Reader response: Neurologic manifestations in hospitalized patients with COVID-19: The ALBACOVID registry

Coronavirus disease-2019 (COVID-19) is primarily a respiratory disease, however, an increasing number of reports indicate that SARS-CoV-2 infection can also cause severe neurological manifestations, including precipitating cases of probable Parkinson's disease. As microglial NLRP3 inflammasome activation is a major driver of neurodegeneration, here we interrogated whether SARS-CoV-2 can promote microglial NLRP3 inflammasome activation. Using SARS-CoV-2 infection of transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) as a COVID-19 pre-clinical model, we established the presence of virus in the brain together with microglial activation and NLRP3 inflammasome upregulation in comparison to uninfected mice. Next, utilising a model of human monocyte-derived microglia, we identified that SARS-CoV-2 isolates can bind and enter human microglia in the absence of viral replication. This interaction of virus and microglia directly induced robust inflammasome activation, even in the absence of another priming signal. Mechanistically, we demonstrated that purified SARS-CoV-2 spike glycoprotein activated the NLRP3 inflammasome in LPS-primed microglia, in a ACE2-dependent manner. Spike protein also could prime the inflammasome in microglia through NF-κB signalling, allowing for activation through either ATP, nigericin or α-synuclein. Notably, SARS-CoV-2 and spike protein-mediated microglial inflammasome activation was significantly enhanced in the presence of α-synuclein fibrils and was entirely ablated by NLRP3-inhibition. Finally, we demonstrate SARS-CoV-2 infected hACE2 mice treated orally post-infection with the NLRP3 inhibitory drug MCC950, have significantly reduced microglial inflammasome activation, and increased survival in comparison with untreated SARS-CoV-2 infected mice. These results support a possible mechanism of microglial innate immune activation by SARS-CoV-2, which could explain the increased vulnerability to developing neurological symptoms akin to Parkinson's disease in COVID-19 infected individuals, and a potential therapeutic avenue for intervention. 

/pdf/sars-cov-2-drives-nlrp3-inflammasome-activation-in-human-2qq31oof.pdf

SARS-CoV-2 drives NLRP3 inflammasome activation in human microglia through spike protein.

Mental and neurological disorders and risk of COVID-19 susceptibility, illness severity and mortality: A systematic review, meta-analysis and call for action.

https://doi.org/10.1016/j.sjbs.2022.02.006

The Impact of COVID-19 On Comorbidities: A Review Of Recent Updates For Combating It

Parkinson's disease (PD) patients who contracted Coronavirus disease 2019 (Covid-19) had a decline in motor functions; nevertheless, there is limited evidence on whether PD patients have a higher risk for contracting Covid-19 or have worse outcomes. This is the first systematic review and meta-analysis to review the impact of PD on the prognosis of Covid-19 patients. We performed a systematic search through seven electronic databases under the recommendations of the Preferred Reporting Items for Systematic Review and Meta-analyses statement (PRISMA) guidelines. The R software version 4.0.2 was used to calculate pooled sample sizes and their associated confidence intervals (95%CI). Finally, we included 13 papers in this study. The pooled prevalence rate of Covid-19 was 2.12% (95%CI: 0.75-5.98). Fever, cough, fatigue and anorexia were the most common symptoms with a rate of 72.72% (95% CI: 57.3 - 92.29), 66.99% (95% CI: 49.08-91.42), 61.58% (95% CI: 46.69-81.21) and 52.55% (95% CI: 35.09-78.68), respectively. The pooled rates were 39.89% (95% CI: 27.09-58.73) for hospitalisation, 4.7% (95% CI: 1.56-14.16) for ICU admission and 25.1% (95%CI: 16.37-38.49) for mortality. On further comparison of hospitalisation and mortality rates among Covid-19 patients with and without PD, there were no significant differences. In conclusion, the prevalence and prognosis of Covid-19 patients seem comparable in patients with PD and those without it. The increased hospitalisation and mortality may be attributed to old age and co-morbidities.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/rmv.2278

The impact of Parkinson's disease on manifestations and outcomes of Covid-19 patients: A systematic review and meta-analysis.

