Favorable responses to upadacitinib, a JAK1 inhibitor, in long COVID patients with predominant neuropsychiatric symptoms: case reports in 2 autistic patients and one typically developing patient.

IF 2.2 3区 医学 Q3 CLINICAL NEUROLOGY
Harumi Jyonouchi, Jeffery Kornitzer, Lee Geng
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引用次数: 0

Abstract

The long-term impact of coronavirus disease 2019 (COVID-19) has become evident over the past 3-4 years, with the recognition of post-COVID long-term sequelae, often referred to as long COVID. Neuropsychiatric symptoms are one of the hallmarks of long COVID. In severe cases, it can even present features of encephalopathy. Since some of the neuropsychiatric symptoms associated with long COVID overlap symptoms found in neuropsychiatric disorders, it has been difficult to sort out the effects of long COVID in such subjects. This is especially true in patients diagnosed with autism spectrum disorders (ASD), given their difficult behavioral symptoms and other co-morbid conditions. COVID-19 is thought to affect the onset or progress of encephalopathy symptoms by activation of the immune system through the type 1 interferon (IFN) signaling pathway. In that case, treatment would require an immunomodulating agent that targets such pathways. However, such measures may not be applied to ASD subjects, in whom long COVID may not even be considered as the cause of their symptoms. In this study, we present the beneficial effects of upadacitinib, a JAK (janus kinase) 1 inhibitor, that blocks downstream signaling of type 1 IFNs, on 3 patients, 2 with ASD and one without ASD. In these patients, long COVID was thought to have triggered or aggravated encephalopathy-like symptoms. The beneficial effects of upadacitinib were not only noted by an improvement of their behavioral symptoms but also shown by an improvement of monocyte cytokine profiles (less activated state); peripheral blood monocytes were used as surrogates of microglial cells. These three cases presented highlight a possible use of JAK inhibitors for treating long COVID-associated neuropsychiatric symptoms in both ASD and non-ASD subjects. The presented cases highlight the inherent difficulty of diagnosing long COVID in ASD cases.

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JAK1抑制剂upadacitinib对具有主要神经精神症状的长COVID患者的有利反应:2例自闭症患者和1例典型发展患者的病例报告
在过去的3-4年里,2019年冠状病毒病(COVID-19)的长期影响已经变得明显,人们认识到COVID后的长期后遗症,通常被称为长COVID。神经精神症状是长期COVID的标志之一。在严重的情况下,它甚至可以表现出脑病的特征。由于在神经精神疾病中发现了一些与长冠状病毒相关的神经精神症状,因此很难理清长冠状病毒对这类受试者的影响。这在被诊断为自闭症谱系障碍(ASD)的患者中尤其如此,因为他们有困难的行为症状和其他合并症。COVID-19被认为通过1型干扰素(IFN)信号通路激活免疫系统,从而影响脑病症状的发生或进展。在这种情况下,治疗将需要一种针对这些途径的免疫调节剂。然而,这些措施可能不适用于ASD受试者,在这些受试者中,长COVID甚至可能不被认为是其症状的原因。在这项研究中,我们报告了upadacitinib(一种JAK (janus kinase) 1抑制剂,可阻断1型IFNs的下游信号传导)对3例患者的有益作用,其中2例患有ASD, 1例非ASD。在这些患者中,长冠状病毒被认为引发或加重了脑病样症状。upadacitinib的有益作用不仅表现在他们的行为症状的改善,而且表现在单核细胞因子谱的改善(较少激活状态);外周血单核细胞作为小胶质细胞的替代物。这三个病例强调了在ASD和非ASD受试者中使用JAK抑制剂治疗长期与新冠病毒相关的神经精神症状的可能性。这些病例突出了诊断ASD患者长COVID的固有困难。
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来源期刊
BMC Neurology
BMC Neurology 医学-临床神经学
CiteScore
4.20
自引率
0.00%
发文量
428
审稿时长
3-8 weeks
期刊介绍: BMC Neurology is an open access, peer-reviewed journal that considers articles on all aspects of the prevention, diagnosis and management of neurological disorders, as well as related molecular genetics, pathophysiology, and epidemiology.
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