COVID-19 outcomes in hospitalized Parkinson's disease patients in two pandemic waves in 2020: a nationwide cross-sectional study from Germany.

BACKGROUND: The individualized clinical and public health management of the COVID-19 pandemic have changed over time, including care of people with PD. The objective was to investigate whether in-hospital COVID-19 outcomes and hospital care utilization of people with PD differed between the first two pandemic waves (W) 2020 in Germany. METHODS: We conducted a nationwide cross-sectional study of inpatients with confirmed COVID-19 and PD between March 1 and May 31 (W1), and October 1 and December 31 (W2), 2020 and 2019, using an administrative database. Outcomes were in-hospital mortality, ICU admission rate, change in hospital care utilization, demographical data, PD clinical characteristics, and selected comorbidities. Differences were assessed between waves, PD/non-PD groups, and years. RESULTS: We identified 2600 PD COVID-19 inpatients in W2 who in total showed higher in-hospital mortality rates and lower ICU admission rates, compared to both W1 (n = 775) and W1/W2 non-PD COVID-19 inpatients (n = 144,355). Compared to W1, W2 inpatients were more long-term care-dependent, older, more of female sex, and had less advanced disease. During both waves, PD inpatients were older, more frequently male and long-term care-dependent, and showed more risk comorbidities than non-PD COVID-19 inpatients. Decreases in hospital care utilization were stronger than average for PD inpatients but relatively weaker during W2. Non-COVID-19 PD inpatients showed poorer in-hospital outcomes in 2020 than in 2019 with better outcomes during W2. CONCLUSIONS: In-hospital COVID-19 outcomes and hospital care utilization of PD patients in Germany differed between the two pandemic waves in 2020 with increased in-hospital mortality for PD COVID-19. Overall hospital care utilization for PD was increased during W2. TRIAL REGISTRATION: No trial registration or ethical approval was required because data were publicly available, anonymized, and complied with the German data protection regulations.

Hypoechogenicity of brainstem raphe in long-COVID syndrome-less common but independently associated with depressive symptoms: a cross-sectional study.

OBJECTIVE: Long coronavirus disease (Long-COVID) syndrome is a hitherto poorly understood phenomenon with a broad spectrum of symptoms, including depression and anxiety. Depressive symptoms have been associated with brainstem raphe (BR) alterations in transcranial sonography (TCS) that might reflect dysfunction of the serotonergic system. The primary aim was to investigate the connection of BR alterations with depressive and anxiety symptoms in patients with Long-COVID syndrome. METHODS: In a cross-sectional study design, we included outpatients fulfilling the criteria of Long-COVID syndrome. All patients were examined by TCS in the axial plane with focus on BR signal alterations. The Hospital Anxiety and Depression Scale (HADS) was used to test for symptoms of anxiety and depression. RESULTS: We included n = 70 patients with Long-COVID syndrome, of which 28.6% (n = 20) exhibited a reduced echogenicity of BR in the TCS examination. Patients with hypoechogenic BR had higher subscores for anxiety and depression compared to normoechogenic patients (HADS depression: median 8 versus 5.5, p = 0.006; HADS anxiety: median 9 versus 6.5, p = 0.006). After adjustment for reasonable confounders, only the odds ratio (OR) for relevant depressive symptoms was higher among Long-COVID patients with hypoechogenic raphe (adjusted OR 3.884, 95% CI 1.244-12.123). DISCUSSION: Hypoechogenic BR alterations are independently associated with depressive symptoms in Long-COVID patients but are not highly frequent. Future studies should investigate whether the hypoechogenicity of the BR is a direct consequence or whether it reflects a priori a higher susceptibility to depressive symptoms after COVID-19, thus enabling to identify COVID-19 patients at higher risk of developing Long-COVID depressive symptoms.

Neurological manifestations of long-COVID syndrome: a narrative review.

