COVID-19 infection after SARS-CoV-2 mRNA vaccination in Multiple Sclerosis, AQP4-antibody NMOSD and MOGAD patients during the Omicron subvariant BA.1/2 wave in Singapore.

BACKGROUND: The SARS-CoV-2 Omicron variant appears to cause milder infections, however, its capacity for immune evasion and high transmissibility despite vaccination remains a concern, particularly in immunosuppressed patients. Herein, we investigate the incidence and risk factors for COVID-19 infection in vaccinated adult patients with Multiple Sclerosis (MS), Aquaporin-4-antibody Neuromyelitis Optica Spectrum Disorder (AQP4-Ab NMOSD), and Myelin Oligodendrocyte Glycoprotein-antibody associated disease (MOGAD) during the Omicron subvariant BA.1/2 wave in Singapore. METHODS: This was a prospective observational study conducted at the National Neuroscience Institute, Singapore. Only patients who had at least two doses of mRNA vaccines were included. Data on demographics, disease characteristics, COVID-19 infections and vaccinations, and immunotherapies were collected. SARS-CoV-2 neutralising antibodies were measured at various time points after vaccination. RESULTS: Two hundred and one patients were included; 47 had COVID-19 infection during the study period. Multivariable logistic regression revealed that receipt of a third SARS-CoV-2 mRNA vaccination (V3) was protective against COVID-19 infection. No particular immunotherapy group increased the risk of infection, however, Cox proportional-hazards regression showed that patients on anti-CD20s and sphingosine-1-phosphate modulators (S1PRMs) had a shorter time to infection after V3, compared to those on other immunotherapies or not on immunotherapy. CONCLUSIONS: The Omicron subvariant BA.1/2 is highly infectious in patients with central nervous system inflammatory diseases; three doses of mRNA vaccination improved protection. However, treatment with anti-CD20s and S1PRMs predisposed patients to earlier infection. Future studies are required to determine the protective efficacy of newer bivalent vaccines that target the Omicron (sub)variant, especially in immunocompromised patients.

Low incidence of neurological recurrent side-effects following COVID-19 reimmunization.

BACKGROUND: Individuals who suffered a neurological adverse event after COVID-19 vaccine could hesitate and defer reimmunization. AIM: We examine the risk of recurrence following reimmunization among patients who developed a neurological event after first dose of COVID-19 mRNA vaccine. DESIGN: Observational study. METHODS: Individuals who developed an adjudicated neurological adverse event (based on Brighton Collaboration criteria) within 6 weeks of first dose of COVID-19 vaccine requiring hospitalization were enrolled into a multi-center national registry in Singapore. Neurological recurrence, defined by development of another neurological event within 6 weeks of second vaccine dose, was reviewed. Clinical characteristics were compared between patients who chose to proceed or withhold further vaccination, and between those who received timely (3-6 weeks) or delayed (>6 weeks) reimmunization. RESULTS: From 235 patients (median age, 67 years; 63% men) who developed an adjudicated neurological event after their first dose of mRNA vaccine between 30 December 2020 and 20 April 2021, 181 (77%) chose to undergo reimmunization. Those who decided against reimmunization were older (median age, 74 vs 66 years) and had greater physical disability following their primary neurological event (46% vs 20%, p < 0.001). Patients who suffered greater physical disability were 3 times more likely to delay their reimmunization (odds ratio 3.36, 95% CI: 1.76-6.40). Neurological recurrence was observed in only 4 individuals (3 with seizures and 1 with myasthenia gravis exacerbation). CONCLUSION: A prior neurological event should not necessarily preclude reimmunization and the decision to proceed with reimmunization should consider the overwhelming benefits conferred by vaccination towards ending this pandemic.

Social–Emotional Learning in Action with Young Elementary Students through StoryWalk

Innovative school-based programs to promote students’ social–emotional skills and academic success have never been more necessary than in the wake of the COVID-19 pandemic (Yoder et al., 2020), particularly in communities disproportionately impacted by the pandemic as well as by high violence and poverty (Schwartz et al., 2021). Remote home-based learning has deprived young people of valuable social, emotional, and academic instruction. In this context, promoting young students’ self-compassion and confidence while encouraging them to develop skills is critical for their long-term success (Yoder et al., 2020). Given the sedentary nature of home-based learning, the advantages of pairing movement and learning in terms of academic outcomes (Lengel & Kuczala, 2010) may be even more important. StoryWalk, an innovative community literary activity, can address a multitude of concern areas. This Practice Highlights column describes the implementation process, challenges, and successes of StoryWalk in a an Illinois community that has predominantly racial/ethnic minority students;high rates of violence, crime, and adverse health behaviors;a 30.5 percent poverty rate (U.S. Census Bureau, 2020);and a ranking of 11 in the list of 101 counties in the state for admissions to its juvenile detention center (Illinois Juvenile Justice Commission, 2020).

