Invited Review: The spectrum of neuropathology in COVID‐19

Al‐Sarraj, Safa; Troakes, Claire; Hanley, Brian; Osborn, Michael; Richardson, Mark; Hotopf, Matthew; Bullmore, Edward T.; Everall, Ian

doi:10.1111/nan.12667

Cited by 117 publications

(170 citation statements)

References 57 publications

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“…Clinically, symptoms are dysphoria, headache, delirium, confusion, mental disorder, loss of consciousness, and coma in severe cases. This histopathological pattern seems to be the most common correlate in COVID-19 patients with clinical CNS involvement [ 116 ].…”

Section: Resultsmentioning

confidence: 99%

Neurological Sequelae in Patients with COVID-19: A Histopathological Perspective

Fisicaro

Napoli²,

Liberto

et al. 2021

IJERPH

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Background: Neuroinvasive properties of SARS-CoV-2 have allowed the hypothesis of several pathogenic mechanisms related to acute and chronic neurological sequelae. However, neuropathological correlates have been poorly systematically investigated, being retrieved from reports of single case or limited case series still. Methods: A PubMed search was carried out to review all publications on autopsy in subjects with “COronaVIrus Disease-19” (COVID-19). Among them, we focused on histological findings of the brain, which were compared with those from the authors’ autoptic studies performed in some COVID-19 patients. Results: Only seven studies reported histological evidence of brain pathology in patients deceased for COVID-19, including three with reverse transcription–quantitative polymerase chain reaction evidence of viral infection. All these studies, in line with our experience, showed vascular-related and infection-related secondary inflammatory tissue damage due to an abnormal immune response. It is still unclear, however, whether these findings are the effect of a direct viral pathology or rather reflect a non-specific consequence of cardiovascular and pulmonary disease on the brain. Conclusions: Notwithstanding the limited evidence available and the heterogeneity of the studies, we provide a preliminary description of the relationship between SARS-CoV-2 and brain sequelae. Systematic autoptic investigations are needed for accurate detection and adequate management of these patients.

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Section: Resultsmentioning

confidence: 99%

Neurological Sequelae in Patients with COVID-19: A Histopathological Perspective

Fisicaro

Napoli²,

Liberto

et al. 2021

IJERPH

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“…The most definitive means to assess for viral neuroinvasion in patients with COVID-19 is via neuropathology studies. In a review of 81 postmortem neuropathological examinations, Al-Sarraj et al concluded that it was difficult to parse out whether the findings were the result of viral neuroinvasion, hypoxia, multiorgan failure, cytokine storming, reduced immune response or strokes; they recommended the need for large-scale molecular and cellular investigations of brain tissue and CSF in conjunction with data on the neurological evaluation and neuroimaging for each patient [ 284 ]. Notably, Paniz-Mondolfi reported the presence of SARS-CoV-2 identified in brain tissue via ultrastructural analysis and molecular testing despite a negative SARS-CoV-2 PCR in CSF [ 285 ].…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid in COVID-19: A systematic review of the literature

Lewis

Frontera

Placantonakis

et al. 2021

Journal of the Neurological Sciences

153

152

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We sought to review the literature on cerebrospinal fluid (CSF) testing in patients with COVID-19 for evidence of viral neuroinvasion by SARS-CoV-2. Methods: We performed a systematic review of Medline and Embase between December 1, 2019 and November 18, 2020 to identify case reports or series of patients who had COVID-19 diagnosed based on positive SARS-CoV-2 polymerase chain reaction (PCR) or serologic testing and had CSF testing due to a neurologic symptom. Results: We identified 242 relevant documents which included 430 patients with COVID-19 who had acute neurological symptoms prompting CSF testing. Of those, 321 (75%) patients had symptoms that localized to the central nervous system (CNS). Of 304 patients whose CSF was tested for SARS-CoV-2 PCR, there were 17 (6%) whose test was positive, all of whom had symptoms that localized to the central nervous system (CNS). The majority (13/17, 76%) of these patients were admitted to the hospital because of neurological symptoms. Of 58 patients whose CSF was tested for SARS-CoV-2 antibody, 7 (12%) had positive antibodies with evidence of intrathecal synthesis, all of whom had symptoms that localized to the CNS. Of 132 patients who had oligoclonal bands evaluated, 3 (2%) had evidence of intrathecal antibody synthesis. Of 77 patients tested for autoimmune antibodies in the CSF, 4 (5%) had positive findings. Conclusion: Detection of SARS-CoV-2 in CSF via PCR or evaluation for intrathecal antibody synthesis appears to be rare. Most neurological complications associated with SARS-CoV-2 are unlikely to be related to direct viral neuroinvasion.

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“…Additionally, the distribution of cortical abnormalities was non-specific and could affect all lobes (15). Anosmia is a common neurological symptom of COVID-19 (41). The neuroimaging findings of COVID-19 patients with anosmia involved asymmetric olfactory bulbs on spin echo MRI, hyperintensities inside bilateral olfactory bulbs on T2 MRI with fat suppression and FLAIR, as well as normal MRI images (42)(43)(44).…”

Section: Other Abnormal Neuroimaging Findingsmentioning

confidence: 99%