TWiV 845 COVID-19 Clinical Update #94

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 25 December 2021

pdf of this transcript available (link)

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

From MicrobeTV, this is TWiV, This Week in Virology, Episode 845, recorded on December 23, 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: Daniel, right outside the Incubator, there are kiosks where you can get rapid COVID tests. Right down the block, there’s a CityMD, and the last week, the lines have been crazy. What are people doing, testing before traveling?

DG: A lot of people are testing before traveling. They’re also testing before they go and spend time with vulnerable people. They’re also testing because, I hate to say it, because they’re feeling sick. We are seeing so many sick people, so many positive cases. You see these numbers, but I just have to say what they reflect is our testing capacity, not necessarily how many people are sick, how many people have COVID. It is amazing. We are clearly seeing more people with COVID now than we saw ever in the pandemic.

I have a lot to cover today, and boy, I’ll cover that, too. My one question for you, so that CityMD – was it shuttered like the 19 shuttered CityMDs because all their staff is isolated with infection, or they’re actually open?

VR: No, they are open. They’ve been open all week and their lines out the door, typically in the morning before work. Then in the afternoon, when I go out for my lunch, there are no lines. But they’re staffed, yes, the one next to the Incubator. I think it’s fitting that it’s right next to the Incubator.

[laughter]

DG: I think it is. Yes, unfortunately, what we’re seeing and a lot of our ProHEALTH Urgent Care is actually, I will say, a bit of bad behavior. There’s only so much capacity. There’s only so many thousands of tests we can do per day, and so we’ll reach a certain point in the day, we’d say we’re booked for the whole day. Then people are going to keep coming in. People start to get pretty aggressive and upset because, “Hey, I don’t feel well. I need to get that test. I was supposed to go see my mom tomorrow.” Whatever it might be. Yes, it is tough.

All right. I will apologize, so this is our Christmas Special, Vincent.

VR: That’s right, releasing on Christmas Day.

DG: That’s all up to Vincent, everyone. If this comes out on–

VR: I have an appropriate mug, Daniel, see?

DG: Oh, let me see. I’m going to move my notes so I can see. Oh, look, that is great. I love that.

VR: This was my mother’s, actually. On the bottom, it says, “Made in West Germany.”

DG: Oh, wow.

VR: That’s how old it is.

DG: You mean like when they used to make mugs in Germany as opposed to everything from China? Is that–

VR: Well, West and East Germany. This is interesting, at the Incubator, the former occupants of our space now used to sell visas to go to Russia. I think I showed you a little glass that says made in the U.S.S.R. I found the plates were made in German Democratic Republic, remember?

DG: Oh, wow. Yes. Many years ago, and this is off-topic, but I actually spent time– My roommate from college was studying in East Berlin, like right after the Wall went down. It was very interesting to spend time there right after that.

Let me start with my quotation. “The only constant in life is change.” That’s by Heraclitus of Ephesus. I think a lot of people are familiar with that. We’ll be talking a little bit about all the changes. Things have really changed, and they continue to change.

All right, so Merry Christmas to all who celebrate. I don’t know if people heard but actually, it looks like Santa got my letter. I sent a letter to Santa asking him for an oral anti-viral approval for treatment of COVID. The highly effective oral antiviral therapy from Pfizer just got authorized. The EUA authorized the emergency use of PAXLOVID. This is nirmatrelvir. All right, let’s say that three times. Co-packaged with ritonavir for the treatment of mild to moderate COVID-19 in adults and pediatric patients 12 years of age and older weighing at least 40 kilograms with positive results of a direct SARS-CoV-2 viral test who are at high risk for progression to severe COVID-19. There are a couple of exciting things in there.

One is, you’ll notice there was no mention of vaccination. You’re not excluded if you’re vaccinated. I’m not seeing anything that says that. I am also seeing that there is no requirement that this be a PCR. This is just a positive test, so that would include a rapid test and antigen test, a lateral flow test, some of these point-of-care tests. I think that’s going to be key in rapidly getting these out there. The PAXLOVID is going to be co-packaged with ritonavir. This is a medicine that prevents it from being metabolized too quickly, so it can stay at that level.

