Acceptance, drivers, and barriers to use eHealth interventions in patients with post-COVID-19 syndrome for management of post-COVID-19 symptoms: a cross-sectional study.

Background: Post-COVID-19 syndrome is a new and debilitating disease without adequate treatment options. eHealth could be a reasonable approach for symptom management. Objectives: This study aims to evaluate the acceptance for eHealth interventions for symptom management in individuals with post-COVID-19 syndrome, as well as drivers and barriers influencing acceptance. Design: Cross-sectional study. Methods: This study was conducted from January 19 until 24 May 2022. Recruitment took place with a web-based survey. Acceptance and predictors of eHealth interventions were measured by the extended UTAUT model. Included in the model were the core predictor performance expectancy, social influence, and effort expectancy. Previously diagnosed mental illness was estimated and mental health by using the well-established Generalized Anxiety Disorder Scale-7 and the Patient Health Questionnaire Depression Scale. The effect of sociodemographic and medical data was assessed. Multiple hierarchical regression analyses as well as group comparisons were performed. Results: 342 individuals with post-COVID-19 syndrome were examined. The acceptance of eHealth interventions for symptom management was moderate to high (M = 3.60, SD = 0.89). Acceptance was significantly higher in individuals with lower/other education, patients with moderate to severe symptoms during initial COVID-19 infection, still significantly impaired patients, and individuals with a mental illness. Identified predictors of acceptance were age (ß = .24, p < .001), current condition including moderate (ß = .49, p = .002) and still significantly impaired (ß = .67, p < .001), digital confidence (ß = .19, p < .001), effort expectancy (ß = .26, p < .001), performance expectancy (ß = .33, p < .001), and social influence (ß = .26, p < .001). Conclusion: Patients with post-COVID-19 syndrome reported a satisfying level of acceptance and drivers and barriers could be identified. These factors need to be considered for the implementation and future use of eHealth interventions.

Immune Response to Seasonal Influenza Vaccination in Multiple Sclerosis Patients Receiving Cladribine.

Cladribine has been approved for the treatment of multiple sclerosis (MS) and its administration results in a long-lasting depletion of lymphocytes. As lymphopenia is known to hamper immune responses to vaccination, we evaluated the immunogenicity of the influenza vaccine in patients undergoing cladribine treatment at different stages vs. controls. The antibody response in 90 cladribine-treated MS patients was prospectively compared with 10 control subjects receiving platform immunotherapy (NCT05019248). Serum samples were collected before and six months after vaccination. Response to vaccination was determined by the hemagglutination-inhibition test. Postvaccination seroprotection rates against influenza A were comparable in cladribine-treated patients and controls (H1N1: 94.4% vs. 100%; H3N2: 92.2% vs. 90.0%). Influenza B response was lower in the cladribine cohort (61.1% vs. 80%). The increase in geometric mean titers was lower in the cladribine group vs. controls (H1N1: +98.5 vs. +188.1; H3N2: +225.3 vs. +300.0; influenza B: +40.0 vs. +78.4); however, titers increased in both groups for all strains. Seroprotection was achieved irrespective of vaccination timing and lymphocyte subset counts at the time of vaccination in the cladribine cohort. To conclude, cladribine-treated MS patients can mount an adequate immune response to influenza independently of treatment duration and time interval to the last cladribine administration.

Post-COVID-19 Syndrome is Rarely Associated with Damage of the Nervous System: Findings from a Prospective Observational Cohort Study in 171 Patients.

