Real-time Tracking of Medical Devices: An Analysis of Multilateration and Fingerprinting Approaches (preprint)

Hospital infrastructures are always in evidence in periods of crisis, such as natural disasters or pandemic events, under stress. The recent COVID-19 pandemic exposed several inefficiencies in hospital systems over a relatively long period. Among these inefficiencies are human factors, such as how to manage staff during periods of high demand, and technical factors, including the management of Portable Medical Devices (PMD), such as mechanical ventilators, capnography monitors, infusion pumps, or pulse oximeters. These devices, which are vital for monitoring patients or performing different procedures, were found to have a high turnover during high-demand, resulting in inefficiencies and more pressure on medical teams. Thus, the work PMD-Track evaluates in detail two popular indoor tracking approaches concerning their accuracy, placement of beacons, and economic impacts. The key novelty of PMD-Track relies on using smartphones provided to hospital employees, replacing typical stationary gateways spread across a hospital, functioning as mobile gateways with a front-end that assists staff in locating PMDs. As employees approach tagged PMDs, their smartphone automatically updates the location of spotted PMDs in real-time, providing room-level localization data with up to 83% accuracy for fingerprinting and 35% for multilateration. In addition, fingerprinting is 45% cheaper than multilateration over the course of five years. Practical experiments were evaluated based on two locations in Z\"urich, Switzerland.

Safety of SARS-CoV2 vaccination and COVID-19 short-term outcome in pediatric acquired demyelinating disorders of central nervous system: A single center experience.

Introduction: Concern of a correlation between disease relapse in patients with acquired demyelinating disorders of central nervous system (CNS) and SARS-CoV2 vaccines has been raised. In this single center study, we retrospectively evaluated safety of SARS-CoV2 vaccination and COVID-19 short-term outcome in pediatric acquired demyelinating disorders of CNS. Materials and methods: Patients with multiple sclerosis (MS), myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD) and neuromyelitis optica spectrum disorder (NMOSD) with disease onset before 18 years of age were included. Demographic and clinical data, and information regarding previous SARS-CoV-2 infection and vaccination were collected. Results: We included nine patients with MOGAD. Six patients received SARS-CoV2 vaccination and complained pain at injection site while only one had fever and fatigue. Median follow-up was 28 weeks (range 20-48). Seven patients had COVID-19 occurring with mild flu-like symptoms and median follow-up was 28 weeks (range 24-34). Nobody had disease relapse. Five patients with NMOSD were included. All patients received SARS-CoV2 vaccination (BNT162b2-Pfizer-BioNTech). The median follow-up was 20 weeks (range 14-24) and only two patients complained pain at injection site, fever and fatigue. Three patients had also COVID-19 with mild flu-like symptoms, despite two of them being under immunosuppressive treatment. Lastly, forty-three patients with MS were included. 35 out of 43 received SARS-CoV2 vaccination with a median follow-up of 24 weeks (range 8-36). Fourteen patients had no side effects, while 21 complained mild side effects (mainly pain at injection site) and one experienced a disease relapse with complete recovery after steroid therapy. At vaccination, all but one were under treatment. Sixteen patients had COVID-19 occurring with mild symptoms. Discussion: COVID-19 outcome was good although many patients were under immunosuppressive treatment. Vaccine-related side effects were frequent but were mild and self-limited. Only one MS patient had a post-vaccination relapse with complete recovery after steroid therapy. In conclusion, our data support the safety of SARS-CoV-2 vaccines in pediatric MS, MOGAD and NMOSD.

Vaccination in neuromyelitis optica spectrum disorders: Friend or enemy?