You want to initiate PAXLOVID treatment as soon as possible after the diagnosis, so within five days of symptom onset. That’s the data we have, 88% reduction, and progression, if you get it in there, 89% within the first three days, so we’re not really dropping much there. The dosage is going to be 300 milligrams, with 100 milligrams of the ritonavir. These will be 150-milligram tablets. You’re going to take two of those, one of the ritonavir tablets. This will be three tablets, twice a day, for five days. This should be– we’re hoping these are well packaged, so it’s sort of, pop them out, take them, keep it all straight. This is great, but we’re going to start off with supply issues. We are going to have a lot eventually, not as much a lot as I would like.

The federal government has ordered enough Pfizer medication to cover 10 million courses of treatment at a cost of $530 per patient, so that’s $5.3 billion. I’m glad that I didn’t have to write that check, but supply is going to be limited at first. We don’t have the pills right now. I’ve been getting calls and emails and texts all day, “I need my script for PAXLOVID.” We physically do not have access to pills right this moment, but we are hearing that within a week, Pfizer is expected to deliver to the United States enough of its pills to cover 65,000 treatment courses. That’s not a lot.

We’re seeing 300,000 new cases a day. We’re going to get another 200,000 treatment courses in January, only 150,000 in February. The pace of deliveries we hear is then really going to shoot up. We think it’ll be March before there’s PAXLOVID aplenty.

VR: Daniel, do you have to be symptomatic to get it?

DG: Let’s see what it says. It says mild to moderate COVID. I’m not seeing anywhere here that they’re talking about– They say within five days of symptom onset.

VR: Okay.

DG: It’s not very clear, I have to say. The biggest issue here, Vincent, is going to be that risk assessment. Is this a person at high risk? This is not, “I’m 32 years old and I just don’t want to get Long COVID,” which is actually reasonable. It’s initially going to be your highest risk people. It’s very short supply, so I think we’re going to have to be–

VR: Daniel, I’m sure you have given drugs with ritonavir in the past, and you know that they can cause liver damage. What’s your thoughts about that?

DG: Yes, the biggest thing that I think people are concerned about is really the drug-drug interactions. This has come up, but I was talking to one of the reporters from USA Today about this issue. We’ve been using as infectious disease physicians protease inhibitors, we’ve been using ritonavir since the 90s. The nice thing is most of us have electronic medical records. There are pharmacists that will be in the loop. I actually think five days, twice a day. I am not too worried that we won’t be able to– I think we will be able to successfully do this without much untoward effects.

I did want to share an observation here right in the front part. This is seeming to be somewhat consistent over the last week. We’re seeing a shorter time from exposure to symptom onset, so a shorter incubation time between exposure and when someone has symptoms and those positive COVID tests. I always like to check this out with other people. Is this consistent? I talked with Adam Fiterstein, the head of our ProHEALTH in New York Urgent Care centers. I also checked in with some of our other urgent care providers. I was on a call with them yesterday. Again, today. This seems to be a consistent pattern with thousands of positive tests.

Now, it’s all Omicron here in the U.S. We are seeing old data from last week, 73% of new infections for the week ending in 12/18. Here in the New York region, too, it was 92%. Is this really something that we have any evidence to support? Let’s turn those anecdotes into data.

We did get the Rapid communication outbreak caused by the SARS-CoV-2 Omicron variant in Norway, November to December 2021, and this paper was actually supportive of this shortening of the exposure to symptom gap, going down from seven for the Wuhan ancestral, five for Alpha, four for Delta, and now three for Omicron. Here, the investigators reported on a closed event with the distribution of infected cases following an exposure on time zero. They have their Christmas party and then about two days later, you start to see people test positive. Three days later, there’s a huge peak. You see another chunk at four, some more at day five, and then you just pick up a couple more cases per day six, seven, and eight.

This is important for us. Clinically, we’re seeing a much shorter time from exposure to the time that people are having symptoms and testing positive. One of the things I am going to bring up a couple times is we are seeing often the symptoms prior to that positive test by about a day. That is different. In the Wuhan ancestral, people would test positive, and then a day or two later, we would be seeing symptoms. This sort of, and I’ll get back to this, reinforces this paradigm for if they come in, it’s the first day of symptoms. They get a negative test, you may want to repeat that test the next day or the next day. That’s true for PCR and the rapids. Just sort of make sure we share what I think is important.

VR: Daniel, I just had a thought that if there’s a shorter asymptomatic phase, then there’s less opportunity for asymptomatic transmission, right? I’m not sure that’s what we’re seeing, so I want to hear more data before I really get–

DG: There is an optimistic spin because we are seeing this shorter time from exposure. I think SantaCon, I don’t know if I talked about SantaCon before. I don’t know if you went to SantaCon, Vincent. That’s where everyone dresses up as Santa Claus, and then apparently goes bar crawling. This was where– [laughs] That was last Saturday night, a week ago, and then we started seeing positive tests on Monday, which I said that is much too soon, and that’s why I was asking these questions.

