Brain autopsies of critically ill COVID-19 patients demonstrate heterogeneous profile of acute vascular injury, inflammation and age-linked chronic brain diseases.

BACKGROUND: This study examined neuropathological findings of patients who died following hospitalization in an intensive care unit with SARS-CoV-2. METHODS: Data originate from 20 decedents who underwent brain autopsy followed by ex-vivo imaging and dissection. Systematic neuropathologic examinations were performed to assess histopathologic changes including cerebrovascular disease and tissue injury, neurodegenerative diseases, and inflammatory response. Cerebrospinal fluid (CSF) and fixed tissues were evaluated for the presence of viral RNA and protein. RESULTS: The mean age-at-death was 66.2 years (range: 26-97 years) and 14 were male. The patient's medical history included cardiovascular risk factors or diseases (n = 11, 55%) and dementia (n = 5, 25%). Brain examination revealed a range of acute and chronic pathologies. Acute vascular pathologic changes were common in 16 (80%) subjects and included infarctions (n = 11, 55%) followed by acute hypoxic/ischemic injury (n = 9, 45%) and hemorrhages (n = 7, 35%). These acute pathologic changes were identified in both younger and older groups and those with and without vascular risk factors or diseases. Moderate-to-severe microglial activation were noted in 16 (80%) brains, while moderate-to-severe T lymphocyte accumulation was present in 5 (25%) brains. Encephalitis-like changes included lymphocytic cuffing (n = 6, 30%) and neuronophagia or microglial nodule (most prominent in the brainstem, n = 6, 30%) were also observed. A single brain showed vasculitis-like changes and one other exhibited foci of necrosis with ball-ring hemorrhages reminiscent of acute hemorrhagic leukoencephalopathy changes. Chronic pathologies were identified in only older decedents: 7 brains exhibited neurodegenerative diseases and 8 brains showed vascular disease pathologies. CSF and brain samples did not show evidence of viral RNA or protein. CONCLUSIONS: Acute tissue injuries and microglial activation were the most common abnormalities in COVID-19 brains. Focal evidence of encephalitis-like changes was noted despite the lack of detectable virus. The majority of older subjects showed age-related brain pathologies even in the absence of known neurologic disease. Findings of this study suggest that acute brain injury superimposed on common pre-existing brain disease may put older subjects at higher risk of post-COVID neurologic sequelae.

Higher ACE2 expression in the brains of individuals with Alzheimer’s disease

Background The emergence of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a major cause of death, particularly in the elderly. The geriatric population in which cognitive decline due to Alzheimer’s disease (AD) is frequent is disproportionately affected by the pandemic. In addition, central nervous system (CNS) manifestations have been reported in a significant subset of SARS‐CoV‐2 infected patients. Method Since the principal entry receptor utilized by SARS‐COV‐2 is Angiotensin‐Converting Enzyme 2 (ACE2), we examined whether ACE2 protein and mRNA levels were altered postmortem in parietal cortex samples from two different AD cohorts, totalling 142 cases. Results Both immunoblot and RT‐qPCR analysis revealed higher concentrations of ACE2 protein and mRNA in persons with a neuropathological diagnosis of AD, compared to age‐matched controls. Brain levels of ACE2 were inversely correlated with antemortem cognitive scores. We found that ACE2 protein was highly enriched in microvessels of mice compared to brain parenchyma, but not in humans. Detachment of ACE2 from brain cell membranes was strongly associated with pericytes loss. No significant change of ACE2 protein was detected in the parietal cortex from the 3xTg‐AD mouse model of AD neuropathology. Conclusion Our data suggest that cognitive impairment is associated with higher levels of ACE2 in the brain, which might contribute the higher risk of CNS SARS‐CoV‐2 infection in cognitively impaired individuals and AD patients.

Leveraging virtual reality to train certified nursing assistants as essential dementia-care personnel in the age of COVID-19.

BACKGROUND: COVID-19 has placed an extraordinary and disproportionate level of responsibility and risk on certified nursing assistants (CNAs) caring for persons with dementia (PWD) relative to their training, resources, and compensation levels. Nearly one-quarter of COVID-19 deaths in the United States have been nursing home residents and staff. Despite providing the majority of direct care, CNAs are amongst the most under-resourced and under-trained frontline workers. Given their essentiality, it is critical to support CNAs during the COVID-19 pandemic. The purpose of this work is to provide CNAs with a space to strengthen their knowledge and confidence in caring for PWD. This pilot study applies a virtual reality (VR) curriculum to train CNAs regarding the lived experiences of PWD and their loved ones. The VR vignette portrays a Latinx woman, Beatriz, through progressive stages of Alzheimer's disease. METHOD: Chicago Methodist Senior Services (CMSS) CNAs were recruited (N=7; 86% female, 86% Black) for a seven-week online training program consisting of 1.5 hours per week. Each class included a didactic lecture and an Embodied Labs VR module depicting a first-person experience of dementia through a distributive model approach. The program concluded with two recorded focus groups. Participants completed the UCLA Geriatric Attitudes Scale, a dementia knowledge assessment, the Interpersonal Reactivity Index surveys, and a COVID-19 Impact questionnaire. Current analyses include qualitative content analysis for focus group data and descriptive, quantitative statistics for pre-and post-VR intervention surveys. RESULT: Preliminary results demonstrate that CNAs endorsed a positive change in attitudes toward older adults (p=0.069), a deepened understanding of dementia, and increased confidence in caregiving skills. Focus groups allowed CNAs to discuss changes in resident behavior and support one another through a virtual platform during a global pandemic. CONCLUSION: Combining traditional didactic lectures with VR-based curricula provided CNAs with foundational knowledge and first-hand experience of dementia pathology. Participants reported greater levels of insight and empathy for PWD. Future aims include expansion of training content to include end-of-life conversations, LGBTQIA aging, and Lewy body dementia.

What HIV in the Brain Can Teach Us About SARS-CoV-2 Neurological Complications?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of COVID-19, a disease that as of July 10, 2020, has infected >12 million people and killed >500,000. COVID-19 infection leads to acute respiratory distress syndrome in a subset of patients and is a primary driver of acute morbidity in infected persons. However, it is becoming increasingly clear that SARS-CoV-2 infection drives dysfunction and pathology outside the lungs, including reports of renal, cardiac, and neurological complications. In this study, we summarize the known incidence and evidence of neurological complications associated with SARS-CoV-2 infection and other pathogenic coronaviruses. These studies describe a poorly understood spectrum of COVID-19 central nervous system symptoms, ranging from common and subclinical issues such as anosmia and headache to more concerning reports of stroke and encephalopathy. We discuss potential mechanisms of pathogenesis, including a discussion of how the understanding of neurological complications known to occur in HIV-1 patients may provide insight into SARS-CoV-2-associated neurological manifestations. Specifically, three hypotheses are discussed that are informed by decades of knowledge about HIV pathogenesis in the brain, which include a potential direct viral effect, an indirect viral effect, and/or a neuroimmune axis effect. Individually or in combination these potential effects may contribute to COVID-19 neurological complications.