Impact of COVID­19 infection in patients with neurodegenerative diseases with particular focus on Alzheimer's and Parkinson's disease.

Neurodegenerative disorders (NDD) are chronic neurological diseases characterized by loss and/or damage to neurons along with the myelin sheath, and patients are at higher risk of severe infection with the SARS­CoV­2. A comprehensive literature search was performed using relevant terms and inclusion­exclusion criteria. Recent articles, subjects older than 50 years, and articles written in the English language were included, whereas letters to the editor and articles related to pregnant women were excluded from the review study. COVID­19 appears to damage angiotensin­II receptors which cause natural killer cells to lose the ability to clear virus­infected cells, owing to worse outcomes in patients with NDD. COVID­19 can worsen the symptoms of Alzheimer's disease. In addition, COVID­19 worsens drug­responsive motor symptoms in Parkinson's disease (PD) and other symptoms like fatigue and urinary complaints. Vitamin D is essential in decreasing pro­inflammatory and increasing anti­inflammatory cytokines in ongoing COVID­19 infections and reducing angiotensin receptors and, hence, decreasing COVID­19 infection severity. Telemedicine shows promise for patients with NDD but is yet to overcome legal issues and personal barriers. COVID­19 has a significant effect on neurodegenerative conditions, which appears partly to the nature of the NDD and the neuro­invasive capabilities of the SARS­CoV­2. The protective role of vitamin D in patients with NDD further supports this hypothesis. Modifications in current health care, like the telemedicine platform, are required to address the increased risk of serious infection in this population. Further studies will be required to clarify conflicting reports in many fields.

Aminoadamantanes: from treatment of Parkinson's and Alzheimer's disease to symptom amelioration of long COVID-19 syndrome?

INTRODUCTION: The aminoadamantanes amantadine and memantine are well known. They mainly act as N-methyl-D-aspartate antagonists. AREAS COVERED: The antiviral drug amantadine moderately ameliorates impaired motor behavior in patients with Parkinson's disease. Memantine provides beneficial effects on memory function in patients with advanced Alzheimer's disease already treated with acetylcholine esterase inhibitors. Both compounds counteract impaired monoamine neurotransmission with associated symptoms, such as depression. They improve vigilance, lack of attention and concentration, fatigue syndromes according to clinical findings in patients with chronic neurodegenerative processes. Their extrasynaptic N-methyl-D-Aspartate receptor blockade weakens a prolonged influx of Ca2+ ions as the main responsible components of neuronal excitotoxicity. This causes neuronal dying and associated functional deficits. EXPERT OPINION: We suggest aminoadamantanes as future therapies for amelioration of short- and long-term consequences of a COVID 19 infection. Particularly the extended-release amantadine formulations will be suitable. They showed better clinical efficacy compared with the conventional available compounds. Amantadine may particularly be suitable for amelioration of fatigue or chronic exhaustion, memantine for improvement of cognitive deficits. Clinical research in patients, who are affected by the short- and long-term consequences of a COVID 19 infection, is warranted to confirm these still hypothetical putative beneficial effects of aminoadamantanes.

The drugs amantadine and memantine are known as aminoadamantanes. Amantadine improves motor skills in patients with Parkinson's disease. It also reduces fatigue in individuals suffering from multiple sclerosis. Memantine improves memory dysfunction linked to Alzheimer's disease. Aminoadamantanes affect communication between nerve cells by supporting neurotransmission of monoamines. Clinical studies have found that these drugs benefit patients with chronic neurodegenerative diseases, who have depression, fatigue, loss of attention or concentration deficits. These brain function problems may also appear to some extent due to COVID-19 infection. We suggest that aminoadamantanes could improve these problems in COVID-19 patients in both the short and long term. Clinical research is needed to confirm this hypothesis.

Morbidity and severity of COVID-19 in patients with Parkinson's disease treated with amantadine - A multicenter, retrospective, observational study.

