Summary
Early after the start of the COVID-19 pandemic, the detection of influenza B/Yamagata cases decreased globally. Given the potential public health implications of this decline, in this Review, we systematically analysed data on influenza B/Yamagata virus circulation (for 2020–23) from multiple complementary sources of information. We identified relevant articles published in PubMed and Embase, and data from the FluNet, Global Initiative on Sharing All Influenza Data, and GenBank databases, webpages of respiratory virus surveillance systems from countries worldwide, and the Global Influenza Hospital Surveillance Network. A progressive decline of influenza B/Yamagata detections was reported across all sources, in absolute terms (total number of cases), as positivity rate, and as a proportion of influenza B detections. Sporadically reported influenza B/Yamagata cases since March, 2020 were mostly vaccine-derived, attributed to data entry errors, or have yet to be definitively confirmed. The likelihood of extinction necessitates a rapid response in terms of reassessing the composition of influenza vaccines, enhanced surveillance for B/Yamagata, and a possible change in the biosafety level when handling B/Yamagata viruses in laboratories.
Introduction
The emergence of SARS-CoV-2 and the resulting COVID-19 pandemic, and the public health measures that were put in place to contain the spread of SARS-CoV-2, caused major disruptions to the circulation of influenza and other respiratory viruses.1 Early in the course of the COVID-19 pandemic, there was a drastic reduction in the circulation of seasonal influenza viruses, with most countries reporting marked decline in influenza positivity rates, and, in some cases, only sporadic detections or even none at all, during the regular epidemic periods that followed.2 In late 2021, during the regular northern hemisphere period, influenza viruses gradually resumed circulation;3 however, whether the pattern of circulation and burden of disease observed before 2020 will be restored, or changes will persist due to the cocirculation of influenza viruses and SARS-CoV-2 is still unknown.
Although the high uncertainty makes predictions difficult, the obvious decrease in the number of influenza B/Yamagata cases has caught the attention of the scientific community. In the years before the emergence of SARS-CoV-2, the B/Victoria and B/Yamagata virus lineages tended to circulate simultaneously, with no clear or consistent pattern in the way the two lineages alternated from one influenza season to another.4 Globally, during 2012–17, B/Yamagata viruses caused a larger proportion of infections than B/Victoria viruses, but in the 2 years before the COVID-19 pandemic, the B/Victoria lineage had become largely prevalent, with the B/Yamagata-to-B/Victoria ratio dropping to 1:4·5 in 2018 and 1:19·3 in 2019.5 Early in the course of the COVID-19 pandemic (ie, from March, 2020), and even after influenza viruses started circulating again in late 2021, B/Yamagata lineage viruses were detected in only a few countries globally,1,6,7 thereby giving rise to the question as to whether B/Yamagata lineage viruses were on the verge of extinction.
To declare the extinction of the B/Yamagata lineage would be premature, since there is a possibility that currently, the viral circulation might be at low levels (sub-threshold to the capabilities of existing surveillance systems) or might be happening in regions not well covered by surveillance systems, thereby leaving scope for a possible resurgence of the B/Yamagata lineage in the future. Indeed, during much of the 1990s, the B/Victoria lineage did not circulate in most regions of the world and was primarily confined to east Asia, before spreading globally again in the early 2000s.8 The current epidemiological situation holds important implications for public health, particularly with respect to strategies for the development of influenza vaccination.1,7 Since quadrivalent influenza vaccines contain virus strains from both the B/Yamagata and B/Victoria lineages, the question arises as to whether a vaccine targeting a virus that is currently not circulating is required. Moreover, there is a concern that the mechanistically attenuated replication of the B/Yamagata strains contained in the live attenuated influenza vaccine (LAIV), which is primarily administered to children, could lead to reintroduction of the haemagglutinin and neuraminidase genes of a potentially extinct virus through reassortment with a co-infecting wild-type B/Victoria lineage.9 During shedding, LAIV retains its cold-adapted nature and a low scope for secondary infections after vaccine-derived influenza B/Yamagata infections, with no reports to date.10 Therefore, continuous monitoring of viral circulation is essential so that influenza-prevention policies, especially those related to vaccine formulation and composition, can be adapted to the current epidemiological landscape.
Here, we aimed to study the circulation of B/Yamagata influenza viruses from 2020 onwards, to understand whether these viruses are extinct and how their extinction could have public health implications. For this purpose, we conducted an updated systematic review that builds upon previous assessments and extends to multiple data sources pertaining to the circulation of B/Yamagata influenza viruses. To achieve this, our search (conducted in January, 2024) has been extended from global databases for influenza virological surveillance (FluNet, Global Initiative on Sharing All Influenza Data [GISAID], and GenBank),7 to include one additional surveillance database (Global Influenza Hospital Surveillance Network [GIHSN]), biomedical literature databases (PubMed and Embase), and webpages of national surveillance systems worldwide.