Covid vaccine in 2026

The short version: the 2024-2025 updated COVID-19 vaccines cut hospitalization by about 40% and prevented death or ventilation by about 79% in adults, but the evidence is from a single manufacturer-funded test-negative study with short follow-up, and the long-term safety picture from earlier doses raises questions that this study does not answer.

The strongest evidence for the 2024-2025 vaccines comes from a US test-negative case-control study of 8,493 adults hospitalized with COVID-like illness, funded by the CDC and published in JAMA in 2026 [7]. It found the updated vaccines reduced COVID-19 hospitalization by about 40% (95% CI 27-51%) and prevented invasive mechanical ventilation or death by about 79% (95% CI 55-92%) [7]. Protection was similar across the KP.3.1.1, XEC, and LP.8.1 lineages and lasted 3-6 months [7]. The study design is reasonable for estimating short-term protection against severe outcomes, but it compares vaccinated to unvaccinated people who chose their status, so healthy-vaccinee bias cannot be ruled out.

The broader all-cause mortality evidence from 2021-2023 is deeply mixed. A Norwegian population-based study of 4.6 million adults found that those with three or more mRNA doses had about 60% lower all-cause mortality than the unvaccinated [4]. A Hungarian study that adjusted for the healthy-vaccinee effect found 49-75% lower all-cause mortality across six different vaccines [5]. But several other analyses point the other way. A US county-level study of over 3,000 counties found that higher vaccine uptake was associated with higher all-cause excess mortality in 2022 and 2023 [2]. An English study of monthly mortality data found that vaccinated individuals initially had lower non-COVID mortality but that this reversed over time, with vaccinated people showing higher non-COVID mortality by the end of the study period [1]. A UK ONS analysis found that all-cause and non-COVID mortality standardized mortality ratios increased over time for vaccinated relative to unvaccinated across all age groups [3]. A Japanese municipal study found that younger adults (20-49) who received 5 or more doses had higher all-cause mortality than those with fewer doses [6].

The myocarditis risk is real and concentrated in young males after the second mRNA dose. A meta-analysis found a relative risk of about 2 after vaccination versus about 15 after SARS-CoV-2 infection [8]. A self-controlled case series in England found that in 16-39 year olds, the relative incidence of myocarditis admission was 5.3 after a second BNT162b2 dose and 56.5 after a second mRNA-1273 dose [9]. The absolute risk is low: about 16 per 100,000 in adolescent males after the second dose [10].

The evidence for the 2024-2025 vaccines shows short-term protection against severe COVID-19, but the long-term safety data from earlier doses is unsettled. The studies that show net benefit tend to be from early pandemic periods with high COVID-19 mortality and from populations where the healthy-vaccinee effect is strongest. The studies that show harm or reversal come from later periods and from analyses that account for baseline health differences. The question of whether repeated mRNA boosting produces net benefit or harm over the long term is not settled by the evidence here.

My call: the 2024-2025 vaccines reduce short-term risk of severe COVID-19, but the evidence does not establish net long-term benefit, especially for younger and lower-risk people, and the unresolved all-cause mortality signals from earlier doses mean the risk-benefit calculation is not settled. Confidence: moderate for short-term protection against severe outcomes; low for long-term net benefit.