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

Transition Cow Management and Outcomes in Northeast Herds

This information was presented at the 2016 Cornell Nutrition Conference for Feed Manufacturers, organized by the Department of Animal Science In the College of Agriculture and Life Sciences at Cornell University. Softcover copies of the entire conference proceedings may be purchased at http://ansci.cals.cornell.edu/extension-outreach/adult-extension/dairy-management/order-proceedings-resources

Protein and Amino Acid Nutrition of the Transition Cow

This information was presented at the 2013 Cornell Nutrition Conference for Feed Manufacturers, organized by the Department of Animal Science in the College of Agriculture and Life Sciences at Cornell University. Softcover copies of the entire conference proceedings may be purchased at http://www.ansci.cornell.edu/dm/proceedings_orders.html or by calling (607)255-4285

Transition cow nutrition and management strategies of dairy herds in the northeastern United States: Part III—Associations of management and dietary factors with analytes, health, milk yield, and reproduction

ABSTRACT: The objective was to evaluate relationships between putative periparturient management and dietary factors at the pen and herd levels with metabolic- and inflammation-related analytes, health disorders, milk yield, and reproductive performance. Multiparous and primiparous cows from 72 farms in the northeastern United States were enrolled in a prospective cohort study. Farms were visited 3 times during the prepartum and postpartum periods: during the far-off dry, close-up dry, and fresh periods. Pen measurements were taken at each visit for the pens where cows sampled were housed, and particle size was determined for the total mixed ration for the pen. A survey was used to acquire data on herd-level management variables. Blood samples were collected from the same 11 to 24 cows per farm during the close-up and fresh period visits. Whole blood was analyzed for postpartum β-hydroxybutyrate (BHB) concentrations, and plasma was analyzed for prepartum and postpartum nonesterified fatty acids (NEFA) and postpartum haptoglobin (Hp) concentrations. Health event, milk yield, and reproductive records were acquired through the records management software program used on the farm. For the pen-level analysis, primiparous and multiparous cows were analyzed separately. For the pen- and herd-level analysis, a simple linear regression was conducted on all possible explanatory variables. Variables were included in the full multivariable general linear model if P < 0.20, and a manual backward stepwise elimination process ensued until all variables had P < 0.10. Our results indicate that pen- and herd-level management factors are associated with blood biomarkers, health, milk yield, and reproductive performance. For the prepartum period, our results support increasing the proportion of particles on the 19-mm sieve of the Penn State Particle Separator, optimizing bunk space, and not overfeeding metabolizable energy (ME), to decrease the prevalence of elevated postpartum NEFA, BHB, and Hp concentrations, decrease disorder incidence, maximize milk yield, and improve pregnancy risk to first service. For the fresh period, our results generally support optimizing bunk space, avoiding commingling, increasing feeding frequency, avoiding high physically effective undigested neutral detergent fiber (NDF) after 240 h of in vitro fermentation and high total fermentable carbohydrate diets while optimizing the inclusion of forage NDF, and ensuring adequate diet ME and metabolizable protein to reduce the prevalence of elevated postpartum NEFA, BHB, and Hp concentrations, minimize disorder incidence, maximize milk yield, and improve pregnancy risk to first service. At the herd level, our results generally support not vaccinating in the calving pen, minimizing the number of prepartum and postpartum pen moves, and avoiding long stays in the calving pen after parturition to reduce the prevalence of elevated biomarker concentrations, decrease disorder incidence, increase milk yield, and improve reproductive performance

Relationships Between Transition Cow Nutrition and Management Strategies and Outcomes in Large Dairy Herds in the Northeastern US

Given an increase in nutrient requirements for milk production, decrease in DMI, parturition, management factors such as frequent pen moves, and diet changes, the transition period is arguably the most demanding time in a dairy cow’s life. The objectives of the first part of this study were 1) to establish thresholds for NEFA, BHB, and haptoglobin concentrations that are associated with disease, 2) evaluate the association between the biomarkers with milk production and reproductive performance, and 3) identify herd-alarm levels for the biomarkers that are associated with herd-level changes in disease, milk, and reproductive performance. In addition, limited field data exist that evaluate different management and nutritional strategies that contribute to cow success in commercial farm settings. Therefore, recommendations are often driven by field experience from concepts established through controlled research with comparatively small numbers of cows. The objective of the second part of this study wasto evaluate management and nutritional factors with outcomes on commercial farms, such as disease, prevalence of elevated biomarkers, milk production, and reproductive performance to provide an understanding of how these factors contribute to transition cow success across a range of farm practices