ABSTRACT
This qualitative study is part of Smart Indigenous Youth, a digital health community trial involving rural schools in Saskatchewan, Canada. Secondary school administrators and educators were engaged as citizen scientists in rural Indigenous communities to understand rapid decision-making processes for preserving school health during the COVID-19 pandemic, and to inform evidence-based safe school policies and practices. After COVID-19 restrictions were implemented, key informant interviews and focus groups were conducted with school administrators and educators, respectively, to understand the impact of school responses and decision-making processes. Two independent reviewers conducted thematic analyses and compared themes to reach consensus on a final shortlist. Four main themes emerged from the administrator interviews, and six main themes were identified from the educator focus group discussions which revealed a pressing need for mental health supports for students and educators. The study findings highlight the challenges faced by schools in rural and remote areas during the COVID-19 pandemic, including school closures, students' reactions to closures, measures taken by schools to preserve health during the pandemic, and different approaches to implement for future closures. Citizen scientists developed a set of recommendations, including the need for structured communication, reflection meetings, adequate funding, and external monitoring and evaluation to guide evidence-based safe school policies and practices during the pandemic.
ABSTRACT
Importance People living with multiple sclerosis (MS) and other disorders treated with immunomodulatory therapies remain concerned about suboptimal responses to coronavirus disease 2019 (COVID-19) vaccines. Important questions persist regarding immunological response to third vaccines, particularly with respect to newer virus variants. Objective Evaluate humoral and cellular immune responses to third COVID-19 vaccine dose in people on anti-CD20 therapy and sphingosine 1-phosphate receptor (S1PR) modulators, including Omicron-specific assays. Design Observational study evaluating immunological response to third COVID-19 vaccine dose in volunteers treated with anti-CD20 agents, S1PR modulators, and healthy controls. Neutralizing antibodies against USA-WA1/2020 (WA1) and B.1.1.529 (BA.1) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were measured before and after third vaccine. Cellular responses to spike peptide pools generated from WA1 and BA.1 were evaluated. Setting Mount Sinai Hospital Participants People treated with anti-CD20 therapy or S1PR modulators and healthy volunteers Exposure Treatment with anti-CD20 therapy, S1PR modulator, or neither Main outcomes and measures Serum neutralizing antibodies and ex vivo T cell responses against SARS-CoV-2 antigens. Results This cohort includes 25 participants on anti-CD20 therapy, 12 on S1PR modulators, and 14 healthy controls. Among those on anti-CD20 therapy, neutralizing antibodies to WA1 were significantly reduced compared to healthy controls (ID50% GM post-vaccination of 8.1 ± 2.8 in anti-CD20 therapy group vs 452.6 ± 8.442 healthy controls, P<0.0001) and neutralizing antibodies to BA.1 were below the threshold of detection nearly universally. However, cellular responses, including to Omicron-specific peptides, were not significantly different from controls. Among those on S1PR modulators, neutralizing antibodies to WA1 were detected in a minority, and only 3/12 had neutralizing antibodies just at the limit of detection to BA.1. Cellular responses to Spike antigen in those on S1PR modulators were reduced by a factor of 100 compared to controls (median 0.0008% vs. 0.08%, p<0.001) and were not significantly “boosted” by a third injection. Conclusions and Relevance Participants on immunomodulators had impaired antibody neutralization capacity, particularly to BA.1, even after a third vaccine. T cell responses were not affected by anti-CD20 therapies, but were nearly abrogated by S1PR modulators. These results have clinical implications warranting further study.