Did the FDA Do the Right Thing?

The messaging on vaccination, now entering its booster phase, has been mismanaged. That said, was the decision by the FDA’s Vaccines and Related Biological Products Advisory Committee “based” on science? Is it reasonable policy?

There is no doubt that the President got out, “in front of his skies,” in announcing September 20th for the rollout of booster shots to all vaccinated Americans whose initial vaccination was eight months ago. Dare I say it echoes our recent problems with the timing and planning around an Afghanistan withdrawal? [THERE IS NO WAY I WOULD BRING THIS UP BUT IT'S YOUR CALL] An obvious question now is was the advisory committee decision [SAY WHAT THE DECISION WAS] is reasonable and supported by data. The answer, for me, is yes, but this opinion is far from unanimous. Let's look at data from Israel; then you decide. One caveat –there is no settled, best science for COVID-19 vaccinations, but in making real-world decisions, you use the data you have.

The Israeli study

The “Israeli” data comes from a pre-print reporting the relative value of vaccine-induced versus infection-acquired, termed natural, immunity on breakthrough infections. I will continue to refer to natural immunity as infection-acquired because more lives are lost in the acquisition of immunity by infection from COVID-19 than have been lost by those seeking immunity through vaccination. [THIS MAKES IT SOUND LIKE IT'S CLOSE. IT'S REALLY MORE LIKE 10 BAZILLION TO ZERO. THIS SHOULD BE EMPHASIZED]

Israel has been the global leader in vaccination with significant coverage of their population, 78%, achieved far earlier than most countries. Because of an arrangement with Pfizer Israelis received the Pfizer mRNA vaccine. Despite the high vaccination number, Israel has recently experienced a surge in cases. This makes it the perfect site for an observational study  [LINK?] of the efficacy of infection-acquired and vaccine-acquired protection. [THIS DOES NOT NECESSARILY FOLLOW. EXPLAIN WHY IT'S THE PERFECT SITE.

The study involved over 700,000 members belonging to one of the four mandatory health systems in Israel.

  • 673,676 were fully vaccinated
  • 62,883 were previously infected and unvaccinated
  • 42,099 were previously infected and subsequently received a single-dose vaccination

Sample populations were taken from each of these groups and matched for their overall demographics and co-morbidities. There were slightly more significant co-morbidities, e.g., immunocompromised, cancer, COPD, and diabetes, among the fully vaccinated than those with infection-acquired immunity with or without that single-dose vaccination.

There is one demographic that stands out and should garner attention: age distribution. The Israeli population is an imperfect reflection of the US. The study included 61% of individuals age 16 to 39 (based on the US census of 2010, 36% of our population is in that age range), 34% age 40 to 59 (US 26%), and 5% over age 60 (13% in the US). So this is a bit like comparing young apples to old oranges.

Vaccination versus Infection acquired immunity

Of the roughly 32,000 patients in this group [WHICH GROUP??], there were 257 documented breakthrough cases or reinfections [1]. The good news is that less than 1% of these groups [PEOPLE?] had a subsequent COVID-19 infection. [2] Two hundred thirty-eight were among the vaccinated, 19 among the infection-acquired immune. <---- [SORRY, BUT I JUST DON'T UNDERSTAND WHAT YOU'RE TRYING TO SAY HERE] So clearly, we can conclude that both vaccine and infection acquired immunities are protective. And, in aggregate infection-acquired immunity appears better – your risk of a COVID-19 infection is 13 times greater if you have been vaccinated than if you have simply been infected and survived. That is the number that advocates of infection acquired immunity are pointing to. But when the researchers stratified the infections based on ages and co-morbidities, the only factor  [DATA POINT?] that achieved statistical significance was age greater than 60. For those under 60, immunity was conferred through vaccination or infection [ISN'T THIS THE CASE FOR EVERYONE IN THE STUDY??]. Only those When only the statistically significant results were (age 60 or greater) were included the 13 fold difference dropped to 2.7 fold.

The same data indicated that the risk of symptomatic infection was 27-fold greater for the vaccinated [VS. WHAT GROUP? THOSE WITH ACQUIRED IMMUNITY?]. But that finding was once again driven by those over age 60; 27-fold became 2.8 fold when only the statistically significant data was considered.

Previously infected versus previously infected and plus a single vaccine dose

Of the roughly 28,000 patients in this cohort, there were 57 subsequent infections – 0.2% overall. Of the reinfected, 68% were symptomatic with no deaths and only one hospitalization. There was a 50% reduction in subsequent infections in the group with infection-acquired immunity that had received a single “booster” vaccination. The biggest drivers were age over 60 and having been immunosuppressed.

What have we learned?

  • For those surviving a COVID-19 infection, this acquired immunity is robust, “better” than the immunity conferred by vaccination. Better is in quotes because you have to survive the infection. For those over 65, you have a 350-fold greater chance of dying from acquiring your immunity through infection versus vaccination. [3]
  • For those with infection acquired immunity, a Pfizer booster confers additional protection
  • Vaccination was still very protective, but its protection seemed to wane in those over 60 – consistent with the general acknowledged decline in our immune response with age.

In my view, the decision of the FDA advisory committee was correct. The Israeli data demonstrate that those over 60 are not as well protected as those younger. From a policy point of view, it is a reasonable additional measure to maximize your safety. As with many government health regulations, it is made “out of an abundance of caution.”

For those of us over 65, who presumably will be eligible within the next few weeks, the choice is simple. Irrespective of whether your immunity was from the vaccination or acquired the old-fashioned way, by being ill, a booster will be more protective than not. If you already feel safe, you needn’t get in the line; if you want that additional edge, get the booster. The same thinking applies to the immunocompromised.

[1] Breakthrough cases refer to those who have been vaccinated, reinfections those previously infected – from an immunity point of view, the terms are interchangeable.

[2] Hospitalizations among those infected 3.5% (0.003% for the entire group), there were no deaths.

[3] The infection fatality rate (deaths among the infected) varies with age; for those over 65, it is 1.4%. In my query of the VAERS database for those receiving an mRNA vaccine, the fatality rate was 0.004%.


Source: Comparing SARS-CoV-2 natural immunity to vaccine-induced immunity: reinfections versus breakthrough infections medRxiv DOI: 10.1101/2021.08.24.21262415