Distinct T cell polyfunctional profile in SARS-CoV-2 seronegative children associated with endemic human coronavirus cross-reactivity

SARS-CoV-2 infection in children typically results in asymptomatic or mild disease. There is a paucity of studies on SARS-CoV-2 antiviral immunity in African children. We investigated SARS-CoV-2-specific T cell responses in 71 unvaccinated asymptomatic South African children who were seropositive or seronegative for SARS-CoV-2. SARS-CoV-2-specific CD4+ T cell responses were detectable in 83% of seropositive and 60% of seronegative children. Although the magnitude of the CD4+ T cell response did not differ significantly between the two groups, their functional profiles were distinct, with SARS-CoV-2 seropositive children exhibiting a higher proportion of polyfunctional T cells compared to their seronegative counterparts. The frequency of SARS-CoV-2-specific CD4+ T cells in seronegative children was associated with the endemic human coronavirus (HCoV) HKU1 IgG response. Overall, the presence of SARS-CoV-2-responding T cells in seronegative children may result from cross-reactivity to endemic coronaviruses and could contribute to the relative protection from disease observed in SARS-CoV-2-infected children

Infection pre-Ad26.COV2.S-vaccination primes greater class switching and reduced CXCR5 expression by SARS-CoV-2-specific memory B cells

Neutralizing antibodies strongly correlate with protection for COVID-19 vaccines, but the corresponding memory B cells that form to protect against future infection are relatively understudied. Here we examine the effect of prior SARS-CoV-2 infection on the magnitude and phenotype of the memory B cell response to single dose Johnson and Johnson (Ad26.COV2.S) vaccination in South African health care workers. Participants were either naïve to SARS-CoV-2 or had been infected before vaccination. SARS-CoV-2-specific memory B-cells expand in response to Ad26.COV2.S and are maintained for the study duration (84 days) in all individuals. However, prior infection is associated with a greater frequency of these cells, a significant reduction in expression of the germinal center chemokine receptor CXCR5, and increased class switching. These B cell features correlated with neutralization and antibody-dependent cytotoxicity (ADCC) activity, and with the frequency of SARS-CoV-2 specific circulating T follicular helper cells (cTfh). Vaccination-induced effective neutralization of the D614G variant in both infected and naïve participants but boosted neutralizing antibodies against the Beta and Omicron variants only in participants with prior infection. In addition, the SARS-CoV-2 specific CD8+ T cell response correlated with increased memory B cell expression of the lung-homing receptor CXCR3, which was sustained in the previously infected group. Finally, although vaccination achieved equivalent B cell activation regardless of infection history, it was negatively impacted by age. These data show that phenotyping the response to vaccination can provide insight into the impact of prior infection on memory B cell homing, CSM, cTfh, and neutralization activity. These data can provide early signals to inform studies of vaccine boosting, durability, and co-morbidities

Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant-dependent manner

The Johnson and Johnson Ad26.COV2.S single-dose vaccine represents an attractive option for coronavirus disease 2019 (COVID-19) vaccination in countries with limited resources. We examined the effect of prior infection with different SARS-CoV-2 variants on Ad26.COV2.S immunogenicity. We compared participants who were SARS-CoV-2 naive with those either infected with the ancestral D614G virus or infected in the second wave when Beta predominated. Prior infection significantly boosts spike-binding antibodies, antibody-dependent cellular cytotoxicity, and neutralizing antibodies against D614G, Beta, and Delta; however, neutralization cross-reactivity varied by wave. Robust CD4 and CD8 T cell responses are induced after vaccination, regardless of prior infection. T cell recognition of variants is largely preserved, apart from some reduction in CD8 recognition of Delta. Thus, Ad26.COV2.S vaccination after infection could result in enhanced protection against COVID-19. The impact of the infecting variant on neutralization breadth after vaccination has implications for the design of second-generation vaccines based on variants of concern

The prevalence of nutritional anemia in pregnancy in an east Anatolian province, Turkey

