Background

Multisystem inflammatory syndrome in children (MIS-C) occurs after infection with SARS-CoV-2 and its incidence is likely to depend on multiple factors, including the variant of the preceding SARS-CoV-2 infection and vaccine effectiveness. We aimed to estimate the incidence of MIS-C, and describe the clinical phenotype, following the delta variant of SARS-CoV-2 (B.1.617.2 and sublineages) according to vaccination status. We aimed to compare the incidence and clinical phenotype of MIS-C from our cohort during the pre-delta era.

Methods

This prospective, population-based cohort study included patients aged 0–17 years hospitalised with MIS-C in Denmark, according to the US Centers for Disease Control and Prevention case definition, from Aug 1, 2021, to Feb 1, 2022, a period dominated by the delta variant. We identified MIS-C cases via a nationwide research collaboration involving real-time data collection from all 18 paediatric departments. Aggregated number of SARS-CoV-2 infections by vaccination status was obtained from the Danish COVID-19 surveillance registries. The incidence of MIS-C was calculated using the estimated number of infected individuals by vaccination status. We calculated the incidence of MIS-C per 1 000 000 vaccinated and unvaccinated person-years, and estimated vaccine effectiveness as 1–incidence rate ratio using Poisson regression. Incidence and phenotype of MIS-C were compared with MIS-C cases from the first year of the pandemic. This study is registered at ClinicalTrials.gov, NCT05186597.

Findings

We identified 51 MIS-C cases among unvaccinated individuals and one in a fully vaccinated adolescent. The incidence of MIS-C was one in 3400 unvaccinated individuals (95% CI 2600–4600) with the delta variant and one in 9900 vaccinated individuals (95% CI 1800–390 000) with breakthrough infection. The estimated vaccine effectiveness against MIS-C after the delta variant was 94% (95% CI 55–99; p=0·0061) in individuals aged 5–17 years. The clinical phenotype during the delta wave was comparable to the pre-delta era.

Interpretation

We found the incidence and phenotype of MIS-C in unvaccinated children during the delta wave to be similar to the incidence during the first year of the pandemic. We found vaccine effectiveness to be high against MIS-C, which we suggest was due to protection from infection and, possibly, a decreased incidence of MIS-C after breakthrough infection. Knowledge of the incidence of MIS-C after different SARS-CoV-2 variants and the effect of vaccination might contribute to the elucidation of the extent to which MIS-C is a vaccine-preventable disease.

Funding

National Ministry of Higher Education and Science and Innovation Fund Denmark.

中文翻译：

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儿童感染 SARS-CoV-2 delta 变异体后多系统炎症综合征的发病率和临床表型（按疫苗接种状态）：丹麦全国前瞻性队列研究

背景

儿童多系统炎症综合征 (MIS-C) 发生在感染 SARS-CoV-2 后，其发病率可能取决于多种因素，包括先前 SARS-CoV-2 感染的变异和疫苗有效性。我们旨在估计 MIS-C 的发病率，并根据疫苗接种状态描述 SARS-CoV-2 的 delta 变体（B.1.617.2 和亚系）的临床表型。我们旨在比较前三角洲时代我们队列中 MIS-C 的发病率和临床表型。

方法

根据美国疾病控制和预防中心的病例定义，这项基于人群的前瞻性队列研究纳入了 2021 年 8 月 1 日至 2022 年 2 月 1 日期间在丹麦因 MIS-C 住院的 0-17 岁患者以 delta 变体为主。我们通过全国性的研究合作确定了 MIS-C 病例，该合作涉及所有 18 个儿科科室的实时数据收集。从丹麦 COVID-19 监测登记处获得按疫苗接种状态分类的 SARS-CoV-2 感染总数。MIS-C 的发生率是使用按疫苗接种状态估计的感染个体数量来计算的。我们计算了每 100 万接种疫苗和未接种疫苗的人年 MIS-C 的发生率，并使用泊松回归将疫苗有效性估计为 1 发生率。将 MIS-C 的发病率和表型与大流行第一年的 MIS-C 病例进行比较。该研究已在 ClinicalTrials.gov 注册，NCT05186597。

发现

我们在未接种疫苗的个体中发现了 51 例 MIS-C 病例，在完全接种疫苗的青少年中发现了 1 例。MIS-C 的发生率是 3400 名未接种疫苗的个体 (95% CI 2600-4600) 有 delta 变异体和 9900 名接种疫苗的个体 (95% CI 1800-390 000) 有一个突破性感染。在 5-17 岁的个体中，delta 变体后针对 MIS-C 的估计疫苗有效性为 94%（95% CI 55-99；p=0·0061）。三角洲波期间的临床表型与三角洲前时代相当。

解释

我们发现三角波期间未接种疫苗儿童的 MIS-C 发病率和表型与大流行第一年的发病率相似。我们发现疫苗对 MIS-C 的有效性很高，我们认为这是由于保护免受感染，并且可能是突破性感染后 MIS-C 发生率降低。了解不同 SARS-CoV-2 变体后 MIS-C 的发病率以及疫苗接种的效果可能有助于阐明 MIS-C 在多大程度上是一种疫苗可预防的疾病。

资金

丹麦国家高等教育和科学与创新基金部。