Beaumont Children's Hospital, Beaumont Health, 3601 West 13 Mile Road, Royal Oak, MI, 48073, USA.
Department of Neuroradiology, Beaumont Health, Royal Oak, MI, USA.
BMC Pediatr. 2020 Sep 9;20(1):429. doi: 10.1186/s12887-020-02308-1.
Central and peripheral nervous system symptoms and complications are being increasingly recognized among individuals with pandemic SARS-CoV-2 infections, but actual detection of the virus or its RNA in the central nervous system has rarely been sought or demonstrated. Severe or fatal illnesses are attributed to SARS-CoV-2, generally without attempting to evaluate for alternative causes or co-pathogens.
A five-year-old girl with fever and headache was diagnosed with acute SARS-CoV-2-associated meningoencephalitis based on the detection of its RNA on a nasopharyngeal swab, cerebrospinal fluid analysis, and magnetic resonance imaging findings. Serial serologic tests for SARS-CoV-2 IgG and IgA showed seroconversion, consistent with an acute infection. Mental status and brain imaging findings gradually worsened despite antiviral therapy and intravenous dexamethasone. Decompressive suboccipital craniectomy for brain herniation with cerebellar biopsy on day 30 of illness, shortly before death, revealed SARS-CoV-2 RNA in cerebellar tissue using the Centers for Disease Control and Prevention 2019-nCoV Real-Time Reverse Transcriptase-PCR Diagnostic Panel. On histopathology, necrotizing granulomas with numerous acid-fast bacilli were visualized, and Mycobacterium tuberculosis complex DNA was detected by PCR. Ventricular cerebrospinal fluid that day was negative for mycobacterial DNA. Tracheal aspirate samples for mycobacterial DNA and culture from days 22 and 27 of illness were negative by PCR but grew Mycobacterium tuberculosis after 8 weeks, long after the child's passing. She had no known exposures to tuberculosis and no chest radiographic findings to suggest it. All 6 family members had normal chest radiographs and negative interferon-γ release assay results. The source of her tuberculous infection was not identified, and further investigations by the local health department were not possible because of the State of Michigan-mandated lockdown for control of SARS-CoV-2 spread.
The detection of SARS-CoV-2 RNA in cerebellar tissue and the demonstration of seroconversion in IgG and IgA assays was consistent with acute SARS-CoV-2 infection of the central nervous infection. However, the cause of death was brain herniation from her rapidly progressive central nervous system tuberculosis. SARS-CoV-2 may mask or worsen occult tuberculous infection with severe or fatal consequences.
在大流行 SARS-CoV-2 感染的个体中，越来越多地认识到中枢和外周神经系统症状和并发症，但很少寻求或证明病毒或其 RNA 存在于中枢神经系统中。严重或致命疾病归因于 SARS-CoV-2，通常不尝试评估其他原因或共病原体。
一名五岁女孩因发热和头痛被诊断为急性 SARS-CoV-2 相关脑膜脑炎，依据是鼻咽拭子、脑脊液分析和磁共振成像结果检测到其 RNA。SARS-CoV-2 IgG 和 IgA 的系列血清学检测显示血清转化，与急性感染一致。尽管进行了抗病毒治疗和静脉注射地塞米松，但精神状态和脑部影像学发现逐渐恶化。在疾病第 30 天，为脑疝行枕下减压颅骨切除术，并进行小脑活检，在死亡前不久，使用疾病预防控制中心 2019-nCoV 实时逆转录酶-PCR 诊断试剂盒在小脑组织中发现 SARS-CoV-2 RNA。组织病理学显示，坏死性肉芽肿中有大量抗酸杆菌，聚合酶链反应检测到结核分枝杆菌复合 DNA。当天的脑室脑脊液中未检测到分枝杆菌 DNA。疾病第 22 天和第 27 天的气管抽吸样本的分枝杆菌 DNA 和培养物通过 PCR 均为阴性，但在 8 周后培养出结核分枝杆菌，远在患儿去世之后。她没有已知的结核接触史，也没有胸部 X 线发现提示结核。所有 6 名家庭成员的胸部 X 线均正常，干扰素-γ释放试验结果均为阴性。未确定她结核感染的来源，由于密歇根州为控制 SARS-CoV-2 传播而强制封锁，当地卫生部门无法进行进一步调查。
小脑组织中 SARS-CoV-2 RNA 的检测以及 IgG 和 IgA 检测中的血清转化表明存在急性 SARS-CoV-2 中枢神经系统感染。然而，死亡的原因是她迅速进展的中枢神经系统结核导致的脑疝。SARS-CoV-2 可能掩盖或加重隐匿性结核感染，导致严重或致命后果。