BACKGROUND: After more than 2 years of the pandemic, effective treatment for COVID-19 is still under research. In recent months, publications hypothesized amantadine's potential beneficial effect on SARS-CoV-2 infection. OBJECTIVE: To compare the groups of Parkinson's Disease (PD) patients who were administered amantadine chronically and those who did not take this medication in the context of the incidence and severity of COVID-19 infection. METHODS: An observational, retrospective, multicenter cohort study was conducted among consecutive patients with idiopathic PD. The structured questionnaires were completed during the patient's follow-up visits at the Outpatient Clinic or during hospitalization. The questionnaire included the following informations: patient's age, duration of PD, Hoehn-Yahr (H-Y) stage, comorbidities, medications, COVID-19 confirmed by reverse transcription polymerase chain reaction (RT-PCR) swab test for SARS-CoV-2 with specified symptoms and their severity (home or hospital treatment). The vaccination status was verified as well. RESULTS: Five hundred fifty-two (n = 552) patients participated in the study - 329 men (60%). The mean H-Y stage was 2.44 (range: 1-4) and the mean duration of PD was 9.6 years (range: 1-34). One hundred four subjects (19%) had confirmed COVID-19 infection. Subjects over 50 years of age had a significantly lower incidence of COVID-19 (17% vs 38%, p = 0.0001) with difference also in mean H-Y stage (2.27 vs 2.49; p = 0.011) and disease duration (8.4 vs 9.9 years, p = 0.007). There were no differences between patients with and without co-morbidities. In the whole analyzed group 219 (40%) subjects were treated with amantadine. Comparing COVID-19 positive and negative patients, amantadine was used by 48/104 (46%) and 171/448 (38%) respectively. 22% of patients on amantadine vs. 17% of patients without amantadine developed COVID-19. These differences were not significant. There were no differences in morbidity and severity of COVID-19 between amantadine users and non-users as well. CONCLUSIONS: COVID-19 was less common in older (>50) with longer duration and more advanced patients. Amantadine did not affect the risk of developing COVID-19 or the severity of infection.

Deep brain stimulation in Parkinson's disease: state of the art and future perspectives.

For more than 30 years, Deep Brain Stimulation (DBS) has been a therapeutic option for Parkinson's disease (PD) treatment. However, this therapy is still underutilized mainly due to misinformation regarding risks and clinical outcomes. DBS can ameliorate several motor and non-motor symptoms, improving patients' quality of life. Furthermore, most of the improvement after DBS is long-lasting and present even in advanced PD. Adequate patient selection, precise electric leads placement, and correct DBS programming are paramount for good surgical outcomes. Nonetheless, DBS still has many limitations: axial symptoms and signs, such as speech, balance and gait, do not improve to the same extent as appendicular symptoms and can even be worsened as a direct or indirect consequence of surgery and stimulation. In addition, there are still unanswered questions regarding patient's selection, surgical planning and programming techniques, such as the role of surgicogenomics, more precise imaging-based lead placement, new brain targets, advanced programming strategies and hardware features. The net effect of these innovations should not only be to refine the beneficial effect we currently observe on selected symptoms and signs but also to improve treatment resistant facets of PD, such as axial and non-motor features. In this review, we discuss the current state of the art regarding DBS selection, implant, and programming, and explore new advances in the DBS field.

Covid-19 and Parkinson's disease: Nursing care, vaccination and impact on advanced therapies.

The Coronavirus Disease 2019 (Covid-19) pandemic has created many challenges for the Parkinson's Disease (PD) care service delivery, which has been established over the past decades. The need for rapid adjustments to the new conditions has highlighted the role of technology, which can act as an enabler both in patient-facing aspects of care, such as clinical consultations, as well as in professional development and training. The Parkinson's Disease Nurse Specialists (PNSs) play a vital role in the effective management of people with PD (PwP). Maintaining optimum functionality and availability of device aided therapies is essential in order to ensure patients' quality of life. PwP are particularly recommended to use vaccination as a basic protection from the virus. The long-term consequences of this pandemic on PwP are highly uncertain, and education, support and reassurance of patients and their families may help ease their burden.

Long-term safety, discontinuation and mortality in an Italian cohort with advanced Parkinson's disease on levodopa/carbidopa intestinal gel infusion.