Neuromyelitis optica spectrum disorders (NMOSDs) are uncommon antibody-mediated autoimmune diseases of the central nervous system (CNS), mainly occurring in optic nerves and spinal cord, which can cause visual impairment, paralysis, and occasionally bulbar dysfunction. Such neurological deficits can adversely affect pulmonary functions and increase complicated infection risk. Besides, most NMOSD patients undergo immunosuppressive therapy. All these factors make NMOSD patients the potential high-risk group under the current pandemic of coronavirus disease 2019 (COVID-19). Meanwhile, COVID-19 infection has already been demonstrated as a risk factor for NMOSD relapses. This review discusses the basic immunology of vaccination and common problems, including immunogenicity, safety, and efficacy of vaccination on NMOSD patients. Additionally, we offered vaccination recommendations, health care and treatment advice for NMOSD patients under the background of COVID-19.

Effects of the COVID-19 Pandemic on Patients With NMO Spectrum Disorders and MOG-Antibody-Associated Diseases: COPANMO(G)-Study.

BACKGROUND AND OBJECTIVES: To evaluate the effects of the coronavirus disease 2019 (COVID-19) pandemic on the life of patients with neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated diseases (MOGAD). METHODS: This multicenter, cross-sectional study included data of 187 patients recruited from 19 different German and Austrian Neuromyelitis Optica Study Group (NEMOS) centers between July 2021 and March 2022. The effects of the pandemic on immunotherapeutic treatment and access to care, the possible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and the potential effect of vaccination against SARS-CoV-2 on disease incidence and relapse risk were assessed using a patient questionnaire. Health-related quality of life (HRQoL) was measured with the EuroQoL Group 5-Dimension 5-Level Scale (EQ-5D-5L). Demographic and clinical characteristics were retrieved from the NEMOS database. RESULTS: One hundred eighty-seven patients (75% women; median age 47 [range 21-86] years; median disease duration 5.5 [range 0-67] years; median Expanded Disability Status Scale 2.0 [range 0-8.0]; 51% aquaporin-4 immunoglobulin G (AQP4-IgG)-positive, 36% myelin oligodendrocyte glycoprotein (MOG)-IgG-positive 13% double-seronegative) were analyzed. Most patients maintained excellent access to healthcare services throughout the pandemic. Immunotherapy was not changed in 88% of patients. Ninety-one percent of all patients were satisfied with medical care during the pandemic. Nearly two-thirds (64%) of patients rated their risk of infection with SARS-CoV-2 as low or moderate. Among this study sample, 23 patients (12%) knowingly acquired an infection with SARS-CoV-2 and predominantly had a nonsevere course of illness (n = 22/23, 96%). The SARS-CoV-2 vaccination rate was 89%, with 4 cases of confirmed attack or first manifestation of NMOSD/MOGAD occurring in temporal association with the vaccination (range 2-9 days). The reported HRQoL did not decline compared with a prepandemic assessment (mean EQ-5D-5L index value 0.76, 95% bootstrap confidence interval [CI] 0.72-0.80; mean EQ-VAS 66.5, 95% bootstrap CI 63.5-69.3). DISCUSSION: This study demonstrates that, overall, patients with NMOSD/MOGAD affiliated with specialized centers received ongoing medical care during the pandemic. Patients' satisfaction with medical care and HRQoL did not decrease.

Optic neuromyelitis after vaccination against SARS-CoV-2.

Neuromyelitis optica is an autoimmune demyelinating astrocytopathy of the central nervous system that primarily affects the optic nerve and spinal cord. It is considered a multifactorial disease associated with antibodies against aquaporin 4, with complement cascade activation and lymphocytic infiltration leading to axonal loss and causing significant morbidity and disability. In addition, cases of inflammatory diseases of the central nervous system have been described after vaccination against SARS-CoV-2, mainly acute disseminated encephalomyelitis. Also, a few cases of neuromyelitis optica spectrum disorder, mostly aquaporin 4+, have been reported. We describe a patient who developed symptoms suggestive of acute disseminated encephalomyelitis the next day after vaccination against SARS-CoV-2. Three months later, a longitudinally extensive transverse myelitis compatible with aquaporin 4+ neuromyelitis optica was successfully treated with an interleukin 6 inhibitor. There is no proven association and research is needed to establish whether optic neuromyelitis is related to vaccination; this is a single case report from which no conclusion can be drawn.