One of the things that is interesting is if people get symptoms before they start testing positive, maybe we start acting more like a flu paradigm, maybe a symptom tracking. Don’t go to work if you feel sick. Don’t go to school if you feel– This could be good because what killed us over the last two years was people were spreading the virus before they even knew, before they even had any symptoms or clues. Yes, this will be interesting to see more of these case-control studies, more of these viral kinetics, because still so many of our recommendations, isolation for the infected that we’ll get into are based upon the viral kinetics of the ancestral strain, contact tracing of the ancestral strain.

What are the kinetics and transmission characteristics of Omicron? Children are at risk for COVID. I’m going to start with a sobering number from the CDC and the American Academy of Pediatrics. For the one week ending 12/16, we had an additional 38 children die of COVID, worst week ever. Just that one week. No presents under the tree for these children. Yes, children are at risk from COVID. Children are dying from COVID, very upsetting, but we do have somewhat I think are positive communiques from the CDC and the MMWR, and this is validation of what we’ve been doing in a number of schools, and this is the “test to stay, test to play.”

We had a couple publications. The first one, Evaluation of Test to Stay Strategy on Secondary and Tertiary Transmission of SARS-CoV-2 in K–12 Schools. This was Lake County, Illinois, August 9 through October 29, 2021. Here during the fall of 2021, 90 Lake County, Illinois schools implemented tests to stay, permitting eligible close contacts with masked COVID-19 exposures to remain in school. Secondary transmission among these test to stay participants was 1.5%. No tertiary transmission. Right on to the next level was observed among school-based contacts, and this implementation preserved up to 8,152 in-person learning days.

This was also tried in California. They can do it there, too. Evaluation of a Test to Stay Strategy in Transitional Kindergarten Through Grade 12 Schools—Los Angeles County, California, very similar time, August 16 to October 31, 2021, and here the “test to stay” strategy enabled unvaccinated students, I’m going to get into that, exposed in school to a person infected with SARS-CoV-2, the virus that causes COVID-19, to remain in school while under this quarantine period if both the infected person and the exposed person wore masks correctly and consistently throughout the exposure to stay in school during the quarantine period.

The exposed student needed to remain asymptomatic. They wore masks at school, and they underwent twice-weekly testing for SARS-CoV-2. Here, again, the student case rates did not increase. No tertiary transmission was identified. I want to clarify, let’s think about, and we’ll get into this again.

If you are vaccinated, there’s no required quarantine. This is unvaccinated who have been exposed, so instead of keeping them home from school, they’re wearing a mask, they’re doing frequent testing, and we are seeing, I hear this all the time, “Oh my gosh, they just shut the schools, there’s all these cases.” You can safely keep those schools open. You can make this a safe place, but part of this strategy to avoid the quarantine is testing, and Dr. Walensky, the CDC Director, actually last Friday, 12/17, at a news conference, talked about students participating in “test to stay” programs, so very encouraging. Vincent, did you have a comment there?

VR: I think that’s great. It’s worth repeating. If you were vaccinated, two or three times, right?

DG: Yes, or four, Vincent.

VR: It could be four. Some countries are moving to four, I hear, and you have a positive test or just an exposure.

DG: If you’re vaccinated, and there’s an exposure, you go about your life as long as you don’t have symptoms. You are not locked away. If you have an exposure and you’re unvaccinated but continue to test negative, we were able to have those kids in school and not see that they’re spreading it to others.

VR: That’s great. I think this is part of getting back to normal, right?

DG: Yes. At some point, I’m not going to be able to use the pandemic excuse to avoid the party invites.

VR: Daniel, you probably heard that Columbia is going to go back to online for the first part of 2022, so why are colleges afraid?

DG: Vincent, it’s good to go in that direction. I don’t think they need to be. It is interesting. This is a topic, well, so many topics in COVID no matter what I say, there are the lovers and the haters out there, right?

VR: Yes, true.

DG: Every time I talk about how we can safely have people in school, and I quote literature like this, we can use testing, we can use vaccination, mask ventilation, there are people who are scared, and “I don’t trust you, Dr. Griffin. I don’t think you should be talking on this stuff.” I’m basically sharing the science, and the science says that you do not need to do that. If people are vaccinated, if you have the right mitigation strategies, education is really important, all social interactions are really important. We can do this safely. We have the science to show that.

