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

In-situ evaluation of the anodic oxide growth on CdxHg1-xTe (MCT) using ellipsometry and second harmonic generation

In-situ measurements of ellipsometry and second harmonic generation (SHG) were carried out to monitor the electrochemical growth of native anodic oxide films on Hg1−xCdxTe (MCT). Growth of the anodic oxide was performed using two different methods viz., by linear sweep voltammetry and by applying a constant current density. The influence of scan rate and the magnitude of the applied current density on the properties of the growing films were examined. From the ellipsometry data, we have shown that the measured refractive index value of 2.19 for the oxide film remains unchanged for moderate and high oxide growth rates. Only at very slow growth rates were significant increases in the refractive index observed (n=2.4), indicating an increase in the compactness of the layer. For film thicknesses in excess of ∼1200 Å, a non-zero value for the extinction coefficient was found, indicating the incorporation of HgTe particles within the anodic oxide film. SHG rotational anisotropy measurements, performed on the MCT with and without an anodic oxide film showed only the four-fold symmetry associated with the MCT and so confirmed that the oxide was centrosymmetric. However, an increase in the SH intensity was observed in the presence of the oxide and this has been attributed to multiple reflections in the thin oxide film and also to the increase in the χ(2) non-linear susceptibility tensor as a result of charge accumulation at the MCT/anodic oxide interface

The Three Basic Types of Residuals for a Linear Model

We consider residuals for the linear model with a general covariance structure. In contrast to the situation where observations are independent there are several alternative definitions. We draw attention to three quite distinct types of residuals: the marginal residuals, the model-specified residuals and the full-conditional residuals. We adopt a very broad perspective including linear mixed models, time series and smoothers as well as models for spatial and multivariate data. We concentrate on defining these different residual types and discussing their interrelationships. The full-conditional residuals are seen to play several important roles. Copyright 2007 The Authors. Journal compilation (c) 2007.