Unravelling Pathophysiology of Neurological and Psychiatric Complications of COVID-19 Using Brain Organoids.

Neuropsychiatric manifestations of coronavirus disease 2019 (COVID-19) have been increasingly recognized. However, the pathophysiology of COVID-19 in the central nervous system remains unclear. Brain organoid models derived from human pluripotent stem cells are potentially useful for the study of complex physiological and pathological processes associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as they recapitulate cellular heterogeneity and function of individual tissues. We identified brain organoid studies that provided insight into the neurotropic properties of SARS-CoV-2. While SARS-CoV-2 was able to infect neurons, the extent of neurotropism was relatively limited. Conversely, choroidal epithelial cells consistently showed a high susceptibility to SARS-CoV-2 infection. Brain organoid studies also elucidated potential mechanism for cellular entry, demonstrated viral replication, and highlighted downstream cellular effects of SARS-CoV-2 infection. Collectively, they suggest that the neuropsychiatric manifestations of COVID-19 may be contributed by both direct neuronal invasion and indirect consequences of neuroinflammation. The use of high throughput evaluation, patient-derived organoids, and advent of "assembloids" will provide a better understanding and functional characterization of the neuropsychiatric symptoms seen in post-acute COVID-19 syndrome. With advancement of organoid technology, brain organoids offer a promising tool for unravelling pathophysiologic clues and potential therapeutic options for neuropsychiatric complications of COVID-19.

Impact of COVID-19 pandemic on patients with Parkinson's disease: A meta-analysis of 13,878 patients.

BACKGROUND: The clinical, neuropsychological, and socioeconomic factors affecting Parkinson's disease (PD) during COVID-19 pandemic across different populations have not been systematically studied. To address this, we conducted a meta-analysis of factors that impact the well-being of PD patients during the pandemic. METHODS: Medline and Embase were searched for articles published between 2020 and 2022. We conducted random-effects pooling of estimates and meta-regression. RESULTS: Twenty-seven studies involving 13,878 patients from America, Europe, Asia, and Africa were included. There is a high prevalence of decreased physical activity and exercise, and worsening motor and neuropsychiatric symptoms (17-56%). Patients in lower-income countries more frequently reported worsening anxiety (adjusted OR [aOR] 8.94, 95% confidence interval [CI] 1.62-49.28, p = 0.012), sleep (aOR 5.16, 95% CI 1.15-23.17, p = 0.032), and PD symptoms (aOR 3.57, 95% CI 0.96-13.34, p = 0.058). Lockdown was associated with decreased exercise levels (aOR 0.13, 95% CI 0.02-0.78, p = 0.025) and worsening mood (aOR 0.48, 95% CI 0.24-0.95, p = 0.035). Younger age correlated with decreased physical activity (ß -0.30, 95% CI -0.53 to -0.07, p = 0.012), exercise (ß -0.11, 95% CI -0.15 to -0.07, p < 0.001), worsening PD symptoms (ß -0.08, 95% CI -0.15 to -0.01, p = 0.018), and sleep (ß -0.14, 95% CI -0.27 to 0, p = 0.044). Female PD patients reported a greater decrease in physical activity (ß 11.94, 95% CI 2.17-21.71, p = 0.017) and worse sleep (ß 10.76, 95% CI 2.81-18.70, p = 0.008). CONCLUSION: This large meta-analysis of PD patients in diverse populations identified a high prevalence of physical and mental worsening during the COVID-19 pandemic, with patients in lower-income countries being exceptionally vulnerable.

Prognosis of Guillain-Barré Syndrome Linked to COVID-19 Vaccination.

There have been increasing reports of Guillain-Barré syndrome (GBS), a rare but debilitating neurological disease, occurring post-COVID-19 vaccination. However, the outcomes and relationships between patient demographics and clinical outcomes of post-COVID-19 vaccination GBS remain unclear. To bridge this gap, our study investigates the outcomes and clinical factors associated with poorer GBS outcomes following COVID-19 vaccination. We conducted a review and pooled analysis of detailed data extracted from 57 published cases with the relevant search strategies and criteria. The groups compared included male versus female patients, 1st dose versus 2nd dose and early onset versus late onset of GBS. Multivariate regression analysis was performed to compare the vaccine type, clinical severity and post-treatment outcomes between these groups of patients. Our results highlight for the first time that females were significantly more likely to have severe clinical presentation and poorer outcomes compared to males. Additionally, viral vector vaccines were the predominant vaccine type administered in early-onset post-COVID-19-vaccination GBS and GBS occurring after the 1st vaccination dose. It was also shown that reported cases of post-vaccination GBS generally displayed a positive response to conventional treatment and had favourable post-treatment outcomes. Through this study, we have established important links and provided assuring evidence for treatment response and post-treatment outcomes of GBS occurring post-COVID-19 vaccination. While the COVID-19 vaccination brings about much greater benefits than risks, our findings provide further impetus for greater vigilance in certain patient groups and more studies to explore the mechanisms behind these links.