VR: In the end, Daniel, we have vaccines, so we’ll get back to our lives, right?

DG: Yes, it is really true, and we’ll be hitting on that. Particularly, what happens if you’re vaccinated and get Omicron? I will throw just a little bit of bad news and before we finish off the child section, and it’s a Christmas Special, it’s a little bit longer than usual. I’ll tell you that upfront. From Pfizer, we heard on Friday the 17th, that following a routine review by their external independent data monitoring committee, so the DMC, the companies are amending their clinical study. Unfortunately, what they were not seeing was the level of immunogenicity in the children six months to five years of age with this, I have to say, incredibly small dose.

What we saw was that for the under 12, the dose was dropped to 10 micrograms. Fantastic from a safety perspective. We are not seeing myocarditis, zero, so that’s huge, but they dropped to three micrograms in this youngest group, and they’re really just not seeing the same levels of protection they anticipate. They’re going to be adding a third dose to the primary series here. A little delay there, so they’re going to get that third dose two months after that second dose.

VR: At least the timing is better than three, four weeks, right?

DG: Maybe this will get us there. We’ll get the combination of that really great safety profile that we demand in children, but maybe we’ll get there with that third dose without having any untoward effect, without bringing myocarditis back.

Some changes here. We are now into the “never miss an opportunity to test.” My wife says that’s the road to financial ruin. Apparently, I’m testing too much in my households. Along the lines of “test to stay,” what about shortening that isolation period in the infected but vaccinated? Could this be dropped down to five, six, or seven days? Does it need to be 10 days? Well, NYU dropped this down to five days of isolation for the infected if vaccinated and symptoms are resolved at the end of those five days.

On Wednesday, New York-Presbyterian– and I got the email from Columbia. New York-Presbyterian, so Columbia, Cornell, this large healthcare system, dropped the isolation of the infected for the vaccinated down to seven. Again, if fever and symptoms are resolved, and then just this morning, Northwell, the largest healthcare system in New York, also dropped it down to seven days. You finish your seven days, if you are feeling better, fever’s gone, symptoms resolved, you’re doing that without any drugs to get that fever down. Day eight, you can be back at work. I think this is consistent with the science we’ve been discussing.

We got the news this week. I was joking with you a little bit there, Vincent, that CityMD, one of our partners in the urgent care arena. I call them partners, other people call them competition. They had to close 19 of their 134 locations due to staff out, infected, isolating, but doing okay, feeling fine. I know my colleagues across the country are hoping the CDC will jump in here and take the lead, and then the state departments of health. I don’t like the idea that academic centers are getting in front of the CDC. I like the CDC to be there, but this is a very time-sensitive issue, and it’s really going to be critical for having healthcare personnel there to take care of our patients.

I don’t understand the analogy of dropping like flies or what that actually means. I’m sure I’ve seen flies falling from the sky but healthcare workers in our area, we’re dropping like flies. We are short-staffed. I was talking to one of my colleagues today and 50% of their division across the hospitals are out sick, isolating for the infected. We’re losing critical care providers, and these people feel fine.

VR: Because they test positive, they have to get out? Is that right?

DG: They test positive, yes. The rule is, they have to isolate for the infected for these periods of time. The other subtle issue that – we touched on a little – is how rapid Omicron seems to be, and perhaps this onset of symptoms might be there and then the test positivity. We are waiting, Vincent, as you and I talked about, waiting for some really good viral replication kinetics, so we know when a person does become contagious, when is the contact tracing, how long does that last. It does look frontloaded, so fingers crossed on this. But remember, if you get that first test and it’s negative, think about that second test, think about resources. There seems to be such a quick upslope here that I’m not sure we’re seeing PCR turning positive that day or two before the rapids like we did early on with the ancestral strain.

Active vaccination, never miss an opportunity to vaccinate. I don’t know how often I can say that, but we did hear some interesting news this last week. Actually, I think Paul Offit may have touched on this. This was the ACIP, they made a recommendation, which was a preferential recommendation of the mRNA vaccines over the Johnson & Johnson COVID-19 vaccines. This was based upon their impression that there was a causal link between the 16 million people vaccinated with the J&J vaccine and eight deaths.

