Go Retire Psychiatrist

Advisory Committee on Immunization Practices Meeting on COVID-19 Vaccine Boosting: Day Two

The ACIP is back for Day Two of the COVID-19 vaccine boosters meeting. Today the focus will be on Moderna, Janssen, and heterologous boosting. They all got the green light from the FDA. I’ll be writing this post in real time according to the meeting schedule. Effectiveness and safety data will dominate the day. The afternoon presentations will cover the evidence, clinical implications, and policy questions. There will be a vote around 3:30 PM, CDT.

Questions were raised about the intention of using the same volume package of Moderna to administer both the primary series or the booster—just withdrawing half of the volume for the booster (50 micrograms in the booster as contrasted with 100 micrograms of the primary series). It sounds like there were concerns about making procedural mistakes in administration. Pharmacists would be concerned about this, and advocated for a separate booster dose package.

The Janssen vaccine booster data show that it’s safe, and increases protection against symptomatic COVID-19 infection. The combination of both humoral and cell-mediated immune responses associated with the Janssen vaccine primary single dose was emphasized. The booster dose is the same as the initial dose. The benefit of the Janssen booster dose might be higher when given at 6 months or later.

The NIH mix and match study showed relatively less boosting from the Janssen vaccine booster. The safety data were mostly reassuring. The study was non-randomized, correlates of protection are not completely elucidated, and not designed to compare between boosts. Heterologous boosts elicited similar or higher serologic responses as compared to their respective homologous booster responses. The 100-microgram dose of Moderna was used as the booster dose initially instead of the 50-microgram dose.

Update after the break:

Safety data were reviewed. Myocarditis/pericarditis rates (Dr. Nicky Klein’s slides) were highest in males age 18-39 years of age who got mRNA COVID-19 vaccines, generally after the second dose (data suggest maybe more from Moderna). Most patients recover. Thrombosis with thrombocytopenia syndrome (TTS) is still being monitored in the Janssen vaccine; it’s more common in women. There may be a causal association with TTS; it’s more common in females and it’s rare. There’s a lack of safety problems identified with current surveillance systems associated with heterologous dosing of mRNA and Janssen vaccines. Rare cases of Guillain-Barre Syndrome (GBS) occur with the Janssen vaccine. Risks of the aforementioned vaccines might be less with the booster doses. A couple of committee members expressed concerns about administration of a 2^nd dose of Janssen as a booster given the rare but serious TTS and GBS adverse events. They favored heterologous boosting with mRNA vaccines instead.

After the break: Data were presented showing waning effectiveness of Moderna and Janssen vaccines. Vaccine effectiveness is lower in the Delta period. There is lower vaccine effectiveness for Janssen in those over age 65. In patients with chronic conditions, vaccine effectiveness in Moderna is better than in Janssen. Moderna has 89-100% protection against severe disease. See the Summary and Conclusions slide of Dr. J. Jones (“COVID-19 vaccine effectiveness, primary series”). Someone asked about the role of risk behavior which could influence the estimate of vaccine effectiveness, which didn’t generate any solid answers.

See slide 5 in “Evidence for Recommendations” slide deck by Dooling for policy questions. Also see Summary slide 16 and slide 41, “Work Group Interpretation.”

The Clinical Considerations slide deck should be reviewed in its entirety. Although homologous boosting was initially recommended, the final language in the voting questions allowed for flexibility for heterologous boosting according to patient preference and product availability as well as taking into account the risk of TTS and GBS in those patients in higher risk groups for those adverse events. There was a consistent preference among some members for more permissive heterologous boosting.

There was a lot of discussion about the voting questions:

Vote #1: A single booster dose is recommended 6 months after completion of an mRNA series, in the same risk groups for whom CDC recommended a booster dose of Pfizer, under FDA EUA. This passed unanimously.

Vote #2: A single booster dose is recommended for persons aged 18 years, 2 months after receipt of the initial Janssen dose, under the FDA EUA. This passed unanimously.

