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

Dynamics of the human upper airway: On the development of a three-dimensional computational model

The advances reported herein form part of a larger project that has as its objective the development of a full flow-structure-interaction model of the human upper airway. Here we first briefly report on a two-dimensional (saggital section) model built using published CT-scan geometric data. For the development of our three-dimensional capability, we use the unique data captured in vivo by an endoscopic optical technique that we have developed. This measurement system, described as anatomical optical coherence tomography (aOCT), allows quantitative real-time imaging of the internal anatomy of the human upper airway with minimal invasiveness. Moreover, the system permits motions of the internal geometry at a fixed location to be recorded. The aOCT data set is insufficient by itself to construct a complete geometry because only the polar coordinates are obtained in a local reference frame. Accordingly, the locus described by the endoscope, in which the aOCT is housed, is obtained by orthogonal CT scans. The combination of CT scans and aOCT measurements then provides the required geometric information for the construction of the computational model. Results of a twodimensional model show how the soft palate responds to the mean-flow variations of the breathing cycle. For the threedimensional work, the key results of this paper rest in the reconstruction of the time-dependent geometry of the upper airway, the first time that this has been accomplished using direct internally-based measurement

Early-type galaxies in the NOAO Fundamental Plane Survey

We review the NOAO Fundamental Plane Survey of nearby X-ray luminous galaxy clusters and present some preliminary results from early data.Peer reviewed: YesNRC publication: Ye

NOAO fundamental plane survey. I. Survey design, redshifts, and velocity dispersion data

We introduce the NOAO Fundamental Plane Survey (NFPS), a wide-field imaging/spectroscopic study of rich, low-redshift galaxy clusters. The survey targets X-rayselected clusters at 0.010 < z < 0.067, distributed over the whole sky, with imaging and spectroscopic observations obtained for 93 clusters. This data set will be used in investigations of galaxy properties in the cluster environment and of large-scale velocity fields through the fundamental plane. In this paper, we present details of the cluster sample construction and the strategies employed to select early-type galaxy samples for spectroscopy. Details of the spectroscopic observations are reported. From observations of 5479 red galaxies, we present redshift measurements for 5388 objects and internal velocity dispersions for 4131. The velocity dispersions have a median estimated error 7%. The NFPS has 15% overlap with previously published velocity dispersion data sets. Comparisons to these external catalogs are presented and indicate typical external errors of 8%

Measurement, reconstruction, and flow-field computation of the human pharynx with application to sleep apnea

Repetitive closure of the upper airway characterizes obstructive sleep apnea. It disrupts sleep causing excessive daytime drowsiness and is linked to hypertension and cardiovascular disease. Previous studies simulating the underlying fluid mechanics are based upon geometries, time-averaged over the respiratory cycle, obtained usually via MRI or CT scans. Here, we generate an anatomically correct geometry from data captured in vivo by an endoscopic optical technique. This allows quantitative real-time imaging of the internal cross section with minimal invasiveness. The steady inhalation flow field is computed using a k- shear-stress transport (SST) turbulence model. Simulations reveal flow mechanisms that produce low-pressure regions on the sidewalls of the pharynx and on the soft palate within the pharyngeal section of minimum area. Soft-palate displacement and side-wall deformations further reduce the pressures in these regions, thus creating forces that would tend to narrow the airway. These phenomena suggest a mechanism for airway closure in the lateral direction as clinically observed. Correlations between pressure and airway deformation indicate that quantitative prediction of the low-pressure regions for an individual are possible. The present predictions warrant and can guide clinical investigation to confirm the phenomenology and its quantification, while the overall approach represents an advancement toward patient-specific modeling