The epidemiology and burden of neuromyelitis optica spectrum disorder, multiple sclerosis, and MOG antibody-associated disease in a province in Thailand: A population-based study.

BACKGROUND: Central nervous system inflammatory demyelinating diseases (CNSIDDs) have notable interracial heterogeneity. The epidemiology of CNSIDDs in Thailand, a mainland Southeast Asian country, is unknown. OBJECTIVES: To determine the cumulative incidence, point prevalence, and disease burden of neuromyelitis optica spectrum disorder (NMOSD) and other CNSIDDs in Thailand using population-based data of Chumphon. METHODS: Searching for CNSIDD patients at a public secondary care hospital in Chumphon, the only neurology center in the province, from January 2016 to December 2021 was implemented using relevant ICD-10-CM codes. All diagnoses were individually ascertained by a retrospective chart review. Cumulative incidence, point prevalence, attack rate, mortality rate, and disability-adjusted life years (DALYs) were calculated. RESULTS: Aquaporin 4-IgG-positive NMOSD was the most prevalent CNSIDD in the Thai population at 3.08 (1.76-5.38) per 100,000 persons. The prevalence of multiple sclerosis (MS) followed at 0.77 (0.26-2.26) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) at 0.51(0.14-1.87) per 100,000 adults. In the pediatric population, the incidence of acute disseminated encephalomyelitis was 0.28 (0.08-1.02) per 100,000 persons/year. Among other idiopathic demyelinating diseases, idiopathic optic neuritis had the highest incidence at 0.58 (0.24-0.92) per 100,000 persons/year, followed by acute transverse myelitis at 0.44 (0.14-0.74). Idiopathic demyelinating brainstem syndrome was also observed at 0.04 (0.01-0.25) per 100,000 persons/year. Although most had a fair recovery, disability was worst among NMOSD patients with DALYs of 3.61 (3.00-4.36) years per 100,000 persons. Mortality rate was the highest in NMOSD as well. CONCLUSION: CNSIDDs are rare diseases in Thailand. The prevalence is comparable to that of East Asian populations. A nationwide CNSIDDs registry would better elaborate the epidemiology of these diseases.

Neuromyelitis Optica Spectrum Disorder After BIBP COVID-19 Vaccine: A Case Report (preprint)

Background: With the availability of the COVID-19 vaccine, post-vaccination neurological complications have occasionally been reported. Case presentation: We present a case of neuromyelitis optica spectrum disorder (NMOSD) that developed 1 month after the second dose of BIBP COVID-19 vaccine (SARS-CoV-2-Vaccine [Vero Cell] Inactived). The patient presented itching, numbness of the hand and right side of the face, associated with nausea, vomiting and hiccups. Brain MRI showed lesions in the area postrema, medulla, and bilateral hypothalamus, typical of NMOSD. Serum antibodies to anti-AQP4 and anti-MOG were negative. Conclusions: The pathogenesis of NMOSD development and the vaccine is still unknown. The presentation of NMOSD is generally aggressive and disabling, it is important for the neurologist to be attentive to the highly variable clinical presentation after vaccination against COVID-9 for early diagnosis and effective treatment.

Acute Inflammatory Diseases of the Central Nervous System After SARS-CoV-2 Vaccination.

