Yesterday, October 30, was a day off for me. To celebrate, I attended the 7-hour online meeting of the Advisory Committee on Immunization Practices (ACIP) of the CDC. The topic was COVID-19 vaccines. This was the last regular meeting of the ACIP until February, although they will convene on an emergency basis before that time if/when a COVID-19 vaccine trial has enough data to merit discussion. Everyone fully expects that to happen within the next few to several weeks.
The day included presentations from 14 speakers representing FDA, CDC, and vaccine manufacturers and covered regulatory, ethical, scientific, and other topics. I found the modeling discussion most enlightening; it was an attempt to display various outcomes for infection rates and deaths based on how effective a potential vaccine might be, what groups are prioritized for vaccine administration in the early stages of vaccine deployment, and what the US epidemic curve is doing at the time immunization is begun. It was definitely not intended to be a predictive model but rather a general methodology to use whenever a vaccine is ready to be released for use. At that time, more specific data regarding vaccine efficacy and current epidemiology can be plugged into the model to help guide early deployment. More about the modeling later. Here are my take-home points for pediatric healthcare providers distilled from those 7 hours.
Worldwide we now have over 200 COVID-19 vaccines in various stages of study. Honing down to the US, we have 5 vaccines in either Phase I or Phase II testing in humans and 4 in Phase III. Let's focus on the Phase III products since 1 or more of those likely will have results to report in the next few weeks to months. Two of them, AZD1222 (AstraZeneca/Oxford, the UK vaccine you've probably heard a lot about) and Ad26CoV2S1 (Janssen) were paused for safety monitoring but now have resumed recruiting volunteers, though the AstraZeneca product is still on hold in the US. mRNA-BMT162 (Pfizer/BioNTech) is recruiting still but is far along, having enrolled around 42,000 subjects of which about 35,000 have received the second dose of the 2-dose series. Finally, mRNA-1273 from Moderna has completed enrollment of around 30,000 people of whom ~25,000 have received the second and final dose of that series. Most likely we will hear trial results on the Moderna product within a few weeks.
An FDA representative (full disclosure, happens to be a longtime colleague and friend of mine) provided an overview of how FDA rules will be applied in this situation. Again, you've probably seen a lot about this, with some back and forth on the application of product release under Emergency Use Authorization (EUA) which can only be applied in national emergency situations like we have now. Understand that in general EUA is a "lower bar" to clear than is full licensure, but the FDA has very clearly laid out their requirements in this situation. It's really a balance of ensuring safety but not delaying consideration for EUA for such a prolonged period of time that we find ourselves in a worse hole with cases and deaths.
Let's get to the modelling discussion. The group at CDC stratified the population into 5 age groups, 0-4 years of age, 5-17, 18-49, 50-64, and 65+. Note that this oldest category consists of 55 million people nationally (including yours truly!). They also stratified by low-risk or high-risk, the latter consisting of at least 1 of the following medical conditions: COPD, heart disease, diabetes, kidney disease, or obesity. Nationally 40% of adults, 100 million people total, fall into the high risk category. Another interesting tidbit is that ~40% of adults 18-64 years of age, or 80 million people, are classified as essential workers; 1/4 of those are healthcare workers. The modelers made various assumptions about vaccine efficacy in different age groups, etc, and the main focus of their presentation was in Phase 1 distribution of 200 million courses of vaccine. This phase has been divided into Phase 1A consisting of healthcare personnel (20 million courses) and Phase 1B for adults 65+, high-risk adults, and essential workers (180 million courses total). The modeling discussion was most interesting in trying to prioritize Phase 1B individuals - which of those 3 groups should go first, second, third. Various modeling assumptions and outcomes (i.e. what strategy prevents the most infections versus what prevents the most deaths) produced slightly different suggestions for vaccine prioritization.
What was most important, however, was that the timing of vaccine in relation to the epidemic surges going on was by far the biggest determinant of how effective a vaccine will be at any of these outcomes. This isn't surprising particularly, it's why we don't target annual flu vaccination to start in the middle of our annual epidemics. However, the modelling numbers were impressive and point to the main take-home message for all of us: it has never been more important than right now to use those SARS-CoV2 mitigation strategies. Failure to do so diminishes the benefit from a COVID-19 vaccine and makes it even more likely that we'll see more preventable deaths and more harm to our economy.
A few other interesting details from the session. Federal officials are working hard to reach out to everyone in our society to provide vaccine information, including providing information sheets in >20 languages. Also, vaccine recipients will be asked to use a smartphone app to provide real-time feedback for safety monitoring and illness after vaccination. CDC officials provided a brief review of the evidence to date regarding possibility of reinfection with SARS-CoV2. So far this is at most an uncommon event in the first 3 months following infection, but possibly could become more common if immunity wanes later after natural infection. Multiple individuals weighed in regarding vaccination during pregnancy. New data from CDC, so far unpublished, indicate that pregnant women are at higher risk for worse outcomes with COVID-19 (earlier published data were a bit more equivocal). We likely won't have a lot of data on vaccine safety in this population very soon, and it seems that pregnancy will be listed as a precaution but not a contraindication for vaccination.
Which brings us to our final group, children. We need to be very careful with the safety of any vaccine being administered to a healthy child, particularly for an infection that has a much lower complication rate than in adults. So far, we have no pediatric data at all about these vaccines. Certainly children will eventually be enrolled in vaccine trials, once we have sufficient longer term safety and efficacy information from the adult studies. We'll have to be a little patient here.
There is so much more I'd love to tell you about this session, but I've probably already used up some of that patience you need to save waiting for the pediatric vaccine trials. Soon more details from this meeting will be available at the ACIP website. Just know this: I am very reassured with the transparency surrounding vaccine development and distribution, and I am confident I'll see enough of the results from these trials that I'll be able to judge independently whether or not to recommend a vaccine for a specific group. Although you won't be providing COVID-19 vaccine for your pediatric patients anytime soon, you undoubtedly will hear a lot of vaccine questions from your patients and families. A primary care provider is probably the most important individual to help families with vaccine decisions, now more than ever. Whenever a vaccine becomes available for use in the US, of course I'll let you know what I think but know that ACIP/CDC will have toolkits available for you to consult and assess as well.
In the meantime, please ensure all your patients receive their seasonal flu vaccine and are practicing safe COVID-19 mitigation strategies.