Risk of severe COVID-19 in unvaccinated patients during the period from wild-type to Omicron variant: real-world evidence from Japan

Abstract

Background

Many studies have reported that the Omicron variant is less pathogenic than the Delta variant and the wild-type. Epidemiological evidence regarding the risk of severe COVID-19 from the wild-type to the Omicron variant has been lacking.

Methods

Study participants were COVID-19 patients aged 18 and older without previous COVID-19 infection who were notified to the Nara Prefecture Chuwa Public Health Center from January 2020 to March 2023, during the periods from the wild-type to the Omicron variant. The outcome variable was severe COVID-19 (i.e., ICU admission or COVID-19-related death). The explanatory variable was SARS-CoV-2 variant type or the number of COVID-19 vaccinations. Covariates included gender, age, risk factors for aggravation, and the number of general hospital beds per population. The generalized estimating equations of negative binomial regression models were used to estimate the adjusted incidence proportion (AIP) with 95% confidence interval (CI) for severe COVID-19.

Results

Among 77,044 patients included in the analysis, 14,556 (18.9%) were unvaccinated and 520 (0.7%) developed severe COVID-19. Among unvaccinated patients, the risk of severe COVID-19 increased in the Alpha/Delta variants and decreased in the Omicron variant compared to the wild-type (AIP [95% CI] was 1.55 [1.06–2.27] in Alpha/Delta and 0.25 [0.15–0.40] in Omicron), but differed by age. Especially in patients aged ≥80, there was no significant difference in the risk of severe COVID-19 between the wild-type and the Omicron variant (AIP [95% CI] = 0.59 [0.27–1.29]). Regarding the preventive effect of vaccines, among all study participants, the number of vaccinations was significantly associated with the prevention of severe COVID-19, regardless of variant type. After stratified analyses by age, patients aged ≥80 remained a significant association for all variant types. On the other hand, the number of vaccinations had no association in Omicron BA.5 of patients aged 18–64.

Conclusions

Patients aged ≥80 had less reduction in risk of severe COVID-19 during the Omicron variant period, and a greater preventive effect of vaccines against severe COVID-19, compared to younger people. Our findings suggest that booster vaccination is effective and necessary for older people, especially aged ≥80.

Supplementary information

The online version contains supplementary material available at https://doi.org/10.1265/ehpm.23-00274.

Graphical Abstract