Impact of Salmonid alphavirus infection in diploid and triploid Atlantic salmon (Salmo salar L.) fry

With increasing interest in the use of triploid salmon in commercial aquaculture, gaining an understanding of how economically important pathogens affect triploid stocks is important. To compare the susceptibility of diploid and triploid Atlantic salmon (Salmo salar L.) to viral pathogens, fry were experimentally infected with Salmonid alphavirus sub-type 1 (SAV1), the aetiological agent of pancreas disease (PD) affecting Atlantic salmon aquaculture in Europe. Three groups of fry were exposed to the virus via different routes of infection: intraperitoneal injection (IP), bath immersion, or cohabitation (co-hab) and untreated fry were used as a control group. Mortalities commenced in the co-hab challenged diploid and triploid fish from 11 days post infection (dpi), and the experiment was terminated at 17 dpi. Both diploid and triploid IP challenged groups had similar levels of cumulative mortality at the end of the experimental period (41.1 % and 38.9 % respectively), and these were significantly higher (p < 0.01) than for the other challenge routes. A TaqMan-based quantitative PCR was used to assess SAV load in the heart, a main target organ of the virus, and also liver, which does not normally display any pathological changes during clinical infections, but exhibited severe degenerative lesions in the present study. The median viral RNA copy number was higher in diploid fish compared to triploid fish in both the heart and the liver of all three challenged groups. However, a significant statistical difference (p < 0.05) was only apparent in the liver of the co-hab groups. Diploid fry also displayed significantly higher levels of pancreatic and myocardial degeneration than triploids. This study showed that both diploid and triploid fry are susceptible to experimental SAV1 infection. The lower virus load seen in the triploids compared to the diploids may possibly be related to differences in cell metabolism between the two groups, however, further investigation is necessary to confirm this and also to assess the outcome of PD outbreaks in other developmental stages of the fish when maintained in commercial production systems

Relations between Financing and Output in the Not-for-Profit Hospital

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68639/2/10.1177_107755878804500204.pd

Ground-based and JWST observations of SN 2022pul. I. Unusual signatures of carbon, oxygen, and circumstellar interaction in a peculiar type Ia supernova

Nebular-phase observations of peculiar Type Ia supernovae (SNe Ia) provide important constraints on progenitor scenarios and explosion dynamics for both these rare SNe and the more common, cosmologically useful SNe Ia. We present observations from an extensive ground- and space-based follow-up campaign to characterize SN 2022pul, a super-Chandrasekhar mass SN Ia (alternatively "03fg-like" SN), from before peak brightness to well into the nebular phase across optical to mid-infrared (MIR) wavelengths. The early rise of the light curve is atypical, exhibiting two distinct components, consistent with SN Ia ejecta interacting with dense carbon–oxygen (C/O)-rich circumstellar material (CSM). In the optical, SN 2022pul is most similar to SN 2012dn, having a low estimated peak luminosity (MB = −18.9 mag) and high photospheric velocity relative to other 03fg-like SNe. In the nebular phase, SN 2022pul adds to the increasing diversity of the 03fg-like subclass. From 168 to 336 days after peak B-band brightness, SN 2022pul exhibits asymmetric and narrow emission from [O i] λλ6300, 6364 (FWHM ≈ 2000 km s−1), strong, broad emission from [Ca ii] λλ7291, 7323 (FWHM ≈ 7300 km s−1), and a rapid Fe iii to Fe ii ionization change. Finally, we present the first ever optical-to-MIR nebular spectrum of an 03fg-like SN Ia using data from JWST. In the MIR, strong lines of neon and argon, weak emission from stable nickel, and strong thermal dust emission (with T ≈ 500 K), combined with prominent [O i] in the optical, suggest that SN 2022pul was produced by a white dwarf merger within C/O-rich CSM

Ground-based and JWST Observations of SN 2022pul. II. Evidence from nebular spectroscopy for a violent merger in a peculiar type Ia supernova

We present an analysis of ground-based and JWST observations of SN 2022pul, a peculiar "03fg-like" (or "super-Chandrasekhar") Type Ia supernova (SN Ia), in the nebular phase at 338 days postexplosion. Our combined spectrum continuously covers 0.4–14 μm and includes the first mid-infrared spectrum of a 03fg-like SN Ia. Compared to normal SN Ia 2021aefx, SN 2022pul exhibits a lower mean ionization state, asymmetric emission-line profiles, stronger emission from the intermediate-mass elements (IMEs) argon and calcium, weaker emission from iron-group elements (IGEs), and the first unambiguous detection of neon in a SN Ia. A strong, broad, centrally peaked [Ne ii] line at 12.81 μm was previously predicted as a hallmark of "violent merger" SN Ia models, where dynamical interaction between two sub-MCh white dwarfs (WDs) causes disruption of the lower-mass WD and detonation of the other. The violent merger scenario was already a leading hypothesis for 03fg-like SNe Ia; in SN 2022pul it can explain the large-scale ejecta asymmetries seen between the IMEs and IGEs and the central location of narrow oxygen and broad neon. We modify extant models to add clumping of the ejecta to reproduce the optical iron emission better, and add mass in the innermost region (<2000 km s−1) to account for the observed narrow [O i] λλ6300, 6364 emission. A violent WD–WD merger explains many of the observations of SN 2022pul, and our results favor this model interpretation for the subclass of 03fg-like SNe Ia

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

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