INTRODUCTION: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect multiple organs. Reports of persistent or newly emergent symptoms, including those related to the nervous system, have increased over the course of the pandemic, leading to the introduction of post-COVID-19 syndrome. However, this novel syndrome is still ill-defined and structured objectification of complaints is scarce. Therefore, we performed a prospective observational cohort study to better define and validate subjective neurological disturbances in patients with post-COVID-19 syndrome. METHODS: A total of 171 patients fulfilling the post-COVID-19 WHO Delphi consensus criteria underwent a comprehensive neurological diagnostic work-up including neurovascular, electrophysiological, and blood analysis. In addition, magnetic resonance imaging (MRI) and lumbar puncture were conducted in subgroups of patients. Furthermore, patients underwent neuropsychological, psychosomatic, and fatigue assessment. RESULTS: Patients were predominantly female, middle-aged, and had incurred mostly mild-to-moderate acute COVID-19. The most frequent post-COVID-19 complaints included fatigue, difficulties in concentration, and memory deficits. In most patients (85.8%), in-depth neurological assessment yielded no pathological findings. In 97.7% of the cases, either no diagnosis other than post COVID-19 syndrome, or no diagnosis likely related to preceding acute COVID-19 could be established. Sensory or motor complaints were more often associated with a neurological diagnosis other than post-COVID-19 syndrome. Previous psychiatric conditions were identified as a risk factor for developing post-COVID-19 syndrome. We found high somatization scores in our patient group that correlated with cognitive deficits and the extent of fatigue. CONCLUSIONS: Albeit frequently reported by patients, objectifiable affection of the nervous system is rare in post-COVID-19 syndrome. Instead, elevated levels of somatization point towards a pathogenesis potentially involving psychosomatic factors. However, thorough neurological assessment is important in this patient group in order to not miss neurological diseases other than post-COVID-19.

Mechanical thrombectomy for acute ischemic stroke in COVID-19 patients: multicenter experience in 111 cases.

BACKGROUND: Data on the frequency and outcome of mechanical thrombectomy (MT) for large vessel occlusion (LVO) in patients with COVID-19 is limited. Addressing this subject, we report our multicenter experience. METHODS: A retrospective cohort study was performed of consecutive acute stroke patients with COVID-19 infection treated with MT at 26 tertiary care centers between January 2020 and November 2021. Baseline demographics, angiographic outcome and clinical outcome evaluated by the modified Rankin Scale (mRS) at discharge and 90 days were noted. RESULTS: We identified 111 out of 11 365 (1%) patients with acute or subsided COVID-19 infection who underwent MT due to LVO. Cardioembolic events were the most common etiology for LVO (38.7%). Median baseline National Institutes of Health Stroke Scale score and Alberta Stroke Program Early CT Score were 16 (IQR 11.5-20) and 9 (IQR 7-10), respectively. Successful reperfusion (mTICI ≥2b) was achieved in 97/111 (87.4%) patients and 46/111 (41.4%) patients were reperfused completely. The procedure-related complication rate was 12.6% (14/111). Functional independence was achieved in 20/108 (18.5%) patients at discharge and 14/66 (21.2%) at 90 days follow-up. The in-hospital mortality rate was 30.6% (33/108). In the subgroup analysis, patients with severe acute COVID-19 infection requiring intubation had a mortality rate twice as high as patients with mild or moderate acute COVID-19 infection. Acute respiratory failure requiring ventilation and time interval from symptom onset to groin puncture were independent predictors for an unfavorable outcome in a logistic regression analysis. CONCLUSION: Our study showed a poor clinical outcome and high mortality, especially in patients with severe acute COVID-19 infection undergoing MT due to LVO.

Oropharyngeal swab for SARS-CoV-2 test causing atypical internal carotid artery dissection and stroke in a patient after mild COVID-19

We report a patient who had recovered from pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presenting with acute cerebral ischemia due to atypical dissection of the left internal carotid artery immediately after an oropharyngeal swab (OPS) for SARS-CoV-2 RT-PCR testing. The symptoms consisting of right-side hemiparesis and aphasia improved after systemic thrombolysis and the patient recovered completely in the further course. We demonstrate findings from imaging (computed tomography, magnetic resonance imaging, neurovascular ultrasound) among other investigations and discuss coronavirus disease 2019 (COVID-19)-related vessel wall vulnerability as well as tissue injury posed by the swab procedure as underlying causes of the dissection. Individuals performing OPSs during the corona pandemic should be aware of this so far undescribed complication.