INTRODUCTION: Levodopa/carbidopa intestinal gel (LCIG) is an effective treatment in patients with advanced Parkinson's disease (PD) with consolidated evidence of clinical efficacy. However, only few studies have assessed long-term safety, causes of discontinuation, mortality, and relative predictors. METHODS: We conducted a retrospective analysis of 79 PD patients treated with LCIG between 2005 and 2020 in two Italian Neurological Centers, recording all adverse events (AEs), including weight loss (WL). Kaplan-Meier curve was used to estimate the time to discontinuation and survival. Cox proportional hazard model was employed to identify predictors of discontinuation and mortality, while Pearson's correlation was used to analyze predictors of WL. RESULTS: The average follow-up was 47.7 ± 40.5 months and the median survival from disease onset was 25 years. There were three cases of polyradiculoneuropathy Guillain-Barre syndrome-like, all occurred in the early years of LCIG treatment. Twenty-five patients died (32%), 18 on LCIG (including one suicide) and seven after discontinuation. The mean WL was 3.62 ± 7.5 kg, which correlated with levodopa dose at baseline (p = 0.002), levodopa equivalent daily dose (LEDD) baseline (p = 0.017) and off-duration (p = 0.0014), but not dyskinesia. Peristomal complications emerged as a negative predictor of discontinuation (p = 0.008). CONCLUSIONS: LCIG has a relatively satisfactory long-term safety profile and efficacy and a relatively low rate of discontinuation. Peristomal complications may represent a predictor of longer duration of therapy. According to the mortality analysis, LCIG patients show a long lifespan. Delaying the initiation of LCIG does not affect the sustainability of LCIG therapy.

D2/D3 Receptor Agonism: Paving the Way for a New Therapeutic Target for Taste Disorders in Parkinson's Disease and Other Conditions?

Chemosensory (i.e., olfaction and taste) dysfunction is common in neurodegenerative (e.g., Parkinson's disease, Alzheimer's disease, and dementia), psychiatric (e.g., depression, bipolar disorders, other conditions), and postinfectious (i.e., long COVID) diseases and in the elderly. Despite its impact on patients' quality of life, no established treatment for taste disorders exists so far. A recent report on the effect of pramipexole, a D2/D3 agonist, on taste performance in healthy participants provides support for a new potential therapeutic target for taste dysfunction to be tested in future randomized, placebo-controlled, clinical trials across several populations reporting gustatory symptoms.

Trial of Cinpanemab in Early Parkinson's Disease.

BACKGROUND: Aggregated α-synuclein plays an important role in Parkinson's disease pathogenesis. Cinpanemab, a human-derived monoclonal antibody that binds to α-synuclein, is being evaluated as a disease-modifying treatment for Parkinson's disease. METHODS: In a 52-week, multicenter, double-blind, phase 2 trial, we randomly assigned, in a 2:1:2:2 ratio, participants with early Parkinson's disease to receive intravenous infusions of placebo (control) or cinpanemab at a dose of 250 mg, 1250 mg, or 3500 mg every 4 weeks, followed by an active-treatment dose-blinded extension period for up to 112 weeks. The primary end points were the changes from baseline in the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) total score (range, 0 to 236, with higher scores indicating worse performance) at weeks 52 and 72. Secondary end points included MDS-UPDRS subscale scores and striatal binding as assessed on dopamine transporter single-photon-emission computed tomography (DaT-SPECT). RESULTS: Of the 357 enrolled participants, 100 were assigned to the control group, 55 to the 250-mg cinpanemab group, 102 to the 1250-mg group, and 100 to the 3500-mg group. The trial was stopped after the week 72 interim analysis owing to lack of efficacy. The change to week 52 in the MDS-UPDRS score was 10.8 points in the control group, 10.5 points in the 250-mg group, 11.3 points in the 1250-mg group, and 10.9 points in the 3500-mg group (adjusted mean difference vs. control, -0.3 points [95% confidence interval {CI}, -4.9 to 4.3], P = 0.90; 0.5 points [95% CI, -3.3 to 4.3], P = 0.80; and 0.1 point [95% CI, -3.8 to 4.0], P = 0.97, respectively). The adjusted mean difference at 72 weeks between participants who received cinpanemab through 72 weeks and the pooled group of those who started cinpanemab at 52 weeks was -0.9 points (95% CI, -5.6 to 3.8) for the 250-mg dose, 0.6 points (95% CI, -3.3 to 4.4) for the 1250-mg dose, and -0.8 points (95% CI, -4.6 to 3.0) for the 3500-mg dose. Results for secondary end points were similar to those for the primary end points. DaT-SPECT imaging at week 52 showed no differences between the control group and any cinpanemab group. The most common adverse events with cinpanemab were headache, nasopharyngitis, and falls. CONCLUSIONS: In participants with early Parkinson's disease, the effects of cinpanemab on clinical measures of disease progression and changes in DaT-SPECT imaging did not differ from those of placebo over a 52-week period. (Funded by Biogen; SPARK ClinicalTrials.gov number, NCT03318523.).