People always ask me, “People died from getting vaccinated?” I say, “Yes, it is a very small number. We have eight confirmed deaths here associated with that J&J vaccine.” I point out that is as many as are dying of COVID every six minutes here in the U.S., so it is a small number. This continues to be a very safe and effective vaccine but if there is an option, the mRNA vaccines are getting a preference.

Now, one of the areas that I get lots of questions about, and maybe this is going to become mute but I did promise to return to this was this whole issue, “If I had COVID before, can I get reinfected?” There seems to be a lot of people that don’t want that to be true. I don’t want that to be true. There was the paper I mentioned last week, Duration of SARS-CoV-2 Natural Immunity and Protection against the Delta Variant: A Retrospective Cohort Study.

We’ve seen a number of studies. This was consistent with this. This was a retrospective cohort study where they reported prior viral infection-induced survivor immunity was giving a reinfection protection of about 85.4%. When you looked at the older individuals, those greater than 65, and again, vaccine efficacy against infection here was dropping to 76%, not quite as good. Then, as I mentioned last time when we looked at severity because people say, “Well, you may get infected but what about severity?”

Here, as I mentioned last time, we were not seeing a significant reduction in risk of hospitalization in reinfections nor progression to ICU and mechanical ventilation nor in deaths. We are seeing people get reinfected, seeing reinfections up to four, we’re seeing deaths. Actually, that seemed to be what my day today was. Getting calls and admitting individuals who were infected in the early days, March and April of 2020, now they are getting reinfected with the Omicron wave.

One of those ladies in the hospital. She’s not doing well. One of the other ladies, so frustrating, her husband was incredibly ill. I took care of him in the ICU for weeks upon weeks. He went home eventually. He got vaccinated. She was following those antibody levels, Vincent. They were staying really high. They were staying above that level. He called me today. She is sick. She’s got COVID. She was reinfected. Stop checking antibodies, go get vaccinated, please. Okay, sorry.

What about severity with Omicron? I feel like my head is spinning. I started to get a headache on this. I thought I would take an Imitrex. It was not a migraine, it was just the bouncing back and forth. We are getting data that having two doses of vaccine is not providing much vaccine efficacy against infection for Omicron, and we’re also hearing from the U.K. that even a recent Delta infection may only give you about an 18% vaccine efficacy or prior infection efficacy against infection. It does seem that getting that booster is important with Omicron. It does seem like getting vaccinated even with prior infection is really important with Omicron, so get vaccinated.

What about disease severity? What if you do get infected? We did hear from the WHO. There are still limited data on the clinical severity of Omicron but, I added the but, hospitalization in the U.K. and South Africa continue to rise, and given rapidly increasing case numbers, it is possible that healthcare systems may become overwhelmed. Looking at data from Africa where it’s all Omicron, we are not seeing a decrease in daily deaths or hospitalization.

Now, it is encouraging that the growing data supports that for most people, an infection with Omicron is much less likely to result in hospitalization but, this is really important, reduction in severity observed in these studies can be explained by immunity, either from high levels of vaccination, in the case of England and Scotland, or high levels of recent exposure to the virus as in South Africa. This may be about the vaccination. This may be about immunity. There is no compelling evidence that I have seen that the virus itself has changed to become less severe.

There is no compelling evidence that I have seen that unvaccinated people are doing better, and I will say, here in New York, we are already past 50% of the hospital capacity that we saw a year ago. A year ago when we didn’t have vaccines. We are starting to climb and it’s regional. I was at three different hospitals today. The first couple of hospitals were reasonable. The third hospital was in an area where there are a lot of individuals that are not excited about vaccination. That hospital is overwhelmed. These people are sick. These people are in the ICU. These people are dying. Yes, I’m not sure Omicold is the right description for this variant if you’re unvaccinated.

VR: Shocking, Daniel.

DG: Yes, but you know what? There is a silver lining here and there is a couple of silver linings, so I’m going to talk about that. If you are vaccinated, people are doing well. There was a nice paper. The JAMA research paper, Antibody Response and Variant Cross-Neutralization After SARS-CoV-2 Breakthrough Infection. I hate that word.

This is this individual. This individual has been vaccinated and then gets infected. I want people to take a deep breath. There is so much Omicron. If you end up testing positive for Omicron, this is not a moral failure. We still love you. You can continue to listen to TWiV. There’s so much virus out there, but what we saw in this study was that most people did well. In this study, they reported a 1,021% increase in the focus reduction neutralization test in these individuals. You remember that poor man’s, that lazy man’s plaque essay?

