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Viruses ; 13(11)2021 10 30.
Article in English | MEDLINE | ID: covidwho-1488764


SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is primarily responsible for coronavirus disease (COVID-19) and it is characterized by respiratory illness with fever and dyspnea. Severe vascular problems and several other manifestations, including neurological ones, have also been frequently reported, particularly in the great majority of "long hauler" patients. SARS-CoV-2 infects and replicates in lung epithelial cells, while dysfunction of endothelial and neuronal brain cells has been observed in the absence of productive infection. It has been shown that the Spike protein can interact with specific cellular receptors, supporting both viral entry and cellular dysfunction. It is thus clear that understanding how and when these receptors are regulated, as well as how much they are expressed would help in unveiling the multifaceted aspects of this disease. Here, we show that SH-SY5Y neuroblastoma cells express three important cellular surface molecules that interact with the Spike protein, namely ACE2, TMPRSS2, and NRP1. Their levels increase when cells are treated with retinoic acid (RA), a commonly used agent known to promote differentiation. This increase matched the higher levels of receptors observed on HUVEC (primary human umbilical vein endothelial cells). We also show by confocal imaging that replication-defective pseudoviruses carrying the SARS-CoV-2 Spike protein can infect differentiated and undifferentiated SH-SY5Y, and HUVEC cells, although with different efficiencies. Neuronal cells and endothelial cells are potential targets for SARS-CoV-2 infection and the interaction of the Spike viral protein with these cells may cause their dysregulation. Characterizing RNA and protein expression tempo, mode, and levels of different SARS-CoV-2 receptors on both cell subpopulations may have clinical relevance for the diagnosis and treatment of COVID-19-infected subjects, including long hauler patients with neurological manifestations.

COVID-19/metabolism , Endothelial Cells/metabolism , Neuroblastoma/metabolism , Receptors, Virus/metabolism , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/metabolism , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/virology , Cell Line, Tumor , Endothelial Cells/virology , Host Microbial Interactions , Human Umbilical Vein Endothelial Cells , Humans , Neuroblastoma/virology , Neuropilin-1/metabolism , Serine Endopeptidases/metabolism , Virus Internalization
World Development ; 145:105533, 2021.
Article in English | ScienceDirect | ID: covidwho-1230814


Ecosystem health and zoonotic diseases are closely interwoven. Even as we grapple with the SARS-Coronavirus-2 pandemic, which may have its origins in wildlife, weakening environmental policies in the Brazilian Amazon are elevating the risk of additional zoonotic spillover events. We examine the links between deforestation and disease emergence in the Amazon, as illustrated by outbreaks of yellow fever virus, Venezuelan equine encephalitis virus, and Oropouche virus. It has been well established that in Brazil, indigenous territories exhibit lower rates of forest conversion and degradation than in areas designated for sustainable use. In this way, Amazonia’s indigenous tribes promote public health while sustaining ecosystem services. However, indigenous land rights are under attack due to current policies enabling illegal land grabbing, mining and logging. Further adding to the existential struggle of indigenous tribes, malaria and SARS-Coronavirus-2 are wreaking havoc on these vulnerable populations. There is a critical need for protection of indigenous people's rights and health, as well as a sustained effort to support the study of mechanisms underlying anthropogenic land use change and zoonotic disease risk.

J Neurotrauma ; 38(1): 1-43, 2021 01 01.
Article in English | MEDLINE | ID: covidwho-1066221


The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus attacks multiple organs of coronavirus disease 2019 (COVID-19) patients, including the brain. There are worldwide descriptions of neurological deficits in COVID-19 patients. Central nervous system (CNS) symptoms can be present early in the course of the disease. As many as 55% of hospitalized COVID-19 patients have been reported to have neurological disturbances three months after infection by SARS-CoV-2. The mutability of the SARS-COV-2 virus and its potential to directly affect the CNS highlight the urgency of developing technology to diagnose, manage, and treat brain injury in COVID-19 patients. The pathobiology of CNS infection by SARS-CoV-2 and the associated neurological sequelae of this infection remain poorly understood. In this review, we outline the rationale for the use of blood biomarkers (BBs) for diagnosis of brain injury in COVID-19 patients, the research needed to incorporate their use into clinical practice, and the improvements in patient management and outcomes that can result. BBs of brain injury could potentially provide tools for detection of brain injury in COVID-19 patients. Elevations of BBs have been reported in cerebrospinal fluid (CSF) and blood of COVID-19 patients. BB proteins have been analyzed in CSF to detect CNS involvement in patients with infectious diseases, including human immunodeficiency virus and tuberculous meningitis. BBs are approved by the U.S. Food and Drug Administration for diagnosis of mild versus moderate traumatic brain injury and have identified brain injury after stroke, cardiac arrest, hypoxia, and epilepsy. BBs, integrated with other diagnostic tools, could enhance understanding of viral mechanisms of brain injury, predict severity of neurological deficits, guide triage of patients and assignment to appropriate medical pathways, and assess efficacy of therapeutic interventions in COVID-19 patients.

Brain Injuries/blood , Brain Injuries/diagnosis , Brain/metabolism , COVID-19/blood , COVID-19/diagnosis , Biomarkers/blood , Brain/pathology , Brain Injuries/etiology , COVID-19/complications , Humans , Nervous System Diseases/blood , Nervous System Diseases/diagnosis , Nervous System Diseases/etiology , Prospective Studies , Retrospective Studies