Author(s): Brown, Ethan G; Chahine, Lana M; Goldman, Samuel M; Korell, Monica; Mann, Emerald; Kinel, Daniel R; Arnedo, Vanessa; Marek, Kenneth L; Tanner, Caroline M | Abstract: BackgroundThe effect of the COVID-19 pandemic on people with Parkinson's disease (PD) is poorly understood.ObjectiveTo rapidly identify areas of need and improve care in people with PD during the COVID-19 pandemic, we deployed a survey to assess COVID-19 symptoms and the pandemic's effect among those with and without COVID-19.MethodsPeople with and without PD participating in the online study Fox Insight (FI) were invited to complete a survey between April 23 and May 23, 2020. Among people reporting COVID-19 diagnoses, we compared symptoms and outcomes in people with and without PD. Among people not reporting COVID-19, we assessed access to healthcare and services and PD symptoms.Results7,209/9,762 active FI users responded (approximately 74% response rate), 5,429 people with PD and 1,452 without PD. COVID-19 diagnoses were reported by 51 people with and 26 without PD. Complications were more frequent in people with longer PD duration. People with PD and COVID-19 experienced new or worsening motor (63%) and nonmotor (75%) symptoms. People with PD not diagnosed with COVID-19 reported disrupted medical care (64%), exercise (21%), and social activities (57%), and worsened motor (43%) and non-motor (52%) symptoms. Disruptions were more common for those living alone, with lower income and non-White race.ConclusionsThe COVID-19 pandemic is associated with wide-ranging effects on people with PD, and certain groups may be at particular risk. FI provides a rapid, patient-centered means to assess these effects and identify needs that can be used to improve the health of people with PD.

/pdf/the-effect-of-the-covid-19-pandemic-on-people-with-parkinson-1dq9k3qab8.pdf

The Effect of the COVID-19 Pandemic on People with Parkinson's Disease.

Objective: To rapidly identify areas of need and improve care in people with Parkinson9s disease (PwPD) affected by the COVID-19 pandemic, we deployed a survey focusing on the presentation and complications of COVID-19 infection and the effect of the COVID-19 pandemic among those not infected.
Methods: Individuals with and without PD participating in the online study Fox Insight (FI) were invited to complete an online survey between April 23-May 23, 2020. Among people reporting COVID-19 diagnosis, we compared the frequency of symptoms and poor outcomes in people with and without PD. Among people not reporting COVID-19, we assessed the effects of the pandemic on access to medical care and other services, and in PwPD, its effects on PD symptoms. 
Results: Among 5,429 PwPD and 1,452 without PD, 77 reported a COVID-19 diagnosis (51 PwPD, 26 without PD). Complications were more frequent in people with longer PD duration. PwPD and COVID-19 experienced new or worsening motor (63%) and nonmotor (75%) PD symptoms. PwPD not diagnosed with COVID-19 reported disrupted medical care (64%), exercise (21%), and social activities (57%), and worsened PD motor (43%) and non-motor (52%) symptoms. Disruptions were more common for PwPD living alone, and for those with lower income and non-white race. 
Conclusions: The COVID-19 pandemic is associated with wide-ranging effects on people with PD, and certain groups may be at particular risk. FI provides a rapid, patient-centered means to assess these effects and identify needs that can be used to improve the health of PwPD.

/pdf/the-effect-of-the-covid-19-pandemic-on-people-with-parkinson-51cb4tku1x.pdf

The Effect of the COVID-19 Pandemic on People with Parkinson's Disease

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The Effect of the COVID-19 Pandemic on People with Parkinson's Disease.

The Effect of the COVID-19 Pandemic on People with Parkinson's Disease