The meeting was adjourned at around 4:20 PM, CDT.

FDA Authorizes COVID-19 Moderna and Janssen Boosters and Heterologous Boosting

The FDA just released a statement this afternoon announcing the extension of the EUA for COVID-19 boosting with Moderna and Janssen vaccine. The FDA also authorized heterologous boosting (mix and match).

Advisory Committee on Immunization Practices Meeting on COVID-19 Vaccine Boosters

I still can’t make heads or tails out of what’s happening with the CDC Advisory Committee on Immunization Practices (ACIP) meeting today and tomorrow. The agenda is still in draft form and it’s dated “Draft—October 14, 2021.” I’m writing this as the ACIP web page is testing it’s incoming and outgoing audio at 8:40 AM, CDT. I’m updating today as the meeting proceeds.

I thought the meeting was going to be mainly about the Moderna and Janssen COVID-19 vaccine boosters, but there are no slides published yet and the agenda looks like it’s mainly about other vaccines. There is one presentation scheduled for this afternoon about influenza vaccines entitled “Phase II safety and immunogenicity study of the coadministration of Fluzone® High-Dose Quadrivalent Influenza Vaccine and a third dose of mRNA-1273 COVID-19 vaccine (Moderna).” I have a stake in the meeting as I wait for the Moderna booster to get the green light.

Tomorrow’s agenda still says “Coronavirus Disease 2019 (COVID-19) Vaccines, TBD.” The only votes so far pertain to the pneumococcal and zoster vaccines, which is for later this afternoon.

There’s also no FDA website update on the final decision regarding recommendations for the Moderna and Janssen booster vaccines. There have been media rumors that the FDA might recommend heterologous boosting (mix and match).

The meeting started on time at approximately 9:00 AM, CDT and the agenda was abruptly updated to final form (which looked like it contained a typo for the presentation about the combination injection of the Fluzone and Moderna booster (omitted after the words “…third dose of…” compare above). The final agenda revealed discussion of the boosters tomorrow starting at 9:15 AM, CDT. Also updated were some of the slide presentations (just for today). There will be a vote tomorrow afternoon on the Moderna and Janssen boosters. This will follow presentations on Moderna and Janssen booster data, NIH mix-and-match booster study, COVID-19 vaccine safety data including data about myocarditis, effectiveness of COVID-19 vaccines, evidence for recommendations, and policy questions.

There was an announcement that the FDA favored using heterologous boosting and that later today that would be posted on the FDA website.

I’ll probably only be spot-checking the proceedings during the day, since it looks like the main event for COVID-19 boosters will take place tomorrow.

Afternoon Update: The presentation “Phase II safety and immunogenicity study of the coadministration of Fluzone® High-Dose Quadrivalent Influenza Vaccine and a third dose of mRNA-1273 COVID-19 vaccine (Moderna)” started around 1:30 PM, CDT this afternoon. Fatigue was the most frequently reported systemic reaction. There were no serious adverse events. The combination can be given safely together without evidence of immunogenicity interference. The shots were given in different arms. All subjects had previously received the primary series (both shots) of the Moderna vaccine. The CDC website already has indicated on their website that the COVID-19 vaccine and the flu vaccine can be given at the same visit.

Stretching Our Legs on the Terry Trueblood Trail

We got out on the Terry Trueblood Trail today to stretch our legs, feel the breeze, and free our minds of the daily news, which is usually bad. It’s nice to just listen to the wind and the birds on the lake.

We see something interesting every time we walk the trail. Caterpillars were pretty busy, trying to cross the sidewalk without getting crushed by bicycle wheels. Some don’t make it. The grasshoppers are a little sluggish.

There’s a myth about woolly bear caterpillars. If they’re all black, some people say it predicts a really bad winter. The longer the brown color band, the milder the winter. We didn’t see any woolly bears today, just some nervous caterpillars trying to avoid getting smashed.