<p>Abstract</p> <p>Background</p> <p>Anemia is considered a severe public health problem by World Health Organization when anemia prevalence is equal to or greater than 40% in the population. The purpose of this study was to determine the anemia prevalence with the associated factors in pregnant women and to determine the serum iron, folate and B12 vitamin status in anaemic pregnants in Malatya province.</p> <p>Methods</p> <p>This is a cross-sectional survey. A multi-sage stratified probability-proportional-to-size cluster sampling methodology was used. A total of 823 pregnant women from sixty clusters were studied. Women were administered a questionnaire related with the subject and blood samples were drawn. Total blood count was performed within four hours and serum iron, folate and B12 vitamin were studied after storing sera at -20 C for six months.</p> <p>Results</p> <p>Anemia prevalence was 27.1% (Hb < 11.0 gr/dl). Having four or more living children (OR = 2.2), being at the third trimester (OR = 2.3) and having a low family income (OR = 1.6) were determined as the independent predictors of anemia in pregnancy. Anemia was also associated with soil eating (PICA) in the univariate analysis (p < 0.05). Of anaemic women, 50.0% had a transferrin saturation less than 10% indicating iron deficiency, 34.5% were deficient in B12 vitamin and 71.7% were deficient in folate. Most of the anemias were normocytic-normochromic (56.5%) indicating mixed anemia.</p> <p>Conclusions</p> <p>In Malatya, for pregnant women anemia was a moderate public health problem. Coexisting of iron, folate and B vitamin deficiencies was observed among anaemics. To continue anemia control strategies with reasonable care and diligence was recommended.</p

Alcohol use and extramarital sex among men in Cameroon

<p>Abstract</p> <p>Background</p> <p>The spread of HIV in sub-Saharan Africa is believed to be driven by unsafe sex, and identification of modifiable risk factors of the latter is needed for comprehensive HIV prevention programming in the region. Some previous studies suggest an association between alcohol abuse and unsafe sexual behaviour, such as multiple concurrent sexual partnerships and inconsistent condom use in sex with non-spousal non-cohabiting partners. However, most of these studies were conducted in developed countries and the few studies in Africa were conducted among well-defined social groups such as men attending beer halls or sexually transmitted infection clinics. We therefore examined the association between alcohol and extramarital sex (a sign of multiple concurrent sexual partnerships) among men in a population-based survey in Cameroon; a low-income country in sub-Saharan Africa with a high rate of alcohol abuse and a generalised HIV epidemic.</p> <p>Methods</p> <p>We analyzed data from 2678 formally married or cohabiting men aged 15 to 59 years, who participated in the 2004 Cameroon Demographic and Health Survey, using a multivariate regression model.</p> <p>Results</p> <p>A quarter of the men (25.8%) declared having taken alcohol before their last sexual intercourse and 21% indicated that the last sex was with a woman other than their wife or cohabiting partner. After controlling for possible confounding by other socio-demographic characteristics, alcohol use was significantly associated with having extramarital sex: adjusted odds ratio (OR) 1.70, 95% confidence intervals (CI) 1.40 to 2.05. Older age (30–44 years: OR 3.06, 95%CI 2.16–4.27 and 45–59 years: OR 4.10, 95%CI 2.16–4.27), higher education (OR 1.25, 95%CI 1.10–1.45), and wealth (OR 1.71, 95%CI 1.50–1.98) were also significantly associated with higher odds of having extramarital sex. The men were more likely to have used a condom in their last sex if it was extramarital (OR 10.50, 95%CI 8.10–13.66). Older age at first sex (16–19 years: OR 0.81, 95%CI 0.72–0.90 and > 19 years: OR 0.74, 95% CI 0.65–0.87) and being the head of a household (OR 0.17, 95%CI 0.14–0.22) significantly decreased the odds of having sex outside of marriage. Religion and place of residence (whether urban or rural) were not significantly associated with extramarital sex.</p> <p>Conclusion</p> <p>Alcohol use is associated with having multiple concurrent non-spousal sexual partnerships among married men in Cameroon. We cannot infer a causal relationship between alcohol abuse and unsafe sex from this cross-sectional study, as both alcohol use and unsafe sexual behaviour may have a common set of causal personal and social factors. However, given the consistency with results of studies in other settings and the biologic plausibility of the link between alcohol intake and unsafe sex, our findings underscore the need for integrating alcohol abuse and HIV prevention efforts in Cameroon and other African countries with similar social profiles.</p

Combining vitamin C and carotenoid biomarkers better predicts fruit and vegetable intake than individual biomarkers in dietary intervention studies.

