COVID-19 vaccines remain effective against severe outcomes

Even as COVID-19 severity wanes and public uptake declines, previous receipt of the 2024-2025 COVID vaccines continues to reduce emergency visits, hospital stays, and deaths among US veterans, as shown in a recent study.

The estimated vaccine effectiveness (VE) was 29.3 per cent against emergency department visits, 39.2 per cent against hospitalizations, and 64 per cent against deaths, reported study author Dr Ziyad Al-Aly from the VA St. Louis Health Care System in Missouri, US.

Contemporary evidence

The severity of COVID-19 infections has decreased since 2020, and the discussion has shifted to the importance of COVID-19 vaccinations in the aftermath of the pandemic.

“The public increasingly questions the need for additional COVID-19 shots because contemporary SARS-CoV-2 variants cause only milder illness as a result of lower intrinsic pathogenicity and higher population immunity from previous infections and vaccinations,” Al-Aly said. “Policymakers are also asking if COVID vaccines still confer meaningful protection in the current epidemiological context.” 

Hence, Al-Aly and colleagues sought to assess the effectiveness of the 2024-2025 COVID-19 vaccines among veterans who received both the COVID-19 and flu vaccines on the same day (164,132 participants), and an active comparator group who received flu shots alone (131,839 participants), between 3 September and 31 December 2024. [N Engl J Med 2025;doi:10.1056/NEJMoa2510226]

Among those who received COVID vaccinations, 64 percent received Moderna’s mRNA vaccine, 35.3 percent received Pfizer-BioNTech’s mRNA vaccine, and 0.7 percent received other COVID vaccines. Of the groups who received and did not receive the COVID shot, 74.7 percent and 73.5 percent, respectively, received the high-dose trivalent flu vaccine.

Mean age of the participants was 71.5 years, 92 percent were men, 70-71 percent were White, and 25-26 percent were Black.

All were followed for 180 days or until an outcome occurred, whichever came first.

VE was estimated using inverse-probability–weighted models (1 minus the risk ratio) for the composite of COVID-19–associated emergency department visits, hospitalizations, and deaths at 6 months.

Overall, VE for a composite of the three outcomes was 28.3 percent, with a risk difference per 10,000 people of 18.2. The absolute risk reductions with vaccination were 18.3 emergency department visits, 7.5 hospitalizations, and 2.2 deaths per 10,000 vaccinated people. “This may reflect the lower severity of current SARS-CoV-2 infections at baseline,” Al-Aly said.

Efficacy over time

Across the combined outcomes, estimated VE was 37.1 percent in the first 60 days after vaccination, decreasing to 32.5 percent at 61–120 days, and to 21.4 percent at 121–180 days.

“The results should be interpreted in the context of a person’s risk of severe COVID-19 and the potential benefits of vaccination against the small but recognized risk of vaccine-related adverse events, including myocarditis," the authors pointed out.

Among the limitations were the study’s population being predominantly White, male, and older, which may limit the generalisability of the findings. The researchers also could not account for behavioural differences that might influence COVID exposure risk. Additionally, there was no interaction between the COVID and flu vaccines.