Accumulating evidence points toward a very high prevalence of prolonged neurological symptoms among coronavirus disease 2019 (COVID-19) survivors. To date, there are no solidified criteria for 'long-COVID' diagnosis. Nevertheless, 'long-COVID' is conceptualized as a multi-organ disorder with a wide spectrum of clinical manifestations that may be indicative of underlying pulmonary, cardiovascular, endocrine, hematologic, renal, gastrointestinal, dermatologic, immunological, psychiatric, or neurological disease. Involvement of the central or peripheral nervous system is noted in more than one-third of patients with antecedent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, while an approximately threefold higher incidence of neurological symptoms is recorded in observational studies including patient-reported data. The most frequent neurological manifestations of 'long-COVID' encompass fatigue; 'brain fog'; headache; cognitive impairment; sleep, mood, smell, or taste disorders; myalgias; sensorimotor deficits; and dysautonomia. Although very limited evidence exists to date on the pathophysiological mechanisms implicated in the manifestation of 'long-COVID', neuroinflammatory and oxidative stress processes are thought to prevail in propagating neurological 'long-COVID' sequelae. In this narrative review, we sought to present a comprehensive overview of our current understanding of clinical features, risk factors, and pathophysiological processes of neurological 'long-COVID' sequelae. Moreover, we propose diagnostic and therapeutic algorithms that may aid in the prompt recognition and management of underlying causes of neurological symptoms that persist beyond the resolution of acute COVID-19. Furthermore, as causal treatments for 'long-COVID' are currently unavailable, we propose therapeutic approaches for symptom-oriented management of neurological 'long-COVID' symptoms. In addition, we emphasize that collaborative research initiatives are urgently needed to expedite the development of preventive and therapeutic strategies for neurological 'long-COVID' sequelae.

Multiple sclerosis is not associated with an increased risk for severe COVID-19: a nationwide retrospective cross-sectional study from Germany.

BACKGROUND: Since the coronavirus disease 2019 (COVID-19) has risen, several risk factors have been identified, predicting a worse outcome. It has been speculated that patients with Multiple sclerosis (MS) have an increased risk for a severe course of COVID-19 due to a suspected higher vulnerability. Therefore, we aimed to analyze the impact of comorbid MS on the outcome of patients with COVID-19 in Germany. METHODS: We conducted a retrospective cross-sectional study using the administrative database of all hospitalized patients diagnosed with PCR-confirmed COVID-19 (n = 157,524) in Germany during 2020. The cohort was stratified according to the presence (n = 551) or absence (n = 156,973) of comorbid MS, including discrimination of MS subtypes. Primary outcome measures were admission to the intensive care unit (ICU), use of invasive or non-invasive ventilation, and in-hospital mortality. Differences were investigated using rates and odds ratios as estimates. Pooled overall estimates, sex-stratified estimates, age-group stratified estimates, and MS subtype stratified estimates were calculated for all outcomes under the random-effects model. RESULTS: Among 157,524 patients hospitalized with COVID-19, 551 had a concurrent MS diagnosis (0.3%). Overall, univariate analysis showed lower rates of ICU admission (17.1% versus 22.7%, p < 0.001), lower use of ventilation (9.8% versus 14.5%, p < 0.001) and lower in-hospital mortality (11.1% versus 19.3%, p < 0.001) among COVID-19 patients with comorbid MS. This finding was stable across the subgroup analysis of sex and MS subtype but was attenuated by age-stratification, confirming equal odds of in-hospital mortality between COVID-19 patients with and without MS (log OR: 0.09 [95% CI: - 0.40, 0.59]). CONCLUSIONS: Although there might be differences in risk within the MS patients' population, this large-scale nationwide analysis found no evidence for a worse outcome of COVID-19 in patients with comorbid MS compared to non-MS individuals.

Hospital Admissions for Neurodegenerative Diseases during the First Wave of the COVID-19 Pandemic: A Nationwide Cross-Sectional Study from Germany.

(1) Background: The COVID-19 pandemic impacts healthcare utilization across all care settings and health conditions. The objective of this study was to determine changes in hospital admissions for neurodegenerative diseases (NDD) during the first COVID-19 wave in Germany; (2) Methods: This cross-sectional study used nationwide administrative claims data covering 1468 hospitals. The primary outcome was the year-to-year relative change in case numbers during a four-month study period (16 January-15 May 2020 vs. 2019) during the first pandemic wave. Secondary outcomes included year-to-year relative changes during a four-week peak phase (16 March-15 April) and changes between differential phases of the wave. The analyzed NDD comprised progressive supranuclear palsy (PSP), multiple system atrophy (MSA), Parkinson's disease, amyotrophic lateral sclerosis (ALS) and Huntington's disease; (3) Results: Hospital admissions for any reason decreased by 16.7% in 2020 during the study period and by 36.6% during the peak phase, whereas admissions for NDD decreased by 27.6% and 65.0%, respectively. PSP cases decreased during the study period (-34.7%) and the peak phase (-68.1%) and stayed reduced in a late phase with falling COVID-19 numbers. MSA and ALS cases increased strongest after the peak, with ALS cases being comparatively weakly reduced during the study period (-17.3%) and peak phase (-51.7%); (4) Conclusions: Inpatient care utilization for NDD changed differentially during the first wave of the COVID-19 pandemic in Germany and showed a greater reduction than overall and general neurological admissions. Mitigating long-term health deterioration of this vulnerable subgroup is important to reduce morbidity and mortality in the future.

