Impact of booster vaccinations and prior infection on COVID-19 symptom resolution during the 2025 NB.1.8.1-dominant epidemic in Japan: A retrospective multicenter study

OBJECTIVE: To evaluate the effect of booster vaccinations and prior infection on the symptoms of outpatients with mild cases of coronavirus disease (COVID-19). METHODS: This retrospective, multicenter study was conducted across 15 Japanese medical institutions during the 2025 COVID-19 epidemic dominated by the NB.1.8.1 variant in Japan. Patients diagnosed with COVID-19 via rapid antigen testing between July 1 and September 30 were enrolled and given a questionnaire to collect the data for this analysis. RESULTS: The data of 375 patients was available for analysis: 40.9% were aged 40-59 years, 37.3% ≥ 60, 61.3% were female, and 47.2% had prior COVID-19. Of them, 6.4% had been vaccinated within the past twelve months, whereas 70.4% had received their last vaccination more than twenty-four months earlier. The maximum body temperature was significantly higher in patients last vaccinated more than twelve months before the current infection than in patients vaccinated within past twelve months (38.2-38.3 °C vs 37.8 °C, p = 0.02, respectively): this difference was also observed among patients without prior COVID-19 (multivariable regression analysis). Neither the number of vaccinations nor the interval since the last vaccination was significantly associated with a shorter duration of fever or symptoms. Among patients with prior COVID-19, fever duration was significantly shorter, and the frequencies of symptom persistence >7 and > 14 days were lower. CONCLUSION: Vaccination within the previous year was effective in reducing fever during the 2025 NB.1.8.1 variant dominant epidemic in Japan, particularly among patients without prior COVID-19.