Prognosis of Guillain–Barré Syndrome Linked to COVID-19 Vaccination

There have been increasing reports of Guillain–Barré syndrome (GBS), a rare but debilitating neurological disease, occurring post-COVID-19 vaccination. However, the outcomes and relationships between patient demographics and clinical outcomes of post-COVID-19 vaccination GBS remain unclear. To bridge this gap, our study investigates the outcomes and clinical factors associated with poorer GBS outcomes following COVID-19 vaccination. We conducted a review and pooled analysis of detailed data extracted from 57 published cases with the relevant search strategies and criteria. The groups compared included male versus female patients, 1st dose versus 2nd dose and early onset versus late onset of GBS. Multivariate regression analysis was performed to compare the vaccine type, clinical severity and post-treatment outcomes between these groups of patients. Our results highlight for the first time that females were significantly more likely to have severe clinical presentation and poorer outcomes compared to males. Additionally, viral vector vaccines were the predominant vaccine type administered in early-onset post-COVID-19-vaccination GBS and GBS occurring after the 1st vaccination dose. It was also shown that reported cases of post-vaccination GBS generally displayed a positive response to conventional treatment and had favourable post-treatment outcomes. Through this study, we have established important links and provided assuring evidence for treatment response and post-treatment outcomes of GBS occurring post-COVID-19 vaccination. While the COVID-19 vaccination brings about much greater benefits than risks, our findings provide further impetus for greater vigilance in certain patient groups and more studies to explore the mechanisms behind these links.

Impact of Covid-19 on research and training in Parkinson's disease.

The Coronavirus Disease 2019 (Covid-19) pandemic and the consequent restrictions imposed worldwide have posed an unprecedented challenge to research and training in Parkinson's disease (PD). The pandemic has caused loss of productivity, reduced access to funding, an oft-acute switch to digital platforms, and changes in daily work protocols, or even redeployment. Frequently, clinical and research appointments were suspended or changed as a solution to limit the risk of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) spread and infection, but since the care and research in the field of movement disorders had traditionally been performed at in-person settings, the repercussions of the pandemic have even been more keenly felt in these areas. In this chapter, we review the implications of this impact on neurological research and training, with an emphasis on PD, as well as highlight lessons that can be learnt from how the Covid-19 pandemic has been managed in terms of restrictions in these crucial aspects of the neurosciences. One of the solutions brought to the fore has been to replace the traditional way of performing research and training with remote, and therefore socially distanced, alternatives. However, this has introduced fresh challenges in international collaboration, contingency planning, study prioritization, safety precautions, artificial intelligence, and various forms of digital technology. Nonetheless, in the long-term, these strategies will allow us to mitigate the adverse impact on PD research and training in future crises.

Remote Prescription During Pandemic: Challenges and Solutions.

The current COVID-19 pandemic has created an awareness and at the same time provides an impetus to transform digitalisation of healthcare delivery. Remote prescription is one key component of telemedicine, but it is the easiest and already practised in most places during the current pandemic even without the framework of virtual medicine in place. However, remote prescription, with its antecedent problems cannot be properly and safely executed in isolation. To ensure patients' safety and health outcomes, specific guidelines will need to be developed to cater for specific medical conditions to address individual drug prescriptions and concerns. There is a need for a robust governance to ensure that patient's safety is the foremost priority, and provisions should be made for requirements of remote prescription in the different medical subspecialities. The pandemic provides an enormous opportunity for stakeholders and policymakers to come together to create a seamless and user friendly and yet innovative healthcare ecosystem to transform clinical healthcare delivery with patient safety as the core driver in the implementation.

Safeguarding Non-COVID-19 Research: Looking Up from Ground Zero.

The COVID-19 pandemic has kicked off a global race to launch clinical trials of experimental vaccines and treatments for the coronavirus. Worldwide, as resources are directed toward accelerating the research into unravelling the mechanism of COVID-19 pathophysiology, concerns have been raised regarding the future of clinical research in United Kingdom and elsewhere during the current pandemic. However, the real immediate impact of these restrictions due to lock-down is most acutely felt by scientists working on non-COVID-19 biomedical research bench and clinical researchers whose drug trials have to be delayed, suspended or ceased. Here, we highlight our views from "ground zero" as we represent those whose work are deeply affected by the restrictions. We draw attention to some of the practical realities and emotions experienced in the laboratory. In addition, we also highlight the difficulties for policy makers to maintain equanimity in prioritizing their decisions cross the different fields of science.