Recently I re-read Huxley's 1932 classic, found a 1967 yellowed paperback (75 cents!) hanging around the house. I give it a mixed review in terms of how well it holds up today, but certainly we have seen very recently how technology both helps and can be used to brainwash some people through modern social media in the 21st century, especially with regard to the pandemic.
However, I was more intrigued with the foreword that Huxley wrote in 1946 which appears in my copy. The gist of his message is that he would offer the principal character, the Savage, a third choice of future life. In the book it is a choice between living in a utopian, high-tech world that would drive him insane, versus going back to his primitive Native American village free to experience more significant attachments to other humans but ultimately a very tough and abnormal existence. Huxley's proposed third choice would be a hybrid existence in the primitive village but with some elements of science and technology available. Huxley thought about writing a new version of the novel but ultimately decided against it. It was no coincidence that he wrote this new foreword right after World War II ended with the use of the atomic bomb, perhaps technology's most devastating innovation.
Our brave new world in COVID-19 is just starting. Now, technology has allowed vaccines to be available down to age 6 months. Effective treatments are available, though less so for children under age 12 years. On June 28 the FDA/VRBPAC will meet to plan our path forward for vaccines for the fall. We are at a bit of a quiet time with new infections - lots of them, but milder symptoms overall. It is very clear that the unvaccinated are at much higher risk for severe disease and death, even if they have experienced prior and recent infection. The subvariants continue to outpace science and technology.
Along these lines, you might be interested in a discussion about right and wrong information in this NEJM opinion piece (subscription required) and a nice JAMA editorial about where we are in the pandemic and why.
On a personal level, I am also entering a brave new world. My staged retirement plan was scuttled by the pandemic, but as of June 30 I will be officially retired. Beyond catching up with family and friends and getting started on the 100 or so projects my long-suffering wife has planned for me, I don't know what else is next. I don't think it will be possible for me to keep this blog going in its present form; I need more direct connection to clinical practice to keep it grounded. So, I will be suspending the blog indefinitely. It may reappear in a different format and purpose if I find the need to keep sounding off.
Thanks to everyone following this blog. I wish you all peace and happiness.
Readers of my generation will recognize the opening line of the Crosby, Stills & Nash song "Long Time Gone." Of course I'm co-opting the phrase to mark our entry into the era of COVID-19 vaccines available for children as young as 6 months. I caught most of last week's FDA VRBPAC and CDC/ACIP meetings plus studied I don't know how many pages of documents, so today I will devote the entire posting to summarizing the data. Unfortunately, as of mid-day June 19 CDC has still not posted specific recommendations, so what you see below are tentative recommendations.
Note that CDC still has not issued official recommendations for Moderna vaccine for children and young adults 6-17 years of age, although FDA has authorized its use for this age group. ACIP is meeting June 23 to discuss that. Furthermore, a very important FDA meeting will take place June 28 to plan for potential vaccine composition and doses next fall.
NOTE THAT THE FOLLOWING INFORMATION SUMMARIZES THE JUNE 17-18 CDC/ACIP MEETINGS BUT IS NOT YET AN OFFICIAL RECOMMENDATION.
The Process
CDC and ACIP followed a standardized process to assess raw data from the Pfizer and Moderna trials. Representatives from these companies presented data at this meeting, as they did at the FDA/VRBPAC meeting, but in general I find this less helpful. Pharmaceutical companies naturally want to put their products in the best light possible, but sometimes I feel these presentations obscure the key points. So, I will be presenting information only from the CDC. I found it to be high-quality, non-biased assessments. For those who wish to dig deeper, you can access all the presentation from both days at the ACIP web site. The key documents in my opinion are from CDC's Drs. Sara Oliver and Elisha Hall.
