Four COVID-19 booster doses most effective way to prevent critical Omicron BA.5

A study published in JAMA Network Open explores the protective efficacy of previous exposure to omicron subvariants and booster vaccination against severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) omicron BA.5 infection.

Study: Estimated Effectiveness of Prior SARS-CoV-2 BA.1 or BA.2 Infection and Booster Vaccination Against Omicron BA.5 Subvariant Infection. Image Credit: Jo Panuwat D / Shutterstock

Background

The coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has become the most significant pandemic of modern times, with more than 760 million infections and over 6.87 million deaths worldwide.

Many viral variants with increased transmission and immune fitness have emerged during the pandemic. These variants have been designated as the variants of concern (VOCs) by the World Health Organization (WHO). Since COVID-19 vaccines have initially been developed against the original Wuhan strain, most exhibits reduced protective efficacy against newly emerged variants containing several mutations in the spike protein.   

SARS-CoV-2 omicron is the most recently emerged VOC with a significantly higher ability to evade pre-existing anti-SARS-CoV-2 immunity than other SARS-CoV-2 VOCs. Among many subvariants of omicron, BA.5 has been found to have the highest ability to evade pre-existing immunity, leading to a significant waning of vaccine efficacy worldwide.

To increase vaccine efficacy, COVID-19 booster vaccination has been introduced worldwide, and studies conducted in real-world setups have confirmed its efficacy in controlling breakthrough infections and severe COVID-19.

In the current study, scientists have investigated the protective efficacy of prior omicron subvariants BA.1 or BA.2 infection and booster vaccination against omicron BA.5 infection.

Study design

The study was conducted in South Korea using a case-control study design. Cases referred to individuals who tested positive for SARS-CoV-2 infection during the BA.5-dominated wave. Individuals who tested negative during this period were regarded as controls.

The information about infection and vaccination status was obtained from the Korea COVID-19 Vaccine Effectiveness (K-COVE) dataset. The cases and controls were compared to estimate the proportion of individuals who never had SARS-CoV-2 infection before and those with previous BA.1 or BA.2 infection. These three study cohorts were also compared to determine the vaccine efficacy against all BA.5 infections and severe BA.5 infections.  

Important observations

A total of 3,415,980 cases and 3,415,980 controls were selected from the K-COVE dataset and analyzed in the study.

The efficacy of a 4-dose vaccination regimen against BA.5 infection was estimated to be 16% in individuals without any previous SARS-CoV-2 exposure. In contrast, vaccine efficacies were estimated to be 89% and 94% in individuals with previous BA.1 and BA.2 infections, respectively.

Considering severe BA.5 infection, the efficacies of a 2-dose vaccination regimen were estimated to be 41%, 53%, and 50% in individuals without previous infection, previous BA.1 infection, and previous BA.2 infection, respectively.

Considering the 4-dose vaccination regimen, the efficacies against severe BA.5 infection were estimated to be 90%, 93%, and 92% in individuals without previous infection, previous BA.1 infection, and previous BA.2 infection, respectively.

Study significance

The study highlights that previous exposure to omicron BA.1 or BA.2 is associated with higher protection against omicron BA.5 infection. The number of vaccine doses is an important determining factor for protecting against severe BA.5 infection. The 4-dose booster vaccination regimen significantly reduces the risk of severe BA.5 infection, irrespective of previous SARS-CoV-2 infection status.

Overall, the study reveals that booster vaccination is more effective than previous BA.1 or BA.2 infections in protecting against severe BA.5 infection.

Written by

Dr. Sanchari Sinha Dutta

Dr. Sanchari Sinha Dutta is a science communicator who believes in spreading the power of science in every corner of the world. She has a Bachelor of Science (B.Sc.) degree and a Master's of Science (M.Sc.) in biology and human physiology. Following her Master's degree, Sanchari went on to study a Ph.D. in human physiology. She has authored more than 10 original research articles, all of which have been published in world renowned international journals.