BACKGROUND AND OBJECTIVES: Acute inflammatory CNS diseases include neuromyelitis optica spectrum disorders (NMOSDs) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Both MOGAD and acute disseminated encephalomyelitis (ADEM) have been reported after vaccination. Consequently, the mass SARS-CoV-2 vaccination program could result in increased rates of these conditions. We described the features of patients presenting with new acute CNS demyelination resembling NMOSDs or MOGAD within 8 weeks of SARS-CoV-2 vaccination. METHODS: The study included a prospective case series of patients referred to highly specialized NMOSD services in the UK from the introduction of SARS-CoV-2 vaccination program up to May 2022. Twenty-five patients presented with new optic neuritis (ON) and/or transverse myelitis (TM) ± other CNS inflammation within 8 weeks of vaccination with either AstraZeneca (ChAdOx1S) or Pfizer (BNT162b2) vaccines. Their clinical records and paraclinical investigations including MRI scans were reviewed. Serologic testing for antibodies to myelin oligodendrocyte glycoprotein (MOG) and aquaporin 4 (AQP4) was performed using live cell-based assays. Patients' outcomes were graded good, moderate, or poor based on the last clinical assessment. RESULTS: Of 25 patients identified (median age 38 years, 14 female), 12 (48%) had MOG antibodies (MOGIgG+), 2 (8%) had aquaporin 4 antibodies (AQP4IgG+), and 11 (44%) had neither. Twelve of 14 (86%) antibody-positive patients received the ChAdOx1S vaccine. MOGIgG+ patients presented most commonly with TM (10/12, 83%), frequently in combination with ADEM-like brain/brainstem lesions (6/12, 50%). Transverse myelitis was longitudinally extensive in 7 of the 10 patients. A peak in new MOGAD cases in Spring 2021 was attributable to postvaccine cases. Both AQP4IgG+ patients presented with brain lesions and TM. Four of 6 (67%) seronegative ChAdOx1S recipients experienced longitudinally extensive TM (LETM) compared with 1 of 5 (20%) of the BNT162b2 group, and facial nerve inflammation was reported only in ChAdOx1S recipients (2/5, 40%). Guillain-Barre syndrome was confirmed in 1 seronegative ChAdOx1S recipient and suspected in another. DISCUSSION: ChAdOx1S was associated with 12/14 antibody-positive cases, the majority MOGAD. MOGAD patients presented atypically, only 2 with isolated ON (1 after BNT162b2 vaccine) but with frequent ADEM-like brain lesions and LETM. Within the seronegative group, phenotypic differences were observed between ChAdOx1S and BNT162b2 recipients. These observations might support a causative role of the ChAdOx1S vaccine in inflammatory CNS disease and particularly MOGAD. Further study of this cohort could provide insights into vaccine-associated immunopathology.

Neuro-ophthalmological Presentation of Optic Neuritis in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a rare demyelinating autoimmune disorder of the central nervous system. MOGAD frequently manifests with severe, bilateral, and episodes of recurrent optic neuritis (ON) and is an important differential diagnosis to multiple sclerosis and aquaporin-4-IgG seropositive neuromyelitis optica spectrum disorders. Besides ON, the clinical manifestations of MOGAD commonly include transverse myelitis, acute disseminated encephalomyelitis, and brain stem encephalitis. In this review, we summarize the current knowledge of the neuro-ophthalmological presentation of MOGAD-ON. We describe epidemiological aspects, including the association with COVID-19 and other infections or vaccinations, clinical presentation, and imaging findings of MOGAD-ON in the acute stage and during remission. Furthermore, we report findings on prognosis, treatment response, and changes in ON-unaffected eyes. We touch upon findings on visual acuity, visual fields, and visual evoked potentials, as well as structural changes assessed with optical coherence tomography. Moreover, we explain how to differentiate MOGAD from its differential diagnoses, including other neuroinflammatory disorders (multiple sclerosis and neuromyelitis optica spectrum disorders), but also idiopathic intracranial hypertension.

Myelin oligodendrocyte glycoprotein-IgG associated disorders (MOGAD) following SARS-CoV-2 infection: A case series.

This case series describes 9 patients diagnosed with myelin oligodendrocyte glycoprotein (MOG)-IgG associated disorder (MOGAD) following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients developed neurological symptoms between 4 days and 5 weeks following SARS-CoV-2 infection. Myelitis was observed in 4 patients; 4 presented with optic neuritis; and encephalopathy was observed in 3. Serum MOG-IgG cell-based assay was medium or high positive in each case. The majority of patients had near-complete recovery following acute immunosuppression. This series adds to the growing number of cases of central nervous system demyelination following SARS-CoV-2 infection and highlights a potential role of infection in the immunopathogenesis of MOGAD.

