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

Serpentine alteration as source of high dissolved silicon and elevated δ 30 5 Si 6 values to the marine Si cycle

Serpentine alteration is recognized as an important process for element cycling, however, related silicon fluxes are unknown. Pore fluids from serpentinite seamounts sampled in the Mariana forearc region during IODP Expedition 366 were investigated for their Si, B, and Sr isotope signatures (δ30Si, δ11B, and 87Sr/86Sr, respectively) to study serpentinization in the mantle wedge and shallow serpentine alteration to authigenic clays by seawater. While serpentinization in the mantle wedge caused no significant Si isotope fractionation, implying closed system conditions, serpentine alteration by seawater led to the formation of authigenic phyllosilicates, causing the highest natural fluid δ30Si values measured to date (up to +5.2 ± 0.2‰). Here we show that seafloor alteration of serpentinites is a source of Si to the ocean with extremely high fluid δ30Si values, which can explain anomalies in the marine Si budget like in the Cascadia Basin and which has to be considered in future investigations of the global marine Si cycle

Influence of hydraulic loading and effluent flux on surface surcharging in soil absorption systems

The goal of this study was to investigate how extreme hydraulic loading influences hydraulic pathways, and thus failure potential, of two soil absorption systems. A grid of tensiometers and piezometers were installed beneath and adjacent to the absorption trenches, and water height was manipulated to simulate different hydraulic loadings. At both sites, measured soil matric potentials along the trench sidewalls increased toward zero as water height increased over time, indicating that water was preferentially flowing laterally above the biomat zones. Saturated hydraulic conductivity (Ks) of the soil and biomat, and other hydraulic parameters were calibrated using inverse modeling procedures in HYDRUS-2D. We found generally good agreement between measured and predicted matric potentials. The calibrated model was then used to predict fluxes through different infiltrative zones under typical and extreme hydraulic loads. Modeling indicated that the overall infiltration rates through the biomat and subbiomat zones fell within a relatively narrow range of 0.025-0.046m/day at the two sites. Under extreme hydraulic loading to trenches, fluxes through the upper trench sidewalls (i.e., the exfiltration zone) were predicted to be substantially greater (i.e., 80% of total flux) than through the biomat zone. This confirms the conclusions made from field results, that a permeable exfiltration zone provides a critical buffer to surface surcharging during extreme trench loading. Conversely, the presence of a high sidewall biomat can reduce sidewall exfiltration of effluent, and therefore increase the likelihood of surface surcharging

The fluid budget of a continental plate boundary fault: Quantification from the Alpine Fault, New Zealand

Fluids play a key role in modifying the chemical and physical properties of fault zones, which may prime them for repeated rupture by the generation of high pore fluid pressures and precipitation of commonly weak, secondary minerals. Fluid flow paths, sources and fluxes, and the permeability evolution of fault zones throughout their seismic cycles remain poorly constrained, despite their importance to understanding fault zone behaviour. Here we use geochemical tracers of fluid–rock exchange to determine budgets for meteoric, metamorphic and mantle fluids on a major compressional tectonic plate boundary. The Alpine Fault marks the transpressional Pacific–Australian plate boundary through South Island, New Zealand and appears to fail in regular ( 329 ± 68   yrs ) large earthquakes ( M w ∼ 8 ) with the most recent event in 1717 AD. Significant convergent motion has formed the Southern Alps and elevated geothermal gradients in the hangingwall, which drive crustal fluid flow. Along the Alpine Fault the Alpine Schist of the Pacific Plate is thrust over radiogenic metasedimentary rocks on the Australian plate. The absence of highly radiogenic (87Sr/86Sr > 0.7200) strontium isotope ratios of hangingwall hot springs and hydrothermal minerals formed at a range of depths in the Alpine Fault damage zone indicates that the fluid flow is restricted to the hangingwall by a cross-fault fluid flow barrier throughout the seismogenic crust. Helium isotope ratios measured in hot springs near to the Alpine Fault (0.15–0.81 R A ) indicate the fault is a crustal-scale feature that acts as a conduit for fluids from the mantle. Rock-exchanged oxygen, but meteoric water-like hydrogen isotope signatures of hydrothermal veins indicate that partially rock-exchanged meteoric fluids dominate down to the top of the brittle to ductile transition zone at ∼6 km. Geochemical tracer transport modelling suggests only ∼0.02 to 0.05% of total rainfall west of the Main Divide penetrates to depth, yet this recharge flux is sufficient to overwhelm other fluid contributions. Calculated mantle fluid fluxes of CO2 and H2O (0.2 and 3 to 13 mol/m2/yr respectively) and metamorphic H2O fluxes (4 to 750 mol/m2/yr) are considerably lower than the focused meteoric water discharge flux up the Alpine Fault (4 × 103 to 7 × 104 mol/m2/yr), driven by the >3000 m hydrologic head of the Southern Alps. Meteoric waters are primarily responsible for modifying fault zone permeability during fluid–rock interactions and may facilitate the generation of high pore fluid pressures that could assist episodic earthquake rupture

