SARS-CoV-2, an Underestimated Pathogen of the Nervous System

Jakhmola, Shweta; Indari, Omkar; Chatterjee, Sayantani; Jha, Hem Chandra

doi:10.1007/s42399-020-00522-7

Cited by 55 publications

(53 citation statements)

References 102 publications

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“…Such studies are important, because they can identify which of the NVU cell types may provide the main route of SARS-CoV-2 entry into the CNS. Previous studies indicated that astrocytes, microglial cells, and endothelial cells express ACE2 (30) (74,75). Recently, high expression levels of ACE2 in adult human heart pericytes (76,77) and mouse olfactory bulb pericytes (78) have been reported.…”

Section: Discussionmentioning

confidence: 99%

Expression of SARS-CoV-2-related Receptors in Cells of the Neurovascular Unit: Implications for HIV-1 Infection

Torices

Cabrera

Stangis

et al. 2021

Preprint

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Background. Neurological complications are common in patients affected by COVID-19 due to the ability of SARS-CoV-2 to infect brains. While the mechanisms of this process are not fully understood, it has been proposed that SARS-CoV-2 can infect the cells of the neurovascular units (NVU), which form the blood-brain barrier (BBB). The aim of the current study was to analyze the expression pattern of the main SARS-CoV-2 receptors in naïve and HIV-1-infected cells of the NVU in order to elucidate a possible pathway of the virus entry into the brain and a potential modulatory impact of HIV-1 in this process. Methods. The gene and protein expression profile of ACE2, TMPRSS2, ADAM17, BSG, DPP4, AGTR2, ANPEP, cathepsin B and cathepsin L was assessed by qPCR and immunoblotting, respectively. In addition, we investigated if brain endothelial cells can be affected by the exposure to the S1 subunit of the S protein, the domain responsible for the direct binding of SARS-CoV-2 to the ACE2 receptors. Results. The receptors involved in SARS-CoV-2 infection are coexpressed in the cells of the NVU, especially in astrocytes and microglial cells. These receptors are functionally active as exposure of endothelial cells to the SARS CoV-2 S1 protein subunit altered the expression pattern of tight junction proteins, such as claudin-5 and ZO-1. Additionally, HIV-1 infection upregulated ACE2 and TMPRSS2 expression in brain astrocytes and microglia cells.Conclusions. These findings provide key insight into SARS-CoV-2 recognition by cells of the NVU and may help to develop possible treatment of CNS complications of COVID-19.

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Section: Discussionmentioning

confidence: 99%

Expression of SARS-CoV-2-related Receptors in Cells of the Neurovascular Unit: Implications for HIV-1 Infection

Torices

Cabrera

Stangis

et al. 2021

Preprint

View full text Add to dashboard Cite

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“…COVID-19 rapidly penetrates into the brain via the olfactory sensory neurons and causes anosmia [ 69 , 70 , 71 ]. A recent postmortem study conducted by brain MRI revealed that COVID-19 olfactory impairment is likely to be restricted to olfactory bulbs [ 72 ] and another study found local inflammation and cytokine release as causative for injury to the olfactory sensory neurons [ 73 ].…”

Section: Covid-19-related Neurological Effectsmentioning

confidence: 99%

Severe COVID-19 Infection Associated with Endothelial Dysfunction Induces Multiple Organ Dysfunction: A Review of Therapeutic Interventions

et al. 2021

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Since December 2019, the SARS-CoV-2 (COVID-19) pandemic has transfixed the medical world. COVID-19 symptoms vary from mild to severe and underlying chronic conditions such as pulmonary/cardiovascular disease and diabetes induce excessive inflammatory responses to COVID-19 and these underlying chronic diseases are mediated by endothelial dysfunction. Acute respiratory distress syndrome (ARDS) is the most common cause of death in COVID-19 patients, but coagulation induced by excessive inflammation, thrombosis, and disseminated intravascular coagulation (DIC) also induce death by multiple-organ dysfunction syndrome. These associations imply that maintaining endothelial integrity is crucial for favorable prognoses with COVID-19 and therapeutic intervention to support this may be beneficial. Here, we summarize the extent of heart injuries, ischemic stroke and hemorrhage, acute kidney injury, and liver injury caused by immune-mediated endothelial dysfunction that result in the phenomenon of multi-organ dysfunction seen in COVID-19 patients. Moreover, the potential therapeutic effect of angiotensin receptor blockers and angiotensin-converting enzyme inhibitors that improve endothelial dysfunction as well as the bradykinin storm are discussed.

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“…Severe acute respiratory syndrome coronavirus (CoV) 2 (SARS-CoV-2), a large ssRNA virus, is the causative agent of COVID-19, which primarily attacks the respiratory tract including associated organs. Additionally, the virus has shown to impact various other organs or body systems like the gastrointestinal system, nervous system etc ( Jakhmola et al, 2020a ; Jakhmola et al, 2020b ; Sonkar et al, 2020 ). Currently new variants of SARS-CoV-2 are reported from different regions of the world.…”

Section: Introductionmentioning

confidence: 99%

An Update on Antiviral Therapy Against SARS-CoV-2: How Far Have We Come?

et al. 2021

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COVID-19 pandemic has spread worldwide at an exponential rate affecting millions of people instantaneously. Currently, various drugs are under investigation to treat an enormously increasing number of COVID-19 patients. This dreadful situation clearly demands an efficient strategy to quickly identify drugs for the successful treatment of COVID-19. Hence, drug repurposing is an effective approach for the rapid discovery of frontline arsenals to fight against COVID-19. Successful application of this approach has resulted in the repurposing of some clinically approved drugs as potential anti-SARS-CoV-2 candidates. Several of these drugs are either antimalarials, antivirals, antibiotics or corticosteroids and they have been repurposed based on their potential to negate virus or reduce lung inflammation. Large numbers of clinical trials have been registered to evaluate the effectiveness and clinical safety of these drugs. Till date, a few clinical studies are complete and the results are primary. WHO also conducted an international, multi-country, open-label, randomized trials-a solidarity trial for four antiviral drugs. However, solidarity trials have few limitations like no placebos were used, additionally any drug may show effectiveness for a particular population in a region which may get neglected in solidarity trial analysis. The ongoing randomized clinical trials can provide reliable long-term follow-up results that will establish both clinical safety and clinical efficacy of these drugs with respect to different regions, populations and may aid up to worldwide COVID-19 treatment research. This review presents a comprehensive update on majorly repurposed drugs namely chloroquine, hydroxychloroquine, remdesivir, lopinavir-ritonavir, favipiravir, ribavirin, azithromycin, umifenovir, oseltamivir as well as convalescent plasma therapy used against SARS-CoV-2. The review also summarizes the data recorded on the mechanism of anti-SARS-CoV-2 activity of these repurposed drugs along with the preclinical and clinical findings, therapeutic regimens, pharmacokinetics, and drug-drug interactions.

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SARS-CoV-2, an Underestimated Pathogen of the Nervous System

Cited by 55 publications

References 102 publications

Expression of SARS-CoV-2-related Receptors in Cells of the Neurovascular Unit: Implications for HIV-1 Infection

Expression of SARS-CoV-2-related Receptors in Cells of the Neurovascular Unit: Implications for HIV-1 Infection

Severe COVID-19 Infection Associated with Endothelial Dysfunction Induces Multiple Organ Dysfunction: A Review of Therapeutic Interventions

An Update on Antiviral Therapy Against SARS-CoV-2: How Far Have We Come?

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