Non-pharmaceutical interventions implemented during the COVID-19 pandemic resulted in a marked reduction in influenza infections globally. The absence of influenza has raised concerns of waning immunity, and potentially more severe influenza seasons after the pandemic. To evaluate immunity towards influenza post-COVID-19 pandemic we have assessed influenza A epidemics in Norway from October 2016 to June 2023 and measured antibodies against circulating strains of influenza A(H1N1)pdm09 and A(H3N2) in different age groups by hemagglutination inhibition (HAI) assays in a total of 3364 serum samples collected in 2019, 2021, 2022 and 2023. Influenza epidemics in Norway from October 2016 until June 2023 were predominately influenza As, with a mixture of A(H1N1)pdm09 and A(H3N2) subtype predominance. We did not observe higher numbers of infections during the influenza epidemics following the COVID-19 pandemic than in pre-COVID-19 seasons. Frequencies of protective HAI titers against A(H1N1)pdm09 and A(H3N2) viruses were reduced in sera collected in 2021 and 2022, compared to sera collected in 2019. The reduction could, however, largely be explained by antigenic drift of new virus strains, as protective HAI titers remained stable against the same strain from one season to the next. However, we observed the development of an immunity gap in the youngest children during the pandemic which resulted in a prominent reduction in HAI titers against A(H1N1)pdm09 in 2021 and 2022. The immunity gap was partially closed in sera collected in 2023 following the A(H1N1)pdm09-dominated influenza seasons of 2022/2023. During the 2022/2023 epidemic, drift variants of A(H1N1)pdm09 belonging to the 5a.2a.1 clade emerged, and pre-season HAI titers were significantly lower against this clade compared to the ancestral 5a.2 clade. The observed reduction in protective antibodies against A(H1N1)pdm09 and A(H3N2) viruses post COVID-19 is best explained by antigenic drift of emerging viruses, and not waning of antibody responses in the general population. However, the absence of influenza during the pandemic resulted in an immunity gap in the youngest children. While this immunity gap was partially closed following the 2022/2023 influenza season, children with elevated risk of severe infection should be prioritized for vaccination.

中文翻译：

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抗原漂移和免疫缺口解释了 COVID-19 大流行期间针对甲型 (H1N1)pdm09 和甲型 (H3N2) 流感病毒的保护性反应的减少：对 2019 年、2021 年、2022 年和 2023 年收集的人类血清进行的横断面研究

COVID-19 大流行期间实施的非药物干预措施导致全球流感感染显着减少。流感的消失引发了人们对免疫力减弱以及大流行后可能出现更严重的流感季节的担忧。为了评估对 COVID-19 大流行后流感的免疫力，我们评估了 2016 年 10 月至 2023 年 6 月挪威的甲型流感流行情况，并通过血凝抑制测量了不同年龄组的甲型（H1N1）pdm09 和甲型（H3N2）流感流行株的抗体对 2019 年、2021 年、2022 年和 2023 年收集的总共 3364 份血清样本进行了 HAI 检测。2016 年 10 月至 2023 年 6 月挪威流行的流感主要是 As 流感，混合有 A(H1N1)pdm09 和 A(H3N2)亚型优势。我们没有观察到 COVID-19 大流行后的流感流行期间的感染人数高于 COVID-19 季节之前的感染人数。与 2019 年收集的血清相比，2021 年和 2022 年收集的血清中针对 A(H1N1)pdm09 和 A(H3N2) 病毒的保护性 HAI 滴度频率降低。然而，这种降低很大程度上可以通过新病毒株的抗原漂移来解释，因为从一个季节到下一季节，针对同一菌株的保护性 HAI 滴度保持稳定。然而，我们观察到大流行期间最小儿童中出现了免疫缺口，导致 2021 年和 2022 年针对 A(H1N1)pdm09 的 HAI 滴度显着降低。在 2023 年收集的血清中，免疫缺口部分消失。 2022/2023 年以 A(H1N1)pdm09 为主的流感季节。在 2022/2023 年流行期间，出现了属于 5a.2a.1 分支的 A(H1N1)pdm09 漂移变体，与祖先 5a.2 分支相比，该分支的季前 HAI 滴度显着降低。COVID-19 后观察到的针对 A(H1N1)pdm09 和 A(H3N2) 病毒的保护性抗体减少的最好解释是新兴病毒的抗原漂移，而不是一般人群中抗体反应的减弱。然而，大流行期间没有流感导致最小的儿童存在免疫力缺口。虽然这种免疫差距在 2022/2023 流感季节后已部分弥补，但严重感染风险较高的儿童应优先接种疫苗。