SARS-CoV-2 pathophysiology and assessment of coronaviruses in CNS diseases with a focus on therapeutic targets.

The novel Coronavirus disease of 2019 (nCOV-19) is a viral outbreak noted first in Wuhan, China. This disease is caused by Severe Acute Respiratory Syndrome (SARS) Coronavirus (CoV)-2. In the past, other members of the coronavirus family, such as SARS and Middle East Respiratory Syndrome (MERS), have made an impact in China and the Arabian peninsula respectively. Both SARS and COVID-19 share similar symptoms such as fever, cough, and difficulty in breathing that can become fatal in later stages. However, SARS and MERS infections were epidemic diseases constrained to limited regions. By March 2020 the SARS-CoV-2 had spread across the globe and on March 11th, 2020 the World Health Organization (WHO) declared COVID-19 as pandemic disease. In severe SARS-CoV-2 infection, many patients succumbed to pneumonia. Higher rates of deaths were seen in older patients who had co-morbidities such as diabetes mellitus, hypertension, cardiovascular disease (CVD), and dementia. In this review paper, we discuss the effect of SARS-CoV-2 on CNS diseases, such as Alzheimer's-like dementia, and diabetes mellitus. We also focus on the virus genome, pathophysiology, theranostics, and autophagy mechanisms. We will assess the multiorgan failure reported in advanced stages of SARS-CoV-2 infection. Our paper will provide mechanistic clues and therapeutic targets for physicians and investigators to combat COVID-19.

Determining the rate of underrecognition of West Nile virus neurologic disease in the province of Quebec in 2012.

BACKGROUND: During a major outbreak of West Nile virus (WNV) infection in the province of Quebec in 2012, public health authorities (PHAs) suspected underrecognition of West Nile neurologic disease (WNND). With data on acute infections detected in blood donors, an estimate of the degree of underrecognition was produced. STUDY DESIGN AND METHODS: All 2012 donors were tested for WNV infection with the use of reverse transcription-polymerase chain reaction (RT-PCR). With the number of cases detected, the number of donors tested, our estimate of the duration of viremia, an estimate of the population at risk, and the ratio of WNND to total cases, an expected number of WNND cases was calculated. A Monte Carlo simulation was used to estimate the range of several of these variables. RESULTS: Seventeen RT-PCR-positive donors were found among 52,309 donations tested. In the base case, the total number of cases was 16,095 and the expected number of WNND cases was 115. In the Monte Carlo simulation, the mean number of expected WNND cases was 136, and the median was 129. Since only 85 cases were reported to PHAs, it is estimated that between 26 and 37.5% of cases occurring in the province went undetected. CONCLUSION: The observation that close to one-third of cases of WNND went undetected because of the omission of appropriate laboratory testing indicates the need for improvement in the investigation of acute neurologic syndrome of suspected infectious etiology in Québec.

Enterovirus infections in Singaporean children: an assessment of neurological manifestations and clinical outcomes.

INTRODUCTION: Enterovirus infections in childhood can be associated with significant neurological morbidity. This study aimed to describe the prevalence and range of neurological manifestations, determine the clinical characteristics and assess differences in clinical outcomes for Singaporean children diagnosed with enterovirus infections. METHODS: In this single-centre, case-control study, clinical data was collected retrospectively from patients admitted to National University Hospital, Singapore, from August 2007 to October 2011 and diagnosed with enterovirus infection, based on the enterovirus polymerase chain reaction test, or cultures from throat and rectal swabs or cerebrospinal fluid samples. The occurrence of neurological manifestations was reviewed and clinical outcomes were assessed. RESULTS: A total of 48 patients (age range: six days-17.8 years) were included in the study. Neurological manifestations were seen in 75.0% of patients, 63.9% of whom presented with aseptic meningitis. Other neurological manifestations included encephalitis, acute cerebellitis, transverse myelitis and autonomic dysfunction. The incidence of neurological manifestations was significantly higher in patients aged > 1 year as compared to younger patients (p = 0.043). In patients without neurological manifestations, a significantly higher proportion presented with hand, foot and mouth disease and poor feeding. Long-term neurological sequelae were seen in 16.7% of patients with neurological manifestations. CONCLUSION: A wide spectrum of neurological manifestations resulting in a relatively low incidence of long-term neurological sequelae was observed in our study of Singaporean children with enterovirus infections. As some of these neurological morbidities were severe, careful evaluation of children with neurological involvement is therefore necessary.