The aim of this study was to determine whether combining potential biomarkers of fruit and vegetables is better at predicting FV intake within FV intervention studies than single biomarkers

Challenges of molecular nutrition research 6: the nutritional phenotype database to store, share and evaluate nutritional systems biology studies

The challenge of modern nutrition and health research is to identify food-based strategies promoting life-long optimal health and well-being. This research is complex because it exploits a multitude of bioactive compounds acting on an extensive network of interacting processes. Whereas nutrition research can profit enormously from the revolution in ‘omics’ technologies, it has discipline-specific requirements for analytical and bioinformatic procedures. In addition to measurements of the parameters of interest (measures of health), extensive description of the subjects of study and foods or diets consumed is central for describing the nutritional phenotype. We propose and pursue an infrastructural activity of constructing the “Nutritional Phenotype database” (dbNP). When fully developed, dbNP will be a research and collaboration tool and a publicly available data and knowledge repository. Creation and implementation of the dbNP will maximize benefits to the research community by enabling integration and interrogation of data from multiple studies, from different research groups, different countries and different—omics levels. The dbNP is designed to facilitate storage of biologically relevant, pre-processed—omics data, as well as study descriptive and study participant phenotype data. It is also important to enable the combination of this information at different levels (e.g. to facilitate linkage of data describing participant phenotype, genotype and food intake with information on study design and—omics measurements, and to combine all of this with existing knowledge). The biological information stored in the database (i.e. genetics, transcriptomics, proteomics, biomarkers, metabolomics, functional assays, food intake and food composition) is tailored to nutrition research and embedded in an environment of standard procedures and protocols, annotations, modular data-basing, networking and integrated bioinformatics. The dbNP is an evolving enterprise, which is only sustainable if it is accepted and adopted by the wider nutrition and health research community as an open source, pre-competitive and publicly available resource where many partners both can contribute and profit from its developments. We introduce the Nutrigenomics Organisation (NuGO, http://www.nugo.org) as a membership association responsible for establishing and curating the dbNP. Within NuGO, all efforts related to dbNP (i.e. usage, coordination, integration, facilitation and maintenance) will be directed towards a sustainable and federated infrastructure

SARS-CoV-2 Beta and Delta variants trigger Fc effector function with increased cross-reactivity

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern (VOCs) exhibit escape from neutralizing antibodies, causing concern about vaccine effectiveness. However, while non-neutralizing cytotoxic functions of antibodies are associated with improved disease outcome and vaccine protection, Fc effector function escape from VOCs is poorly defined. Furthermore, whether VOCs trigger Fc functions with altered specificity, as has been reported for neutralization, is unknown. Here, we demonstrate that the Beta VOC partially evades Fc effector activity in individuals infected with the original (D614G) variant. However, not all functions are equivalently affected, suggesting differential targeting by antibodies mediating distinct Fc functions. Furthermore, Beta and Delta infection trigger responses with significantly improved Fc cross-reactivity against global VOCs compared with D614G-infected or Ad26.COV2.S-vaccinated individuals. This suggests that, as for neutralization, the infecting spike sequence affects Fc effector function. These data have important implications for vaccine strategies that incorporate VOCs, suggesting these may induce broader Fc effector responses.The EDCTP2 program of the European Union’s Horizon 2020 program, Wellcome Centre for Infectious Diseases Research in Africa, the SA-MRC, MRC UK, NRF, the Lily and Ernst Hausmann Trust, the South African Research Chairs Initiative of the Department of Science and Innovation and National Research Foundation of South Africa, the SA Medical Research Council SHIP program, the Center for the AIDS Program of Research (CAPRISA) and an L’Oreal/UNESCO Women in Science South Africa Young Talents award.http://www.cell.com/cell-host-microbe/homeam2023ImmunologyInternal Medicin

Mass-spectrometry-based metabolomics: limitations and recommendations for future progress with particular focus on nutrition research

Mass spectrometry (MS) techniques, because of their sensitivity and selectivity, have become methods of choice to characterize the human metabolome and MS-based metabolomics is increasingly used to characterize the complex metabolic effects of nutrients or foods. However progress is still hampered by many unsolved problems and most notably the lack of well established and standardized methods or procedures, and the difficulties still met in the identification of the metabolites influenced by a given nutritional intervention. The purpose of this paper is to review the main obstacles limiting progress and to make recommendations to overcome them. Propositions are made to improve the mode of collection and preparation of biological samples, the coverage and quality of mass spectrometry analyses, the extraction and exploitation of the raw data, the identification of the metabolites and the biological interpretation of the results