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Coronavirus infections from 2002-2021: Neuropsychiatric Manifestations

ABSTRACT: Coronaviruses have been known to infect humans for several decades and there are four endemic subtypes: HCoV (human coronavirus) -229E, -NL63, -OC43 and -HKU1. These mainly cause a mild upper respiratory illness, but occasionally in vulnerable individuals they can result in more severe respiratory disease and, rarely, CNS involvement. Prior exposure to these viruses has also been associated with an increased odds of having a major psychiatric illness. The severe acute respiratory syndrome (SARS), caused by SARS-CoV, started in 2002 and, as well as causing a more severe respiratory phenotype, was also associated with delirium and affective symptoms acutely. Psychosis occurred in about 1% of individuals and was generally thought to be due to corticosteroid administration. The Middle East respiratory syndrome (MERS), caused by MERS-CoV, revealed similar findings. Survivors of both SARS and MERS reported persistent physical and psychological symptoms at least several months after the acute illness. The reported neuropsychiatric symptoms of COVID-19 range from the common symptoms of systemic and upper respiratory infections to severe and disabling conditions. Delirium has been described using varying terminology; as well as being a possible presenting feature of COVID-19, it has also been shown to be a marker of severe disease. Stroke, both ischaemic and haemorrhagic, have been reported to be more common in COVID-19 than in other medical illnesses. Mood and anxiety disorders are likely to be common at follow-up, while psychosis remains rare and controversial. ‘Long Covid’ is likely to represent a highly clinically and aetiologically heterogeneous group.

SUBMITTER: Barthorpe A

PROVIDER: S-EPMC8651478 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description: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-Barré 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.

Project description:Neuropsychiatric lupus (NPSLE), the nervous system presentation of systemic lupus erythematosus (SLE), remains challenging to treat due to its unclear pathogenesis and lack of available targeted therapies. A potential contributor to disease progression is brain tertiary lymphoid structures (TLS); these ectopic lymphoid follicles that can develop tissue-targeted antibodies have recently been described in the MRL/lpr lupus mouse strain, a classic model for studying NPSLE. The brains of MRL/lpr mice show a significant increase of CXCL13, an important chemokine in lymphoid follicle formation and retention that may also play a role in the disease progression of NPSLE. The aim of the present study was to inhibit CXCL13 and examine the effect of this intervention on lymphoid formation and the development of neurobehavioral manifestations in lupus mice. Female MRL/lpr mice were injected with an anti-CXCL13 antibody, an IgG1 isotype-matched antibody, or PBS either three times a week for 12 weeks intraperitoneally (IP) starting at 6-8 weeks of age, or continuously intracerebroventricularly (ICV) with an osmotic pump over a two-week period starting at 15 weeks of age. Cognitive dysfunction and depression-like behavior were assessed at the end of treatment. When treatment was delivered IP, anti-CXCL13 treated mice showed significant improvement in cognitive function when compared to control treated mice. Depression-like behavior was attenuated as well. Furthermore, mice that received anti-CXCL13 by the ICV route showed similar beneficial effects. However, the extent of lymphocyte infiltration into the brain and the general composition of the aggregates were not substantively changed by anti-CXCL13 irrespective of the mode of administration. Nevertheless, analysis of brain gene expression in anti-CXCL13 treated mice showed significant differences in key immunological and neuro-inflammatory pathways that most likely explained the improvement in the behavioral phenotype. Our results indicate that CXCL13 affects the behavioral manifestations in the MRL/lpr strain and is important to the pathogenesis of murine NPSLE, suggesting it as a potential therapeutic target.

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Coronavirus infections from 2002-2021: Neuropsychiatric Manifestations

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