Influenza B viruses (Victoria and Yamagata lineages) co-circulate seasonally in China, with shifting dominance patterns. During 2005–2016, B/Yamagata caused fewer epidemics than B/Victoria but exhibited prolonged activity during summer months in lower-latitude regions . Post-2020, B/Yamagata circulation declined globally, while B/Victoria became predominant, as observed in Nanchang (2014–2022) and Beijing (2021–2022) .
The B/Victoria lineage has evolved into clade 1A.3a.2, characterized by specific mutations in hemagglutinin (HA) and neuraminidase (NA). In Beijing (2021–2022), strains showed:
HA mutations: N150K, G181E, S194D (receptor-binding region) .
NA mutations: D53N, N59S, G233E .
These mutations likely enhance viral fitness under COVID-19 non-pharmaceutical interventions (NPIs) .
Lineage | Antigenic Drift Rate (Years) | Key Clades (Post-2010) |
---|---|---|
B/Victoria | 3.9–5.1 | 1A.3, 1A.3a.2 |
B/Yamagata | 6.3–7.2 | Clade 2, Clade 3 (pre-2020) |
During the 2021–2022 influenza season in Beijing, B/Victoria caused severe disease in younger populations, with secondary infections driving mortality:
Parameter | Severe Cases (n=35) | Non-Severe Cases (n=149) |
---|---|---|
Mean Age | 40.9 ± 24.1 years | 34.2 ± 18.5 years |
Thrombocytopenia | 28.6% | 0% |
LDH Elevation | 682.4 U/L | 245.6 U/L |
Mortality Rate | 19.0% (7/35) | 0% |
Secondary bacterial/fungal infections were present in 85.7% of fatal cases .
NPIs during the pandemic suppressed B/Yamagata circulation, while B/Victoria persisted due to:
Faster antigenic drift .
Post-2022, China’s shift from "Zero-COVID" policies may alter influenza B seasonality, necessitating updated vaccination strategies .
Diagnostic Challenges: RT-PCR remains critical for lineage-specific detection .
Vaccine Mismatch: Current trivalent vaccines (B/Washington/02/2019-like) lack coverage for clade 1A.3a.2 mutations (e.g., S194D) .
Though direct data from Qingdao is limited, provincial surveillance (e.g., Shandong Province) aligns with national trends:
Influenza B accounts for a median proportion of 22.6% of all influenza cases globally, with no statistically significant differences observed across seasons according to the Global Influenza B Study (GIBS). The distribution varies geographically across the Northern and Southern hemispheres and the intertropical belt. To study this distribution, researchers should implement consistent virological surveillance systems that report both the total number of influenza cases and the breakdown by virus type and subtype/lineage on a weekly basis .
Effective surveillance methodology combines both virological and epidemiological approaches. Virological surveillance involves collecting respiratory specimens from patients with influenza-like illness (ILI) or acute respiratory infection (ARI), followed by RT-PCR testing and genetic characterization. Epidemiological surveillance tracks ILI/ARI rates through established sentinel systems. In Qingdao, as in other regions of China, these systems have helped identify co-circulation patterns, with respiratory viral co-infection found in up to ~25% of cases . Researchers should establish representative sentinel sites, implement standardized case definitions, and employ consistent laboratory methods for virus identification and characterization .
Researchers employ RT-PCR with lineage-specific primers, genetic sequencing, and antigenic characterization using reference antisera to identify whether Victoria or Yamagata lineages predominate. According to GIBS data, during seasons where influenza B was dominant or co-circulated (>20% of total detections), the Victoria lineage predominated during 64% of seasons, while the Yamagata lineage predominated during 36% of seasons . In China, studies have reported a dramatic circulating subtype change with the Victoria strain responsible for over 99% of cases during the 2020-2021 season .
The classification of severe versus critical influenza B infections requires precise clinical criteria. According to studies conducted in China, researchers classify severity based on established consensus guidelines, such as the Chinese expert consensus on diagnosis and treatment of influenza in children. Critical cases are distinguished by the presence of extra-pulmonary complications, which occur at significantly higher rates than in severe cases. Methodologically, researchers should document fever characteristics, underlying conditions, laboratory parameters, and radiological findings to enable accurate classification .
Studies comparing severe and critical influenza B cases have identified several key laboratory markers. Critical cases demonstrate significantly higher percentages of neutrophils and significantly lower percentages of CD4+ T cells compared to severe cases. Additionally, altered inflammatory markers may indicate more severe disease. Researchers should incorporate comprehensive immunological profiling, including complete blood counts with differential, lymphocyte subset analysis, and inflammatory biomarkers to identify severity predictors. Statistical analyses should employ appropriate tests for normally and non-normally distributed data to identify significant differences .
