The 2025-26 Pfizer COVID-19 vaccine is about 57% effective against emergency department/urgent care (ED/UC) visits and 54% effective against outpatient visits among adults roughly 4 weeks after vaccination, with considerable uncertainty, according to preliminary estimates published on the preprint server medRxiv.
A team that included researchers from the Providence Veterans Affairs (VA) Healthcare System and Pfizer used a test-negative case-control design to estimate the early vaccine effectiveness (VE) of Pfizer’s BNT162b2 LP.8.1 vaccine against ED/UC and outpatient visits.
Participants were VA patients who had an acute respiratory infection (ARI) and underwent COVID-19 testing from September 10 to November 30, 2025.
“The availability of timely real-world effectiveness data for the LP.8.1–adapted vaccine plays an important role in informing clinical decision-making, reinforcing vaccination recommendations, and supporting vaccine uptake throughout the respiratory virus season,” the authors wrote.
The study has not yet been peer-reviewed.
Similar effectiveness as last year’s vaccine
Among patients with 34,455 ARI cases, 10.7% had COVID-19, and 2.4% were vaccinated. Of 3,696 cases and 30,759 controls, 1.2% and 2.6% received the Pfizer vaccine, respectively. Most ARI episodes (68.7%) were ED/UC visits.
Patients 65 years and older made up 53.7% of the study population, and 85.1% were men. More than one-third of these patients had a Charlson Comorbidity Index score of three or higher (36.2%)—indicating a substantial burden of underlying disease—and 41.3% had weakened immune systems.
VE was 57% with considerable uncertainty (95% confidence interval [CI], 39% to 70%) against ED/UC visits and 54% (95% CI, 15% to 75%) against outpatient visits four weeks post-vaccination. The results of sensitivity analyses among patients who received both the COVID-19 and influenza vaccines were consistent with those of the primary analysis.
The estimates are comparable to those from an early-season analysis of BNT162b2 KP.2 VE in 2024-25, which was 57% against ED/UC visits and 56% against outpatient visits. The researchers did not assess how long the protection lasted.
Lower uptake than last year
“These findings inform shared decision-making in clinical practice and support the continued importance of COVID-19 vaccination in populations for whom it is recommended,” the study authors wrote.
In clinical discussions, it is important that patients and others involved in their care decisions understand that COVID-19 vaccines provide protection not only against severe disease but also against milder COVID-19 outcomes.
They noted that COVID-19 vaccination uptake continues to decline despite recommendations from public health agencies and infectious disease experts. By early December 2025, only 15.0% of all adults and 32.5% of those aged 65 years and older had been vaccinated. In comparison, 2024–25 vaccine coverage was 21% among all adults and 45% among those 65 and older.
This year’s lower uptake may be related to delays in COVID-19 vaccine recommendations from the Centers for Disease Control and Prevention (CDC), as well as a shift from a universal recommendation for all people 6 months or older to a recommendation for individual-based clinical decision-making, the researchers said.
“In clinical discussions, it is important that patients and others involved in their care decisions understand that COVID-19 vaccines provide protection not only against severe disease but also against milder COVID-19 outcomes,” they wrote.
“Strategies such as risk-based outreach, clinician decision support tools, and expanded pharmacist-led vaccination programs may help improve acceptance and uptake of COVID-19 vaccines,” they concluded.
