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:
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.
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.