A full year of the COVID-19 pandemic with two infection waves and its impact on ischemic stroke patient care in Germany.

BACKGROUND AND PURPOSE: Many countries worldwide, including Germany, reported that the first wave of the coronavirus disease 2019 (COVID-19) pandemic in early 2020 influenced the care of acute ischemic stroke (AIS) patients, but data are lacking for further pandemic wave periods. METHODS: We conducted a nationwide, retrospective, cross-sectional study of all hospitalized patients with the main diagnosis of AIS in 2019 and 2020. Primary outcomes were the number of hospitalizations for AIS, the application of stroke unit care, intravenous thrombolysis (IVT), and mechanical thrombectomy (MT), as well as the in-hospital mortality during the different pandemic periods in 2020 compared to the corresponding periods in 2019. Secondarily, we analyzed differences in outcomes between patients with and without concurrent COVID-19. RESULTS: We included 429,841 cases with AIS, of which 1268 had concurrent COVID-19. Hospitalizations for AIS declined during both pandemic wave periods in 2020 (first wave: -10.9%, second wave: -4.6%). MT rates were consistently higher throughout 2020 compared to 2019, whereas the IVT rate dropped during the second wave period (16.0% vs. 17.0%, p < 0.001). AIS patients with concurrent COVID-19 frequently received recanalization treatments, with an overall MT rate of 8.4% and IVT rate of 15.9%. The in-hospital mortality was high (22.8% vs. 7.5% in noninfected AIS patients, p < 0.001). CONCLUSIONS: These findings demonstrate a smaller decline in hospitalizations for AIS in the more severe second wave of the COVID-19 pandemic. AIS patients with and without concurrent COVID-19 who did seek acute care continued to receive recanalization treatments in Germany.

The impact of the COVID-19 pandemic on hospitalizations and plasmapheresis therapy in multiple sclerosis and neuromyelitis optica spectrum disorder: a nationwide analysis from Germany.

BACKGROUND: Many countries worldwide reported side effects of the coronavirus disease 2019 (COVID-19) pandemic that have influenced the care of patients with other diseases in both acute and elective settings. Patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) represent the major patient population suffering from an autoimmune inflammatory demyelinating disease of the central nervous system. We aimed to analyze MS and NMOSD hospitalizations, the application of plasmapheresis therapy, and the dynamic during different periods of the COVID-19 pandemic in Germany. METHODS: We conducted a nationwide retrospective cross-sectional study using the administrative database of all hospitalized patients with the main diagnosis of MS and NMOSD, including the information on the application of plasmapheresis therapy. We included full-year data from 1463 hospitals of all MS and NMOSD patients hospitalized in 2019 and 2020 in Germany (n = 87,453). We compared case numbers and plasmapheresis therapy rates of the different pandemic periods in 2020 with the corresponding periods in 2019. RESULTS: We observed a substantial decline of MS and NMOSD patients' hospitalizations during the different pandemic periods, with the most remarkable decline during the first wave of the pandemic (First diagnosis of MS: -16.8%; relapsing-remitting MS: -34.0%; secondary progressive MS: -48.9%; primary progressive MS: -43.8%; NMOSD: -19.2%). Treatment rates with plasmapheresis increased for MS and NMOSD patients in 2020 compared to 2019 (1.8% versus 1.6%, p = 0.003; 14.0% versus 9.3%, p < 0.001), with a substantial increase during the first wave of the pandemic, especially in NMOSD patients (19.7% versus 8.4%, p < 0.001). CONCLUSION: There was a marked decline of MS and NMOSD patients' hospitalizations during the different pandemic periods in 2020, with the most substantial reduction during the pandemic's first wave and in progressive MS patients. MS and NMOSD patients who needed rescue relapse treatment continued to receive plasmapheresis therapy in Germany.

Clinical Profiles and Mortality of COVID-19 Inpatients with Parkinson's Disease in Germany.