Depression in Patients with Parkinson's Disease: Current Understanding of its Neurobiology and Implications for Treatment.

Depression is one of the most frequent and burdensome non-motor symptoms in Parkinson's disease (PD), across all stages. Even when its severity is mild, PD depression has a great impact on quality of life for these patients and their caregivers. Accordingly, accurate diagnosis, supported by validated scales, identification of risk factors, and recognition of motor and non-motor symptoms comorbid to depression are critical to understanding the neurobiology of depression, which in turn determines the effectiveness of dopaminergic drugs, antidepressants and non-pharmacological interventions. Recent advances using in vivo functional and structural imaging demonstrate that PD depression is underpinned by dysfunction of limbic networks and monoaminergic systems, depending on the stage of PD and its associated symptoms, including apathy, anxiety, rapid eye movement sleep behavior disorder (RBD), cognitive impairment and dementia. In particular, the evolution of serotonergic, noradrenergic, and dopaminergic dysfunction and abnormalities of limbic circuits across time, involving the anterior cingulate and orbitofrontal cortices, amygdala, thalamus and ventral striatum, help to delineate the variable expression of depression in patients with prodromal, early and advanced PD. Evidence is accumulating to support the use of dual serotonin and noradrenaline reuptake inhibitors (desipramine, nortriptyline, venlafaxine) in patients with PD and moderate to severe depression, while selective serotonin reuptake inhibitors, repetitive transcranial magnetic stimulation and cognitive behavioral therapy may also be considered. In all patients, recent findings advocate that optimization of dopamine replacement therapy and evaluation of deep brain stimulation of the subthalamic nucleus to improve motor symptoms represents an important first step, in addition to physical activity. Overall, this review indicates that increasing understanding of neurobiological changes help to implement a roadmap of tailored interventions for patients with PD and depression, depending on the stage and comorbid symptoms underlying PD subtypes and their prognosis.

Clozapine Use in a Movement Disorder Clinic.

BACKGROUND: Clozapine is an effective antipsychotic for Parkinson's disease (PD) that does not worsen motor function and can improve tremor. It is approved for PD psychosis in Europe and Australia. OBJECTIVE: The aim of this study was to report on the use of clozapine in a movement disorder clinic. METHODS: We report on patients monitored during the COVID-19 pandemic in clinic over a 7-month period. RESULTS: Sixty-five patients were seen, of whom 50 had PD. Thirty-one were treated for psychosis, 18 for refractory tremor and 1 for levodopa dyskinesias. The remainder had psychotic symptoms with dementia with Lewy bodies (n = 2) or other movement disorders. Four had clozapine discontinued because of sedation and 1 for agranulocytosis. Three had clozapine temporarily halted because of granulocytopenia but were rechallenged successfully. CONCLUSIONS: When comparing clozapine use in this clinic as compared with others, we deduce that clozapine is likely significantly underutilized in the United States.

Parkinson's Disease Drug Therapies in the Clinical Trial Pipeline: 2022 Update.

BACKGROUND: As the international community dealt with the ongoing COVID-19 pandemic, important progress continued to be made in the development of new drug-based therapies for the neurodegenerative condition of Parkinson's disease (PD) in 2021. This progress included both "symptomatic treatments" (ST - improves/reduces symptoms of the condition) and "disease modifying treatments" (DMT - attempts to delay/slow progression by addressing the underlying biology of PD), which can be categorised further based on their mechanisms of action and class of drug. OBJECTIVE: This report continues previous efforts to provide an overview of the pharmacological therapies - both ST and DMT - in clinical trials for PD during 2021- 2022, with the aim of creating greater awareness and involvement in the clinical trial process. We also hope to stimulate collaboration amongst all stakeholders, including industry, academia, advocacy organizations, and most importantly patient community. METHODS: We conducted a review of clinical trials of drug therapies for PD using trial data obtained from the ClinicalTrials.gov and World Health Organisation (WHO) registries, and performed a breakdown analysis of studies that were active as of January 31st 2022. We also assessed active drug development projects that had completed one clinical phase but were yet to start the next. RESULTS: There was a total of 147 clinical trials registered on the ClinicalTrials.gov website as active during the period of analysis. Of these trials, 91 (62%)were investigating STs, while 56 (38%)focused on DMTs. Approximately 1/3 of the studies (34.7%; 51 trials) were in Phase 1, while over half of the trials were in Phase 2 (50.3%; 74 trials). Only 15% (22 trials) of the studies were in Phase 3, of which only 3 trials were evaluating DMTs. Novel therapeutics (42%)were the most common type of agents being tested across all phases of testing, followed by repurposed agents (34%)and reformulations (20%). CONCLUSION: Despite significant global health constraints, the development of new drug-based therapies for PD continued in 2021. Hopefully with a shift towards a post-pandemic world in which COVID-19 is better managed, we will see an increase in the number of clinical trials focused on drug development for PD. The need for more Phase 3 studies for DMTs remains acute.

