Assessing COVID-19 vaccine effectiveness against Omicron subvariants: Report from a meeting of the World Health Organization

Emerging in November 2021, the SARS-CoV-2 Omicron variant of concern exhibited marked immune evasion resulting in reduced vaccine effectiveness against SARS-CoV-2 infection and symptomatic disease. Most vaccine effectiveness data on Omicron are derived from the first Omicron subvariant, BA.1, which caused large waves of infection in many parts of the world within a short period of time. BA.1, however, was replaced by BA.2 within months, and later by BA.4 and BA.5 (BA.4/5). These later Omicron subvariants exhibited additional mutations in the spike protein of the virus, leading to speculation that they might result in even lower vaccine effectiveness. To address this question, the World Health Organization hosted a virtual meeting on December 6, 2022, to review available evidence for vaccine effectiveness against the major Omicron subvariants up to that date. Data were presented from South Africa, the United Kingdom, the United States, and Canada, as well as the results of a review and meta-regression of studies that evaluated the duration of the vaccine effectiveness for multiple Omicron subvariants. Despite heterogeneity of results and wide confidence intervals in some studies, the majority of studies showed vaccine effectiveness tended to be lower against BA.2 and especially against BA.4/5, compared to BA.1, with perhaps faster waning against severe disease caused by BA.4/5 after a booster dose. The interpretation of these results was discussed and both immunological factors (i.e., more immune escape with BA.4/5) and methodological issues (e.g., biases related to differences in the timing of subvariant circulation) were possible explanations for the findings. COVID-19 vaccines still provide some protection against infection and symptomatic disease from all Omicron subvariants for at least several months, with greater and more durable protection against severe disease.