Reorganizing stroke and neurological intensive care during the COVID-19 pandemic in Germany.

The outbreak of coronavirus disease 19 (COVID-19) has dramatically imposed healthcare systems to reorganize their departments, including neurological wards. We aimed to describe the rearrangements made by stroke units (SU) and neurological intensive care units (ICU) in several German community and university hospitals facing the pandemic. This cross-sectional, survey-based, nationwide study collected data of 15 university and 4 community hospitals in Germany, being part of IGNITE Study Group, from April 1 to April 6, 2020. The rearrangements and implementation of safety measures in SUs, intermediate care units (IMC), and neurological ICUs were compared. 84.2% of hospitals implemented a separated area for patients awaiting their COVID-19 test results and 94.7% had a dedicated zone for their management. Outpatient treatment was reduced in 63.2% and even suspended in 36.8% of the hospitals. A global reduction of bed capacity was observed. Hospitals reported compromised stroke treatment (52.6%) and reduction of thrombolysis and thrombectomy rates (36.8%). All hospitals proposed special training for COVID-19 management, recurrent meetings and all undertook measures improving safety for healthcare workers. In an unprecedented global healthcare crisis, knowledge of the initial reorganization and response of German hospitals to COVID-19 may help finding effective strategies to face the ongoing pandemic.

Case report: cerebral sinus vein thrombosis in two patients with AstraZeneca SARS-CoV-2 vaccination.

SARS-CoV-2 infection is associated with an increased rate of thromboembolic events and mortality. Different vaccines are globally used to limit the pandemic. In this report, we present the case of two young female patients with newly diagnosed cerebral sinus vein thrombosis occurring after injection of the vector-based ChAdOx1 vaccine. Both patients presented with unusual headache only. The two of them used an estrogen-containing contraception, had had a history of deep venous thrombosis, and both had MTHFR mutations. Both patients developed SARS-CoV-2 specific humoral and cellular immunity including both CD4 and CD8 T cells. This rare, but serious complication needs to be considered after vaccination of young females, even if there is no evidence of heparin-induced thrombocytopenia.

Stroke Care during the COVID-19 Pandemic: International Expert Panel Review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has placed a tremendous strain on healthcare services. This study, prepared by a large international panel of stroke experts, assesses the rapidly growing research and personal experience with COVID-19 stroke and offers recommendations for stroke management in this challenging new setting: modifications needed for prehospital emergency rescue and hyperacute care; inpatient intensive or stroke units; posthospitalization rehabilitation; follow-up including at-risk family and community; and multispecialty departmental developments in the allied professions. SUMMARY: The severe acute respiratory syndrome coronavirus 2 uses spike proteins binding to tissue angiotensin-converting enzyme (ACE)-2 receptors, most often through the respiratory system by virus inhalation and thence to other susceptible organ systems, leading to COVID-19. Clinicians facing the many etiologies for stroke have been sobered by the unusual incidence of combined etiologies and presentations, prominent among them are vasculitis, cardiomyopathy, hypercoagulable state, and endothelial dysfunction. International standards of acute stroke management remain in force, but COVID-19 adds the burdens of personal protections for the patient, rescue, and hospital staff and for some even into the postdischarge phase. For pending COVID-19 determination and also for those shown to be COVID-19 affected, strict infection control is needed at all times to reduce spread of infection and to protect healthcare staff, using the wealth of well-described methods. For COVID-19 patients with stroke, thrombolysis and thrombectomy should be continued, and the usual early management of hypertension applies, save that recent work suggests continuing ACE inhibitors and ARBs. Prothrombotic states, some acute and severe, encourage prophylactic LMWH unless bleeding risk is high. COVID-19-related cardiomyopathy adds risk of cardioembolic stroke, where heparin or warfarin may be preferable, with experience accumulating with DOACs. As ever, arteritis can prove a difficult diagnosis, especially if not obvious on the acute angiogram done for clot extraction. This field is under rapid development and may generate management recommendations which are as yet unsettled, even undiscovered. Beyond the acute management phase, COVID-19-related stroke also forces rehabilitation services to use protective precautions. As with all stroke patients, health workers should be aware of symptoms of depression, anxiety, insomnia, and/or distress developing in their patients and caregivers. Postdischarge outpatient care currently includes continued secondary prevention measures. Although hoping a COVID-19 stroke patient can be considered cured of the virus, those concerned for contact safety can take comfort in the increasing use of telemedicine, which is itself a growing source of patient-physician contacts. Many online resources are available to patients and physicians. Like prior challenges, stroke care teams will also overcome this one. Key Messages: Evidence-based stroke management should continue to be provided throughout the patient care journey, while strict infection control measures are enforced.

Pharmacological Inhibition of Acid Sphingomyelinase Prevents Uptake of SARS-CoV-2 by Epithelial Cells.

The acid sphingomyelinase/ceramide system plays an important role in bacterial and viral infections. Here, we report that either pharmacological inhibition of acid sphingomyelinase with amitriptyline, imipramine, fluoxetine, sertraline, escitalopram, or maprotiline or genetic downregulation of the enzyme prevents infection of cultured cells or freshy isolated human nasal epithelial cells with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or vesicular stomatitis virus (VSV) pseudoviral particles (pp-VSV) presenting SARS-CoV-2 spike protein (pp-VSV-SARS-CoV-2 spike), a bona fide system mimicking SARS-CoV-2 infection. Infection activates acid sphingomyelinase and triggers a release of ceramide on the cell surface. Neutralization or consumption of surface ceramide reduces infection with pp-VSV-SARS-CoV-2 spike. Treating volunteers with a low dose of amitriptyline prevents infection of freshly isolated nasal epithelial cells with pp-VSV-SARS-CoV-2 spike. The data justify clinical studies investigating whether amitriptyline, a safe drug used clinically for almost 60 years, or other antidepressants that functionally block acid sphingomyelinase prevent SARS-CoV-2 infection.

Sphingosine prevents binding of SARS-CoV-2 spike to its cellular receptor ACE2.

Sphingosine has been shown to prevent and eliminate bacterial infections of the respiratory tract, but it is unknown whether sphingosine can be also employed to prevent viral infections. To test this hypothesis, we analyzed whether sphingosine regulates the infection of cultured and freshly isolated ex vivo human epithelial cells with pseudoviral particles expressing SARS-CoV-2 spike (pp-VSV-SARS-CoV-2 spike) that served as a bona fide system mimicking SARS-CoV-2 infection. We demonstrate that exogenously applied sphingosine suspended in 0.9% NaCl prevents cellular infection with pp-SARS-CoV-2 spike. Pretreatment of cultured Vero epithelial cells or freshly isolated human nasal epithelial cells with low concentrations of sphingosine prevented adhesion of and infection with pp-VSV-SARS-CoV-2 spike. Mechanistically, we demonstrate that sphingosine binds to ACE2, the cellular receptor of SARS-CoV-2, and prevents the interaction of the receptor-binding domain of the viral spike protein with ACE2. These data indicate that sphingosine prevents at least some viral infections by interfering with the interaction of the virus with its receptor. Our data also suggest that further preclinical and finally clinical examination of sphingosine is warranted for potential use as a prophylactic or early treatment for coronavirus disease-19.