背景:非药物措施和旅行限制阻止了2019年冠状病毒病(COVID-19)和流感的传播。尽管如此,随着COVID-19限制的解除,在2021年底爆发了B型流感/维多利亚病毒,并在2022年中在广东爆发了另一次H3N2流感,中国南方。这种现象的潜在机制仍然未知。为了更好地为COVID-19大流行期间潜在的流感暴发做好准备,我们研究了在COVID-19大流行期间在该地区传播的甲型(H3N2)和乙型/维多利亚流感的分子流行病学和系统发育学.
方法:从2018年1月1日至2022年12月31日,我们收集了广东173,401例急性呼吸道感染患者的咽拭子。样本中的流感病毒使用逆转录-聚合酶链反应进行检测,然后进行血凝素(HA)和神经氨酸酶(NA)基因的亚型鉴定和测序。对403个样品的两个基因进行了系统发育和遗传多样性分析。将严格的分子钟与系统发育树对齐,以测量病毒进化率,并使用回归曲线模型评估不同年份的菌株内根到尖端的距离,以确定相关性。
结果:在COVID-19控制的早期,在呼吸道标本中几乎检测不到各种流感病毒.2020年1月放松控制措施时,流感感染率在2021年12月达到4.94%(39/789)的峰值,其中乙型流感/维多利亚型流感占总流感病例的87.18%(34/39)。六个月后,流感感染率再次上升,并在2022年6月达到峰值11.34%(255/2248);甲型/H3N2流感占2022年秋季流感总病例的94.51%(241/255).B/Victoria和A/H3N2的HA基因的不同地理分布急剧减少,大多数菌株来自中国。B/VictoriaHA进化速率(3.11×10-3,P<0.05)是COVID-19爆发前(1.80×10-3,P<0.05)的1.7倍。同样,H3N2HA基因的进化速率为7.96×10-3(P<0.05),比COVID-19前菌株进化速率快2.1倍(3.81×10-3,P<0.05)。
结论:尽管流感感染率非常低,在严格控制COVID-19的过程中,个体之间可能发生隐性流感传播。这最终导致病毒突变的积累和H3N2和B/维多利亚病毒的加速进化。监测流感的演变可能会提供有关未来潜在流行病的见解和警报。
BACKGROUND: Non-pharmaceutical measures and travel restrictions have halted the spread of coronavirus disease 2019 (COVID-19) and influenza. Nonetheless, with COVID-19 restrictions lifted, an unanticipated outbreak of the influenza B/Victoria virus in late 2021 and another influenza H3N2 outbreak in mid-2022 occurred in Guangdong, southern China. The mechanism underlying this phenomenon remains unknown. To better prepare for potential influenza outbreaks during COVID-19 pandemic, we studied the molecular epidemiology and phylogenetics of influenza A(H3N2) and B/Victoria that circulated during the COVID-19 pandemic in this region.
METHODS: From January 1, 2018 to December 31, 2022, we collected throat swabs from 173,401 patients in Guangdong who had acute respiratory tract infections. Influenza viruses in the samples were tested using reverse transcription-polymerase chain reaction, followed by subtype identification and sequencing of hemagglutinin (HA) and neuraminidase (NA) genes. Phylogenetic and genetic diversity analyses were performed on both genes from 403 samples. A rigorous molecular clock was aligned with the phylogenetic tree to measure the rate of viral evolution and the root-to-tip distance within strains in different years was assessed using regression curve models to determine the correlation.
RESULTS: During the early period of COVID-19 control, various influenza viruses were nearly undetectable in respiratory specimens. When control measures were relaxed in January 2020, the influenza infection rate peaked at 4.94% (39/789) in December 2021, with the influenza B/Victoria accounting for 87.18% (34/39) of the total influenza cases. Six months later, the influenza infection rate again increased and peaked at 11.34% (255/2248) in June 2022; influenza A/H3N2 accounted for 94.51% (241/255) of the total influenza cases in autumn 2022. The diverse geographic distribution of HA genes of B/Victoria and A/H3N2 had drastically reduced, and most strains originated from China. The rate of B/Victoria HA evolution (3.11 × 10-3, P < 0.05) was 1.7 times faster than before the COVID-19 outbreak (1.80 × 10-3, P < 0.05). Likewise, the H3N2 HA gene\'s evolution rate was 7.96 × 10-3 (P < 0.05), which is 2.1 times faster than the strains\' pre-COVID-19 evolution rate (3.81 × 10-3, P < 0.05).
CONCLUSIONS: Despite the extraordinarily low detection rate of influenza infection, concealed influenza transmission may occur between individuals during strict COVID-19 control. This ultimately leads to the accumulation of viral mutations and accelerated evolution of H3N2 and B/Victoria viruses. Monitoring the evolution of influenza may provide insights and alerts regarding potential epidemics in the future.