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

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Impacts of spatial patterns in pasture on animal grazing behavior, intake, and performance

Control over the quantity and quality of food ingested by grazing ruminants in temperate pasture systems remains elusive. This is due in part to the foraging choices that animals make when grazing from communities of mixed plant species. Grazing behavior and intake interact strongly with the feed supply-demand balance, pasture composition, and grazing method. These interactions are not completely understood, even for relatively simple pasture communities such as a perennial ryegrass (Lolium perenne L.)-white clover (Trifolium repens L.) mixture. When offered a free choice between these species, ruminants exhibit a partial preference for clover compared to grass (about 0.7:0.3) and have a higher intake rate from clover but do not graze to maximize their daily intake of dry matter (DM). When monocultures of grass and clover are offered as a free choice in 50:50 area ratio, animal performance is no different than from a clover monoculture alone. Thus, all of the feeding value benefits of clover are available when only 0.5 of the grazing area is sown to clover. These observations accord with the satiety theory and imply that there are constraints to eating pure clover that animals can overcome by adding grass to their diet, provided their ability to locate and ingest each food is not seriously limited. The challenge for grassland management is to present feed to animals at pasture in ways that allow them to meet their dietary preferences, while also allowing high rates of animal production per hectare

The effect of the density and physical properties of grass stems on the foraging behaviour and instantaneous intake rate by cattle grazing an artificial reproductive tropical sward

in reproductive swards, stems appear to act as vertical or horizontal barriers to bite formation, influencing instantaneous intake rate (IIR). The hypothesis was tested that the stems' barrier effect is determined by the physical properties and density of stems. Artificial microswards, consisting of 20-cm leaves and 15-cm stems of Panicum maximum, were offered to three steers (362 kg) in a factorial combination of three stem densities (0, 100 and 400 stems m(-2)) and two levels of stem tensile resistance [low (LTRS) and high tensile-resisting stems (HTRS)]. LTRS were not a barrier to defoliation and did not affect bite depth and bite mass. HTRS acted as both a horizontal barrier and a vertical barrier depressing bite depth (13.4, 13.6 and 5.1 cut for 0, 100 and 400 stems m(-2), respectively), bite area (89.3, 50.8 and 47.6 cm(2) for 0, 100 and 400 stems M-2, respectively), bite mass (0.51, 0.29 and 0.11 g for 0, 100 and 400 stems m(-2), respectively) and IIR (23.8, 10.5 and 3.6 g sec(-2) for 0, 100 and 400 Stems m(-2), respectively). The results confirmed the importance of the density and physical properties of stems as determinants of the stems' barrier effect on bite dimensions and IIR

Características da ingestão de forragem por cordeiras nos estádios fenológicos da pastagem de azevém

Foram estudadas as características do processo de ingestão de forragem por cordeiras em azevém (Lolium multiflorum Lam.) nos estádios fenológicos vegetativo, pré-florescimento e florescimento, por meio de testes de pastejo e da técnica da dupla pesagem. O delineamento experimental foi o inteiramente ao acaso, com três tratamentos e cinco repetições no estádio vegetativo e seis nos demais estádios. Os diferentes estádios fenológicos não influenciam a taxa de ingestão, a massa do bocado e a profundidade de bocado quando a oferta de forragem não é limitante ao consumo. O aumento na taxa de bocados é o mecanismo utilizado por cordeiras para manter a taxa de ingestão constante. Os modelos de regressão múltipla indicam que, dentre os atributos do pasto, sua altura é o de maior importância para determinar mudanças no comportamento ingestivo de cordeiras