The Protective Effect of a Unique Mix of Polyphenols and Micronutrients against Neurodegeneration Induced by an In Vitro Model of Parkinson's Disease.

Parkinson's disease (PD) is second-most common disabling neurological disorder worldwide, and unfortunately, there is not yet a definitive way to prevent it. Polyphenols have been widely shown protective efficacy against various PD symptoms. However, data on their effect on physio-pathological mechanisms underlying this disease are still lacking. In the present work, we evaluated the activity of a mixture of polyphenols and micronutrients, named A5+, in the murine neuroblastoma cell line N1E115 treated with 6-Hydroxydopamine (6-OHDA), an established neurotoxic stimulus used to induce an in vitro PD model. We demonstrate that a pretreatment of these cells with A5+ causes significant reduction of inflammation, resulting in a decrease in pro-inflammatory cytokines (IFN-γ, IL-6, TNF-α, and CXCL1), a reduction in ROS production and activation of extracellular signal-regulated kinases (ERK)1/2, and a decrease in apoptotic mechanisms with the related increase in cell viability. Intriguingly, A5+ treatment promoted cellular differentiation into dopaminergic neurons, as evident by the enhancement in the expression of tyrosine hydroxylase, a well-established dopaminergic neuronal marker. Overall, these results demonstrate the synergic and innovative efficacy of A5+ mixture against PD cellular pathological processes, although further studies are needed to clarify the mechanisms underlying its beneficial effect.

Comprehensive telemedicine solution for remote monitoring of Parkinson's disease patients with orthostatic hypotension during COVID-19 pandemic.

OBJECTIVE: Orthostatic hypotension (OH) represents a frequent but under-recognized phenomenon in Parkinson's disease (PD). During COVID-19 pandemic, Information and Communication Technologies (ICT) have become pivotal in the management of chronic diseases like PD, not only to assess motor impairment, but also for vital signs monitoring. This pilot study aimed to propose a real-time remote home-monitoring system and protocol for PD patients with OH. METHODS: Vital parameters were acquired by wireless devices and transmitted to an ICT platform, providing data and smart notifications to the healthcare provider through an interactive web portal. Eight patients with idiopathic PD and OH underwent 5-day monitoring. Data about OH episodes, therapeutic interventions, impact on daily activities, and patient satisfaction were collected and analyzed. RESULTS: The proposed solution allowed the identification of 65 OH episodes and subsequent medical interventions. Thirty-five episodes were asymptomatic, especially in the postprandial and in the afternoon recordings. Systolic-blood-pressure (SBP) and diastolic-blood-pressure (DBP) were significantly lower in symptomatic episodes, while the pressure drops resulted significantly higher in presence of symptoms. High usability and patient satisfaction scores were observed. CONCLUSION: The proposed home-monitoring system and protocol have proved to provide useful information and to allow prompt interventions in the management of PD patients with OH during COVID-19 pandemic.

[Risk and course of COVID-19 in patients with Parkinson's disease]. / Risk razvitiya i techenie COVID-19 u patsientov s bolezn'yu Parkinsona.

