A 4-dose COVID-19 vaccine regimen and prior infection with either the BA.1 or BA.2 variants were extremely effective against the Omicron BA.5 subvariant.

The updated bivalent booster shot has been proven effective against COVID-19, and especially against severe disease progression. However, there has been little investigation into the protective effect of prior Omicron infection followed by booster vaccination.

A new study, published yesterday in JAMA Network Open, sought to estimate the protective effectiveness of prior COVID-19 BA.1 or BA.2 infection and booster vaccination against the Omicron BA.5 subvariant.

The nationwide population-based study was conducted in South Korea and utilized a risk-set sampled nested case-control design. Study patients and at-risk controls were selected from the Korea COVID-19 Vaccine Effectiveness (K-COVE) data set. The cohorts were matched by age, sex, and place of residence.

The study patients had all tested positive for COVID-19 during the period of BA.5 predominance (August 1-31, 2022). Cases and controls who had never contracted COVID-19 were proportionally compared to patients who had a prior BA.1 or BA.2 infection.

Vaccine effectiveness was estimated, using a logistic regression model to adjust for covariates such as health status, vaccination status, and infection history. Vaccine efficacy against BA.5 infection and severe infection were compared among patients with no prior infection, prior BA.1 infection, and prior BA.2 infection.

A total of 3415980 cases and 3415980 controls were included in the study. The cohorts were 53.9% female and averaged 40.2 years of age. In people without a history of COVID-19, vaccine efficacy of 4 doses (2 shots for a primary series, 1 booster, and 1 bivalent booster) was estimated to be 16.1%. Vaccine efficacy was 89.5% in persons with a prior BA.1 infection, and 94.3% in persons with a prior BA.2 infection.

Against critical BA.5 infection, 4-dose vaccine efficacy was 90.9% in infection-naïve patients, 93.9% in persons previously infected with BA.1, and 92.9% in persons with a prior BA.2 infection.

It is not surprising that a prior COVID-19 BA.1 or BA.2 infection, in conjunction with bivalent booster vaccination, is highly protective against the Omicron BA.5 subvariant. As shown in previous studies, 4-dose vaccination is far more effective than 2-dose, especially against critical COVID-19 infection.

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