Neuropsychological assessment of HIV-infected populations in international settings.

Resource-limited regions of the world represent the areas most affected by the global HIV epidemic. Currently, there are insufficient data on the neurocognitive effects of HIV in these areas and neuropsychological studies that have been carried out thus far are marked by inconsistent methods, test batteries, and rating systems for levels of cognitive impairment. These differences in methods, along with genetic variability of both virus and host, differences in co-infections and other co-morbidities, differences in language and culture, and infrastructural deficiencies in many international settings create challenges to the assessment of neurocognitive functioning and interpretation of neuropsychological data. Identifying neurocognitive impairment directly attributable to HIV, exploring relationships between HIV-associated neurocognitive impairment, disease variables, and everyday functioning, evaluating differences in HIV-1 subtype associated neuropathology, and determining implications for treatment remain complicated and challenging goals. Endeavors to establish a more standardized approach to neurocognitive assessments across international studies in addition to accumulating appropriate normative data that will allow more accurate rating of neuropsychological test performance will be crucial to future efforts attempting to achieve these goals.

Functional consequences of HIV-associated neuropsychological impairment.

This review focuses on the "real world" implications of infection with HIV/AIDS from a neuropsychological perspective. Relevant literature is reviewed which examines the relationships between HIV-associated neuropsychological impairment and employment, driving, medication adherence, mood, fatigue, and interpersonal functioning. Specifically, the relative contributions of medical, cognitive, psychosocial, and psychiatric issues on whether someone with HIV/AIDS will be able to return to work, adhere to a complicated medication regimen, or safely drive a vehicle will be discussed. Methodological issues that arise in the context of measuring medication adherence or driving capacity are also explored. Finally, the impact of HIV/AIDS on mood state, fatigue, and interpersonal relationships are addressed, with particular emphasis on how these variables interact with cognition and independent functioning. The purpose of this review is to integrate neuropsychological findings with their real world correlates of functional behavior in the HIV/AIDS population.

Pattern of varicella and associated complications in children in Unite Arab Emirates: 5-year descriptive study.

The objective of this study was to characterize the epidemiology of varicella and varicella-associated complications in Al-Ain, United Arab Emirates (UAE) during 2000-04. The annual number of reported cases varied from 373 to 790 per 100 000 population. Most (89%) occurred in children < 15 years old. Of 187 children requiring hospital admission, 50.3% had febrile illness due to secondary bacterial infection and 17.6% had neurological complications. The overall mortality rate among hospitalized children was 1.1%, all due to invasive group A Streptococcus. Varicella and associated complications in previously healthy children is becoming an important clinical and public health problem in the UAE.

Molecular analysis of cerebrospinal fluid in viral diseases of the central nervous system.

The use of nucleic acid (NA) amplification techniques has transformed the diagnosis of viral infections of the central nervous system (CNS). Because of their enhanced sensitivity, these methods enable detection of even low amounts of viral genomes in cerebrospinal fluid. Following more than 10 years of experience, the polymerase chain reaction or other NA-based amplification techniques are nowadays performed in most diagnostic laboratories and have become the test of choice for the diagnosis of several viral CNS infections, such as herpes encephalitis, enterovirus meningitis and other viral infections occurring in human immunodeficiency virus-infected persons. Furthermore, they have been useful to establish a viral etiology in neurological syndromes of dubious origin and to recognise unusual or poorly characterised CNS diseases. Quantitative methods have provided a valuable additional tool for clinical management of these diseases, whereas post-amplification techniques have enabled precise genome characterisation. Current efforts are aiming at further improvement of the diagnostic efficiency of molecular techniques, their speed and standardisation, and to reduce the costs. The most relevant NA amplification strategies and clinical applications of to date will be the object of this review.