VR: I do.

DG: I know people who test positive after vaccination can feel demoralized. Take a deep breath, change that mindset. The goal of COVID-Zero, it’s gone. It’s here. At some point, most of us will test positive. What will happen for most of us? It will be asymptomatic. It’ll be a mild case. You’ll get better. You will probably not get Long COVID. You will probably not end up in the hospital. Your chance of death is incredibly low. All wins here. Will there be some Long COVID? We’re not at zero. Will there be some hospitalizations and deaths? Yes, but if you’re not vaccinated, that’s the problem.

VR: Daniel, I feel the pundits are getting the press all excited and it scares people. They really should dial it down and say vaccines work and you’ll be fine.

DG: Vincent, we are scaring the wrong people. I’m going to put a big chunk in here and some carrots. If you are vaccinated, you’re in really good shape. If you’re vaccinated, even if you test positive, the vast majority of our population, they’re going to do well. Even, let’s say, we have a few outbreaks going on in our nursing homes, and these people are fully vaccinated, whatever that means. Here, in New York, that means three doses. We’re only seeing a couple of people show up at the hospital, and these are older individuals. These individuals are over 65. They have multiple medical problems. They have enough illness and comorbidities that they’re actually in a skilled nursing facility. They’re doing okay. They’re mostly doing okay.

Who should be scared? If you’re unvaccinated, if you’re relying on the horse paste, yes, that’s who should be scared. The rest of you, if you’re vaccinated, make smart decisions, use testing. I think I’m going to agree with a lot of the people. If you’re vaccinated and you want to spend Christmas with vaccinated people, everyone test before you get together, I think that’s reasonable.

Passive vaccination. Last week we discussed some concerning data regarding the impact of Omicron on the monoclonals. Regeneron were concerned about a pretty significant reduction in efficacy. Not sure it’s really doing much at all. The Eli Lilly cocktail again.

What about Evusheld? We heard from AstraZeneca that despite earlier reports, Evusheld, the long-acting antibody combination retains neutralizing activity against the Omicron variant in an independent FDA study. I just have to say, there is about a hundredfold reduction in activity. They’re going from potency of about 171 nanograms and 277 nanograms per milliliter down to about 1.3 and 1.5. They suggest that that will still be enough to provide protection. I will say in all honestly, that’s just Omicron. We still have the potential return after what I am hoping is a spike up and a spike down. This will continue to provide good protection against the ancestral, the Alpha, the Beta, the Gamma, the Delta. They are suggesting that they will actually still have some potency here.

The period of detectable viral replication, the time for monitoring, and I guess some monoclonals were starting to get some sotrovimab here in the New York area. A couple of thousand doses arrived today. We need much more, but this is not the time for antibiotics, not the time for steroids, but it is for a lot of people the time for isolation of the infected. This is going to come up. I know a lot of people having these discussions around the Christmas table.

What are those? We talked a little bit about how some institutions have shortened those for the return to work, but isolation for the infected is 10 days from symptom onset or that first positive test. Quarantine, remember, gets a little tricky. If you are vaccinated, you do not need to physically quarantine. The recommendation is just to go ahead, do your normal stuff, wear a mask, get a test three to five days after that exposure. If you are unvaccinated, then the CDC says it’s still a 14-day default but there are a couple of shorter options. You can do 10 days without testing. That is the only option in New York State. In some other states, you can go out to day seven as long as you have a negative test on day five, six, or seven.

Remember, if you’re living with someone who is isolating for the infected, the clock does not start for you until the isolation, until their infectious period ends. That can be a little bit frustrating, and you could think about a number of tests being suggested during those periods of time.

Molnupiravir, how come there’s an article in the New England Journal of Medicine, but I can’t have any? Well, the article of Molnupiravir for oral treatment of COVID-19 in non-hospitalized patients was published peer review article. This is the breakdown of the molnupiravir move-out trial. This is the final analysis. We discussed this data before. There were 1,433 participants. What did we find out?

Day 29, there was a 9.7 reduction down to 6.8 in this composite endpoint of hospitalizations or death. We saw an absolute impact about a 3% reduction. One death was reported in the molnupiravir group, nine reported in the placebo group. We’re seeing a number needed to treat of about 30. Then what we were looking at is, can we find out? Maybe there’s a high-risk group, maybe we give this to people over 65. Maybe we give this to a certain subgroup, but unfortunately, and I want everyone to go ahead. This is open access. I know what you want to do on Christmas Day. I’m going to suggest you do this.