Determining the Prevalence and Correlates of COVID-19 Booster Vaccine Hesitancy in the Singapore Population Following the Completion of the Primary Vaccination Series.

In response to declining vaccine-induced immunity and the emergence of new COVID-19 variants, COVID-19 booster vaccination programmes have been widely launched in several high-income countries. However, public response has been slow, and scepticism about these programmes is rising in these settings. This study sought to identify the sociodemographic, emotional, and psychological factors associated with COVID-19 booster vaccine hesitancy in Singapore. Derived from a community cohort, 1005 fully vaccinated adults (62.1% female, mean age = 42.6 years) that had not received their COVID-19 booster shots completed an online survey between October and November 2021 on vaccination beliefs, intentions, and behaviours. Results indicated that despite completing the primary COVID-19 vaccination, 30.5% of those surveyed were hesitant about receiving the booster shot (25.9% unsure; 4.7% refused the booster), and 39.2% perceived more vaccine risks than benefits. Multivariable models indicated that a tertiary education, lower COVID-19 threat perception, lower perceived benefits, higher perceived concerns, a decreased need for booster vaccination, and a lower benefit/concerns differential score were associated with higher odds of booster vaccine hesitancy. Success in the primary vaccination series may not warrant widespread public acceptance for recurrent COVID-19 vaccination doses. In addressing booster vaccine hesitancy as restrictive measures and mandates are lifted, health perceptions relevant or unique to booster vaccine uptake should be considered.

COVID-19 infection after two doses of SARS-CoV-2 mRNA vaccine in multiple sclerosis, AQP4-antibody NMOSD and MOGAD.

BACKGROUND: In pre-vaccinated people with multiple sclerosis (MS), certain disease-modifying therapies (DMTs), particularly the anti-CD20 treatments, appear to be associated with an increased risk of COVID-19 infection and indeed with severe infection. It is still not known if such observations extend to vaccinated individuals and there have been considerably fewer studies in aquaporin-4-antibody neuromyelitis optica spectrum disorder (AQP4-NMOSD) and myelin oligodendrocyte glycoprotein-antibody associated disease (MOGAD) patients. In this study, we investigated the rates of symptomatic COVID-19 infection in adult patients with MS, AQP4-NMOSD and MOGAD who had received 2 doses of SARS-CoV-2 mRNA vaccine. METHODS: This was a prospective observational study conducted at the 2 main neuroimmunology referral centres in Singapore. Only patients on active follow-up were recruited to ensure robust data collection. Data on demographics, disease history, DMTs and SARS-CoV-2 mRNA vaccinations were recorded, and for those infected with COVID-19, data on COVID-19 infection was collected. RESULTS: Nineteen (13 MS, 5 AQP4-NMOSD, 1 MOGAD) out of 365 (231 MS, 106 AQP4-NMOSD, 28 MOGAD) patients had COVID-19 infection despite 2 doses of SARS-CoV-2 mRNA vaccine. Amongst the infected patients, 11 patients were on DMTs (3 rituximab, 2 interferons, 1 azathioprine, 1 mycophenolate, 1 prednisolone, 1 cladribine, 1 alemtuzumab, 1 fingolimod), while 8 patients were untreated. The crude infection rate was calculated using time-at-risk analysis, revealing that rituximab had the highest infection rate amongst all the DMTs. A lower crude infection rate was observed in patients who received a third vaccination. The majority of infections were mild and no patients required oxygen supplementation. CONCLUSION: Our findings suggest that patients on rituximab are still at risk of COVID-19 infection after 2 vaccinations and the receipt of a third vaccination may help to prevent infection. Future large scale studies will be required to better delineate the infection risk of different DMTs after the second and subsequent vaccinations.

Effective online large-group teaching in health professions education.

Online large-group teaching (OLGT), employed to reach a large group of learners in separate physical locations, allows asynchronous learning and facilitates social distancing. While online large-groups can be a powerful and resource-lean means of health professions education, it has challenges and potential pitfalls that may affect the learning process and outcomes. Through a sociomateriality framework, this article describes strategies for effective online large-group teaching in health professions education in three key strands. Firstly, to optimize learning, OLGT sessions should match learning needs with appropriate OLGT platforms, incorporate strategies to sustain learner attention, and accommodate learners of different abilities. Secondly, to develop a learning culture, OLGT must not only focus on cognitive aspects of learning but also build a community of practice, nurture digital professionalism and professional identity. Thirdly, we discuss the avoidance of pitfalls such as cognitive overload of both tutors and learners, technical issues and security risks, mitigating inequities in access to online learning, and the use of program evaluation to plan for sustained improvements. We conclude with a case vignette that discusses the challenges of OLGT and the application of the above strategies in a teaching scenario.

