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

Desempenho produtivo de vacas leiteiras alimentadas com silagem pré-seca de alfafa adicionada de inoculante microbiano Performance of lactating dairy cows fed alfalfa haylage with microbial inoculant

Objetivou-se, com o presente estudo, avaliar os efeitos da inoculação microbiana da silagem pré-seca de alfafa sobre o consumo de matéria seca, a produção e composição do leite de vacas da raça Holandesa, multíparas, com 135 ± 16,4 dias de lactação, distribuídas em delineamento em reversão simples com seqüência balanceada ("cross-over"), com dois períodos sucessivos. Os tratamentos corresponderam à silagem pré-seca de alfafa (50,0% de MS e 16,5% de PB) controle ou inoculada com o produto Silobac® (Lactobacillus plantarum e Pediococcus pentosaceus). Cada período experimental teve duração de 21 dias, sendo os cinco últimos dias destinados à coleta de dados. Não se observou efeito da inoculação sobre o CMS (inoculada = 17,8 vs. controle = 17,8 kg/animal/dia), a produção de leite corrigida para 4,0% de gordura (21,0 vs. 20,4 kg/dia), produção de leite (23,0 vs. 22,4 kg/dia), porcentagem de gordura (3,46 vs. 3,47%), proteína (2,96 vs. 2,93%), lactose (4,64 vs. 4,67%), sólidos totais (11,9 vs. 11,9%) e sólidos desengordurados (8,49 vs. 8,48%), CCS (5,43 vs. 5,16 log cel/10³/mL), NUL (11,7 vs. 12,1 mg/dl), acidez (15,9 vs. 16,4ºD), densidade (1030,1 vs. 1030,0) e crioscopia (-0,529 vs. -0,531ºH).<br>The objective of this study was to evaluate the effects of feeding alfalfa haylage with microbial inoculat on dry matter intake, milk yield and composition in Holstein cows, at 135 ± 16.4 days in milk. A cross-over design with two periods of sampling was used. Treatments were alfalfa haylage (50.0% DM and 16.5% CP) control or microbially inoculated with Silobac® product (Lactobacillus plantarum and Pediococcus pentosaceus). Each experimental period extended for twenty-one days, the last five used for data collection. The inoculation did not influence DMI (inoculated = 17.8 vs. control = 17.8 kg/animal/day), 4%FCM (21.0 vs. 20.4 kg/day), milk yield (23.0 vs. 22.4 kg/day), fat (3.46 vs. 3.47%), protein (2.96 vs. 2.93%), lactose (4.64 vs. 4.67%), total solids (11.9 vs. 11.9%) and fat free solids percentage (8.49 vs. 8.48%), SCC (5.43 vs. 5.16 log cell/10³/mL), MUN (11.7 vs. 12.1 mg/dl), acidity (15.9 vs. 16.4ºD), density (1030.1 vs. 1030.0) and cryoscopic index (-0.529 vs. -0.531ºH)

Human pulmonary dirofilariasis: a review

The authors presented a detailed summary of the geographical distribution, clinical and pathological aspects of human pulmonary dirofilariasis. Although benign, this zoonosis, of which Dirofilaria immitis is the major etiological agent, represents a medical problem since it produces symptoms which may be confused with neoplasia and thus may subject patients to unnecessary thoracic surgery. Of 229 cases cited in the literature, only 17 were reported in Brazil, despite the existence of highly favorable conditions for the transmission of this infection in man. Thus it may well be that this parasitic infection remains underdiagnosed. Finally, the importance of a differential diagnosis between dirofilariasis and pulmonary neoplasia is emphasized in cases where there is a solitary subpleural nodule ("coin lesion") present. In addition, the development and improvement of modern immunological diagnostic techniques are essential to distinguish this benign disease from other pathological conditions and thus avoid unneccessary surgery. These techniques may reveal the true prevalence of this parasitic infection in our environment

Óleo de copaíba (Copaifera sp.): histórico, extração, aplicações industriais e propriedades medicinais Copaiba oil (Copaifera sp.): history, extraction, industrial applications and medicinal properties

Este trabalho teve como objetivo realizar uma revisão de literatura sobre o gênero Copaifera sp. Foi realizado levantamento bibliográfico do período de 1792 a 2008 utilizando bibliotecas da Universidade de São Paulo, Universidade Federal de Viçosa, Universidade Federal de Alfenas e Universidade José do Rosário Vellano, pesquisas às bases de dados SCOPUS e PubMed, além de ferramentas de busca na web. Utilizou-se para a busca palavras chave como "Copaiba", "Copaifera", "Copaíba oil" "Óleo de Copaíba". Como resultado desta pesquisa obteve-se a seleção de 63 referências incluindo livros, artigos, cadernos técnicos, resumos de congressos, teses, dissertações e patentes. Estes dados apontaram o óleo de copaíba como um exsudato produzido pelas copaibeiras como defesa contra seus predadores, que vem sendo utilizado pela medicina tradicional popular e silvícola há mais de 500 anos. Ele é extraído destas árvores através de perfurações realizadas em seus troncos. Além das inúmeras aplicações do óleo em cosméticos e outras indústrias, ainda há uma série de indicações para seu uso na medicina. Existem hoje descritas algumas dezenas de propriedades medicinais diferentes, que vem sendo em alguns casos comprovadas cientificamente, como atividade antimicrobiana, antiinflamatória, anti-neoplásica entre outras. Estudos recentes têm demonstrado também grande potencial de uso do óleo de copaíba na odontologia, na composição de cimentos endodônticos e na prevenção e combate da doença periodontal. As informações contidas neste trabalho demonstram uma grande variabilidade de aplicações do óleo de copaíba. Entretanto uma quantidade limitada de pesquisas sobre suas propriedades medicinais tem sido realizada, apresentando assim a necessidade de novas pesquisas sobre estas.<br>The aim of this study was to conduct a literature review concerning the genus Copaifera sp. The survey involved the period from 1792 to 2008 and was done in the libraries of University of São Paulo, Federal University of Viçosa, Federal University of Alfenas and University Jose do Rosario Vellano, using SCOPUS and PubMed databases, and web search engines. The words "Copaiba", "Copaifera," "Óleo de copaiba" and "Copaiba oil" were used. This research resulted in the selection of 63 references including books, articles, technical specifications, conference abstracts, theses, dissertations and patents. These data indicate copaiba oil is an exudate from copaiba trees, produced as a defense against their predators and that has been used in traditional, popular and forestry medicine for over 500 years. It is extracted from trees through holes made in their trunks. Besides the oil applications in cosmetic and other industries, there are still a number of indications for its use in medicine. So far, dozens of different medicinal properties have been described and, in some cases, scientifically proven, including antimicrobial, anti-inflammatory, and anti-cancer activity. Recent studies have also shown great potential for the use of copaiba oil in dentistry like in endodontic cement composition, as well as in the prevention and therapy of periodontal diseases. This work showed a great variety of applications to copaiba oil. However, few studies on its medicinal properties have been performed, showing thus the need for further research