BACKGROUND: Comprehensive, nationwide data regarding Parkinson's disease (PD) hospitalizations, coronavirus disease 2019 (COVID-19) in-hospital frequency, and COVID-19-associated inpatient mortality during the first wave of the COVID-19 pandemic are not available. OBJECTIVE: To provide a nationwide analysis on hospitalized PD patients in Germany and evaluate the impact of the COVID-19 pandemic. METHODS: We conducted a cross-sectional study using an administrative claims database covering 1468 hospitals and 5,210,432 patient hospitalizations including a total of 30,872 COVID-19+ cases between January 16 and May 15, 2020. RESULTS: Compared to 2019, hospitalizations for PD transiently decreased by up to 72.7% in 2020. COVID-19 frequency was significantly higher in the population of 64,434 PD patients (693 being COVID-19+ ) than in non-PD patients (1.1% vs. 0.6%, P < 0.001), especially in subjects with advanced age (≥ 65 years). Regarding established COVID-19 risk comorbidities, COVID-19+ inpatients with PD showed higher incidences than non-PD COVID-19+ subjects, particularly hypertension and chronic kidney disease. Advanced age and male sex were significantly more frequent in COVID-19+ than in COVID-19- PD patients. The COVID-19 inpatient mortality rate was much higher in PD patients than in non-PD patients (35.4% vs. 20.7%, P < 0.001), especially in patients aged 75-79 years. Of note, overall inpatient mortality of PD patients was significantly higher in 2020 than in 2019 (5.7% vs. 4.9%, P < 0.001). CONCLUSIONS: PD inpatients are more frequently affected by COVID-19 and suffer from increased COVID-19-associated mortality in comparison to non-PD patients. More comprehensive studies are needed to assess the significance of associated comorbidities for COVID-19 risk and mortality in PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

SARS-CoV-2 and Stroke Characteristics: A Report From the Multinational COVID-19 Stroke Study Group.

[Figure: see text].

Analysis of nationwide multimodal complex treatment and drug pump therapy in Parkinson's disease in times of COVID-19 pandemic in Germany.

INTRODUCTION: During the first peak phase of the COVID-19 pandemic, the German Ministry of Health recommended that elective treatments should be postponed to increase hospital capacities. This has also compromised the capacity for application of specialized Parkinson's disease (PD) therapies to an unknown extent. METHODS: We conducted a nationwide cross-sectional study using administrative database of all hospitalized patients with main diagnosis of PD receiving multimodal complex treatment (PD-MCT), initial setup of levodopa/carbidopa intestinal gel (LCIG) or continuous subcutaneous apomorphine infusion (CSAI) in Germany. We compared case numbers and clinical characteristics of the pandemic (March 16th - May 15th, 2020) and post-lockdown (July 16th - September 15th, 2020) period with the pre-pandemic (January 16th - March 15th, 2020) and historical control period (March 16th - May 15th, 2019). RESULTS: We identified a strong decline for PD-MCT(-62.8%) and for the application of drug pump-based therapies (-69.4%) during the first peak phase of the pandemic as compared to the pre-pandemic period while specialized PD treatment procedures increased again in the post-lockdown phase. Advanced disease was a marker for PD-MCT patients during the pandemic period. CONCLUSION: Besides the marked decline in specialized PD treatments during the first peak phase of the COVID-19 pandemic, we found recuperative effects for these procedures in the post-lockdown period without reaching pre-pandemic levels. Strengthening treatment capacities for PD patients, even in the event of a persistent pandemic, is urgently needed in order to maintain the quality of care.

COVID-19: Neuroimaging Features of a Pandemic.

BACKGROUND AND PURPOSE: The ongoing Coronavirus Disease 2019 (COVID-19) pandemic is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is occasionally associated with manifold diseases of the central nervous system (CNS). We sought to present the neuroimaging features of such CNS involvement. In addition, we sought to identify typical neuroimaging patterns that could indicate possible COVID-19-associated neurological manifestations. METHODS: In this systematic literature review, typical neuroimaging features of cerebrovascular diseases and inflammatory processes associated with COVID-19 were analyzed. Reports presenting individual patient data were included in further quantitative analysis with descriptive statistics. RESULTS: We identified 115 studies reporting a total of 954 COVID-19 patients with associated neurological manifestations and neuroimaging alterations. A total of 95 (82.6%) of the identified studies were single case reports or case series, whereas 660 (69.2%) of the reported cases included individual information and were thus included in descriptive statistical analysis. Ischemia with neuroimaging patterns of large vessel occlusion event was revealed in 59.9% of ischemic stroke patients, whereas 69.2% of patients with intracerebral hemorrhage exhibited bleeding in a location that was not associated with hypertension. Callosal and/or juxtacortical location was identified in 58.7% of cerebral microbleed positive images. Features of hemorrhagic necrotizing encephalitis were detected in 28.8% of patients with meningo-/encephalitis. CONCLUSIONS: Manifold CNS involvement is increasingly reported in COVID-19 patients. Typical and atypical neuroimaging features have been observed in some disease entities, so that familiarity with these imaging patterns appears reasonable and may assist clinicians in the differential diagnosis of COVID-19 CNS manifestations.

Analysis of Nationwide Stroke Patient Care in Times of COVID-19 Pandemic in Germany.