Look at figure 3. Check it out. Look at male versus female. Look at first three days, after the first three days. Look at obesity, diabetes over or under the age of 65. Really we’re not able to pull out any high benefit group from that analysis. A little bit tough there. Concerns about potential safety issues, concerns about potential impact on the virus, and the production of new variants. Molnupiravir has still not received FDA EUA, so it’s still sitting there being evaluated.

Any thoughts, Vincent, on that sitting on the shelf?

VR: I think they should move on it, shouldn’t they?

DG: You know what the tough thing is, and I’m going to agree with you. Actually, I’m going to say, yes. We have 2,000 people dying a day, and that number is only going up. We have very limited access to PAXLOVID. You approve something FDA, but we have enough for a day, and then in January, we have enough for two days, and then February, we have enough for two days, and then in March, okay, it finally rolls out. The molnupiravir, this stuff was produced. This stuff was distributed. I think it would be reasonable to give clinicians the option of using this in certain patients.

I would like to have physicians go through a lot of training. I think it would be great. Something that could reduce progression hospitalization death by 30%, yes, I would like to have access to it as an option.

VR: Hey, you remember the early days of AIDS, Daniel? They fast-tracked a number of drugs in response to complaints from patients. Patients start making noise.

DG: Yes, make lots of noise. I, unfortunately, remember those days quite well. If our listeners remember, but I grew up in Greenwich Village. In the early 80s, I was living in Greenwich Village when our neighborhood was being decimated.

Convalescent plasma, there was another paper out of Hopkins, Randomized Controlled Trial of Early Outpatient COVID-19 Treatment with High-Titer Convalescent Plasma, posted as a preprint, just to really cut here to the chase. This was high-titer plasma being used early in disease, and they actually reported a 54% risk reduction. It was an absolutely risk reduction 3.4%, sort of sounds similar to that molnupiravir number, a number needed to treat 30 to keep one person out of the hospital. Remember, Merck wants $700 per treatment. What are a few comments here?

With regard to what we’ve seen on convalescent plasma, and this echoes the Brazilian results, if you can get high-titer convalescent plasma in early, we’re now seeing more data to support that. If you wait until patients are in the hospital, you wait until they’re in that early inflammatory and hypercoagulable phase, and you give them a product full of clotting factors, I would not expect it to be helpful. Timing really matters, but it was interesting.

I was having a discussion with one of my unvaccinated patients yesterday and we continue the conversation today, but he has never received a vaccine in his life, and he has made it to 70, and he is doing great. I did point out the fact that he is prone and being on high-flow nasal cannula was not really a ringing endorsement of forgoing the vaccine.

I asked him. I said, “Let me ask you, so you’re an anti-vaxxer.” He proudly took on that moniker. I said, “One of the things we’re hearing talk about is, why don’t we give convalescent plasma from triple vaccinated people? It’s not really convalescent, it’s this high-potency vaccine needs here. What about that?” We thought about it. We had this whole discussion, like, “If you don’t want to take a vaccine, how do you feel about getting the benefits of the antibodies from a vaccinated individual?” He was not sure he was up for that.

We’re going to jump ahead, because I know this is long, and people probably want to spend time with friends and family, and not just listen to TWiV.

VR: Shocking. I can’t imagine.

DG: Can you imagine that? I did get a little follow-up on that young lady who got COVID after her vaccination, and she had a little bit of hair thinning, a little bit of hair loss. We are seeing a little bit of post-COVID, even in vaccinated people, the Long COVID things, but we’re tending to see less of it. It’s tending to be milder. We haven’t gotten rid of Long COVID with vaccinations, but I am seeing some encouraging experiences. This is along with some of the studies we’ve talked about before.

The other, no one is safe until everyone is safe. Actually, that’s the battle cry of the WHO now. That was nice. I do want to just echo back as we finish here. I think we are scaring the wrong people. I don’t think that people who are fully vaccinated need to be scared. Those numbers are going to go up. Most of those people who are vaccinated are going to get the sniffles. They’re going to have a few days of feeling a little bit under the weather. Now they’re going to have over 1,000% higher neutralizing capacity.

I said it was a free boost to my wife. She’s like, “The vaccines are free. It’s just you don’t have to go to the Javits Center to get that boost.” It’s really people who are unvaccinated that I’m concerned about. I’m also concerned about the people who can’t generate that immunity, so little disturbed by Omicron. I’m hoping that the Evusheld actually continues to be effective. I’m hoping we get more of the sotrovimab. I’m hoping we get more oral anti-virus.

