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

Colorimetric determination of in vitro feed protein degradation

A colorimetric method for determining protein degradation us' ing a diazonium chromophore was compared with the dacron bag technique.D iazotizedf ish meal, maizeg luten meal and soya-bean were incubated with strained rumen fluid and a suitableg rowth medium. Only 49o/oa nd 18% of the colour bound to soya-bean was bound to fish meal and corn gluten meal, respectivelyD. egradationv aluese xpresseda s a percentage of the total amount actually bound to the dye were in reasonablea greementw ith dacron bag estimates.H owever,i ni' tial hydrolysis of the diazo feeds was very rapid with little increment in breakdown after two hours incubation. lt was con' cluded that this problem was probably largely a result of limited penetration of the chromophore to potentially reactive sites within the feed particles owing to the large molecular size of the diazonium chromophore.'n Kolorimetriesem etodev ir die bepalingv an proteTenafbraak met 'n diazonium kromofoor is met die dakronsak tegniek vergelyk. Diazo vismeel, mielie glutenmeel en sojaboon is met rumenvloeistofe n groeimediumg einkubeer.S legs 49ohe n 18oh van die kleur gebind aan sojaboon is aan vismeel en mielie glutenmeelo nderskeidelikg ebind.P rotelenafbraawk aardes, uitgedruka s 'n persentasiev an die totale hoeveelheidg ebind deur die kleurstofw as in redelikeo oreenstemmingm et dakron' sak waardes.A anvanklikeh idrolisev an die diazo-voerew as baie vinnig,m et slegs klein veranderingsin afbraakn a twee ure. Daar is tot die gevolgtrekkingg ekom dat hierdiep robleem waarskynlik toe te skryf is aan die beperkte indringing van die kromofoor na potensieel reaktiewe punte binne die voer partikels weens die groot molekulOreg roottev an die diazonium kromofoor.Keywords: Nitrogen,protein,degradability diazotization in vitro, dacron ba

Processing ruminal ingesta to release bacteria attached to feed particles

A comparison was made of different methods of processing ingesta to release bacteria attached to solid particles, prior to making viable counts. Initially processing was performed under a stream of anaerobic gas and counts were made using the roll tube technique. Later, processing was done in an anaerobic cabinet and counts were made using the plating technique. On long hay diets counts of total culturable and lactateutilizing bacteria were twice as high with the Stomacher and Ultra-Turraxt reatment of ingesta when compared with the Minimal treatment. On the chopped hay and high concentrate diets there was little difference between the processing methods in respect of counts of these two groups of bacteria. Counts of cellulolytic bacteria which are attached to ingesta particles were higher with the Minimal treatment than with the other two methods. In contrast, counts of the ciliate protozoa showed a marked difference owing to processing. Results from the later experiments done in the anaerobic cabinet showed that poor anaerobiosis was responsible for at least some of the lethal action of the Ultra-Turraxa ndStomacher. 'n Vergelykendes tudie is gedoenv an die verskillende behandelingsv an verteringsmateriaaol m baterie€ wat vassit aan die vaste deeltjies te bevry voordat lewensvatbare tellings gedoenw ord. Oorspronkliki s die behandelingo nder'n stroom ana6robe gas gedoen en tellings is in rolbuise gedoen. Later is die behandelingsi n 'n ana6robek abinetg edoene n die tellings is volgens die plaattegniek gedoen. Op rantsoene van lang hooi was die tellings van die totale telbare en die melksuur-benuttendeb aterie6 twee maal so hoog vir die 'Stomacher'e n die 'Ultra-Turraxb' ehandelinga, s vir die Minimum behandelingO. p die gemaaldeh ooi en ho€ konsentraat rantsoene was daar baie min verskil tussen die behandelingst en opsigtev an tellings van die twee groepe bakterie€.T ellingsv an die sellulolitieseb akterie€w at vassit aan die deel t j iesw as ho€rv i r die Minimumb ehandel inga s vi r die ander twee metodes. In teenstelling hiermee, het die tellings van die siliaat protoso€ merkbare verskille getoon ten opsigte van die behandelings. Resultatev an lateree ksperimentew at in die ana6robe kabinet gedoen is, het getoon dat swak ana6robiose verantwoordelik was vir ten minste sommige van die nadelige uitwerkingv an die 'Ultra-Turraxe' n die 'Stomacher'.Keywords: Ruminal bacteria, ciliate protozoa, processing ruminal ingesta, viable count