MOG antibody-associated encephalomyelitis mimicking bacterial meningomyelitis following ChAdOx1 nCoV-19 vaccination: a case report.

We report a case of anti-myelin oligodendrocyte glycoprotein (MOG) antibody-associated encephalomyelitis following vector-based vaccination against SARS-CoV-2 that mimicked bacterial meningomyelitis upon initial presentation. A 43-year-old woman who had received a first dose of ChAdOx1 nCoV-19 (Vaxzevria; Astra Zeneca, UK Limited) 9 days earlier presented with subacute sensorimotor paraparesis, urinary retention, headache, meningism, and fever. Clinical findings and cerebrospinal fluid (CSF) features were highly suggestive of bacterial infection; however, despite receiving broad anti-infective treatment alongside with high-dose glucocorticoids, symptoms deteriorated. Imaging findings and the detection of immunoglobulin G against MOG substantiated diagnosis of an anti-MOG associated disorder. Treatment with high-dose intravenous (IV) methylprednisolone and plasma exchange resulted in substantial clinical improvement, which sustained under monthly regimen of IV Tocilizumab at 3-month follow-up. Awareness of this post-vaccinal presentation of a rare autoimmune disorder is important to not miss potential treatment options.

Cerebrospinal fluid findings in COVID-19: a multicenter study of 150 lumbar punctures in 127 patients.

BACKGROUND: Comprehensive data on the cerebrospinal fluid (CSF) profile in patients with COVID-19 and neurological involvement from large-scale multicenter studies are missing so far. OBJECTIVE: To analyze systematically the CSF profile in COVID-19. METHODS: Retrospective analysis of 150 lumbar punctures in 127 patients with PCR-proven COVID-19 and neurological symptoms seen at 17 European university centers RESULTS: The most frequent pathological finding was blood-CSF barrier (BCB) dysfunction (median QAlb 11.4 [6.72-50.8]), which was present in 58/116 (50%) samples from patients without pre-/coexisting CNS diseases (group I). QAlb remained elevated > 14d (47.6%) and even > 30d (55.6%) after neurological onset. CSF total protein was elevated in 54/118 (45.8%) samples (median 65.35 mg/dl [45.3-240.4]) and strongly correlated with QAlb. The CSF white cell count (WCC) was increased in 14/128 (11%) samples (mostly lympho-monocytic; median 10 cells/µl, > 100 in only 4). An albuminocytological dissociation (ACD) was found in 43/115 (37.4%) samples. CSF L-lactate was increased in 26/109 (24%; median 3.04 mmol/l [2.2-4]). CSF-IgG was elevated in 50/100 (50%), but was of peripheral origin, since QIgG was normal in almost all cases, as were QIgA and QIgM. In 58/103 samples (56%) pattern 4 oligoclonal bands (OCB) compatible with systemic inflammation were present, while CSF-restricted OCB were found in only 2/103 (1.9%). SARS-CoV-2-CSF-PCR was negative in 76/76 samples. Routine CSF findings were normal in 35%. Cytokine levels were frequently elevated in the CSF (often associated with BCB dysfunction) and serum, partly remaining positive at high levels for weeks/months (939 tests). Of note, a positive SARS-CoV-2-IgG-antibody index (AI) was found in 2/19 (10.5%) patients which was associated with unusually high WCC in both of them and a strongly increased interleukin-6 (IL-6) index in one (not tested in the other). Anti-neuronal/anti-glial autoantibodies were mostly absent in the CSF and serum (1509 tests). In samples from patients with pre-/coexisting CNS disorders (group II [N = 19]; including multiple sclerosis, JC-virus-associated immune reconstitution inflammatory syndrome, HSV/VZV encephalitis/meningitis, CNS lymphoma, anti-Yo syndrome, subarachnoid hemorrhage), CSF findings were mostly representative of the respective disease. CONCLUSIONS: The CSF profile in COVID-19 with neurological symptoms is mainly characterized by BCB disruption in the absence of intrathecal inflammation, compatible with cerebrospinal endotheliopathy. Persistent BCB dysfunction and elevated cytokine levels may contribute to both acute symptoms and 'long COVID'. Direct infection of the CNS with SARS-CoV-2, if occurring at all, seems to be rare. Broad differential diagnostic considerations are recommended to avoid misinterpretation of treatable coexisting neurological disorders as complications of COVID-19.