Basis for Recommendations
The primary basis for recommending these vaccines down to 6 months of age is from antibody levels, which was the original primary objective of the trials. Two doses of the Moderna vaccine and three doses of the Pfizer vaccine achieved neutralizing antibody titers similar to the titers seen in 16 (or 18 for Moderna) through 25 year-old trial participants who were protected from infection at that level, albeit well before the omicron era. Additionally, the Moderna trial was able to accumulate enough SARS-CoV-2 cases to provide some assessment of vaccine efficacy for symptomatic infection during the omicron era: VE point estimate was 37.8%, but the confidence interval was relatively wide at 20.9-51.1%. Note that CIs are merely a reflection of how large the number of events is; as time goes on and more cases accumulate, they may be able to report new data with a more precise VE and smaller CI. For Pfizer, just ignore any VE number you might have heard from the manufacturer. The number of cases so far are too small to make any prediction from that data alone. However, extrapolating to older children and adults using the neutralizing antibody data alone, we should expect similar VE. The problem is our moving target as the virus changes. Neutralizing titers and VE in the omicron era are lower, and we don't even have data yet on the rapidly emerging BA.4 and BA.5 subvariants.
Another way to look at this is using Number Needed to Vaccinate (NNV). Using a range of possibilities for VE, CDC estimated for mRNA COVID vaccines that 1660-3320 vaccinations would be needed to prevent 1 hospitalization for COVID-19 disease in children 6 months-4 years of age. This compares with influenza vaccination where the NNV is 1030-6890. (This is all contained in Dr. Oliver's presentation starting with slide 64.)
We do have good safety data with no significant concerns in either the Moderna or Pfizer trials. Of course, rare reactions would not be expected to be seen in trials that combined have about 8000 participants. However, note that just in the US alone around 600 million doses of mRNA vaccines have been administered, surrounded by the most intense reporting system for vaccine side effects ever seen. This should be very reassuring to everyone that these vaccines are very safe and orders of magnitude safer than SARS-CoV-2 infection itself.
Which Vaccine to Choose?
Well, it depends on who is asking. If it is a healthcare provider, go with the product that is easier to implement in your practice. You want to be able to continue providing your high quality care to all patients, and minimizing disruption will help. It may boil down to storage and packaging, with screens shots as below:
Hall slide 17Hall slide 21
For example, you can see that the Pfizer product requires diluent whereas Moderna does not. Neither vaccine requires ultra-low freezer use for everyday practice. CDC should have more guidance available on their website soon.
If, however, it is the parent asking which to receive, that's a different consideration. The principal difference is the need for 2 doses for Moderna versus 3 for Pfizer, although note it is very likely Moderna will need a 3rd dose anyway. Still, a family who is anxious to get the best protection the fastest might want to go with Moderna. The side effects from the Moderna vaccine are a bit higher, more children with fever and lymphadenopathy, so this is the tradeoff.
Vaccine Interchangeability and Coadministration
We have no studies of mixing the Pfizer and Moderna vaccine administration for the same patient, nor any studies of administering these vaccines simultaneously with other childhood vaccines in these age groups. CDC likely will advise to use the same vaccine product throughout the primary series and to allow coadministration with other vaccines.
What are the Recommended Regimens?
As I stated at the top, CDC has not yet published the recommendations online. However, I can show you Dr. Oliver's slide 128 since it is part of the public record. Just be advised to check the official recommendations before administering any vaccine to this age group. Watch for CDC announcements; they also plan to provide all kinds of examples of specific situations such as those involving inadvertent interchangeability.
The interval range between doses 1 and 2 for immunocompetent young children reflects studies in older children and adults suggesting better response with the 8-week intervals; studies in this younger age group have not been performed.
Parting Shot
C, S & N also said, "The darkest hour is always/Always just before the dawn." I don't think that is exactly accurate, but please recognize we are at a new dawn in managing this pandemic. We still have a bumpy road ahead, but we also have much better tools to protect our children.
This past week was relatively quiet in infectious disease land, but next week could be a blockbuster.
COVID-19 Vaccines for Young Children
Unless you've been playing that head-in-the-sand game, you know that FDA and ACIP have meetings planned in the next few days to review data and make decisions and recommendations.
First up is the FDA VRBPAC meetings June 14 and 15. The first day will be devoted to discussion of the Moderna vaccine data for children 6 - 17 years of age. Both FDA and pharmaceutical company Moderna briefing documents were posted recently. I don't expect much controversy for authorization for this older age group based on FDA's briefing. Wednesday's session will cover both Pfizer and Moderna requests for EUA for vaccines for children under 5 and under 6, respectively. The briefing documents for Moderna cover this age group, but the Pfizer briefing documents aren't yet posted at the time I write this. Vaccine authorization for the younger children could be a little more controversial given the risk/benefit calculations and uncertainties about protection levels for omicron subvariants.
