SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination

BACKGROUND: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. METHODS: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. FINDINGS: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. INTERPRETATION: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. FUNDING: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript

Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain–gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials

Concepções de professores sobre inclusão escolar e interações em ambiente inclusivo: uma revisão da literatura Conceptions of teachers on school inclusion and inclusive environment interactions: a review of the literature

A educação inclusiva tem sido um desafio para diferentes profissionais que trabalham na promoção do desenvolvimento de alunos com deficiência. Estes têm a escola como um espaço fundamental para promover o desenvolvimento social, emocional e acadêmico, a partir de oportunidades de vivências estimuladoras da interação e mediação para a aprendizagem de significados e sentidos e que contribuem para processos de resiliência. Este estudo analisou o conteúdo de publicações nacionais da última década (2000-2010) sobre concepções de professores a respeito da inclusão de alunos com alguma necessidade educativa especial (NEE) e interações no contexto educacional inclusivo, também identificando fatores facilitadores e impeditivos da efetivação das diretrizes educacionais existentes. Após busca sistemática na Biblioteca Virtual em Saúde - Psicologia (BVS-PSI), com as palavras-chave: professor, educação inclusiva, interação, educação especial, escola, aprendizagem, concepções, deficiência intelectual, mediação, desenvolvimento e relacionamento, 29 artigos foram recuperados e lidos na íntegra. Verificou-se um predomínio de autores da área da Psicologia e de coletas de dados realizadas via entrevista e questionário. Os estudos apresentaram concepções sobre deficiência ligadas a características individuais que causam limitações. A falta de apoio de equipe especializada, de materiais didáticos e assistivos, de formação e preparo foram apontados como principais fatores que dificultam a efetivação dos princípios inclusivos. A literatura mostra a necessidade de capacitação dos professores. Diante disso, sugerem-se novos estudos sobre a saúde do professor e suas concepções sobre a inclusão escolar, além da necessidade de intervenções escolares baseadas na problematização dos determinantes sociais e históricos associados às deficiências apresentadas e ao mal-estar docente.<br>Inclusive education has been a challenge for different professionals engaged in promoting the development of students with disabilities. Schools have been an essential place for promoting social, emotional and academic development, because they enable opportunities for experiences that stimulate interaction and mediation of learning of significant content, while contributing towards resilience processes. This study analyzed the content of national studies published between 2000 and 2010 on teachers' conceptions of inclusion of pupils with educational needs and interactions in the context of inclusive education; it also aimed to identify factors that facilitate and hinder effectiveness of educational guidelines. After a systematic search of the BVS-PSI portal using the keywords teacher, inclusive education, interaction, special education, school, learning, conceptions, mental disability, mediation, development and relationship, 29 articles were encountered. There was a predominance of authors in the field of psychology. Data collection was conducted via interview and questionnaire. The studies showed deficiencies linked to concepts of individual characteristics that may cause limitations. The lack of support from specialized staff, teaching materials and assistive training and preparation were identified as the main factors hindering successful implementation of inclusive principles. The literature shows the need for teacher development. Given the results, the authors suggest further studies on the health of teachers, investigation into their conceptions of inclusion, as well as the need for intervention in schools considering historical and social determinants of disabilities and factors undermining teacher well-being