Anti-GFAP-antibody positive postinfectious acute cerebellar ataxia and myoclonus after COVID-19: a case report.

We present a case of acute cerebellar ataxia and myoclonus with detected anti-GFAP-antibodies in a patient recently recovered from COVID-19. Main symptoms consisted of acute gait and limb ataxia and myoclonus. The patient improved considerably upon treatment with high-dose intravenous (IV) steroids. While cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) findings were unremarkable, anti-GFAP-antibodies were detected in the patient's serum and disappeared upon clinical remission at a 3-month follow-up. This case suggests that anti-GFAP-antibodies might be associated with some of the increasingly observed cases of postinfectious acute cerebellar ataxias in COVID-19 patients and aid in the diagnosis of this autoimmune complication. We recommend searching for these antibodies in serum and CSF in suspected cases. Early steroid treatment may prove beneficial for these patients.

Oropharyngeal swab for SARS-CoV-2 test causing atypical internal carotid artery dissection and stroke in a patient after mild COVID-19.

We report a patient who had recovered from pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presenting with acute cerebral ischemia due to atypical dissection of the left internal carotid artery immediately after an oropharyngeal swab (OPS) for SARS-CoV-2 RT-PCR testing. The symptoms consisting of right-side hemiparesis and aphasia improved after systemic thrombolysis and the patient recovered completely in the further course. We demonstrate findings from imaging (computed tomography, magnetic resonance imaging, neurovascular ultrasound) among other investigations and discuss coronavirus disease 2019 (COVID-19)-related vessel wall vulnerability as well as tissue injury posed by the swab procedure as underlying causes of the dissection. Individuals performing OPSs during the corona pandemic should be aware of this so far undescribed complication.

Vaccination in multiple sclerosis patients treated with highly effective disease-modifying drugs: an overview with consideration of cladribine tablets.

Infectious diseases are an important consideration in autoimmune conditions such as multiple sclerosis. Infective episodes may trigger relapses and significantly deteriorate the course of the disease. Some immunotherapies may cause increased rates of infection-related adverse events. Thus, infection and vaccine-related issues should be included in the individualized patient-specific treatment strategy and counseling before starting therapy and regularly on treatment. Clinical and epidemiological studies as well as pharmacovigilance data repeatedly demonstrated the safety of the great majority of vaccines in multiple sclerosis patients. Moreover, studies have shown that vaccinations with killed/inactivated vaccines do not increase the short-term risk of relapse or deterioration in multiple sclerosis, whereas infections have been shown to provoke relapses. The available evidence indicates reduced humoral vaccination efficacy on treatment with MS drugs acting on the S1P receptor, natalizumab, and B-cell depleting therapies. Recent data for cladribine tablets suggest the potential of effective immunization in the interval of the two treatment courses and after completion of therapy. Regardless of treatment, vaccine efficacy may be optimized with proper timing of application. Multiple sclerosis patients receiving highly effective therapies should be vaccinated according to general recommendations for healthy adults. Immunization against COVID-19 is highly recommended for all multiple sclerosis patients regardless of age and comorbidities. Preliminary data show the potential of adequate responses in patients treated with cladribine tablets.

Ocrelizumab Extended Interval Dosing in Multiple Sclerosis in Times of COVID-19.

