Search

Background Many nutrients have powerful immunomodulatory actions with the potential to alter susceptibility to coronavirus disease 2019 (COVID-19) infection, progression to symptoms, likelihood of severe disease, and survival. Objective The aim was to review the latest evidence on how malnutrition across all its forms (under- and overnutrition and micronutrient status) may influence both susceptibility to, and progression of, COVID-19. Methods We synthesized information on 13 nutrition-related components and their potential interactions with COVID-19: overweight, obesity, and diabetes; protein-energy malnutrition; anemia; vitamins A, C, D, and E; PUFAs; iron; selenium; zinc; antioxidants; and nutritional support. For each section we provide: 1) a landscape review of pertinent material; 2) a systematic search of the literature in PubMed and EMBASE databases, including a wide range of preprint servers; and 3) a screen of 6 clinical trial registries. All original research was considered, without restriction to study design, and included if it covered: 1) severe acute respiratory syndrome coronavirus (CoV) 2 (SARS-CoV-2), Middle East respiratory syndrome CoV (MERS-CoV), or SARS-CoV viruses and 2) disease susceptibility or 3) disease progression, and 4) the nutritional component of interest. Searches took place between 16 May and 11 August 2020. Results Across the 13 searches, 2732 articles from PubMed and EMBASE, 4164 articles from the preprint servers, and 433 trials were returned. In the final narrative synthesis, we include 22 published articles, 38 preprint articles, and 79 trials. Conclusions Currently there is limited evidence that high-dose supplements of micronutrients will either prevent severe disease or speed up recovery. However, results of clinical trials are eagerly awaited. Given the known impacts of all forms of malnutrition on the immune system, public health strategies to reduce micronutrient deficiencies and undernutrition remain of critical importance. Furthermore, there is strong evidence that prevention of obesity and type 2 diabetes will reduce the risk of serious COVID-19 outcomes. This review is registered at PROSPERO as CRD42020186194.

Background: Maternal nutrition in pregnancy has been linked to offspring health in early and later life, with changes to DNA methylation (DNAm) proposed as a mediating mechanism. Objective: We investigated intervention-associated DNAm changes in children whose mothers participated in 2 randomized controlled trials of micronutrient supplementation before and during pregnancy, as part of the EMPHASIS (Epigenetic Mechanisms linking Preconceptional nutrition and Health Assessed in India and sub-Saharan Africa) study (ISRCTN14266771). Design: We conducted epigenome-wide association studies with blood samples from Indian (n = 698) and Gambian (n = 293) children using the Illumina EPIC array and a targeted study of selected loci not on the array. The Indian micronutrient intervention was food based, whereas the Gambian intervention was a micronutrient tablet. Results: We identified 6 differentially methylated CpGs in Gambians [2.5-5.0% reduction in intervention group, all false discovery rate (FDR)

Accumulating evidence suggests that the intrauterine environment can have an impact on long-term offspring health, so-called ‘fetal programming’. A number of environmental stressors have been studied in humans including maternal nutrition, smoking, substance misuse and mental illness. Although various biological mechanisms are likely to underpin fetal programming effects, there has been a particular focus on epigenetic modifications as potential mediators of observed associations between early environmental exposures and later health outcomes. In this review, we give an overview of evidence supporting a role for epigenetics in fetal programming, highlighting key human and animal studies. We also discuss challenges for research in this area, along with recommendations for future work, and potential therapeutic applications.

Proopiomelanocortin (POMC) is a key mediator of satiety. Epigenetic marks such as DNA methylation may modulate POMC expression and provide a biological link between early life exposures and later phenotype. Animal studies suggest epigenetic marks at POMC are influenced by maternal energy excess and restriction, prenatal stress and Triclosan exposure. Postnatal factors including energy excess, folate, vitamin A, conjugated linoleic acid and leptin may also affect POMC methylation. Recent human studies suggest POMC DNA methylation is influenced by maternal nutrition in early pregnancy and associated with childhood and adult obesity. Studies in children propose a link between POMC DNA methylation and elevated lipids and insulin, independent of body habitus. This review brings together evidence from animal and human studies and suggests that POMC is sensitive to nutritional programming and is associated with a wide range of weight-related and metabolic outcomes.

Background We have previously identified an association between lipids and features of diffusion tensor imaging in preterm infants, highlighting the KEGG peroxisome proliferator-activated receptor pathway (PPAR) as the most highly ranked in association with a white matter phenotype. Here we applied a penalised linear regression model—the graph-guided group lasso (GGGL)—to select single nucleotide polymorphisms within functionally related genes associated with the imaging trait. The GGGL model utilises network-based prior knowledge to improve the selection of variables of interest. Methods Images acquired with a 3T MR scanner were collected along with saliva for 72 preterm infants (mean gestational age 28 weeks [+4 days], mean postmenstrual age at scan 40 weeks [+3 days]). Salivary DNA was extracted and genotyped with HumanOmniExpress-12 arrays (Illumina, San Diego, CA, USA). Fractional anisotropy maps were constructed from diffusion tensor imaging, and tract-based spatial statistics were used to obtain a group white matter skeleton varying with degree of prematurity, adjusting for age at scan. GGGL was applied to the genes in the PPAR pathway. Findings The GGGL method selected five of the 69 genes in the PPAR pathway, and these were functionally related in terms of Gene Ontology Biological Process and linearly correlated with white matter fractional anisotropy ( AQP7, ME1, PLIN1, SLC27A1 , and ACAA1 ). Analysis of transcriptional regulation with the PASTAA algorithm indicated that ACAA1, AQP7, ME1 , and SLC27A1 were jointly regulated by the EGR4 transcription factor (adjusted p=7·7×10 −4 ). Interpretation Our GGGL analysis of genes in the PPAR pathway identified five highly ranked genes involved in neuronal growth, myelinogenesis, and nervous system response to inflammation, and jointly transcriptionally regulated. Since preterm infants are at increased risk of mental illness and cardiovascular morbidity in later life, this work uses an integrative data-driven strategy to propose a unifying mechanism for these systemic effects, suggesting a promising avenue for intervention. Funding Medical Research Council, National Institute for Health Research Biomedical Research Centre.