Chungbuk, Republic of Korea—How protective was prior infection by different COVID-19 Omicron subvariants, especially if the cases were followed by booster vaccination?

That was the question raised by researchers from the Korean Disease Control and Prevention Agency in the Republic of Korea. A research letter in the Journal of the American Medical Association Network Open suggested, “Prior SARS-CoV-2 infection during the BA.1 and BA.2 periods was associated with greater protection from SARS-CoV-2 infection during BA.5 period, which is in line with a previous study. Moreover, protection against critical BA.5 infection was also associated with the number of booster doses, compared with the 2-dose vaccination.”

The authors pointed out that the four-dose was associated with higher protection against critical BA.5 infection, as shown in previous studies, without regard to any history of SARS-CoV-2 infection.

The study sought to estimate protective effectiveness of prior SARS-CoV-2 BA.1 or BA.2 infection and booster vaccination during Omicron BA.5 predominance in South Korea. To do that, researchers conducted a nationwide, population-based study that used a risk-set sampled nested case-control study design. Data came from the Korea COVID-19 Vaccine Effectiveness (K-COVE) data set. The study team selected controls who were at risk with the same sex, age, and place of residence.

The study included people who had tested positive for SARS-CoV-2 during the period of BA.5 predominance between August 1, 2022, and August 31, 2022. Ultimately, the study involved 3.4 million cases and controls. Those were 53.9% female with a mean age of 40.2 years.

“In persons without history of SARS-CoV-2 infection, 4-dose estimated VE [vaccine effectiveness] was 16.1% (95% CI, 15.5% to 16.6%), while in persons with prior BA.1 and BA.2 infections, the estimated VEs were 89.5% (95% CI, 89.2% to 89.8%) and 94.3% (95% CI, 94.1% to 94.4%), respectively,” according to the authors. “Two-dose VEs against critical BA.5 infection was low in persons with no prior infection (41.5%; 95% CI, 32.1% to 49.6%), prior BA.1 infection (53.1%; 95% CI, 15.0% to 74.1%), and prior BA.2 infection (50.0%; 95% CI, –0.29% to 75.0%). Four-dose VEs against critical BA.5 infection was higher at 90.9% (95% CI, 89.8% to 91.9%) in persons without COVID-19 history, and to 93.9% (95% CI, 90.5% to 96.1%) and 92.9% (95% CI, 89.2% to 95.3%) in persons with prior BA.1 and BA.2 infections, respectively.”

The researchers pointed to limitations to the case-control study, including that not all positive cases during the observed period might have been identified. In addition, protection from prior infection might be overestimated if exposed people were more likely than unexposed people to get tested. “Importantly, the observation that the protection against critical BA.5 infection depends more on 4-dose booster, rather than previous BA.1 or BA.2 infection highlights the importance of booster vaccination,” the researchers added.

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