised. It’s not like you’re taking the Evusheld from that next person in line. This stuff is sitting on shelves. We can make more. You can’t make more, people. I guess you can, but not directly, so sorry.

VR: All right. The last one you’ve really addressed, but I think it’s worth repeating again. Peter writes, “I’m a non-practicing ID doc. Thanks for your continuing brilliantly informative clinical updates. I have not seen any data on the 325 people still dying of COVID in the U.S. each day. Who are these people? Are they mostly the unvaccinated? What can we learn from this group to give confidence to those who are fully vaccinated?”

DG: We went through this, but I’ll hit it again because this is great. If you look at, let’s say, 300 people a day, about half of those individuals are unvaccinated. Of the ones that are vaccinated, we just went through the data, there’s a chunk that are immune compromised that are not, will say, up to date with their vaccines, have not been given Evusheld. We also have older individuals, the majority of people dying are over the age of 75. I will also say, the majority of those individuals did not have an effective action plan that was brought to bear.

If you look at these, these are not people who were diagnosed and then quickly started in the first three to five days on Paxlovid. That is a rare patient among those 300. These are patients, I feel like the majority of these are deaths that can be avoided. We get folks vaccinated. We’re not doing great there. We get those who are eligible, passive antibodies, passive vaccination with Evusheld, and we have action plans so that when a person tests positive, you don’t wait and see, you don’t let that window close, you jump in with effective early treatment.

VR: That’s COVID-19 clinical update number 123 with Dr Daniel Griffin. Thank you, Daniel.

DG: All right, thank you. Everyone, be safe out there.

[music]

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