Early evidence of pronounced brain involvement in fatal COVID-19 outcomes

Weyhern, Claus Hann von; Kaufmann, Inès; Neff, Frauke; Kremer, Marcus

doi:10.1016/s0140-6736(20)31282-4

Cited by 269 publications

(331 citation statements)

References 6 publications

Supporting

Mentioning

299

Contrasting

Unclassified

Order By: Relevance

“…However, IFN-γ demonstrates opposing roles in other neuroinflammatory conditions, regulating both proinflammatory and neuroprotectant properties in oligodendroglial cells, microglia, and astrocytes 18 . Elevated levels of intracranial CXCL chemokines have been described in a wide array of infectious and non-infectious CNS pathologies.The subsequent intracerebral accumulation of monocyte-macrophages, T lymphocytes, and chemokines downstream of IFN-γ propogates further neurologic injury [19][20][21][22] , mirroring a pattern of lymphocytic infiltration identified in the brains of COVID-19 patients 23 . Similarly, a report following the 2003 SARS outbreak All rights reserved.…”

Section: Main Textmentioning

confidence: 92%

Inflammatory leptomeningeal cytokines mediate delayed COVID-19 encephalopathy

Remšík¹,

Ja²,

Ne³

et al. 2020

Preprint

View full text Add to dashboard Cite

SARS-CoV-2 infection induces a wide spectrum of neurologic dysfunction. Here we show that a particularly vulnerable population with neurologic manifestations of COVID-19 harbor an influx of inflammatory cytokines within the cerebrospinal fluid in the absence of viral neuro-invasion. The majority of these inflammatory mediators are driven by type 2 interferon and are known to induce neuronal injury in other disease models. Levels of matrix metalloproteinase-10 within the spinal fluid correlate with the degree of neurologic dysfunction. Furthermore, this neuroinflammatory process persists weeks following convalescence from the acute respiratory infection. These prolonged neurologic sequelae following a systemic cytokine release syndrome lead to long-term neurocognitive dysfunction with a wide range of phenotypes.

show abstract

Section: Main Textmentioning

confidence: 92%

Inflammatory leptomeningeal cytokines mediate delayed COVID-19 encephalopathy

Remšík¹,

Ja²,

Ne³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…87 Additionally, exclusively for SARS-CoV-2, intracranial hemorrhages and cerebral microbleeds have been reported, potentially provoked by endothelial damage/dysfunction. 53,64,77 Second, encephalopathies with clinical features of delirium have been observed among SARS-CoV-2 patients. 53,66 Many of these patients showed full clinical recovery.…”

Section: Findings In the Context Of Existing Evidencementioning

confidence: 99%

Neurological manifestations of coronavirus infections – a systematic review

Almqvist

Granberg

Tzortzakakis

et al. 2020

Ann Clin Transl Neurol

View full text Add to dashboard Cite

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 ...

show abstract

“…Even though severe multifocal intracerebral parenchymal hemorrhage of the gray matter is occasionally found in patients undergoing ECMO therapy ( 1 , 2 ), the bleeding pattern of the patients presented here appeared unusual and therefore suggestive for a potential association with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or endothelialitis. A literature review on cerebral hemorrhage in COVID-19 patients revealed recent retrospective analyses and case reports describing occasional bleeding events ( 3 – 7 ). Here, parenchymal hemorrhage is found merely sporadic but diffuse petechial and in different lobes of the cerebrum or cerebellum.…”

mentioning

confidence: 99%