novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged from Wuhan, China, in December 2019, resulting in a severe outbreak of pneumonia 1 ; SARS-CoV-2 causes a clinical syndrome, coronavirus disease 2019 (COVID-19), and its pulmonary manifestations have been well described. There is growing evidence of neurological complications and disease in patients with COVID-19. Two similar human coronaviruses (CoV), Middle East respiratory syndrome (MERS-CoV) and severe acute respiratory syndrome (SARS-CoV-1), have also been associated with neurological disease in rare cases. This raises the questions of whether SARS-CoV-2 is neurotropic and whether it contributes to postinfectious neurologic complications. A handful of case reports have described neurological complications in patients with COVID-19. 1-4 However, it remains unknown to what extent SARS-CoV-2 damages the central nervous system (CNS) or if neurological symptoms are attributable to secondary mechanisms. Search Strategy and Selection Criteria References for this review were identified by searches of PubMed from April to May 2020 for articles published between 1969 and April 2020, as well as references from relevant articles. The search terms COVID-19, SARS-CoV-2, SARS-CoV, MERS-CoV, HCoV-OC43, neurotropism, neuroinvasion, and coronavirus were used. There were no language restrictions. The final list of included articles was generated on the basis of relevance to the topics covered in this review. Neurotropic Coronaviruses Coronaviruses (CoV) are large, enveloped, positive-sense RNA viruses divided into 3 genera: alphacoronavirus, betacoronavirus, and gammacoronavirus. 5 These viruses infect humans and numerous animal species, generally causing upper or lower respiratory tract, IMPORTANCE Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019, causing human coronavirus disease 2019 (COVID-19), which has now spread into a worldwide pandemic. The pulmonary manifestations of COVID-19 have been well described in the literature. Two similar human coronaviruses that cause Middle East respiratory syndrome (MERS-CoV) and severe acute respiratory syndrome (SARS-CoV-1) are known to cause disease in the central and peripheral nervous systems. Emerging evidence suggests COVID-19 has neurologic consequences as well. OBSERVATIONS This review serves to summarize available information regarding coronaviruses in the nervous system, identify the potential tissue targets and routes of entry of SARS-CoV-2 into the central nervous system, and describe the range of clinical neurological complications that have been reported thus far in COVID-19 and their potential pathogenesis. Viral neuroinvasion may be achieved by several routes, including transsynaptic transfer across infected neurons, entry via the olfactory nerve, infection of vascular endothelium, or leukocyte migration across the blood-brain barrier. The most common neurologic complaints in COVID-19 are anosmia, ageusia, and headache, but other diseases, such as s...

Genetic defects in distinct domains of the nuclear-envelope proteins lamin A and lamin C selectively cause dilated cardiomyopathy with conduction-system disease or autosomal dominant Emery-Dreifuss muscular dystrophy. Missense mutations in the rod domain of the lamin A/C gene provide a genetic cause for dilated cardiomyopathy and indicate that this intermediate filament protein has an important role in cardiac conduction and contractility.

BackgroundCerebrospinal fluid (CSF) neurofilament light chain protein (NFL) is a sensitive marker of neuronal injury in a variety of neurodegenerative conditions, including the CNS dysfunction injury that is common in untreated HIV infection. However, an important limitation is the requirement for lumbar puncture. For this reason, a sensitive and reliable blood biomarker of CNS injury would represent a welcome advance in both clinical and research settings.MethodsTo explore whether plasma concentrations of NFL might be used to detect CNS injury in HIV infection, an ultrasensitive Single molecule array (Simoa) immunoassay was developed. Using a cross-sectional design, we measured NFL in paired CSF and plasma samples from 121 HIV-infected subjects divided into groups according to stage of their systemic disease, presence of overt HIV-associated dementia (HAD), and after antiretroviral treatment (ART)-induced viral suppression. HIV-negative controls were also examined.FindingsPlasma and CSF NFL concentrations were very highly correlated (r = 0.89, P < 0.0001). While NFL was more than 50-fold lower plasma than CSF it was within the quantifiable range of the new plasma assay in all subjects, including the HIV negatives and the HIV positives with normal CSF NFL concentrations. The pattern of NFL changes were almost identical in plasma and CSF, both exhibiting similar age-related increases in concentrations along with highest values in HAD and substantial elevations in ART-naïve neuroasymptomatic subjects with low blood CD4+ T cells.InterpretationThese results show that plasma NFL may prove a valuable tool to evaluate ongoing CNS injury in HIV infection that may be applied in the clinic and in research settings to assess the presence if active CNS injury. Because CSF NFL is also elevated in a variety of other CNS disorders, sensitive measures of plasma NFL may similarly prove useful in other settings.

CSF HIV RNA was detectable in humans as early as 8 days after exposure. CNS inflammation was apparent by CSF analysis and MRS in some individuals during acute HIV infection.