Incidence of Cerebral Venous Thrombosis Following SARS-CoV-2 Infection vs mRNA SARS-CoV-2 Vaccination in Singapore.

Importance: Reports of cerebral venous thrombosis (CVT) after messenger RNA (mRNA)-based SARS-CoV-2 vaccination has caused safety concerns, but CVT is also known to occur after SARS-CoV-2 infection. Comparing the relative incidence of CVT after infection vs vaccination may provide a better perspective of this complication. Objective: To compare the incidence rates and clinical characteristics of CVT following either SARS-CoV-2 infection or mRNA-based SARS-CoV-2 vaccines. Design, Setting, and Participants: Between January 23, 2020, and August 3, 2021, this observational cohort study was conducted at all public acute hospitals in Singapore, where patients hospitalized with CVT within 6 weeks of SARS-CoV-2 infection or after mRNA-based SARS-CoV-2 vaccination (BNT162b2 [Pfizer-BioNTech] or mRNA-1273 [Moderna]) were identified. Diagnosis of SARS-CoV-2 infection was based on quantitative reverse transcription-polymerase chain reaction or positive serology. National SARS-CoV-2 infection data were obtained from the National Centre for Infectious Disease, Singapore, and vaccination data were obtained from the National Immunisation Registry, Singapore. Exposures: SARS-CoV-2 infection or mRNA-based SARS-CoV-2 vaccines. Main Outcomes and Measures: Clinical characteristics, crude incidence rate (IR), and incidence rate ratio (IRR) of CVT after SARS-CoV-2 infection and after mRNA SARS-CoV-2 vaccination. Results: Among 62 447 individuals diagnosed with SARS-CoV-2 infections included in this study, 58 989 (94.5%) were male; the median (range) age was 34 (0-102) years; 6 CVT cases were identified (all were male; median [range] age was 33.5 [27-40] years). Among 3 006 662 individuals who received at least 1 dose of mRNA-based SARS-CoV-2 vaccine, 1 626 623 (54.1%) were male; the median (range) age was 50 (12-121) years; 9 CVT cases were identified (7 male individuals [77.8%]; median [range] age: 60 [46-76] years). The crude IR of CVT after SARS-CoV-2 infections was 83.3 per 100 000 person-years (95% CI, 30.6-181.2 per 100 000 person-years) and 2.59 per 100 000 person-years (95% CI, 1.19-4.92 per 100 000 person-years) after mRNA-based SARS-CoV-2 vaccination. Six (66.7%) received BNT162b2 (Pfizer-BioNTech) vaccine and 3 (33.3%) received mRNA-1273 (Moderna) vaccine. The crude IRR of CVT hospitalizations with SARS-CoV-2 infection compared with those who received mRNA SARS-CoV-2 vaccination was 32.1 (95% CI, 9.40-101; P < .001). Conclusions and Relevance: The incidence rate of CVT after SARS-CoV-2 infection was significantly higher compared with after mRNA-based SARS-CoV-2 vaccination. CVT remained rare after mRNA-based SARS-CoV-2 vaccines, reinforcing its safety.

Leveraging Social–Emotional Learning to Promote Excellence and Diversity, Equity, and Inclusion: A District–University Partnership

Social–emotional learning (SEL) has never been more important as the nation rebuilds after the COVID-19 pandemic and grapples with ongoing racial injustice. More work is needed to promote racial healing in our nation’s schools. Diversity, equity, and inclusion (DEI) work in the midst and aftermath of the pandemic is challenging;effort, engagement, and trust-building are required to produce sustainable change that truly makes a difference for students. This column features a successful district–university partnership that focuses on SEL as a lever to promote student excellence and DEI. We reflect on the process of beginning this partnership, highlight three key principles, and offer suggestions for establishing and sustaining such partnerships.

Evaluating Rates and Determinants of COVID-19 Vaccine Hesitancy for Adults and Children in the Singapore Population: Strengthening Our Community's Resilience against Threats from Emerging Infections (SOCRATEs) Cohort.