The article provides an overview of the data on the impact of Parkinson's disease on the risk of infection and the course of COVID-19, and also assesses the possible pathogenetic relationship between the SARS-CoV-2 virus, COVID-19 and PD. By penetrating the central nervous system, SARS-CoV-2 can cause not only neurological symptoms, but also exacerbate the course of an existing neurological disease. The impact of Parkinson's disease on the risk of infection and the course of COVID-19 is controversial. However, a number of authors support the opinion that PD is an anti-risk factor for the development of COVID-19, which is associated both with the pathogenesis of the disease and with the used antiparkinsonian drugs, in particular amantadines. There are no clear data indicating higher risk of infection and higher severity of COVID-19 in patients with PD. On the contrary, experimental and clinical data suggest a possible modifying role of α-synuclein and antiparkinsonian drugs.

Parkinson's Disease Drug Therapies in the Clinical Trial Pipeline: 2021 Update.

BACKGROUND: Despite the COVID-19 pandemic, there has been considerable activity in the clinical development of novel and improved drug-based therapies for the neurodegenerative condition of Parkinson's disease (PD) during 2020. The agents that were investigated can be divided into "symptomatic" (alleviating the features of the condition) and "disease modifying" (attempting to address the underlying biology of PD) treatments, ST and DMT respectively, with further categorisation possible based on mechanism of action and class of therapy. OBJECTIVE: Our goal in this report was to provide an overview of the pharmacological therapies -both ST and DMT - in clinical trials for PD during 2020-2021, with the aim of creating greater awareness and involvement in the clinical trial process. We also hope to stimulate collaboration amongst commercial and academic researchers as well as between the research and patient communities. METHODS: We conducted a review of clinical trials of drug therapies for PD using trial data obtained from the ClinicalTrials.gov and World Health Organisation (WHO) registries, and performed a breakdown analysis of studies that were active as of February 18th 2021. We also assessed active drug development projects that had completed one clinical phase but were yet to start the next. RESULTS: We identified 142 trials on ClinicalTrials.gov and 14 studies on the WHO registries that met our analysis criteria. Of these 156 trials, 91 were ST and 65 were DMT, Of the 145 trials registered on ClinicalTrials.gov in our 2020 analysis, 45 fell off the list and 42 were added. Despite this change, the balance of ST to DMT; the distribution across phases; the profile of therapeutic categories; and the proportion of repurposed therapies (33.5%); all remained very similar. There are only two DMTs in phase 3, and we identified 33 in-between-phase projects. CONCLUSIONS: Despite the effects of the coronavirus pandemic, investment and effort in clinical trials for PD appears to remain strong. There has been little change in the profile of the clinical trial landscape even though, over the past year, there has been considerable change to the content of the list.

COVID-19 in Parkinson's disease: what holds the key?

INTRODUCTION: Parkinson's disease (PD) is more frequent in the elderly and increases the risk of respiratory infections. Previous data on PD and SARS-CoV-2 are scarce, suggesting a poor prognosis in advanced disease and second-line therapies. METHODS: A retrospective case-control study comparing patients with PD and COVID-19 and patients with PD without COVID-19 was conducted during the pandemic period in Spain (March 1st-July 31st 2020) in a tertiary university hospital. RESULTS: Thirty-nine (COVID-19 +) and 172 (COVID-19-) PD patients were included. Fifty-nine percent were males in both groups, with similar age (75.9 ± 9.0 COVID-19 + , 73.9 ± 10.0 COVID-19-), disease duration (8.9 ± 6.2 COVID-19 + , 8.5 ± 5.6 COVID-19-) and PD treatments. COVID-19 was mild in 10 (26%), required admission in 21 (54%) and caused death in 8 (21%) patients. Dementia was the only comorbidity more frequent in COVID-19 + patients (36% vs. 14%, p = 0.0013). However, in a multivariate analysis, institutionalization was the only variable associated with COVID-19 + (OR 17.0, 95% CI 5.0-60.0, p < 0.001). When considering severe COVID-19 (admission or death) vs. mild or absent COVID-19, institutionalization, neoplasm, dementia and a lower frequency of dopamine agonists were associated with severe COVID-19. In multivariate analysis, only institutionalization [OR 5.17, 95% CI 1.57-17, p = 0.004] and neoplasm [OR 8.0, 95%CI 1.27-49.8, p = 0.027] remained significantly associated. CONCLUSION: In our experience, institutionalization and oncologic comorbidity, rather than PD-related variables, increased the risk of developing COVID-19, and impacted on its severity. These findings suggest that epidemiologic factors and frailty are key factors for COVID-19 morbidity/mortality in PD. Appropriate preventive strategies should be implemented in institutionalized patients to prevent infection and improve prognosis.