Schmidt Marius, Hébert Steven, Wallukat Gerd, Ponader Rolf, Krickau Tobias, Galiano Matthias, Reutter Heiko, Woelfle Joachim, Agaimy Abbas, Mardin Christian, Hoerning André, Hohberger Bettina
Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, 91054 Erlangen, Germany.
Berlin Cures GmbH, 13125 Berlin, Germany.
Children (Basel). 2023 Nov 22;10(12):1836. doi: 10.3390/children10121836.
An infection with SARS-CoV-2 can trigger a systemic disorder by pathological autoimmune processes. A certain type of this dysregulation is known as Multisystemic inflammatory syndrome in children (MIS-C). However, similar symptoms may occur and have been described as Multisystemic inflammatory syndrome after SARS-CoV-2 Vaccination (MIS-V) following vaccination against SARS-CoV-2. We report the case of a 12-year-old boy who was identified with MIS-C symptoms without previous SARS-CoV-2 infection after receiving two doses of the Pfizer-BioNTech COVID-19 vaccine approximately one month prior to the onset of symptoms. He showed polyserositis, severe gastrointestinal symptoms and, consequently, a manifestation of a multiorgan failure. IgG antibodies against spike proteins of SARS-CoV-2 were detected, indicating a successful vaccination, while SARS-CoV-2 Nucleocapsid protein antibodies and SARS-CoV-2 PCR were not detected. Several functional, active autoantibodies against G-protein-coupled receptors (GPCR-fAAb), previously associated with Long COVID disease, were detected in a cardiomyocyte bioassay. Immunosuppression with steroids was initiated. Due to side effects, treatment with steroids and later interleukin 1 receptor antagonists had to be terminated. Instead, immunoadsorption was performed and continued with tacrolimus and mycophenolic acid therapy, leading to improvement and discharge after 79 days. GPCR-fAAb decreased during therapy and remained negative after clinical curing and under continued immunosuppressive therapy with tacrolimus and mycophenolic acid. Follow-up of the patient showed him in good condition after one year.
Infection with SARS-CoV-2 shows a broad and severe variety of symptoms, partly due to autoimmune dysregulation, which, in some instances, can lead to multiorgan failure. Despite its rarity, post-vaccine MIS-C-like disease may develop into a serious condition triggered by autoimmune dysregulation. The evidence of circulating GPCR-fAAb and their disappearance after therapy suggests a link of GPCR-fAAb to the clinical manifestations. Thus, we hypothesize a potential role of GPCR-fAAb in pathophysiology and their potential importance for the therapy of MIS-C or MIS-V. However, this observation needs further investigation to prove a causative correlation.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染可通过病理性自身免疫过程引发全身性疾病。这种失调的一种特定类型被称为儿童多系统炎症综合征（MIS-C）。然而，类似症状可能会出现，并且在接种SARS-CoV-2疫苗后被描述为接种后多系统炎症综合征（MIS-V）。我们报告了一例12岁男孩的病例，该男孩在症状出现前约一个月接种两剂辉瑞-BioNTech新冠疫苗后出现MIS-C症状，但此前没有SARS-CoV-2感染。他表现出多发性浆膜炎、严重的胃肠道症状，进而出现多器官功能衰竭。检测到针对SARS-CoV-2刺突蛋白的IgG抗体，表明疫苗接种成功，而未检测到SARS-CoV-2核衣壳蛋白抗体和SARS-CoV-2聚合酶链反应（PCR）结果。在心肌细胞生物测定中检测到几种先前与长期新冠疾病相关的针对G蛋白偶联受体（GPCR-fAAb）的功能性活性自身抗体。开始使用类固醇进行免疫抑制治疗。由于副作用，不得不终止类固醇治疗以及后来的白细胞介素1受体拮抗剂治疗。取而代之的是进行免疫吸附，并继续使用他克莫司和霉酚酸治疗，79天后病情改善并出院。治疗期间GPCR-fAAb水平下降，临床治愈后以及在继续使用他克莫司和霉酚酸进行免疫抑制治疗期间一直保持阴性状态。对该患者的随访显示，一年后他状况良好。
SARS-CoV-2感染表现出广泛而严重的各种症状，部分原因是自身免疫失调，在某些情况下可导致多器官功能衰竭。尽管疫苗接种后出现类似MIS-C的疾病很罕见，但可能会发展为由自身免疫失调引发的严重病症。循环GPCR-fAAb的证据及其治疗后消失表明GPCR-fAAb与临床表现之间存在联系。因此，我们推测GPCR-fAAb在病理生理学中可能发挥作用，并且对MIS-C或MIS-V的治疗可能具有潜在重要性。然而，这一观察结果需要进一步研究以证明因果关系。
