Neuromechanisms of SARS-CoV-2: A Review

DosSantos, Marcos F.; Devalle, Sylvie; Aran, Veronica; Capra, Daniela; Roque, Natália R.; Coelho-Aguiar, Juliana de Mattos; Spohr, Tânia Cristina Leite de Sampaio e; Subilhaga, Janice Gonçalves; Pereira, Cláudia Maria; Meira, Isabella D’Andrea; Filho, Paulo Niemeyer; Moura‐Neto, Vivaldo

doi:10.3389/fnana.2020.00037

Cited by 127 publications

(184 citation statements)

References 96 publications

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“…The neuroinvasive aspects of COVID-19 are becoming more appreciated (12) meningitis and hemorrhage, emulating many of the human findings. SARS-CoV has been shown to infect the human and mouse brains and data suggest it replicates in neurons.…”

Section: Discussion Golden Jw Et Al Sars-cov-2 Pathogenesis In K18-hmentioning

confidence: 94%

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Human angiotensin-converting enzyme 2 transgenic mice infected with SARS-CoV-2 develop severe and fatal respiratory disease

Golden

Cline

Zeng

et al. 2020

Preprint

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ABSTRACTThe emergence of SARS-CoV-2 has created an international health crisis. Small animal models mirroring SARS-CoV-2 human disease are essential for medical countermeasure (MCM) development. Mice are refractory to SARS-CoV-2 infection due to low affinity binding to the murine angiotensin-converting enzyme 2 (ACE2) protein. Here we evaluated the pathogenesis of SARS-CoV-2 in male and female mice expressing the human ACE2 gene under the control of the keratin 18 promotor. In contrast to non-transgenic mice, intranasal exposure of K18-hACE2 animals to two different doses of SARS-CoV-2 resulted in acute disease including weight loss, lung injury, brain infection and lethality. Vasculitis was the most prominent finding in the lungs of infected mice. Transcriptomic analysis from lungs of infected animals revealed increases in transcripts involved in lung injury and inflammatory cytokines. In the lower dose challenge groups, there was a survival advantage in the female mice with 60% surviving infection whereas all male mice succumbed to disease. Male mice that succumbed to disease had higher levels of inflammatory transcripts compared to female mice. This is the first highly lethal murine infection model for SARS-CoV-2. The K18-hACE2 murine model will be valuable for the study of SARS-CoV-2 pathogenesis and the assessment of MCMs.

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Section: Discussion Golden Jw Et Al Sars-cov-2 Pathogenesis In K18-hmentioning

confidence: 94%

“…of cases include signs of neurological disease such as headache, anosmia (loss of smell), ataxia, meningitis, seizures and impaired consciousness (12)(13)(14). To-date, SARS-CoV-2 has infected over eight million people world-wide and resulted in the death of more than 400,000.…”

Section: Introductionmentioning

confidence: 99%

Human angiotensin-converting enzyme 2 transgenic mice infected with SARS-CoV-2 develop severe and fatal respiratory disease

Golden

Cline

Zeng

et al. 2020

Preprint

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“…Moreover, a correlation between the ACE2 mRNA and the expression of various proteins in of the nucleus tractus solitaries, the dorsal vagal nucleus, and the caudal ventrolateral medulla has been reported [50], suggesting a crucial role of ACE2 in the modulation of autonomic nervous system. The expression of ACE2 has been also shown in the olfactory system and other important cerebral regions, such as the brain ventricles and the substantia nigra as well as areas that are directly or indirectly related to the olfactory pathways, including the hypothalamic nuclei, the amygdala, the hippocampus, and the frontal cortex [21].…”

Section: Ace2 Distribution In the Brainmentioning

confidence: 99%

“…Moreover, SARS virus genome sequences have been detected in the brain. According to the clinical and laboratory findings, SARS-CoV-2 (COVID-19) also is a neurotropic virus and can invade nervous tissues, and coating-mediated endo/ exocytosis can be a possible route of entry to enter and transmit within the cells [21].…”

Section: How Does Covid-19 Invade the Nervous System?mentioning

confidence: 99%

“…So far, the most widely accepted theory was that COVID-19 directly attacks the CNS via the olfactory nerve. It has been shown that CoVs reach the cerebrospinal fluid (CSF) through the olfactory tract a week after the contamination of nasal cells [21]. Interestingly, after the cut of the olfactory bulb, invasion of CoVs into the CNS was sparse in mice [2,22].…”

Section: How Does Covid-19 Invade the Nervous System?mentioning

confidence: 99%

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A Review on the Neurological Manifestations of COVID-19 Infection: a Mechanistic View

2020

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There is increasing evidence of neurological manifestations and complications in patients with coronavirus disease 19 (COVID-19). More than one-quarter of patients with COVID-19 developed various neurological symptoms, ranging from headache and dizziness to more serious medical conditions, such as seizures and stroke. The recent investigations introduced hyposmia as a potential early criterion of infection with COVID-19. Despite the high mortality and morbidity rate of COVID-19, its exact mechanism of action and pathogenesis is not well characterized. The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could interact with angiotensin-converting enzyme 2 (ACE2) in the endothelial, neural, and glial cells. In the present study, we reviewed the most common neurological manifestations and complications that emerged after infection with the SARS-CoV-2 and discussed their possible relation to the expression and function of ACE2. Comprehensive and detailed studies are required to uncover how this virus invades the neural system as well as other critical organs.

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Does COVID‐19 contribute to development of neurological disease?

Mahalakshmi

Ray

Tuladhar

et al. 2020

Immunity Inflam & Disease

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Background Although coronavirus disease 2019 (COVID‐19) has been associated primarily with pneumonia, recent data show that the causative agent of COVID‐19, the coronavirus severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), can infect a large number of vital organs beyond the lungs, such as the heart, kidneys, and the brain. Thus, there is evidence showing possible retrograde transmission of the virus from the olfactory epithelium to regions of the brain stem. Methods This is a literature review article. The research design method is an evidence‐based rapid review. The present discourse aim is first to scrutinize and assess the available literature on COVID‐19 repercussion on the central nervous system (CNS). Standard literature and database searches were implemented, gathered relevant material, and extracted information was then assessed. Results The angiotensin‐converting enzyme 2 (ACE2) receptors being the receptor for the virus, the threat to the central nervous system is expected. Neurons and glial cells express ACE2 receptors in the CNS, and recent studies suggest that activated glial cells contribute to neuroinflammation and the devastating effects of SARS‐CoV‐2 infection on the CNS. The SARS‐CoV‐2‐induced immune‐mediated demyelinating disease, cerebrovascular damage, neurodegeneration, and depression are some of the neurological complications discussed here. Conclusion This review correlates present clinical manifestations of COVID‐19 patients with possible neurological consequences in the future, thus preparing healthcare providers for possible future consequences of COVID‐19.

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Neuromechanisms of SARS-CoV-2: A Review

Cited by 127 publications

References 96 publications

Human angiotensin-converting enzyme 2 transgenic mice infected with SARS-CoV-2 develop severe and fatal respiratory disease

Human angiotensin-converting enzyme 2 transgenic mice infected with SARS-CoV-2 develop severe and fatal respiratory disease

A Review on the Neurological Manifestations of COVID-19 Infection: a Mechanistic View

Does COVID‐19 contribute to development of neurological disease?

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