OBJECTIVE: To evaluate the clinical consequences of extended interval dosing (EID) of ocrelizumab in relapsing-remitting multiple sclerosis (RRMS) during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: In our retrospective, multicenter cohort study, we compared patients with RRMS on EID (defined as ≥4-week delay of dose interval) with a control group on standard interval dosing (SID) at the same period (January to December 2020). RESULTS: Three hundred eighteen patients with RRMS were longitudinally evaluated in 5 German centers. One hundred sixteen patients received ocrelizumab on EID (median delay [interquartile range 8.68 [5.09-13.07] weeks). Three months after the last ocrelizumab infusion, 182 (90.1%) patients following SID and 105 (90.5%) EID patients remained relapse free (p = 0.903). Three-month confirmed progression of disability was observed in 18 SID patients (8.9%) and 11 EID patients (9.5%, p = 0.433). MRI progression was documented in 9 SID patients (4.5%) and 8 EID patients (6.9%) at 3-month follow-up (p = 0.232). Multivariate logistic regression showed no association between treatment regimen and no evidence of disease activity status at follow-up (OR: 1.266 [95% CI: 0.695-2.305]; p = 0.441). Clinical stability was accompanied by persistent peripheral CD19+ B-cell depletion in both groups (SID vs EID: 82.6% vs 83.3%, p = 0.463). Disease activity in our cohort was not associated with CD19+ B-cell repopulation. CONCLUSION: Our data support EID of ocrelizumab as potential risk mitigation strategy in times of the COVID-19 pandemic. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with RRMS, an EID of at least 4 weeks does not diminish effectiveness of ocrelizumab.

Observational cohort study of neurological involvement among patients with SARS-CoV-2 infection.

BACKGROUND: A growing number of reports suggest that infection with SARS-CoV-2 often leads to neurological involvement; however, data on the incidence and severity are limited to mainly case reports and retrospective studies. METHODS: This prospective, cross-sectional study of 102 SARS-CoV-2 PCR positive patients investigated the frequency, type, severity and risk factors as well as underlying pathophysiological mechanisms of neurological involvement (NIV) in COVID-19 patients. RESULTS: Across the cohort, 59.8% of patients had NIV. Unspecific NIV was suffered by 24.5%, mainly general weakness and cognitive decline or delirium. Mild NIV was found in 9.8%; most commonly, impaired taste or smell. Severe NIV was present in 23.5%; half of these suffered cerebral ischaemia. Incidence of NIV increased with respiratory symptoms of COVID-19. Mortality was higher with increasing NIV severity. Notably, 83.3% with severe NIV had a pre-existing neurological co-morbidity. All cerebrospinal fluid (CSF) samples were negative for SARS-CoV-2 RNA, and SARS-CoV-2 antibody quotient did not suggest intrathecal antibody synthesis. Of the patients with severe NIV, 50% had blood-brain barrier (BBB) disruption and showed a trend of elevated interleukin levels in CSF. Antibodies against neuronal and glial epitopes were detected in 35% of the patients tested. CONCLUSION: Cerebrovascular events were the most frequent severe NIV and severe NIV was associated with high mortality. Incidence of NIV increased with respiratory symptoms and NIV and pre-existing neurological morbidities were independent risk factors for fatality. Inflammatory involvement due to BBB disruption and cytokine release drives NIV, rather than direct viral invasion. These findings might help physicians define a further patient group requiring particular attention during the pandemic.

Neurological Manifestations of COVID-19 Feature T Cell Exhaustion and Dedifferentiated Monocytes in Cerebrospinal Fluid.

