R Marcucio

I have written an article critically assessing what we can and cannot conclude from Levi and Ladapo's recently published Florida Pfizer vs. Moderna all-cause deaths study. Updating a preprint they published in April 2025, Levi, Ladapo, and colleagues have published a paper in Global Epidemiology reporting substantially higher mortality among Florida residents who received Pfizer rather than Moderna during the initial COVID-19 vaccination campaign: a 40% higher all-cause mortality hazard, 37% higher mortality not attributed to COVID, and nearly twice the hazard of COVID-attributed death. These are substantial associations that warrant serious consideration, but their interpretation depends on how much of the difference is causal, what produced it, and whether either vaccine actually increased mortality relative to remaining unvaccinated. I raised a number of concerns in the earlier version of the paper. The authors have since made worthwhile improvements, and their matching scheme is reasonable. Nevertheless, important uncertainties remain, and the evidence presented does not establish that Pfizer caused deaths through direct vaccine toxicity. Even if the mortality difference were entirely causal, it could reflect Moderna providing greater protection against COVID and its complications rather than Pfizer causing harm. Before getting into the details, I want to raise four questions that are important to keep in mind when interpreting these findings. 1. How much of the Pfizer–Moderna difference is causal? The authors controlled for several important demographic, geographic, and vaccination-related factors, but do not establish whether the groups were balanced on important comorbidities, frailty measures, and underlying medical risks. The unusually large COVID-death difference relative to other studies raises additional concerns about possible residual confounding, which could explain some substantial portion of the observed associations. 2. What would a causal difference represent? Other studies have found that Moderna provided better protection against several COVID outcomes. Greater protection could prevent deaths officially attributed to COVID, but also deaths following infections and complications that were never recorded as COVID-related. Florida's expanded sensitivity analysis meaningfully addresses deaths following documented infections, but cannot account for infections that went unrecorded, a potentially important issue during the state's intense Delta wave. Any difference arising through this pathway would represent better COVID protection with Moderna, not direct Pfizer toxicity. 3. Does the same mortality pattern recur elsewhere? Other large studies failed to reproduce a Pfizer disadvantage approaching 37–40% in non-COVID or all-cause mortality. Several direct comparisons found much smaller differences, sometimes in opposite directions, including a recent English study following over one million matched booster recipients for nearly a year. Although these are not exact replications, the lack of consistent independent corroboration weakens the interpretation that Florida identified a large, persistent, broadly applicable harmful effect of Pfizer. 4. Did either vaccine actually increase mortality relative to remaining unvaccinated? The Florida study cannot determine this. Both vaccines could have reduced mortality, with Moderna reducing it more. Claims that both vaccines increase deaths imply an even larger harmful effect from Pfizer relative to no vaccination, which is difficult to reconcile with large population studies reporting substantially lower observed mortality among vaccinated individuals, including over longer follow-up periods. These comparisons are susceptible to healthy-vaccinee bias and other confounding, but very large hypothesized harmful effects would require correspondingly substantial and persistent bias or offsetting benefits to explain the observed results. These questions are essential because the interpretation of the Florida findings has often gone well beyond what the evidence establishes. Much public commentary has treated the results as proof that Pfizer caused deaths through vaccine toxicity, or even as grounds for withdrawing both mRNA vaccines. Yet whether the observed difference is causal, whether any causal difference reflects vaccine harm rather than greater protection with Moderna, and whether either vaccine increased mortality compared with no vaccination are fundamentally different questions. The Florida study does not resolve them, and the broader evidence provides little corroboration for a large, persistent nonspecific harmful effect. These uncertainties need to be acknowledged before assigning a definitive causal interpretation to the findings. The article linked below explores these questions in detail, and discusses what we can and cannot conclude from this study based on the evidence it provides. @RetsefL @FLSurgeonGen @HHSGov @SecKennedy @NIHDirector_Jay @APPCPenn @UPennDBEI @PennMedCSO @PennMedicine @UPennIBI