Severe disease exacerbation after mRNA COVID-19 vaccination unmasks suspected multiple sclerosis as neuromyelitis optica spectrum disorder: a case report.

BACKGROUND: Since the beginning of the COVID-19 pandemic and development of new vaccines, the issue of post-vaccination exacerbation or manifestation of demyelinating central nervous system (CNS) disorders has gained increasing attention. CASE PRESENTATION: We present a case of a 68-year-old woman previously diagnosed with multiple sclerosis (MS) since the 1980s who suffered a rapidly progressive severe sensorimotor paraparesis with loss of bladder and bowel control due to an acute longitudinal extensive transverse myelitis (LETM) after immunization with the mRNA Pfizer-BioNTech COVID-19 vaccine. Detection of Aquaporin-4-antibodies (AQP4) in both serum and CSF led to diagnosis of AQP4-antibody positive neuromyelitis optica spectrum disorder (NMOSD). Treatment with intravenous corticosteroids and plasmapheresis led to a slight improvement of the patient's symptoms. CONCLUSIONS: Pathogenic mechanisms of post-vaccination occurrence of NMOSD are still unknown. However, cases like this should make aware of rare neurological disorders manifesting after vaccination and potentially contribute to improvement of management of vaccinating patients with inflammatory CNS disorders in the future. So far two cases of AQP4-antibody positive NMOSD have been reported in association with viral vector COVID-19 vaccines. To our knowledge, we report the first case of AQP4-antibody positive NMOSD after immunization with an mRNA COVID-19-vaccine.

Watch out for neuromyelitis optica spectrum disorder onset or clinical relapse after COVID-19 vaccination: What neurologists need to know?

INTRODUCTION: The ongoing global COVID-19 pandemic has dramatically impacted our lives. We conducted this systematic review to investigate the safety of the COVID-19 vaccines in NMOSD patients. METHODS: We systematically searched PubMed, Scopus, Web of Science, and Embase from the beginning of the COVID-19 vaccination to March 1, 2022. Except for the letters, posters, and reviews, we included all related articles to answer two main questions. Our first question examined the occurrence of NMOSD onset as an adverse effect of the COVID-19 vaccine. Our second question investigated the safety of the COVID-19 vaccines in NMOSD patients. RESULTS: Out of 262 records, nine studies, including five studies for the first question and four studies for the second question, met the inclusion criteria. Out of the six patients with NMOSD onset after COVID-19 vaccination, five (83.3%) were female. The median time to NMOSD onset was 6.5 days, and the frequency of the COVID-19 vaccine type was identical in all patients. The most common presentation was longitudinally extensive transverse myelitis, significantly improved by pulse methylprednisolone with or without plasma exchange. The maintenance therapy was described only in three patients: rituximab (n=2) and azathioprine (n=1). Regarding the second question, out of 67 patients, 77.61% were female, with a mean age of 54.75 years old, a mean EDSS of 2.83, and a mean disease duration of 9.5 years. 77% reported at least one preexisting comorbidity. 88.05% were under treatment, most of which were rituximab and azathioprine. 98.50% received two doses of the COVID-19 vaccine. mRNA vaccines were the most commonly used vaccine(86.56%), which were well tolerated. No significant adverse event was reported, and local pain was the most frequently reported. 4.67% of the patients experienced a clinical relapse after a mean interval of 49.75 days, which was mainly mild to moderate in severity. Unfortunately, the data on the COVID-19 vaccines were missing. CONCLUSION: The analysis suggests the safety profile of the COVID-19 vaccines. All NMOSD patients are strongly recommended to vaccinate for COVID-19. To maximize the effectiveness of the COVID-19 vaccines, further studies are needed to draw the best practice for vaccination.

Aquaporin-4 protein antibody-associated optic neuritis related to neuroendocrine tumor after receiving an inactive COVID-19 vaccine.

