Acute necrotizing encephalopathy with SARS-CoV-2 RNA confirmed in cerebrospinal fluid

Virhammar, Johan; Kumlien, Eva; Fällmar, David; Frithiof, Robert; Jackmann, Sven; Sköld, Markus; Kadir, Mohamed Hakimi Abdul; Frick, Jens Eklinder; Lindeberg, J̇onas; Olivero-Reinius, Henrik; Ryttlefors, Mats; Cunningham, Janet L.; Wikström, Johan; Grabowska, Anna; Bondeson, Kåre; Bergquist, Jonas; Zetterberg, Henrik; Rostami, Elham

doi:10.1212/wnl.0000000000010250

Cited by 226 publications

(305 citation statements)

References 8 publications

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“…While there was a small fraction of case reports and studies that showed its presence in CSF RT-PCR [ During our analysis, we found four cases where CSF IGM was positive [17,37],whereas Wang et al reported a case where both IgG and IgM antibodies against COVID -19 were positive [17]. In addition, CSF IGG was positive for COVID-19 in 2 cases [5,16].…”

Section: Discussionmentioning

confidence: 65%

A Comprehensive Systematic Review of CSF analysis that defines Neurological Manifestations of COVID-19

Tandon

Mehta

Daimee

et al. 2020

Preprint

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Background: Here we performed a systematic review of literature of CSF findings associated with neurological complications in coronavirus disease-2019 (COVID-19) to establish a pattern and understand the significance of CSF analysis which can possibly be useful in deciding prognosis and exploring therapeutic options in the future. Methods: We screened all articles resulting from a search of PubMed, Google Scholar and Scopus, using the keywords “SARS-CoV-2 in cerebrospinal fluid”, “SARS-CoV-2 and CNS Complication”.Results: We performed CSF analysis results in total of 113 patients from 67 papers. There were 7 patients out of 113 patients (6.2 %) were fatal and 35 patients (31 %) were considered severe and rest non-severe. Elevated cell counts (>5 cells/µL) were found in 43% (3/7) of the fatal cases, 25.7% (9/35) of the severe cases and 29.4% (15/51) of non-severe cases. The average CSF protein of 110.0 mg/dl found in fatal, and in 85.4mg/dl in non-fatal cases. Whereas, average CSF protein levels were 78 mg/dl in severe and 103 mg/dl in non-severe cases. In addition, 76.5% (13/17) of the patients with CNS complications and 74.1% (40/54) of the patients with a PNS manifestation showed elevated protein levels.Conclusion: The most common finding of CSF analysis in the setting of neurological manifestations in Covid-19 is noted to be elevated CSF protein with occasionally elevated, predominantly lymphocytic cell count. Interestingly, CSF protein is noted to be majorly elevated in all spectrums of severity of neurological illness including CNS and PNS complications. This may be indicative of only one common pathophysiological mechanism of neurological illness. In future, A combination of SARS-CoV-2 CSF RT-PCR, CSF IgM testing, and CNS targeting antibodies should be further studied to understand pathophysiology of neurological complications in Covid-19.

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Section: Discussionmentioning

confidence: 65%

A Comprehensive Systematic Review of CSF analysis that defines Neurological Manifestations of COVID-19

Tandon

Mehta

Daimee

et al. 2020

Preprint

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“…However, the analyzed data further suggest that the prevalence of LA is higher in this patient population than expected for age. Other possible interpretations may include encephalitis as suggested in several reports (Anzalone et al, 2020;Asfar et al, 2020;Espinosa et al, 2020;Hayashi et al, 2020;Kremer et al, 2020), acute necrotizing encephalitis (Virhammar et al, 2020), encephalomyelitis (Abdi et al, 2020;Zoghi et al, 2020), demyelination (Zanin et al, 2020;Parsons et al, 2020;Zoghi et al, 2020), or microangiopathy (Fischer et al, 2020). Therefore, we encourage future studies to report more detailed description of the WM changes in order to establish differential characteristics of COVID-19-related vs. age-related changes in WM.…”

Section: Discussionmentioning

confidence: 72%

“…Diffuse subcortical and deep WM abnormalities were the most prominent. A cumulative of 62/124 (50%) of cases presented brain abnormality in either anterior areas [D (Asfar et al, 2020); N (Hepburn et al, 2020); α (Zanin et al, 2020), X : 9/242 cases, Z (Virhammar et al, 2020) (Zanin et al, 2020). Unspecified brain location for brain waves slowing on EEG recording was reported in four cases [G (Espinosa et al, 2020); H (Fischer et al, 2020); U (Parsons et al, 2020); Z (Virhammar et al, 2020).…”