Waiting for Another Jab

I’m still waiting for my Moderna booster, which has to be blessed by the CDC Advisory Committee on Immunization Practices (ACIP). Every time I check the schedule for their next meeting on October 20, 21, I still see a draft agenda. The CDC still does not recommend heterologous boosting, although last week the FDA advisory committee discussed the preliminary results from an ongoing study about it and the data showed it was safe and resulted in impressive boosting. They had a discussion question about it, but there was no vote.

My wife Sena, got her Pfizer booster last week. She had a sore arm for about a day and no other side effects. When I got my first Moderna shot, my left arm swelled up and got red and sore. If I had gotten another injection in the other arm, I would have looked buff.

I just remembered that when I was playing junior league baseball, I got hit with a bat in that same arm in the same spot. I think it took longer for that to heal up. I always struck out anyway. I think the pneumovax I got last month hurt more than the COVID shot.

After my second jab, I got pretty tired for about a day, but still exercised and didn’t really limit my activities beyond my usual laziness. I was still able to sprint away at top speed from Sena when she came looking for me to do some chores. She didn’t have any side effects at all from her primary series.

Before the vaccines were available about a year and a half ago and I was still working at the hospital as a psychiatric consultant, I saw patients who had COVID-19. In the general hospital, all of them were pretty sick, although at that time we were not supposed to see any ICU COVID-19 patients. I saw a patient with a catatonic-like syndrome, who didn’t respond to an intravenous benzodiazepine challenge test (see yesterday’s post about the catatonic variant of delirium). I always wore the proper Personal Protective Equipment (PPE).

Anyway, it sounds like more and more people are getting COVID-19 vaccines. I believe it’s the right thing to do. I’m not a big fan of mandates. Million-dollar lotteries didn’t seem to get the vaccination rates up very much. I don’t think scaring people is the ideal way to motivate them. I guess it’s up to you.

Catatonia and Delirium in COVID-19

This is just a short post on delirium and catatonia in patients sick with COVID-19, which is important to look out for. There are two references below that are pertinent. One is a case report of a patient diagnosed with both catatonia and delirium in a woman with COVID-19 (Amouri et al). One of the co-authors is critical care intensivist, Dr. Wes Ely, Every Deep-Drawn Breath. Anecdotally, when Dr. Ely gave his talk on delirium at an Internal Medicine Grand Rounds presentation on April 12, 2019, I asked him what he thought should be the role of the consulting psychiatrist’s role in ICU delirium. He seemed to remember me and said we would be helpful in identifying the catatonic variant of delirium. What is ironic about this is that, while benzodiazepines are known to cause delirium, they can treat reverse catatonia in the setting of delirium and other neuropsychiatric and medical conditions.

The other article (Baller et al) is an excellent summary of pharmacological recommendations for delirium associated with COVID-19. There’s a nice pharmacologic treatment algorithm on page 589.

References:

Amouri J, Andrews PS, Heckers S, Ely EW, Wilson JE. A Case of Concurrent Delirium and Catatonia in a Woman With Coronavirus Disease 2019. J Acad Consult Liaison Psychiatry. 2021 Jan-Feb;62(1):109-114. doi: 10.1016/j.psym.2020.09.002. Epub 2020 Sep 15. PMID: 33069380; PMCID: PMC7491455.

Baller EB, Hogan CS, Fusunyan MA, Ivkovic A, Luccarelli JW, Madva E, Nisavic M, Praschan N, Quijije NV, Beach SR, Smith FA. Neurocovid: Pharmacological Recommendations for Delirium Associated With COVID-19. Psychosomatics. 2020 Nov-Dec;61(6):585-596. doi: 10.1016/j.psym.2020.05.013. Epub 2020 May 21. PMID: 32828569; PMCID: PMC7240270.