Patients suffering from Coronavirus disease 2019 (COVID-19) can develop neurological sequelae, such as headache and neuroinflammatory or cerebrovascular disease. These conditions-termed here as Neuro-COVID-are more frequent in patients with severe COVID-19. To understand the etiology of these neurological sequelae, we utilized single-cell sequencing and examined the immune cell profiles from the cerebrospinal fluid (CSF) of Neuro-COVID patients compared with patients with non-inflammatory and autoimmune neurological diseases or with viral encephalitis. The CSF of Neuro-COVID patients exhibited an expansion of dedifferentiated monocytes and of exhausted CD4+ T cells. Neuro-COVID CSF leukocytes featured an enriched interferon signature; however, this was less pronounced than in viral encephalitis. Repertoire analysis revealed broad clonal T cell expansion and curtailed interferon response in severe compared with mild Neuro-COVID patients. Collectively, our findings document the CSF immune compartment in Neuro-COVID patients and suggest compromised antiviral responses in this setting.

Effects of Life Events and Social Isolation on Stroke and Coronary Heart Disease.

The current coronavirus disease 2019 (COVID-19) pandemic represents a severe, life-changing event for people across the world. Life changes may involve job loss, income reduction due to furlough, death of a beloved one, or social stress due to life habit changes. Many people suffer from social isolation due to lockdown or physical distancing, especially those living alone and without family. This article reviews the association of life events and social isolation with cardiovascular disease, assembling the current state of knowledge for stroke and coronary heart disease. Possible mechanisms underlying the links between life events, social isolation, and cardiovascular disease are outlined. Furthermore, groups with increased vulnerability for cardiovascular disease following life events and social isolation are identified, and clinical implications of results are presented.

Experience in Multiple Sclerosis Patients with COVID-19 and Disease-Modifying Therapies: A Review of 873 Published Cases.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic is a challenge for all participants in the healthcare system. At the beginning of the pandemic, many physicians asked themselves what risk their patients, especially those with chronic diseases, were exposed to. We present an overview of all patients with multiple sclerosis (MS) and SARS-CoV-2 infection published in the literature so far. In total, there are publications on 873 SARS-CoV-2 positive MS patients and information on the outcome can be given for 700 patients. With regard to the different disease modifying therapies (DMTs), by far the most cases were described under anti-CD20 treatment (n = 317). The mortality rate of all MS patients was 4% and a further 3% required invasive or non-invasive ventilation. When looking at the severe and fatal cases, it is particularly noticeable that patients without DMTs, with previous cardiovascular diseases, or with a severe degree of disability are at risk. Immunosuppressive therapy itself does not appear to be a substantial risk factor. Rather, it is reasonable to assume that the therapies could be protective, either directly, by mitigating the cytokine storm, or indirectly, by reducing the disease activity of MS.

Implications of COVID-19 Outbreak on Immune Therapies in Multiple Sclerosis Patients-Lessons Learned From SARS and MERS.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic keeps the world in suspense. In addition to the fundamental challenges for the health care system, the individual departments must decide how to deal with patients at risk. Neurologists are confronted with the question, how they should advise their patients regarding immunosuppressive treatment. In particular, the large number of different disease-modifying therapies (DMTs) in the treatment of neuroimmunological diseases such as multiple sclerosis poses a challenge. To a limited extent, it might be useful to transfer knowledge from previous SARS- and Middle East respiratory syndrome (MERS) coronavirus outbreaks in 2002/2003 and 2012 to the current situation. Overall, immunosuppressive therapy does neither seem to have a major impact on infection with SARS- and MERS-CoV nor does it seem to lead to a severe disease course in many cases. Considering the immunological responses against infections with novel coronaviruses in humans, interferons, glatiramer acetate, and teriflunomide appear to be safe. As lymphopenia seems to be associated with a more severe disease course, all DMTs causing lymphopenia, such as cladribine, alemtuzumab, and dimethyl fumarate, need to be reviewed more thoroughly. As they are, in general, associated with a higher risk of infection, depleting anti-CD20 antibodies may be problematic drugs. However, it has to be differentiated between the depletion phase and the phase of immune reconstitution. In summary, previous coronavirus outbreaks have not shown an increased risk for immunocompromised patients. Patients with severe neuroimmunological diseases should be kept from hasty discontinuation of immunotherapy.