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

Long-term trends in production and composition of ryegrass-white clover pasture intensively grazed by dairy-beef cattle

A measure of pasture persistence is stability of yield and proportion of desirable species over a long period. Long-term data on animal production and pasture yield and composition of old permanent pasture in the Manawatu were examined for trends indicative of persistence. The data were collected from two sets of replicated 1.6-ha farmlets intensively grazed by dairybeef bulls stocked at 7.4 yearlings wintered/ha for 16 of 18 years from 1969-1986, and 11 years from 1978 and 1988, respectively. Annual total LWG, total yield of DM and the yields of ryegrass, white clover and other species showed year-to-year variation. There was no long-term decline in production indicating that for this environment and management system ryegrass and white clover were inherently persistent under intensive grazing at high stocking rates. These results are discussed in the context of anecdotal reports of poor persistence of modern cultivars, with particular emphasis on the effects that high stocking rates, intensive utilisation and defoliation management may have on persistence. Keywords: cattle, grazing, pasture, persistence, ryegrass, white clover</jats:p

GRAZING DURATION STUDIES ON LUCERNE

A grazing study was conducted on irrigated Wairau lucerne (Medicago sativa L.) 'during summer and autumn using mixed-aged ewes. Two treatments were imposed: grazing durations of 3 and 12 days, with similar spells to the early flower stage of growth between successive grazings. This was carried out over two grazing and regrowth cycles.</jats:p

PASTURE STRATEGIES FOR DAIRY BEEF PRODUCTION

Improved pasture species, irrigation and nitrogen fertilizer options for increasing pasture growth rate during inter and Summer have been evaluated in growth rate and annual production of young Friesian bulls. Effective increases in Summer pasture production have been obtained from the use of irrigation, Pawera red clover, Matua prairie grass and particularly a combination of irrigation and Matua, Nitrogen fertilizer, Matua and carryover effects of irrigation have increased cool Season pasture growth rates. Liveweight gains reflect these increases except on Matua pastures where poor growth rate of calves occurs durmg summer. The negative effects of the different pasture treatments on Spring liveweight gain are attributed partly to the effects of compensatory growth in bulls but also to treatment effects which reduce pasture growth rate during this season. For this reason the most effective gains are made by 15-18 month old bulls during summer. Pasture species and pasture mixtures react differently to applications of irrigation and nitrogen fertilizer. The most appropriate Strategies and combinations are discussed</jats:p

Grazing management influences on seasonality and performance of ryegrass and red clover in a mixture

Grazing management influences on the production and species composition of a ryegrass, red and white clover pasture were evaluated over 3 years. Pastures were grazed by cattle frequently in either winter or summer and infrequently for the remainder of the year or grazed infrequently all year. Frequency was determined by the height of herbage pre-grazing and was lo-12 cm for frequent grazing and 15-20 cm for infrequent grazing. Annual herbage production of 15.1 t DM/ha was not influenced by grazing management but seasonal production was. Management caused both instantaneous and longer term effects on production of component species. Lower summer production because of frequent grazing in that season resulted from a reduction in red clover production from 2.75 to 1.3 t DM/ha. However, ryegrass production in spring was increased by 60% and in summer it was more than doubled by this grazing treatment. Frequent grazing in winter also increased ryegrass and reduced red clover production in summer compared with infrequent grazing all year but had no effect on ryegrass production in spring. Red clover plant density was unaffected by the different grazing managements imposed for two and a half years but subsequently was lower under frequent summer grazing. Red clover dominance in summer and its effect on ryegrass production in spring can be controlled by more frequent grazing in summer and a more even species balance results. Emphasis on spring or summer production can be achieved through grazing management without affecting total production. Keywords: Red clover, ryegrass, grazing frequency, cattle grazing, herbage production, seasonal production</jats:p

Hill country pastures, botanical composition and productive capacity

Botanical composition of pastures is indicative of their dry matter production and nutritive value and so capacity for animal production. Two previous national pasture surveys were conducted in 1935/1940 and in 1987/1988, and one regional survey in 1967/1968, to assess the state of this resource across all land classes. Among many purposes, results from these surveys were used to assess the outcomes of technological advances such as aerial topdressing and oversowing in hill country from the 1950s onwards, and to record changes in the abundance of particular species such as C4 grasses that could indicate effects of climate change, and identify research needs and opportunities. In the 28 years since the most recent survey, there have been many changes in the farm operating environment. This is particularly so in hill country, where other sectors such as forestry and dairy have encroached on traditional sheep and beef land, and poor profitability has forced variable and often sub-maintenance applications of phosphate (P) and sulphur (S) fertilisers. However, the low use of P and S has been partly offset by increased use of nitrogen (N) fertiliser. The declining number of beef cows, substituted by growing dairy and dairy-beef cattle, and the remarkable increase in the per head productivity of sheep are probably the biggest changes shifting the feed demand profile and the ratio of mature: young livestock. These changes affect pasture utilisation. This paper will consider the possible effects of those changes over the 28 years since the most recent national survey of pasture botanical composition, and the future capacity and resilience of this important resource to cope with continuing farm system change, emerging pressures for productivity growth, and regulatory and compliance requirements. Keywords: hill country pasture, botanical composition, resource status, survey</jats:p