COVID-19 vaccines are crucial for achieving sufficient immunisation coverage to manage the pandemic, but vaccine hesitancy persists. This study aimed to investigate the prevalence and determinants of vaccine hesitancy in adults and in parents for vaccinating their children using an integrated social cognition model. A community-based cohort in Singapore [N = 1623] completed a survey (wave 25) between June and July 2021 which measured their risk perceptions, distress, trust, vaccination beliefs, and vaccine intentions/behaviours. Results indicated low rates of hesitancy (9.9%) for own vaccination, with most concerns citing side effects, safety, and hasty development. Remaining respondents were vaccinated (69%) or intended to vaccinate (21%). The multivariable model (non-vaccinated respondents) indicated that, living with people in poor health, subjective norm, moral norm, benefits, and necessity of vaccination were associated with lower vaccine hesitancy (R2 Cox & Snell: 51.4%; p < 0.001). Hesitancy rates were higher for children's vaccination (15.9%), with male gender, lower perceived vaccine benefits, high COVID-19 risk perceptions, vaccination concerns, and necessity beliefs associated with higher odds of parental vaccine hesitancy (R2 Cox & Snell = 36.4%; p < 0.001). While levels of vaccine acceptance are high, more targeted messages are needed. For adults' vaccination, more emphasis should be on benefits and social gains, while for parental hesitancy, messages related to safety should be prioritised.

Impact of Covid-19 on the therapeutic plasma exchange service within the South East Asian region: Consensus recommendations and global perspectives.

INTRODUCTION: Therapeutic plasma exchange (TPE) for neuroimmunological disorders has played an increasingly important role within the Southeast Asian (SEA) region. The South East Asian Therapeutic Plasma exchange Consortium (SEATPEC) was formed in 2018 to promote education and research on TPE within the region. The advent of the Covid-19 pandemic has produced challenges for the development and expansion of this service. METHODOLOGY: A qualitative and semi-quantitative questionnaire-based survey was conducted by SEATPEC member countries from January to June 2020 (Phase 1) and then from July 2020 to January 2021 in (Phase 2) to assess the impact of Covid-19 on regional TPE. OBJECTIVES: The study's main objectives were to explore the challenges experienced and adaptations/adjustments taken by SEATPEC countries in order to continue safe and efficient TPE during the Covid-19 pandemic. RESULTS: The pandemic was found to disrupt the delivery of TPE services in all SEATPEC countries. Contributing factors were multifactorial due to overstretched medical services, staff shortages, quarantines and redeployments, fear of acquiring Covid-19, movement restriction orders, and patient's psychological fear of attending hospitals/testing for Covid-19. All SEATPEC countries practiced careful stratification of cases for TPE (electives vs emergencies, Covid-19 vs non-Covid-19 cases). SEATPEC countries had to modify TPE treatment protocols to include careful preprocedure screening of patient's for Covid-19, use of personal protective equipment (PPE) and post-TPE sanitization of machines and TPE suites. CONCLUSION: Based on the responses of the survey, SEATPEC countries produced a consensus statement with five recommendations for safe and effective TPE within the region.

Personal protective equipment training for non-healthcare workers in the Covid-19 pandemic: Effectiveness of an evidence-based skills training framework.

BACKGROUND: Large-scale quarantine facilities staffed with non-healthcare workers (NHCW) were instrumental in preventing community spread of COVID-19 (coronavirus disease of 2019). The objective of this study was to determine the effectiveness of a newly developed procedural skills training framework in ensuring personal protective equipment (PPE) compliance of PPE-naïve NHCWs. METHODS: We developed a PPE procedural skills training framework for NHCWs using the Learn, See, Practice, Prove, Do, and Maintain (LSPPDM) framework and international guidelines on PPE for healthcare workers. The NHCWs underwent PPE training using this framework, conducted by a team of Infection Prevention nurses, prior to being stationed within the CCF. Effectiveness of the LSPPDM PPE training framework was assessed using: 1) competency assessment scores for NHCWs, 2) PPE compliance rates from daily audit findings, and, 3) healthcare-associated COVID-19 infection rates of NHCWs. RESULTS: A total of 883 NHCWs had completed the PPE training and demonstrated competency in PPE compliance, fulfilling 100% of the checklist requirements. Mean PPE compliance of all NHCWs during the 11-week study period was noted to be >96%. The post-implementation improvement was statistically significant when the compliance was expressed in 3-days blocks) and in bed management staff (P = < 0.05). None of the 883 NHCWs who underwent PPE training via the LSPPDM framework were diagnosed with healthcare-associated COVID-19 infection. CONCLUSION: An evidence-based skills training framework is effective in PPE training of large numbers of NHCWs, resulting in high compliance of appropriate PPE use and prevention of healthcare-associated COVID-19 infection.

Kidcope and the COVID-19 Pandemic: Understanding High School Students' Coping and Emotional Well-Being.

