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

Current studies of K?-lau-ea and Mauna Kea Volcanoes by the Hawaiian Volcano Observatory of the U.S. Geological Survey

Western Region, National Park Service, Contract #CX8000 6 003

Zircon U-Pb geochronology and trace element dataset from the Southern Rocky Mountain Volcanic Field, Colorado, USA

This contribution provides in-situ LA-ICP-MS U-Pb ages and trace element determinations of zircons from dacitic to rhyolitic lavas, ignimbrites and intrusions in the Southern Rocky Mountain Volcanic Field (SRMVF) in Colorado, USA. The data record a period of intense magmatic activity in the Oligocene-early Miocene (∼37–22 Ma) which gave rise to some of the largest explosive ignimbrites in the geological record (e.g. the Fish Canyon Tuff). Age data are drift corrected, but not corrected for radiation dosage or Th disequilibrium, in order to allow users to apply their own algorithms. Xenocrysts (much older crystals up to 2 Ga from the Proterozoic basement) are included in this record

Gravitational spreading and formation of new rift zones on overlapping volcanoes

Large volcanic edifices are often shaped by the coalescence of adjacent volcanoes as well as intrusive rift zones and gravitational spreading. To better understand the structure of such volcanoes we designed analogue experiments simulating gravitational spreading of an edifice made by overlapping cones of different age, and examined the formation of rift zones. The results allow distinction of two main rift geometries. (i) Spreading edifices of similar age that partly overlap, tend to develop a rift zone approximately perpendicular to the boundary of both volcanoes. Such a rift zone causes two volcanoes to grow together and form an elongated topographic ridge. (ii) Partly overlapping volcanoes of different age are spreading at different rates and thus form a rift zone parallel to the boundary of both volcanoes. Such a rift zone causes two volcanoes to structurally separate. The results are widely applicable for large volcanoes subject to rifting and flank spreading, which we demonstrate for Réunion Island and for southern Hawaii

The effects and consequences of very large explosive volcanic eruptions

Every now and again Earth experiences tremendous explosive volcanic eruptions, considerably bigger than the largest witnessed in historic times. Those yielding more than 450km3 of magma have been called super-eruptions. The record of such eruptions is incomplete; the most recent known example occurred 26000 years ago. It is more likely that the Earth will next experience a super-eruption than an impact from a large meteorite greater than 1km in diameter. Depending on where the volcano is located, the effects will be felt globally or at least by a whole hemisphere. Large areas will be devastated by pyroclastic flow deposits, and the more widely dispersed ash falls will be laid down over continent-sized areas. The most widespread effects will be derived from volcanic gases, sulphur gases being particularly important. This gas is converted into sulphuric acid aerosols in the stratosphere and layers of aerosol can cover the global atmosphere within a few weeks to months. These remain for several years and affect atmospheric circulation causing surface temperature to fall in many regions. Effects include temporary reductions in light levels and severe and unseasonable weather (including cool summers and colder-than-normal winters). Some aspects of the understanding and prediction of super-eruptions are problematic because they are well outside modern experience. Our global society is now very different to that affected by past, modest-sized volcanic activity and is highly vulnerable to catastrophic damage of infrastructure by natural disasters. Major disruption of services that society depends upon can be expected for periods of months to, perhaps, years after the next very large explosive eruption and the cost to global financial markets will be high and sustained

Age and nature of deposits on the submarine flanks of Piton de la Fournaise (Reunion Islands).

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