Research from the Global Influenza B Study demonstrates that patients infected with influenza B are typically younger (5-17 years) than those infected with influenza A. To investigate this pattern, researchers should design age-stratified surveillance systems with consistent age categories (0-4, 5-17, 18-64, and ≥65 years) and calculate virus type-specific median ages with interquartile ranges. Statistical comparisons can be conducted using chi-square tests for percentage differences by age group and Wilcoxon rank sum tests to detect differences in median age between influenza A and B cases .
To investigate whether influenza B seasons differ in intensity from influenza A-dominated seasons, researchers should calculate the country-specific Z-score of weekly ILI/ARI rates (defined as the number of standard deviations above or below the country-specific average) and determine the Pearson's correlation coefficient between maximum values and the proportion of influenza B cases. The GIBS study demonstrated an inverse correlation between the proportion of influenza B and maximum ILI rate in the Northern and Southern hemispheres, suggesting that influenza B may cause less intense but potentially longer epidemics compared to influenza A .
Studies examining co-infection patterns should employ multiplex PCR panels capable of simultaneously detecting multiple respiratory pathogens. Research from Qingdao, China (Xing Q et al., unpublished 2020) found respiratory viral co-infection in up to ~25% of cases . Study designs should include adequate sample sizes to detect co-infections, comprehensive demographic data collection, and detailed clinical outcome measures to assess the impact of co-infections compared to single infections. Time-series analyses can help identify temporal relationships between circulating pathogens.
Researchers should compare the predominant circulating influenza B lineage with the lineage included in the trivalent vaccine for each season. According to GIBS data, a vaccine mismatch (defined as a season where the predominant circulating B lineage differed from the vaccine B lineage) was observed in approximately 24-25% of seasons globally . Study designs should incorporate both virological surveillance data and vaccine effectiveness estimates, ideally using test-negative case-control designs to calculate lineage-specific vaccine effectiveness. Researchers should also calculate the proportion of characterized influenza B viruses to ensure adequate sampling.
Advanced research into immunopathological mechanisms should integrate clinical data with comprehensive immunological profiling. Studies in China have observed that children with critical influenza B may have higher levels of inflammation and lower levels of adaptive immunity compared to those with severe disease . Research approaches should include flow cytometry to quantify immune cell subsets, cytokine/chemokine profiling to assess inflammatory responses, and functional immune assays to evaluate both innate and adaptive immunity. Longitudinal sampling throughout the disease course can provide insights into temporal relationships between immune responses and clinical progression.
Genomic research should employ whole-genome sequencing with adequate sampling across different time periods and patient populations. Phylogenetic analyses can trace lineage evolution and identify the introduction of new variants. Analysis of selection pressure on viral genes can identify mutations that may confer evolutionary advantages. In regions like Qingdao, where specific strains have dominated (such as the Victoria lineage reported in China in recent seasons ), comparative genomics between local isolates and global reference strains can identify region-specific adaptations.
Studies of bacterial co-infections require both molecular diagnostic approaches and traditional culture methods. Research from China indicates that a substantially higher proportion of children with critical influenza B have bacterial co-infections compared to those with severe disease . Methodological approaches should include multiplex PCR for common bacterial pathogens, blood cultures, and testing of respiratory specimens. Researchers should document antibiotic usage before sampling and employ multivariate analyses to control for confounding factors. Biomarkers like procalcitonin may help differentiate viral from bacterial infections but should be interpreted cautiously.
Therapeutic research requires stratification by disease severity, time from symptom onset to treatment initiation, and presence of underlying conditions. According to Chinese expert consensus guidelines, treatment approaches for severe and critical influenza B should include appropriate antiviral therapy, consideration of antibiotics for bacterial co-infections, and supportive care . Research designs should include randomized controlled trials where ethical, or prospective observational studies with propensity score matching to account for treatment selection biases. Outcome measures should encompass both clinical endpoints (duration of hospitalization, need for intensive care) and virological endpoints (viral clearance rates).
Given the evidence that critical influenza B cases may involve dysregulated immune responses, research into immunomodulatory treatments represents an important area of investigation. Study designs should carefully select patient populations based on immunological parameters and disease stage. Researchers should define clear endpoints related to both immune response normalization and clinical improvement. Monitoring of both beneficial and adverse effects is essential, with particular attention to the risk of secondary infections. Biomarker-guided approaches may help identify which patients are most likely to benefit from specific immunomodulatory interventions.
The Influenza B virus is an enveloped virus with a segmented, negative-sense, single-stranded RNA genome. The genome consists of eight segments, each encapsidated in a separate nucleocapsid and surrounded by an envelope . The virus has surface projections made of hemagglutinin (HA) and neuraminidase (NA), which are crucial for the virus’s ability to infect host cells .
The B/Qingdao/102/91 strain was isolated from allantoic fluid of 10-day-old embryonated eggs inoculated with the virus. The virus was then purified using ultracentrifugation with a 10-40% sucrose gradient . This method ensures high purity, with the virus being greater than 90% pure as determined by SDS-PAGE .