Fullerton Heather J, Hills Nancy K, Wintermark Max, Dlamini Nomazulu, Fox Christine K, Cummings Dana D, Bernard Timothy J, Beslow Lauren A, Sun Lisa R, Grose Charles, Norris Phillp J, Di Germanio Clara
Departments of Neurology (H.J.F., N.K.H., C.K.F.), University of California San Francisco.
Pediatrics (H.J.F., C.K.F.), University of California San Francisco.
Stroke. 2025 May;56(5):1200-1209. doi: 10.1161/STROKEAHA.124.049909. Epub 2025 Apr 2.
The VIPS (Vascular Effects of Infection in Pediatric Stroke) II prospective cohort study aimed to better understand published findings that common acute infections, particularly respiratory viruses, can trigger childhood arterial ischemic stroke (AIS). The COVID-19 pandemic developed midway through enrollment, creating an opportunity to assess its impact.
Twenty-two sites (North America, Australia) prospectively enrolled 205 children (aged 28 days to 18 years) with AIS from December 2016 to January 2022, including 100 cases during the COVID-19 pandemic epoch, defined here as January 2020 to January 2022. To assess background rates of subclinical infection, we enrolled 100 stroke-free well children, including 39 during the pandemic. We measured serum SARS-CoV-2 nucleocapsid total antibodies (present after infection, not vaccination; half-life of 3-6 months). We assessed clinical infection via parental interview.
The monthly rate of eligible AIS cases declined from spring through fall 2020, recovering in early 2021 and peaking in the spring. The prepandemic and pandemic cases were similar except pandemic cases had fewer clinical infections in the prior month (17% versus 30%; =0.02) and more focal cerebral arteriopathy (20% versus 11%; =0.09). Among pandemic cases, 26 of 100 (26%) had positive antibodies, versus 4 of 39 (10%) of pandemic-era well children (=0.04). The first SARS-CoV-2 positive case occurred in July 2020. Ten of the 26 (38%) positive cases had a recent infection by parental report, and 7 of those 10 had received a diagnosis of COVID-19. Only 1 had multisystem inflammatory syndrome in children. Median (interquartile range) nucleocapsid IgG total levels were 50.1 S/CO (specimen to calibrator absorbance ratio; 26.9-95.3) in the positive cases and 18.8 (12.0-101) in the positive well children (=0.33).
The COVID-19 pandemic may have had dual effects on childhood AIS: an indirect protective effect related to public health measures reducing infectious exposure in general, and a deleterious effect as COVID-19 emerged as another respiratory virus that can trigger childhood AIS.
小儿卒中感染的血管效应(VIPS)II前瞻性队列研究旨在更好地理解已发表的研究结果,即常见的急性感染,尤其是呼吸道病毒,可引发儿童动脉缺血性卒中(AIS)。在研究入组进行到一半时出现了新冠疫情,从而有机会评估其影响。
22个研究地点(北美、澳大利亚)在2016年12月至2022年1月期间前瞻性地招募了205例年龄在28天至18岁之间的AIS患儿,其中包括新冠疫情期间(此处定义为2020年1月至2022年1月)的100例病例。为评估亚临床感染的背景发生率,我们招募了100例无卒中的健康儿童,其中包括疫情期间的39例。我们检测了血清严重急性呼吸综合征冠状病毒2(SARS-CoV-2)核衣壳总抗体(感染后而非接种疫苗后出现;半衰期为3 - 6个月)。我们通过家长访谈评估临床感染情况。
2020年春季至秋季,符合条件的AIS病例月发生率下降,2021年初恢复并在春季达到峰值。疫情前和疫情期间的病例相似,只是疫情期间的病例在前一个月的临床感染较少(17%对30%;P = 0.02),而局灶性脑动脉病变较多(20%对11%;P = 0.09)。在疫情期间的病例中,100例中有26例(26%)抗体呈阳性,而疫情期间健康儿童的39例中有4例(10%)抗体呈阳性(P = 0.04)。首例SARS-CoV-2阳性病例出现在2020年7月。26例阳性病例中有10例(38%)经家长报告近期有感染,其中10例中有7例被诊断为新冠。只有1例儿童患有多系统炎症综合征。阳性病例中核衣壳IgG总水平的中位数(四分位间距)为50.1 S/CO(样本与校准物吸光度比值;26.9 - 95.3),阳性健康儿童为18.8(12.0 - 101)(P = 0.33)。
新冠疫情可能对儿童AIS产生了双重影响:一方面,与公共卫生措施总体上减少感染暴露相关的间接保护作用;另一方面,新冠作为另一种可引发儿童AIS的呼吸道病毒产生的有害作用。