As few studies have evaluated the waning of vaccine effectiveness against severe SARS-CoV-2 Omicron infection outcomes, the researchers sought to examine changes in vaccine effectiveness against hospitalization and mortality due to the Omicron variant over time. They focused on Hong Kong, which provides inactivated and mRNA vaccines, but had a population with limited protection from natural infections before the Omicron variant emerged.

This case-control study included adults with SARS-CoV-2 Omicron variant infection who died or were hospitalized in Hong Kong from January 1 to June 5, 2022 (case participants), and adults with SARS-CoV-2 Omicron sampled from the public health registry during the study period (control participants), who were matched to case participants by propensity score.

The estimated vaccine effectiveness against death, death or hospitalization, and death among hospitalized patients was calculated as an odds ratio of 1.0, indicating that the odds of vaccine effectiveness among case participants were similar to the odds of vaccine effectiveness among controls. The adjusted odds ratio was obtained by conditional logistic regression adjusted with covariates for each period following vaccination.

There were 32,823 case participants. Of these, 25,546 or 77.8% were 65 years of age or older; 16,930 or 47.4% were female. Of the 131,328 control participants, 100,041 or 76.2% were 65 years of age or older; 66,625 or 46.6% were female in the sample analyzed for the death or hospitalization outcome.

Vaccine effectiveness against death or hospitalization was maintained for at least six months after the second dose of both CoronaVac and BNT162b2 vaccines. Vaccine effectiveness against death in those aged 18 to 49 years was found to be 86.4% and 92.9% for those receiving two doses of CoronaVac and BNT162b2, respectively, while effectiveness dropped for patients aged 80 years or older to 61.4% and 52.7% for CoronaVac and BNT162b2, respectively. Nevertheless, overall vaccine effectiveness against death four to six months after the third dose was greater than 90% for CoronaVac, BNT162b2, and a mixed vaccine schedule.

The researchers concluded that while vaccines were generally estimated to be effective against severe outcomes caused by SARS-CoV-2 Omicron infection, protection in older patients was more likely to wane six months after the second dose. Therefore, they recommend older patients have booster doses to restore immunity, particularly in areas like Hong Kong, where third-dose coverage is insufficient among older residents.