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

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

A theory of the blockage effects on bluff bodies and stalled wings in a closed wind tunnel

SIGLEAvailable from British Library Document Supply Centre- DSC:0678.231F(AD-A--955243)(microfiche) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Impacts of nitrogen deposition on vascular plants in Britain: an analysis of two national observation networks

Large areas of Great Britain currently have nitrogen (N) deposition at rates which exceed the thresholds above which there is risk of damage to sensitive components of the ecosystem (critical loads). Previous studies have focussed primarily on the relationship of species richness to nitrogen, whereas here we look at individual species. We used data from two national observation networks over Great Britain to examine the response of individual vascular plant species to N in acid grasslands, calcareous grasslands and heathlands. Presence absence records of individual species, along with mean Ellenberg N scores, within 10 km hectads were modelled against N deposition whilst at the same time controlling for the effects of climate, land use and sulphur deposition using generalised additive models. Ellenberg N showed a significant increase with increasing N deposition in almost all habitats across both surveys indicating increased fertility. Many individual species showed strong relationships with N deposition and clear negative trends in species prevalence to increasing nitrogen were found in all habitats. A number of these species were either habitat dominants or possessed traits known to be influential in controlling ecosystem function. Many community dominants showing significant negative relationships with N deposition highlight a potentially significant loss of function. Some species that showed negative relationships to N showed signs of decline at low levels, far below the current critical load levels. Some species also showed continuous changes as N deposition levels rose above the current critical load values. This work contributes to the growing evidence base suggesting species level impacts at low N deposition values

Incidence and risk factors for food hypersensitivity in UK infants: results from a birth cohort study

BACKGROUND: The prevalence of food hypersensitivity in the UK is still largely open to debate. Additionally its pathogenesis is also unclear although it is known that there are differing phenotypes. Determining its prevalence, along with identifying those factors associated with its development will help to assess its clinical importance within the national setting and also add to the debate on appropriate prevention strategies.METHODS: A population based birth cohort study conducted in Hampshire, UK as part of the EuroPrevall birth cohort study. 1140 infants were recruited with 823 being followed up until 2 years of age. Infants with suspected food reactions were assessed including specific IgE measurement and skin prick testing. Diagnosis of food hypersensitivity was by positive double-blind, placebo-controlled food challenge (DBPCFC) where symptoms up to 48 h after the end of the food challenge were considered indicative of a food hypersensitivity. Factors associated with food hypersensitivity and its two phenotypes of IgE-mediated and non-IgE-mediated disease were modelled in a multivariable logistic regression analysis.RESULTS: Cumulative incidence of food hypersensitivity by 2 years of age was 5.0 %. The cumulative incidence for individual food allergens were hens' egg 2.7 % (1.6-3.8); cows' milk 2.4 % (1.4-3.5); peanut 0.7 % (0.1-1.3); soy 0.4 % (0.0-0.8); wheat 0.2 % (0.0-0.5) and 0.1 % (0.0-0.32) for fish. The cumulative incidence of IgE-mediated food allergy was 2.6 % with 2.1 % reacting to hens' egg. For non-IgE-mediated food allergy the cumulative incidence was 2.4 % (cows' milk 1.7 %). Predictors for any food hypersensitivity were wheeze, maternal atopy, increasing gestational age, age at first solid food introduction and mean healthy dietary pattern score. Predictors for IgE mediated allergy were eczema, rhinitis and healthy dietary pattern score whereas for non-IgE-mediated food allergy the predictors were dog in the home, healthy dietary pattern score, maternal consumption of probiotics during breastfeeding and age at first solid food introduction.CONCLUSIONS: Just under half the infants with confirmed food hypersensitivity had no demonstrable IgE. In an exploratory analysis, risk factors for this phenotype of food hypersensitivity differed from those for IgE-mediated food allergy except for a healthy infant diet which was associated with less risk for both phenotypes

Introduction of complementary foods and the relationship to food allergy

Objectives: To address questions regarding breastfeeding, complementary feeding, allergy development, and current infant-feeding recommendations. Methods: This was a nested, case-control within a cohort study in which mothers of 41 infants diagnosed with food allergy by the age of 2 years (according to double-blind, placebo-controlled food challenge) and their 82 age-matched controls kept prospective food diaries of how their infants were fed in the first year of life. Results: Infants who were diagnosed with food allergy by the time they were 2 years of age were introduced to solids earlier (?16 weeks of age) and were less likely to be receiving breast milk when cow’s milk protein was first introduced into their diet. Conclusions: This study supports the current American Academy of Pediatrics’ allergy prevention recommendations and the European Society of Pediatric Gastroenterology, Hepatology and Nutrition recommendations on complementary feeding to not introduce solids before 4 to 6 months of age. It also supports the American Academy of Pediatrics’ breastfeeding recommendations that breastfeeding should continue while solids are introduced into the diet and that breastfeeding should continue for 1 year, or longer, as mutually desired by mother and infant