Section: Topography Of Brain Abnormalities In Covid-19mentioning

confidence: 99%

“…The midline structures of the brain were affected in 12/124 (10%) affected cases and mainly included abnormalities in the corpus callosum, i.e., hyperintensities [L (Hayashi et al, 2020); β (Zoghi et al, 2020)], hemorrhage [I] (Franceschi et al, 2020) Additionally, one of those patients [F] (Dixon et al, 2020) showed signs of swelling and hemorrhage in brain stem and hemorrhage in pons. Hyperintensities were noted in midbrain [A (Abdi et al, 2020); Z (Virhammar et al, 2020)] and pons [D (Asfar et al, 2020); β (Zoghi et al, 2020)].…”

Section: Topography Of Brain Abnormalities In Covid-19mentioning

confidence: 99%

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Brain abnormalities in COVID-19 acute/subacute phase: A rapid systematic review

Egbert

Cankurtaran

Karpiak

2020

Brain, Behavior, and Immunity

101

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Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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“…53,64,66 Nevertheless, CSF from a small subset of patients with encephalitic features did test positive for SARS-CoV-2 RNA. 70,71 Seizures have been reported in SARS-CoV-2 patients; in a Chinese cohort, 4/78 hospitalized patients (0.5%) suffered at least one seizure. 40 This was mirrored in a Spanish cohort, where 6/841 hospitalized patients (0.7%) had at least one seizure.…”

Section: Neurological Complicationsmentioning

confidence: 99%

Neurological manifestations of coronavirus infections – a systematic review

Almqvist

Granberg

Tzortzakakis

et al. 2020

Ann Clin Transl Neurol

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To optimize diagnostic workup of the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, we systematically reviewed neurological and neuroradiological manifestations of SARS-CoV-2 and all other known human coronavirus species (HCoV). Which lessons can we learn? We identified relevant publications (until 26 July 2020) using systematic searches in PubMed, Web of Science, and Ovid EMBASE with predefined search strings. A total of 4571 unique publications were retrieved, out of which 378 publications were selected for in-depth analysis by two raters, including a total of 17549 (out of which were 14418 SARS-CoV-2) patients. Neurological complications and associated neuroradiological manifestations are prevalent for all HCoVs (HCoV-229E, HKU1, NL63, OC43, Middle East respiratory syndrome (MERS)-CoV, SARS-CoV-1, and SARS-CoV-2). Moreover there are similarities in symptomatology across different HCoVs, particularly between SARS-CoV-1 and SARS-CoV-2. Common neurological manifestations include fatigue, headache, and smell/taste disorders. Additionally, clinicians need to be attentive for at least five classes of neurological complications: (1) Cerebrovascular disorders including ischemic stroke and macro/micro-hemorrhages, (2) encephalopathies, (3) para-/postinfectious immune-mediated complications such as Guillain-Barr e syndrome and acute disseminated encephalomyelitis, (4) (meningo-)encephalitis, potentially with concomitant seizures, and (5) neuropsychiatric complications such as psychosis and mood disorders. Our systematic review highlights the need for vigilance regarding neurological complications in patients infected by SARS-CoV-2 and other HCoVs, especially since some complications may result in chronic disability. Neuroimaging protocols should be designed to specifically screen for these complications. Therefore, we propose practical imaging guidelines to facilitate the diagnostic workup and monitoring of patients infected with HCoVs. additional HCoV species (HCoV-229E, HCoV-HKU1, HCoV-NL63, and HCoV-OC43) cause disease in humans, albeit typically with milder clinical courses. 3 While coronaviruses primarily target the human respiratory system, 4 they can also enter the central nervous system (CNS). This is evident from pre-clinical research, where murine coronaviruses have been used to model human encephalitis for decades. 5 HCoVs also show neurotropism. SARS-CoV-1 6 and SARS-CoV-2 7 both use the cell membrane-bound human angiotensin-converting enzyme 2 for cellular entry, which is, among other tissues, expressed on vascular endothelial cells in the brain. 8 Yet, SARS-CoV-2 seems to have an even higher affinity to bind to this receptor compared to SARS-CoV-1. 9 SARS-CoV-1 and SARS-CoV-2 are also most related genetically, with 79% genome homology. 10 Therefore, it is not surprising that several studies have described neurological symptomatology in both SARS-CoV-1 and SARS-CoV-2 infections. 3,11 Neurological complications have also been described in other HCoVs. 12 The aim of this study ...

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Acute necrotizing encephalopathy with SARS-CoV-2 RNA confirmed in cerebrospinal fluid

Cited by 226 publications

References 8 publications

A Comprehensive Systematic Review of CSF analysis that defines Neurological Manifestations of COVID-19

A Comprehensive Systematic Review of CSF analysis that defines Neurological Manifestations of COVID-19

Brain abnormalities in COVID-19 acute/subacute phase: A rapid systematic review

Neurological manifestations of coronavirus infections – a systematic review

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