FDA Advisory Committee on Janssen Booster and Heterologous Dosing: Day 2

Dr. Arnold Monto, Acting Chair “Arnie” couldn’t get his camera to work right off the bat on this, Day Two of the FDA Advisory Committee meeting on COVID-19 vaccine boosters. The microphone mute virus was also an issue—again. One committee member had real problems with audio skipping, which the on-screen captioning could not fix. There were many on-screen notices of “indiscernible,” as well as comical errors, “public urine speakers.” That captioning reminded me of voice recognition software, which I tried to use when I dictated my clinical notes.

Early in the meeting, Arnie asked for a clarification of the voting question:

“10/15 Voting Question:

Question 1) Do available data support the safety and effectiveness of Janssen COVID-19 Vaccine for use under EUA as a booster dose in individuals 18 years and older at least 2 months after a single dose primary vaccination?

1a. If yes to # 1, do available data support that an interval of at least 6 months between a single primary dose and a booster dose may result in a more robust booster response?

2b. If no to # 1, do available data support the safety and effectiveness of Janssen COVID-19 Vaccine for use under EUA as a booster dose in individuals 18 years and older at least 6 months after a single dose primary vaccination?”

This led to what Sena and I thought was a hilarious “clarification” interaction between Arnie and Dr. Peter Marks. We couldn’t really follow it, mainly because we couldn’t stop laughing. It reminded me of the “Who’s on First” routine by Abbott and Costello. However, Arnie said he understood it.

The Q&A session between the committee, the sponsor, and FDA seemed conflicted about the data on the efficacy of the Janssen vaccine. The FDA received a large amount of data from Janssen, but apparently got it too late to conduct its own analysis of it. There was the overall impression that the Janssen vaccine efficacy is lower than the mRNA vaccines. The participants on both the FDA and the sponsor side acknowledged that maybe part of the reason to hold today’s meeting was in view of the urgency to do something for those patients who got the Janssen vaccine. Most people acknowledged that the Janssen vaccine had good durability. Arnie kept the proceedings on a short leash as usual, and by the break for lunch at 11:25 AM CDT, it wasn’t very clear what the outlook was for the Janssen booster.

I’ll update after the break.

Several committee members advanced the idea that the Janssen vaccine is actually best considered a 2-dose vaccine rather than a 1 dose vaccine. They moved toward not calling the 2^nd dose as a booster per se, and also seemed agreeable to simplifying the voting question above to only number 1, setting aside the a and b questions. Arnie called out “We need a simplification” and the group went along with it. Dr. Perlman suggested that it might be helpful to hear the presentation about heterologous boosting prior to addressing the voting question; however, Arnie and Dr. Marks thought heterologous boosting might be addressed as a separate EUA in the near future.

The committee voted only on the revised question:

The above was upvoted unanimously. The word “booster” might be changed to something like 2^nd dose later.

After a 15-minute break, the heterologous (mix and match) vaccine boosting presentation will be given. I’ll update after that.

After the presentation on heterologous boosting, it seemed like mRNA boosting was stronger than Janssen boosting. A limitation was that this was an antibody data study only. The committee was impressed with the safety data. The discussion question to the committee was about what other studies they would want to see in order to evaluate an EUA to help guide decisions on, for example, how to boost the Janssen vaccine. Not all members thought an EUA was necessary for this issue. It sounded like some members wanted to see some flexibility in allowing for a fact sheet that would provide clear guidance on how to use heterologous boosting. In fact, some heterologous boosting is already happening out in the real world, which members acknowledged.

The meeting was adjourned at 2:30 PM CDT on the proverbial and a celebratory “You’re muted” reminder.

FDA Advisory Committee Meeting on EUA for Moderna COVID-19 Vaccine Booster Today

Today I’m watching the FDA meeting on extending the Emergency Use Authorization (EUA) for Moderna COVID-19 Vaccine Booster application. Right now, I’m in-between presentations and I’ll be updating later this afternoon. I’m skipping the Open Public Hearing.