Neuromyelitis optica (NMO), also known as Devic's disease, is a rare, autoimmune, and recurrent demyelinating disorder that primarily affects the spinal cord and optic nerve. We report a case with recurrent optic neuritis caused by the paraneoplastic NMO spectrum disorder in the setting of a gastric neuroendocrine tumor 2 weeks after receiving an inactive COVID-19 vaccine.

Neuromyelitis optica spectrum disorder post-COVID-19 infection: A rare case report from Northeast India.

Multiple sclerosis and neuromyelitis optica spectrum disorder may be seen in the acute setting of coronavirus disease 2019 (COVID-19) infection or even post-recovery. Such patients may present with optic neuropathy along with weakness in the back and lower limbs. Ascending paralysis can present with respiratory distress in acute COVID-19 infection and may even prove to be fatal. We report a unique case of a 16-year-old female with past history of COVID-19 infection having optic neuropathy, and radioimaging showing demyelinating plaques in the central nervous system with spinal cord edema. Serology showed positivity for rheumatoid arthritis, and the patient was managed with steroids and rituximab.

Antibody-Positive Neuromyelitis Optica Spectrum Disorder After Second COVID-19 Vaccination: A Case Report. (preprint)

Background: We report a case of de novo aquaporin-4 positive neuromyelitis optica spectrum disorder following BNT162b SARS-CoV-2 vaccination. Case Presentation: An 80-year-old South Asian man presented two days following his second dose of the Pfizer-BioNTech COVID-19 mRNA BNT162b2 vaccine with progressive left-sided leg weakness and numbness resulting in falls. MRI of the spine revealed a longitudinally extensive transverse myelitis from T3-T4 to T9-T10. Serum antibody testing revealed positive aquaporin-4 (AQP4) antibodies. He was diagnosed with de novo AQP4 positive neuromyelitis optica spectrum disorder (NMOSD) and was treated with high dose intravenous methylprednisolone and plasma exchange with some improvement. He was subsequently treated with mycophenolate mofetil and a slow steroid wean. Conclusions: : Evidence suggests vaccinations may trigger de novo NMOSD or NMOSD relapses in some individuals. Ongoing vaccine surveillance and research are needed to understand the risk of NMOSD post-COVID-19 vaccinations further.

Comparative diagnostic performance of the new chromatographic Affimer(R)-based rapid antigen detection against SARS-CoV-2 and other standard antigen tests for COVID-19 in a clinical setting. (preprint)

The availability of accurate and rapid diagnostic tools for COVID-19 is essential for tackling the ongoing pandemic. In this context, researchers in the UK have started testing a new Lateral Flow Device (LFD) based on proprietary Biotinylated anti SARS-CoV-2 S1 Affimer(R) technology that binds to the SARS-CoV2-S1 protein in anterior nasal swab samples, generating an ultra-sensitive method for detection. This international study aimed to compare its performance against other available antigen-detecting rapid diagnostic tests (Ag-RDTs) in a real-world clinical setting. The study was completed under the frame of Project SENSORNAS RTC-20176501 in collaboration with MiRNAX Biosens Ltd. and Hospital Carlos III, it was documented internally and deposited in agreement to the ISO 13485 norm. All the data obtained are currently under submission and review from the Ethics Committee of Universidad Autonoma de Madrid.

First Manifestation of AQP4-IgG-Positive Neuromyelitis Optica Spectrum Disorder Associated with the COVID-19 mRNA Vaccine BNT162b2 (preprint)

