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Whilst most individuals with SARS-CoV-2 infection have relatively mild disease, managed in the community, it was noted early in the pandemic that individuals with cardiovascular risk factors were more likely to experience severe acute disease, requiring hospitalisation. As the pandemic has progressed, increasing concern has also developed over long symptom duration in many individuals after SARS-CoV-2 infection, including among the majority who are managed acutely in the community. Risk factors for long symptom duration, including biological variables, are still poorly defined. Here, we examine post-illness metabolomic profiles, using nuclear magnetic resonance (Nightingale Health Oyj), and gut-microbiome profiles, using shotgun metagenomic sequencing (Illumina Inc), in 2561 community-dwelling participants with SARS-CoV-2. Illness duration ranged from asymptomatic (n = 307) to Post-COVID Syndrome (n = 180), and included participants with prolonged non-COVID-19 illnesses (n = 287). We also assess a pre-established metabolomic biomarker score, previously associated with hospitalisation for both acute pneumonia and severe acute COVID-19 illness, for its association with illness duration. We found an atherogenic-dyslipidaemic metabolic profile, including biomarkers such as fatty acids and cholesterol, was associated with longer duration of illness, both in individuals with and without SARS-CoV-2 infection. Greater values of a pre-existing metabolomic biomarker score also associated with longer duration of illness, regardless of SARS-CoV-2 infection. We found no association between illness duration and gut microbiome profiles in convalescence. This highlights the potential role of cardiometabolic dysfunction in relation to the experience of long duration symptoms after symptoms of acute infection, both COVID-19 as well as other illnesses., (© 2023. The Author(s).)

Bovine fertility remains a critical issue underpinning the sustainability of the agricultural sector. Phenotypic records collected on >7,000 bulls used in artificial insemination (AI) were used to identify 160 reliable and divergently fertile bulls for a dual strategy of targeted sequencing (TS) of fertility-related β-defensin genes and whole exome sequencing (WES). A haplotype spanning multiple β-defensin genes and containing 94 SNPs was significantly associated with fertility and functional analysis confirmed that sperm from bulls possessing the haplotype showed significantly enhanced binding to oviductal epithelium. WES of all exons in the genome in 24 bulls of high and low fertility identified 484 additional SNPs significantly associated with fertility. After validation, the most significantly associated SNP was located in the FOXJ3 gene, a transcription factor which regulates sperm function in mice. This study represents the first comprehensive characterisation of genetic variation in bovine β-defensin genes and functional analysis supports a role for β-defensins in regulating bull sperm function. This first application of WES in AI bulls with divergent fertility phenotypes has identified a novel role for the transcription factor FOXJ3 in the regulation of bull fertility. Validated genetic variants associated with bull fertility could prove useful for improving reproductive outcomes in cattle.

We hypothesised that epigenetic regulation of CD4(+) T lymphocytes contributes to a shift toward a dysfunctional T cell phenotype which may impact on their ability to clear mycobacterial infection. Combined RNA-seq transcriptomic profiling and Reduced Representation Bisulfite Sequencing identified 193 significantly differentially expressed genes and 760 differentially methylated regions (DMRs), between CD4(+) T cells from M. bovis infected and healthy cattle. 196 DMRs were located within 10 kb of annotated genes, including GATA3 and RORC, both of which encode transcription factors that promote TH2 and TH17 T helper cell subsets respectively. Gene-specific DNA methylation and gene expression levels for the TNFRSF4 and Interferon-γ genes were significantly negatively correlated suggesting a regulatory relationship. Pathway analysis of DMRs identified enrichment of genes involved in the anti-proliferative TGF-β signaling pathway and TGFB1 expression was significantly increased in peripheral blood leukocytes from TB-infected cattle. This first analysis of the bovine CD4(+) T cell methylome suggests that DNA methylation directly contributes to a distinct gene expression signature in CD4(+) T cells from cattle infected with M. bovis. Specific methylation changes proximal to key inflammatory gene loci may be critical to the emergence of a non-protective CD4(+) T cell response during mycobacterial infection in cattle.