I’m wondering if the question to vote on will get changed like it did last month for the Pfizer booster. So far, today’s question is:

“10/14 Voting Question:

Question 1) Do available data support the safety and effectiveness of Moderna COVID-19 Vaccine for use under EUA as a booster dose (50 mcg mRNA-1273) at least 6 months after completion of a primary series in the following populations:

• Individuals 65 years of age and older,

• Individuals 18 through 64 years of age at high risk of severe COVID-19, and

• Individuals 18 through 64 years of age whose frequent institutional or occupational exposure to SARS-CoV-2 puts them at high risk of serious complications of COVID-19 including severe COVID-19.”

Dr. Arnold Monto is in fine form and has already starting limiting the number of questions participants can ask. But we’re ahead of schedule and he’s very pleased overall.

My wife, Sena, finally got her Pfizer booster this morning. It has been kind of complicated for her to schedule and she went through a telephone algorithm about a half dozen times. She showed up on the day scheduled a couple of days ago and the pharmacy manager cancelled it, saying it was too early for the 6-month mark (by 2 days) following her 2^nd primary series dose. This morning he apologized for being the “Vaccine Nazi.”

My Moderna booster depends on what happens today, and after the CDC advisory committee makes its decision at their meeting next week Oct 20-21. If approved, I’d get half the dose I received during my primary series (50 mcg instead of 100 mcg)—provided I don’t run into the Vaccine Nazi.

Anyway, this morning’s meeting went fairly well; only 2 people forgot to unmute their microphones. The Israeli researchers gave a presentation on their updated booster program that impressed committee members, who called the data “compelling.” As I recall, last month, some people raised questions about their definition of COVID-19 disease severity, making it hard to judge how applicable their data results would be in the United States. This morning, they clarified that the disease severity criteria actually came from the NIH (slide 15).

Update around 2:15 PM today: The committee upvoted the question above unanimously.

Tomorrow the committee will take up the issues of J&J boosters and heterologous vaccinations.

Music Beat

We listen to the Music Choice Channel almost every night on our TV. I know that must sound odd, listening to a music channel on television. What makes it more interesting are the biographical sketches. The Light Classical Channel bios occasionally have typos and word usage oddities as well as eyebrow raising facts:

Mozart’s full name was Johannes Chrysostomas Wolfgangus Theophilus “Bud” Mozart.

Frederic Chopin is not pronounced “Choppin” as in his well-known tune “I’m Choppin’ Onions in My Stew and Crying Over Losing You.”

Edvard Grieg was taught the violin by Ole Bull, which is a lot of bull since, at least in Iowa, bulls go “mooooo” and chase red bandanas.

Antonin Dvorak spent a summer in Spillville, Iowa in 1893 where he drank beer and toppled into the Turkey River.

Riveting stuff like that is usual for the Music Choice Light Classical Channel. On the other hand, some months ago, I heard a song called “The Penguin” by somebody named Raymond Scott. I looked him up today and he was a jazz composer and Music Choice must have misfiled him.

I can’t really make fun of his bio because it’s eccentric enough by itself. His music ended up in a lot of cartoons, but he didn’t do that on purpose. Scott sold the publishing rights to his work to Warner Bros. Music in 1943. The music director at that time was Carl Stalling, who used a lot of Scott’s compositions in cartoons, such as Looney Tunes and many others.

Raymond Scott wasn’t even his real name. He looked it up in a phone book and used it partly because it sounded cool. The other reason is more complicated. His real name was Harry Warnow and he was playing piano in a radio orchestra conducted by his brother, Mark in the 1930s. The band started playing Harry’s off-beat compositions and, in order to avoid the appearance of nepotism, Harry adopted the new name.

Scott also invented electronic musical instruments, and after a while, he spent most of his time doing that, working with engineers on many inventions.

I haven’t heard him on the Light Classical Channel for a long while now. Maybe Music Choice finally got him filed to the Jazz Channel.