The COVID-19 pandemic has resulted in social isolation, grief, and loss among many adolescents. As the pandemic continues to impact individuals and communities across the globe, it is critical to address the psychological well-being of youths. More studies are needed to understand the effective ways adolescents cope with pandemic-related psychological distress. In this study, 146 students from 1 high school in a U.S. midwestern state completed an adapted version of Kidcope, a widely used coping instrument in disaster research, and measures were taken on generalized distress and COVID-19-related worries. Findings indicated that most students experienced COVID-19-related fears and general emotional distress. Additionally, we found that disengagement coping strategies were associated with lower general distress (p ≤ 0.05) and COVID-19 worries (p ≤ 0.10). Active coping was not associated with general distress and COVID-19 worries. Overall, our findings highlight the need to develop tailored interventions targeting youth coping strategies to reduce and prevent emotional distress and amplify healthy coping skills as the pandemic persists.

Combination Treatment With Remdesivir and Ivermectin Exerts Highly Synergistic and Potent Antiviral Activity Against Murine Coronavirus Infection.

The recent COVID-19 pandemic has highlighted the urgency to develop effective antiviral therapies against the disease. Murine hepatitis virus (MHV) is a coronavirus that infects mice and shares some sequence identity to SARS-CoV-2. Both viruses belong to the Betacoronavirus genus, and MHV thus serves as a useful and safe surrogate model for SARS-CoV-2 infections. Clinical trials have indicated that remdesivir is a potentially promising antiviral drug against COVID-19. Using an in vitro model of MHV infection of RAW264.7 macrophages, the safety and efficacy of monotherapy of remdesivir, chloroquine, ivermectin, and doxycycline were investigated. Of the four drugs tested, remdesivir monotherapy exerted the strongest inhibition of live virus and viral RNA replication of about 2-log10 and 1-log10, respectively (at 6 µM). Ivermectin treatment showed the highest selectivity index. Combination drug therapy was also evaluated using remdesivir (6 µM) together with chloroquine (15 µM), ivermectin (2 µM) or doxycycline (15 µM) - above their IC50 values and at high macrophage cell viability of over 95%. The combination of remdesivir and ivermectin exhibited highly potent synergism by achieving significant reductions of about 7-log10 of live virus and 2.5-log10 of viral RNA in infected macrophages. This combination also resulted in the lowest cytokine levels of IL-6, TNF-α, and leukemia inhibitory factor. The next best synergistic combination was remdesivir with doxycycline, which decreased levels of live virus by ~3-log10 and viral RNA by ~1.5-log10. These results warrant further studies to explore the mechanisms of action of the combination therapy, as well as future in vivo experiments and clinical trials for the treatment of SARS-CoV-2 infection.

Neurology of COVID-19 in Singapore.

PURPOSE: To describe the spectrum of COVID-19 neurology in Singapore. METHOD: We prospectively studied all microbiologically-confirmed COVID-19 patients in Singapore, who were referred for any neurological complaint within three months of COVID-19 onset. Neurological diagnoses and relationship to COVID-19 was made by consensus guided by contemporaneous literature, refined using recent case definitions. RESULTS: 47,572 patients (median age 34 years, 98% males) were diagnosed with COVID-19 in Singapore between 19 March to 19 July 2020. We identified 90 patients (median age 38, 98.9% males) with neurological disorders; 39 with varying certainty of relationship to COVID-19 categorised as: i) Central nervous system syndromes-4 acute disseminated encephalomyelitis (ADEM) and encephalitis, ii) Cerebrovascular disorders-19 acute ischaemic stroke and transient ischaemic attack (AIS/TIA), 4 cerebral venous thrombosis (CVT), 2 intracerebral haemorrhage, iii) Peripheral nervous system-7 mono/polyneuropathies, and a novel group, iv) Autonomic nervous system-4 limited dysautonomic syndromes. Fifty-one other patients had pre/co-existent neurological conditions unrelated to COVID-19. Encephalitis/ADEM is delayed, occurring in critical COVID-19, while CVT and dysautonomia occurred relatively early, and largely in mild infections. AIS/TIA was variable in onset, occurring in patients with differing COVID-19 severity; remarkably 63.2% were asymptomatic. CVT was more frequent than expected and occurred in mild/asymptomatic patients. There were no neurological complications in all 81 paediatric COVID-19 cases. CONCLUSION: COVID-19 neurology has a wide spectrum of dysimmune-thrombotic disorders. We encountered relatively few neurological complications, probably because our outbreak involved largely young men with mild/asymptomatic COVID-19. It is also widely perceived that the pandemic did not unduly affect the Singapore healthcare system.