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

A multi-criteria weight of evidence approach for deriving ecological benchmarks for radioactive substances

Dose rate benchmarks are required in the tiered approaches used to screen out benign exposure scenarios in radiological ecological risk assessment. Such screening benchmarks, namely the predicted no-effect dose rates (PNEDR), have been derived by applying, as far as possible, the European guidance developed for chemicals. To derive the ecosystem level (or generic) PNEDR, radiotoxicity EDR10 data (dose rates giving a 10% effect in comparison with the control) were used to fit a species sensitivity distribution (SSD) and estimate the HDR5 (the hazardous dose rate affecting 5% of species with a 10% effect). Then, a multi-criteria approach was developed to justify using an assessment factor (AF) to apply to the HDR5 for estimating a PNEDR value. Several different statistical data treatments were considered which all gave reasonably similar results. The suggested generic screening value of 10 μGy h−1 (incremental dose rate) was derived using the lowest available EDR10 value per species, an unweighted SSD, and an AF of 2 applied to the estimated HDR5. Consideration was also given to deriving screening benchmark values for organism groups but this was not thought to be currently appropriate due to few relevant data being currently available

Protection of the environment from ionising radiation in a regulatory context (PROTECT): Review of current regulatory approaches to both chemicals and radioactive substances

Assessment tools and frameworks have been developed that allow environmental assessments to be conducted and which can be used to demonstrate whether non-human species are protected from the impact of exposure to ionising radiation released under regulation. Frameworks are often tiered, increasing in the level of complexity, input data requirements and need for expert involvement as the assessment moves to successively higher tiers. These are, conceptually, similar to assessment approaches available for chemical risk assessment. What criteria (e.g. numeric benchmarks) should be used, and how these should be defined, are currently under debate, but it is likely that use will be made of approaches developed for setting assessment criteria for chemicals. However it will be necessary to ensure that any assessment criteria developed are fit for use in a regulatory context. This paper reviews the similarities and differences between regulation of, and assessment methods for, chemicals and radioactive substances and presents recommendations regarding how components of chemicals risk assessment may be adopted for radioactive substances

Protection of the environment from ionising radiation in a regulatory context - an overview of the PROTECT coordinated action project

The outcome of the PROTECT project (Protection of the Environment from Ionising Radiation in a Regulatory Context) is summarised, focusing on the protection goal and derivation of dose rates which may detrimentally affect wildlife populations. To carry out an impact assessment for radioactive substances, the estimated dose rates produced by assessment tools need to be compared with some form of criteria to judge the level of risk. To do this, appropriate protection goals need to be defined and associated predefined dose rate values, or benchmarks, derived and agreed upon. Previous approaches used to estimate dose rates at which there may be observable changes in populations or individuals are described and discussed, as are more recent derivations of screening benchmarks for use in regulatory frameworks. We have adopted guidance and procedures used for assessment and regulation of other chemical stressors to derive benchmarks. On the basis of consultation with many relevant experts, PROTECT has derived a benchmark screening dose rate, using data on largely reproductive effects to derive species sensitivity distributions, of 10 μGy h−1 which can be used to identify situations which are below regulatory concern with a high degree of confidence