BACKGROUND AND PURPOSE: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, many countries have introduced strict hygiene measures of social distancing to prevent further spreading of the disease. This may have led to a decreased presentation to hospital of patients with acute medical conditions and time-dependent management, such as stroke. METHODS: We conducted a nationwide cohort study using administrative database of all hospitalized patients with main diagnosis of acute ischemic stroke (AIS), transient ischemic attack, or intracerebral hemorrhage. Data from a total of 1463 hospitals in Germany were included. We compared case numbers and treatment characteristics of pandemic (March 16 to May 15, 2020) and prepandemic (January 16 to March 15, 2020) cases and also with corresponding time period in 2019. RESULTS: We identified a strong decline for hospitalization of AIS (-17.4%), transient ischemic attack (-22.9%), and intracerebral hemorrhage (-15.8%) patients during the pandemic compared with prepandemic period. IVT rate in patients with AIS was comparable (prepandemic versus pandemic: 16.4% versus 16.6%, P=0.448), whereas mechanical thrombectomy rate was significantly higher during the pandemic (8.1% versus 7.7%, P=0.044). In-hospital mortality was significantly increased in patients with AIS during the pandemic period (8.1% versus 7.6%, P=0.006). CONCLUSIONS: Besides a massive decrease in absolute case numbers, our data suggest that patients with AIS who did seek acute care during the pandemic, continued to receive acute recanalization treatment in Germany.

COVID-19 and cerebrovascular diseases: a comprehensive overview.

Neurological manifestations are not uncommon during infection with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A clear association has been reported between cerebrovascular disease and coronavirus disease 2019 (COVID-19). However, whether this association is causal or incidental is still unknown. In this narrative review, we sought to present the possible pathophysiological mechanisms linking COVID-19 and cerebrovascular disease, describe the stroke syndromes and their prognosis and discuss several clinical, radiological, and laboratory characteristics that may aid in the prompt recognition of cerebrovascular disease during COVID-19. A systematic literature search was conducted, and relevant information was abstracted. Angiotensin-converting enzyme-2 receptor dysregulation, uncontrollable immune reaction and inflammation, coagulopathy, COVID-19-associated cardiac injury with subsequent cardio-embolism, complications due to critical illness and prolonged hospitalization can all contribute as potential etiopathogenic mechanisms leading to diverse cerebrovascular clinical manifestations. Acute ischemic stroke, intracerebral hemorrhage, and cerebral venous sinus thrombosis have been described in case reports and cohorts of COVID-19 patients with a prevalence ranging between 0.5% and 5%. SARS-CoV-2-positive stroke patients have higher mortality rates, worse functional outcomes at discharge and longer duration of hospitalization as compared with SARS-CoV-2-negative stroke patients in different cohort studies. Specific demographic, clinical, laboratory and radiological characteristics may be used as 'red flags' to alarm clinicians in recognizing COVID-19-related stroke.

Comparison of stroke care parameters in acute ischemic stroke patients with and without concurrent Covid-19. A Nationwide analysis.

BACKGROUND: Comparing health care parameters of acute ischemic stroke (AIS) patients with and without concurrent coronavirus disease 2019 (Covid-19, SARS-CoV-2 infection), may be helpful in terms of optimizing clinical and public health care during pandemic. METHODS: We evaluated a nationwide administrative database of all hospitalized patients with main diagnosis of acute ischemic stroke with/without diagnosis of Covid-19 who were hospitalized during the time period from January 16th to May 15th, 2020. Data from a total of 1463 hospitals in Germany were included. We compared case numbers, treatment characteristics (intravenous thrombolysis, IVT; mechanical thrombectomy, MT; treated on an intensive care unit, stroke unit or regular ward) and in-hospital mortality of AIS with and without concurrent diagnosis of Covid-19. RESULTS: From a total of 30,864 hospitalized Covid-19 patients during the evaluation period in Germany, we identified a subgroup of 213 patients with primary diagnosis of AIS. Compared to the 68,700 AIS patients without Covid-19, this subgroup showed a similar rate of IVT (16.4% vs. 16.5%, p = 0.985) but a significantly lower rate of MT (3.8% vs. 7.9%, p = 0.017). In-hospital mortality rate was significantly higher in patients with AIS and concurrent Covid-19 compared to non-infected AIS patients (22.5% vs. 7.8%, p < 0.001). CONCLUSION: These nationwide data point out differences in mortality and medical treatment regime between AIS patients with and without concurrent Covid-19. Since the pandemic is still ongoing, these data draw attention to AIS as a less frequent but often fatal comorbidity in Covid-19 patients.