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

Further education outside the jurisdiction of local authorities in post-war England

This paper revisits the three decades following the end of World War Two – a time when, following the 1944 Education Act, local education authorities (LEAs) were the key agencies responsible for running the education system across England. For the first time there was a statutory requirement for LEAs to secure adequate facilities for further education (FE), and the post-war era is generally remembered as a period when they dominated FE. Yet this is not the full story of further education in post-war England: it is often forgotten that a significant amount of FE existed outside the municipal framework. This paper returns to the post-war decades and begins to uncover the largely forgotten history of FE outside local authority control at that time. It highlights how voluntary and private organisations offered various forms of post-compulsory education outside the municipal framework, and how they contributed to the eclectic and diverse nature of FE across England. This, I argue, reflected not only the expedience, compromise and inertia that characterised further education in post-war England but was rooted in a capture of educational policy more generally by a privileged elite intent on maintaining a social order characterised by social, economic and cultural divisions

Problem solving for breast health care delivery in low and middle resource countries (LMCs): consensus statement from the Breast Health Global Initiative.

Item does not contain fulltextInternational collaborations like the Breast Health Global Initiative (BHGI) can help low and middle income countries (LMCs) to establish or improve breast cancer control programs by providing evidence-based, resource-stratified guidelines for the management and control of breast cancer. The Problem Solving Working Group of the BHGI 2010 Global Summit met to develop a consensus statement on problem-solving strategies addressing breast cancer in LMCs. To better assess breast cancer burden in poorly studied populations, countries require accurate statistics regarding breast cancer incidence and mortality. To better identify health care system strengths and weaknesses, countries require reasonable indicators of true health system quality and capacity. Using qualitative and quantitative research methods, countries should formulate cancer control strategies to identify both system inefficiencies and patient barriers. Patient navigation programs linked to public advocacy efforts feed and strengthen functional early detection and treatment programs. Cost-effectiveness research and implementation science are tools that can guide and expand successful pilot programs.1 april 201