Neuroinfection may contribute to pathophysiology and clinical manifestations of COVID‐19

Steardo, Luca; Zorec, Robert; Verkhratsky, Alexei

doi:10.1111/apha.13473

Cited by 323 publications

(411 citation statements)

References 31 publications

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“…There is strong evidence for a neurotropic action of SARS-CoV-2 infection. It has been demonstrated that β-coronaviruses to which the SARS-CoV-2 belongs, do not limit their presence to the respiratory tract and have been shown to frequently invade the CNS [10]. This propensity has been convincingly documented for the SARS-CoV-1, MERS-CoV and the coronavirus responsible for porcine hemagglutinating encephalomyelitis (HEV 67N).…”

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confidence: 99%

“…In light of the high similarity between SARS-CoV-1 and SARS-CoV-2, it is quite likely that SARS-CoV-2 also possesses a similar potential. Neuroinfection has been proposed to potentially contribute to the pathophysiology and clinical manifestations of Covid-19 [10] with the neuroinvasive potential of SARS-CoV-2 suggested to play a role in the respiratory failure of Covid-19 patients [11,12]. Our nicotinic hypothesis proposes that the virus could enter the body through neurons of the olfactory system and/or through the lung leading to different clinical features with different outcome, and contrasts with the currently accepted view that ACE2 is the principal receptor of SARS-CoV-2 for its entry into cells.…”

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confidence: 99%

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A nicotinic hypothesis for Covid-19 with preventive and therapeutic implications

Changeux¹,

Amoura²,

Rey³

et al. 2020

Comptes Rendus. Biologies

222

134

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Background: Ivermectin is a widely used antiparasitic drug with known e cacy against several single-strain RNA viruses. Recent data shows signi cant reduction of SARS-CoV-2 replication in vitro by ivermectin concentrations not achievable with safe doses orally. Inhaled therapy has been used with success for other antiparasitics. Methods: An ethanol-based ivermectin formulation was administered once to 14 rats using a nebulizer capable of delivering particles with alveolar deposition. Rats were randomly assigned into three target dosing groups, lower dose (80-90 mg/kg), higher dose (110-140 mg/kg) or ethanol vehicle only. A toxicology pro le including behavioral and weight monitoring, full blood count, biochemistry, necropsy and histological examination of the lungs was conducted. The pharmacokinetic pro le of ivermectin in plasma and lungs was determined in all animals. Results: There were no relevant changes in behavior or body weight. There was a delayed elevation in muscle enzymes compatible with rhabdomyolysis, that was also seen in the control group and has been attributed to the ethanol dose which was up to 11 grams/kg in some animals. There were no histological anomalies in the lungs of any rat. Male animals received a higher ivermectin dose adjusted by adipose weight and reached higher plasma concentrations than females in the same dosing group (mean C max 86.2 ng/ml vs 26.2 ng/ml in the lower dose group and 152 ng/ml vs 51.8 ng/ml in the higher dose group). All subjects had detectable ivermectin concentrations in the lungs at seven days post intervention, up to 524.3 ng/g for high-dose male and 27.3 ng/g for lowdose females. Conclusion: nebulized ivermectin can reach pharmacodynamic concentrations in the lung tissue of rats, additional experiments are required to assess the safety of this formulation in larger animals.

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confidence: 99%

mentioning

confidence: 99%

A nicotinic hypothesis for Covid-19 with preventive and therapeutic implications

Changeux¹,

Amoura²,

Rey³

et al. 2020

Comptes Rendus. Biologies

222

134

View full text Add to dashboard Cite

show abstract

“…T here is strong evidence for a neurotropic action of SARS-CoV-2 infection. It has been demonstrated that β-coronaviruses to which the SARS-CoV-2 belongs, do not limit their presence to the respiratory tract and have been shown to frequently invade the CNS [10] . T his propensity has been convincingly documented for the SARS-CoV-1, MERS-CoV and the coronavirus responsible for porcine hemagglutinating encephalomyelitis (HEV 67N).…”

mentioning

confidence: 99%

A nicotinic hypothesis for Covid-19 with preventive and therapeutic implications

Changeux¹,

Amoura

Rey

et al. 2020

Preprint

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SARS-CoV-2 epidemics raises a considerable issue of public health at the planetary scale. T here is a pressing urgency to find treatments based upon currently available scientific knowledge. T herefore, we tentatively propose a hypothesis which hopefully might ultimately help saving lives. Based on the current scientific literature and on new epidemiological data which reveal that current smoking status appears to be a protective factor against the infection by SARS-CoV-2 [1], we hypothesize that the nicotinic acetylcholine receptor (nAChR) plays a key role in the pathophysiology of Covid-19 infection and might represent a target for the prevention and control of Covid-19 infection.

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“…A retrospective study of knowledge from the COVID-19 outbreak in China showed that the incidence of stroke among hospitalized patients with COVID-19 was approximately 5%. (9). Stroke among patients with COVID-19 can affect any age although the incidence of stroke increase among patients with severe diseases like hypertension, diabetes, coronary artery diseases, and previous attack of cerebrovascular accident.…”

Section: Discussionmentioning

confidence: 99%

COVID-19 and Ischemic Stroke

Sidig

Abbasher

Hussien

et al. 2020

Preprint

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Background: SARS-CoV-2 causes COVID-19 disease. It was identified in December 2019 and rapidly evolved into a pandemic. During the outbreak of COVID-19, researches demonstrated its effect on many systems, including the nervous system. In our clinic, we have reported an impact of SARS-CoV-2, causing the ischaemic stroke.Case Report: A 62-year-old Sudanese male with some comorbidities brought to the A&E with fever, chest symptoms, and acute evolving left-sided hemiplegia power grade 0/5 MRCS with left upper motor neuron facial palsy. Investigations: CT brain: right middle cerebral artery MCA infarction. CT- chest: bilateral ground-glass appearance. COVID-19 Test was positive. elevated D-dimer and C-reactive protein.Discussion: A retrospective study of data from the COVID-19 outbreak in China showed that the incidence of stroke among hospitalized patients was approximately 5%. The fact that COVID-19 is an acute inflammatory condition associated with an increased incidence of fatty plaques formation, injury of the vascular wall, and hypercoagulability, causing brain infarct can be a reasonable hypothesis.ConclusionPatients with COVID-19 are at increased risk of thrombo-embolization, leading to arterial and venous cerebrovascular accident. This case report enhances the importance of further studies to clarify the relationship between stroke and COVID-19.

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Neuroinfection may contribute to pathophysiology and clinical manifestations of COVID‐19

Cited by 323 publications

References 31 publications

A nicotinic hypothesis for Covid-19 with preventive and therapeutic implications

A nicotinic hypothesis for Covid-19 with preventive and therapeutic implications

A nicotinic hypothesis for Covid-19 with preventive and therapeutic implications

COVID-19 and Ischemic Stroke

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