Then, the CDC/ACIP is scheduled to meet on June 17 and 18. The agenda isn't yet posted, but my educated guess is that they will discuss Moderna's vaccine on Friday and Pfizer's on Saturday, if either or both have been authorized by FDA. If the ACIP vote is favorable and Dr. Walensky approves, vaccines could be going into arms of children under 5 soon thereafter.
I'm certainly going to be tuned in to the live presentations as much as my schedule will permit. I'll try to summarize things in next week's post.
Local Monkeypox Follow-up
You recall I mentioned some questionable cases in Maryland in last week's post. I have some limited follow-up, all second- or third-hand so the true story might be slightly different. The first case was tested by Maryland DOH with negative results. I was surprised. I don't know what clinical follow-up has been done. For the second case that my colleague helped with over the phone, Maryland DOH decided not to test, said they would follow up with family in a few days, but so far have not contacted the family.
In the meantime, a third questionable case presented to our hospital and another of my colleagues saw the child and helped with collecting specimens. Although the clinical picture is not as strong for monkeypox, skin biopsies and several other samples were collected that will be very helpful for piecing this together. As the 3 of us shared ideas, the main alternative diagnoses for the first 2 cases would be a very unusual presentation of hand, foot, and mouth disease. The third child had enterovirus specimens collected so hoping that can help all of us in the DMV area manage these cases. Atypical hand/foot/mouth disease in the middle of a monkeypox watch? Stay tuned.
Yes, everyone is tired of worrying about COVID-19, and with rising cases across the US it's difficult to see evidence that the population in general is trying to be any more careful now that recommendations have replaced mandates. Pediatric healthcare providers still need to be vigilant.
Another Note on Monkeypox
No, it's not the next pandemic in terms of massive transmission like SARS-CoV-2, but it is a global problem. This past week I was involved with 2 events illustrating that front-line providers need to be prepared.
First I fielded emails and calls from a pediatric practice in Maryland. A toddler who had returned from a stay in West Africa had presented to the office with sores around the mouth. The clinical history including progression of lesions and associated symptoms, plus the rash appearance, was strongly suggestive of monkeypox in my assessment. How to go from there?
First step: ensure patient is medically stable, not needing emergent care, and child and parent are in an exam room with the door closed. Don't allow staff to enter without permission, and anyone who does need to enter must don gown, gloves, and mask, preferably N95 mask. Then, call for help/advice. I was able to help a bit by calling the Maryland DOH provider phone line, and after a few minute wait got a call back. The DOH took it from there and last I heard was going to arrange for sample collection at the family's home. The child and parent exited through the back door of the office, not through the waiting room. I don't know what happened subsequently, but I did provide the pediatrician with links to information about exposure management for the office staff, while they await word on whether preliminary evaluation determines that this is truly a monkeypox PUI (Person Under Investigation).
The second instance, 2 days later, was a text from one of my ID colleagues, again regarding a toddler in a pediatric office in Maryland. The photo looked very much like monkeypox to me, although the exact epidemiology and other details weren't available at that time. My colleague was planning to go through the same procedures as above.
I mention this not to alarm but to reinforce to providers to be prepared to act on this type of scenario. Have in mind how you would "phone a friend" for advice and be sure you know your local health department's provider access details. This will save you and your staff a lot of worry and ensure your patients and families get the care they need.
Omicron Subvariants Continue to Spread
I shouldn't be surprised by now, but it is quite remarkable how SARS-CoV-2 variants continue to evolve to evade prior immunity and spread so easily. Consider the most recent US data:
The BA.2.12.1 omicron subvariant quickly took over the landscape from its BA.2 parent.
In spite of all the US cases and rapid spread, we still aren't seeing a large uptick in hospitalizations:
The same seems to be true in South Africa, where BA.4 and BA.5 reign, and also in the UK. This at least is encouraging. Let's hope we continue to receive relatively good news about hospitalizations and deaths.
Oh, and I learned something new about the whole ostrich/head in sand thing. It turns out that is a complete myth, dating back to Pliny the Elder!