Fault rock lithologies and architecture of the central Alpine fault, New Zealand, revealed by DFDP-1 drilling

The first phase of the Deep Fault Drilling Project (DFDP-1) yielded a continuous lithological transect through fault rock surrounding the Alpine fault (South Island, New Zealand). This allowed micrometer- to decimeter-scale variations in fault rock lithology and structure to be delineated on either side of two principal slip zones intersected by DFDP-1A and DFDP-1B. Here, we provide a comprehensive analysis of fault rock lithologies within 70 m of the Alpine fault based on analysis of hand specimens and detailed petrographic and petrologic analysis. The sequence of fault rock lithologies is consistent with that inferred previously from outcrop observations, but the continuous section afforded by DFDP-1 permits new insight into the spatial and genetic relationships between different lithologies and structures. We identify principal slip zone gouge, and cataclasite-series rocks, formed by multiple increments of shear deformation at up to coseismic slip rates. A 20−30-m-thick package of these rocks (including the principal slip zone) forms the fault core, which has accommodated most of the brittle shear displacement. This deformation has overprinted ultramylonites deformed mostly by grain-size-insensitive dislocation creep. Outside the fault core, ultramylonites contain low-displacement brittle fractures that are part of the fault damage zone. Fault rocks presently found in the hanging wall of the Alpine fault are inferred to have been derived from protoliths on both sides of the present-day principal slip zone, specifically the hanging-wall Alpine Schist and footwall Greenland Group. This implies that, at seismogenic depths, the Alpine fault is either a single zone of focused brittle shear that moves laterally over time, or it consists of multiple strands. Ultramylonites, cataclasites, and fault gouge represent distinct zones into which deformation has localized, but within the brittle regime, particularly, it is not clear whether this localization accompanies reductions in pressure and temperature during exhumation or whether it occurs throughout the seismogenic regime. These two contrasting possibilities should be a focus of future studies of fault zone architecture

Drilling reveals fluid control on architecture and rupture of the Alpine Fault, New Zealand

Rock damage during earthquake slip affects fluid migration within the fault core and the surrounding damage zone, and consequently coseismic and postseismic strength evolution. Results from the first two boreholes (Deep Fault Drilling Project DFDP-1) drilled through the Alpine fault, New Zealand, which is late in its 200–400 yr earthquake cycle, reveal a &gt;50-m-thick “alteration zone” formed by fluid-rock interaction and mineralization above background regional levels. The alteration zone comprises cemented low-permeability cataclasite and ultramylonite dissected by clay-filled fractures, and obscures the boundary between the damage zone and fault core. The fault core contains a &lt;0.5-m-thick principal slip zone (PSZ) of low electrical resistivity and high spontaneous potential within a 2-m-thick layer of gouge and ultracataclasite. A 0.53 MPa step in fluid pressure measured across this zone confirms a hydraulic seal, and is consistent with laboratory permeability measurements on the order of 10?20 m2. Slug tests in the upper part of the boreholes yield a permeability within the distal damage zone of ?10?14 m2, implying a six-orders-of-magnitude reduction in permeability within the alteration zone. Low permeability within 20 m of the PSZ is confirmed by a subhydrostatic pressure gradient, pressure relaxation times, and laboratory measurements. The low-permeability rocks suggest that dynamic pressurization likely promotes earthquake slip, and motivates the hypothesis that fault zones may be regional barriers to fluid flow and sites of high fluid pressure gradient. We suggest that hydrogeological processes within the alteration zone modify the permeability, strength, and seismic properties of major faults throughout their earthquake cycles