BNT162b2 is one of the effective COVID-19 vaccines. However, some researchers have also reported that the vaccines caused some neurological complications. Here, we present a case of a 52-year-old female who developed aquaporin (AQP) 4-IgG-positive neuromyelitis optica spectrum disorder (NMOSD) fourteen days after the first dose of BNT162b2. She experienced pain of the neck, weakness of the left arm and leg, numbness of the left hand, and impaired temperature sensation of the right leg. MRI showed T2WI hyperintense lesions in the area postrema and cervical spinal cord ranging from C1 to C6 level, and Gd-enhanced lesions from C3 to C5 level; especially left lateral column was predominantly enhanced. Cell-based assays showed anti-AQP4 antibody (AQP4Ab) was positive. We diagnosed AQP4-IgG-positive NMOSD. After high-dose glucocorticoid therapy, she is showing improved symptoms. The present case was characterized by the findings that a Gd-enhanced lesion in the cervical cord localized dominantly at the left lateral column, consistent with the side of the shoulder where the vaccine was injected. Many studies suggested that AQP4-IgG-positive NMOSD development has multistep mechanisms following the blood-brain barrier (BBB) breakdown. We suspected that BNT162b2-associated immune responses lead to BBB disruptions. Through the limitedly damaged BBB, the plasma cells producing AQP4Abs might be recruited to CNS, and AQP4Abs might bind to the cervical cord and the area postrema. A large population-based study revealed that BNT162b2-associated complications were less likely to be observed than COVID-19 infectious symptoms. However, considering the present case, neurologists need to observe the conditions following vaccination.

Humoral and cellular immune responses to SARS CoV-2 vaccination in Persons with Multiple Sclerosis and NMOSD patients receiving immunomodulatory treatments (preprint)

Abstract Background: Vaccination against SARS CoV-2 results in excellent personal protection against a severe course of COVID19. In persons with Multiple Sclerosis (PwMS) vaccination efficacy may be reduced by immunomodulatory medications. Objective: To assess the vaccination induced cellular and humoral immune response in PwMS receiving disease modifiying therapies. Methods: In a monocentric observational study on PwMS and patients with Neuromyelitis optica we quantified the cellular and humoral immune responses to SARS CoV-2. Results: PwMS receiving Glatirameracetate, Interferon-beta, Dimethylfumarate, Cladribine or Natalalizumab had intact humoral and cellular immune responses following vaccination against SARS CoV-2. B-cell depleting therapies reduced B-cell responses but did not affect T cell responses. S1P inhibitors strongly reduced humoral and cellular immune responses. There was a good agreement between the Interferon gamma release assay and the T-SPOT assay used to measure viral antigen induced T-cell responses. Conclusion: This study demonstrates that S1P inhibitors impair the cellular and humoral immune response in SARS CoV-2 vaccination, whereas patients receiving B-cell depleting therapies mount an intact cellular immune response. These data can support clinicians in counselling their PwMS and NMOSD patients during the COVID 19 pandemic.

Feasibility and acceptability of daily testing at school as an alternative to self-isolation following close contact with a confirmed case of COVID-19: A qualitative analysis (preprint)

Background Daily testing using a rapid Lateral Flow Device (LFD) has been suggested as an alternative to self-isolation. A randomised trial comparing daily contact testing (DCT) in schools with self-isolation found that SARS-CoV-2 transmission within school was comparable and low in both groups. However, if this approach is to be adopted widely, it is critical that we understand the perspective of those who will be delivering and receiving DCT. The aim of this qualitative process study embedded in the randomised controlled trial (RCT) was to improve understanding of a range of behavioural factors that could influence implementation. Methods Interviews were conducted with 63 participants, including staff, students, and parents of students who had been identified as being in close contact with someone with COVID-19. The topic guide explored perceptions of daily testing, understanding of positive and negative test results, and adherence to guidance. Data were analysed using an inductive thematic approach. Results Results were organised under three main headings: (1) factors influencing daily testing (2) interpretation of test results (3) behaviour during testing period. Participants recognized that daily testing may allow students to remain in school, which was viewed as necessary for both education and social needs. Whilst some felt safer as a result of daily testing, others raised concerns about safety. Participants did not always understand how to interpret and respond to test results, and although participants reported high levels of adherence to the guidance, improved communications were desired. Conclusion Daily testing may be a feasible and acceptable alternative to self-isolation among close contacts of people who test positive. However, improved communications are needed to ensure that all students and parents have a good understanding of the rationale for testing, what test results mean, how test results should be acted on, and how likely students are to test positive following close contact. Support is needed for students and parents of students who have to self-isolate and for those who have concerns about the safety of daily testing.