Cerebral Micro-Structural Changes in COVID-19 Patients – An MRI-based 3-month Follow-up Study

Lu, Yiping; Li, Xuanxuan; Geng, Daoying; N, Mei; Wu, Pu-Yeh; Huang, Chu-Chung; Jia, Tianye; Zhao, Yajing; Wang, Dongdong; Xiao, Anling; Yin, Bo

doi:10.1016/j.eclinm.2020.100484

Cited by 485 publications

(649 citation statements)

References 39 publications

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“…The first hint of rSpike toxicity was the distinct swimming behavior that adult females presented after the protein injection. In fact, some recent studies have reported that the SARS-CoV-2 may affect the nervous system 26–28 as the peripheral nervous system 29–31 , particularly in the most severe cases of infection 32 .…”

Section: Discussionmentioning

confidence: 99%

Zebrafish studies on the vaccine candidate to COVID-19, the Spike protein: Production of antibody and adverse reaction

Fernandes¹,

Feitosa²,

Barbosa³

et al. 2020

Preprint

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Establishing new experimental animal models to assess the safety and immune response to the antigen used in the development of COVID-19 vaccine is an imperative issue. Based on the advantages of using zebrafish as a model in research, herein we suggest doing this to test the safety of the putative vaccine candidates and to study immune response against the virus. We produced a recombinant N-terminal fraction of the Spike SARS-CoV-2 protein and injected it into adult female zebrafish. The specimens generated humoral immunity and passed the antibodies to the eggs. However, they presented adverse reactions and inflammatory responses similar to severe cases of human COVID-19. The analysis of the structure and function of zebrafish and human Angiotensin-converting enzyme 2, the main human receptor for virus infection, presented remarkable sequence similarities. Moreover, bioinformatic analysis predicted protein-protein interaction of the Spike SARS-CoV-2 fragment and the Toll-like receptor pathway. It might help in the choice of future therapeutic pharmaceutical drugs to be studied. Based on the in vivo and in silico results presented here, we propose the zebrafish as a model for translational research into the safety of the vaccine and the immune response of the vertebrate organism to the SARS-CoV-2 virus.

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Section: Discussionmentioning

confidence: 99%

Zebrafish studies on the vaccine candidate to COVID-19, the Spike protein: Production of antibody and adverse reaction

Fernandes¹,

Feitosa²,

Barbosa³

et al. 2020

Preprint

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show abstract

“…The integrity of subcortical white matter is critically important for maintenance of cognitive function [71,72], and one of the consequences of white matter damage in COVID-19 is likely to be cognitive impairment. This was highlighted by the neuroradiological demonstration that damage to white matter and disruption of functional integrity in brain regions such as the hippocampus, at 3-month follow-up in recovered COVID-19 patients, was associated with memory loss [9].…”

Section: The Types Of Cerebral Ischaemic Damage Seen In Covid-19 Arementioning

confidence: 99%

“…A recent report described a 'dysexecutive syndrome consisting of inattention, disorientation, or poorly organised movements in response to command' in 33% of 43 patients discharged from hospital [7]. Moreover, neuroradiological evidence of microstructural damage and disruption of functional brain integrity at 3-month follow-up in recovered COVID-19 patients [9] indicates potential long-term neurological consequences in severely affected COVID-19 patients (reviewed [10]). Acute cerebrovascular disease (CVD), typically presenting as ischaemic stroke but occasionally as intracerebral haemorrhage (ICH), has emerged as an important clinical feature in COVID-19 (reviewed in [5]).…”

Section: Introductionmentioning

confidence: 99%

Cognitive impact of COVID-19: looking beyond the short term

2020

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COVID-19 is primarily a respiratory disease but up to two thirds of hospitalised patients show evidence of central nervous system (CNS) damage, predominantly ischaemic, in some cases haemorrhagic and occasionally encephalitic. It is unclear how much of the ischaemic damage is mediated by direct or inflammatory effects of virus on the CNS vasculature and how much is secondary to extracranial cardiorespiratory disease. Limited data suggest that the causative SARS-CoV-2 virus may enter the CNS via the nasal mucosa and olfactory fibres, or by haematogenous spread, and is capable of infecting endothelial cells, pericytes and probably neurons. Extracranially, SARS-CoV-2 targets endothelial cells and pericytes, causing endothelial cell dysfunction, vascular leakage and immune activation, sometimes leading to disseminated intravascular coagulation. It remains to be confirmed whether endothelial cells and pericytes in the cerebral vasculature are similarly targeted. Several aspects of COVID-19 are likely to impact on cognition. Cerebral white matter is particularly vulnerable to ischaemic damage in COVID-19 and is also critically important for cognitive function. There is accumulating evidence that cerebral hypoperfusion accelerates amyloid-β (Aβ) accumulation and is linked to tau and TDP-43 pathology, and by inducing phosphorylation of α-synuclein at serine-129, ischaemia may also increase the risk of development of Lewy body disease. Current therapies for COVID-19 are understandably focused on supporting respiratory function, preventing thrombosis and reducing immune activation. Since angiotensin-converting enzyme (ACE)-2 is a receptor for SARS-CoV-2, and ACE inhibitors and angiotensin receptor blockers are predicted to increase ACE-2 expression, it was initially feared that their use might exacerbate COVID-19. Recent meta-analyses have instead suggested that these medications are protective. This is perhaps because SARS-CoV-2 entry may deplete ACE-2, tipping the balance towards angiotensin II-ACE-1-mediated classical RAS activation: exacerbating hypoperfusion and promoting inflammation. It may be relevant that APOE ε4 individuals, who seem to be at increased risk of COVID-19, also have lowest ACE-2 activity. COVID-19 is likely to leave an unexpected legacy of long-term neurological complications in a significant number of survivors. Cognitive follow-up of COVID-19 patients will be important, especially in patients who develop cerebrovascular and neurological complications during the acute illness.

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“…A recent MRI-based 3-month follow-up study demonstrates that 55% of patients who recovered from COVID-19 infection had neurological symptoms and exhibited significantly higher gray matter area in brain regions relevant to memory, smell, tremor etc. (Yiping et al, 2020). Together, these data indicate that neurological manifestations of COVID-19 are relatively frequent especially in patients with severe disease, raising questions about mechanism, chronic consequences, and management since neither a vaccine nor specific treatment is available.…”

Section: Sars-cov-2 and The Central Nervous Systemmentioning

confidence: 98%