If you’re listening to TWiV, if you are vaccinated, you are not the person who needs to be scared. Just sort of put all this in perspective. Now we will close. Our listeners, you’ve been incredibly generous. I feel MicrobeTV is really going to appreciate how generous we can be, really been a lot of tremendous donations during this holiday season. We are going to continue to support MicrobeTV the rest of this month, all through January, and we’re going to keep doing this for years to come. Thank you so much for continuing to listen and continuing to support us.

VR: Time for some email questions for Daniel. You can send yours to daniel@microbe.tv. Natalie writes, “Our company has made COVID vaccination mandatory. Several employees have received a temporary extension due to medical exemption. I understand that each individual’s situation is unique. However, I would like to better understand the clinical reasons for delaying vaccination in the following situations.

One, individual tested positive for COVID beginning of October, still symptomatic. The doctor stated that an individual cannot receive vaccine while symptomatic. Presuming this individual did not receive a monoclonal treatment, why can’t that individual receive vaccination two months after infection? CDC only notes that individuals who receive monoclonal should wait 90 days to get vaccinated.” Let’s start with that.

DG: Yes, let’s start with that one. In that situation, I would actually recommend the person go ahead and get vaccinated. What we’ve encouraged organizations to do is you could have a letter from the person’s doctor, but then you want to have a separate, because it’s really hard. The physician is probably trying to maintain a relationship with that patient. Often, they feel pressured. We had that woman, the pregnant woman who got an OB note saying, “You don’t need to get vaccinated.” Then she ended up getting infected. You want to try to separate that.

No, there’s no medical reason here. Once that person is passed that acute phase, and now we’re in December and this infection was October, so there’s no reason, and there also is what we’ve seen, some people actually feel better after they get vaccinated. Go ahead. Get that vaccination therapeutically. Get that vaccination as a prevention. There’s no medical reason why that person should not be vaccinated.

VR: Second question. “An individual who has multiple blood clots in arms and chest blocked carotid artery on the left side, recent blood work showed high red blood count, is delaying vaccination out of fear. Should an individual with this medical history receive the vaccine and which one would be the best, or is there a better alternative for them?”

DG: This would be an individual that I would strongly recommend that they go ahead and I would say an mRNA vaccination that in keeping with the ACIP and the CDC recommendations there. This individual, if they get COVID, they’re incredibly high risk. We saw what, 30% of individuals in the hospital with COVID end up with venous, with arterial clotting, even a number of individuals losing limbs. You can imagine how horrifying that was for the patient and for me as the provider. Now, this individual should go ahead and get vaccinated.

VR: Kemin writes, and Kemin is a dentist, he would like your advice. “I had a second dose of Moderna vaccine back in March. Eight months later, I got COVID, mild symptoms, recuperated in 10 days. Now I am almost a month after my first symptoms started. My big question is, when is optimal to get the booster? I’m healthy except I’ve had meningitis twice. I take Valtrex daily, and also my thyroid is hypo, no medications.”

DG: We are not really factoring infection into our booster recommendations, because we’re not really sure what exact level. We don’t have a blood test, as I reiterated again today. Go ahead. I would go ahead and get that shot. What we do think is for about four months after the shots, you’re getting a vaccine efficacy against infection. Then, you’ll be happy to hear that people at Pfizer would like us to get vaccinated every four months. I have to say I’m okay with that. I’m very pro-vaccine. We don’t really count that. Go ahead. Get that booster. Next thing, we’ll be like Israel. We’ll be getting our shots every four months.

VR: Finally, Louise writes, and Louise is a primary care doctor, “Patient is worried about the delay in vaccine availability for her toddler, and was considering taking hormones to reinstitute breastfeeding. Mom never had disease, but had a J&J shot and a Moderna booster. Thanks.”

DG: That’s interesting. There is some amount of antibodies that are being transferred maternally in the breast milk. We also talked about. There’s also a transfer of cellular immunity as well. That seems pretty extreme. I’m not sure I can go beyond just the science there. That’s a lot, boy. You love your child.

VR: That’s COVID-19 clinical update #94, with Dr. Daniel Griffin. Thank you, Daniel.

DG: Thank you so much. Everyone, have a happy and safe holiday season.

[00:49:00] [END OF AUDIO]