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

Exploring Query Patterns in Email Search

Despite Email being the most popular communication medium currently in use and that people have been shown to regularly re-use messages, very little is known about how people actually search within email clients. In this paper we present a detailed analysis of email search behaviour obtained from a study of 47 users. We uncover a number of behavioral patterns that contrast with those previously observed in web search. From our findings, we describe ways in which email search could be improved and conclude with a short discussion of possible future work

A multivariable assessment quantifying effects of cohort-level factors associated with combined mortality and culling risk in cohorts of U.S. commercial feedlot cattle

Economic losses due to cattle mortality and culling have a substantial impact on the feedlot industry. Since criteria for culling may vary and may affect measures of cumulative mortality within cattle cohorts, it is important to assess both mortality and culling when evaluating cattle losses over time and among feedlots. To date, there are no published multivariable assessments of factors associated with combined mortality and culling risk. Our objective was to evaluate combined mortality and culling losses in feedlot cattle cohorts and quantify effects of commonly measured cohort-level risk factors (weight at feedlot arrival, gender, and month of feedlot arrival) using data routinely collected by commercial feedlots. We used retrospective data representing 8,904,965 animals in 54,416 cohorts from 16 U.S. feedlots from 2000 to 2007. The sum of mortality and culling counts for each cohort (given the number of cattle at risk) was used to generate the outcome of interest, the cumulative incidence of combined mortality and culling. Associations between this outcome variable and cohort-level risk factors were evaluated using a mixed effects multivariable negative binomial regression model with random effects for feedlot, year, month and week of arrival. Mean arrival weight of the cohort, gender, and arrival month and a three-way interaction (and corresponding two-way interactions) among arrival weight, gender and month were significantly (P < 0.05) associated with the outcome. Results showed that as the mean arrival weight of the cohort increased, mortality and culling risk decreased, but effects of arrival weight were modified both by the gender of the cohort and the month of feedlot arrival. There was a seasonal pattern in combined mortality and culling risk for light and middleweight male and female cohorts, with a significantly (P < 0.05) higher risk for cattle arriving at the feedlot in spring and summer (March–September) than in cattle arriving during fall, and winter months (November–February). Our results quantified effects of covariate patterns that have been heretofore difficult to fully evaluate in smaller scale studies; in addition, they illustrated the importance of utilizing multivariable approaches when quantifying risk factors in heterogeneous feedlot populations. Estimated effects from our model could be useful for managing financial risks associated with adverse health events based on data that are routinely available