IntroductionDespite numerous efforts to describe COVID-19's immunological landscape, there is still a gap in our understanding of the virus's infections after-effects, especially in the recovered patients. This would be important to understand as we now have huge number of global populations infected by the SARS-CoV-2 as well as variables inclusive of VOCs, reinfections, and vaccination breakthroughs. Furthermore, single-cell transcriptome alone is often insufficient to understand the complex human host immune landscape underlying differential disease severity and clinical outcome.MethodsBy combining single-cell multi-omics (Whole Transcriptome Analysis plus Antibody-seq) and machine learning-based analysis, we aim to better understand the functional aspects of cellular and immunological heterogeneity in the COVID-19 positive, recovered and the healthy individuals.ResultsBased on single-cell transcriptome and surface marker study of 163,197 cells (124,726 cells after data QC) from the 33 individuals (healthy=4, COVID-19 positive=16, and COVID-19 recovered=13), we observed a reduced MHC Class-I-mediated antigen presentation and dysregulated MHC Class-II-mediated antigen presentation in the COVID-19 patients, with restoration of the process in the recovered individuals. B-cell maturation process was also impaired in the positive and the recovered individuals. Importantly, we discovered that a subset of the naive T-cells from the healthy individuals were absent from the recovered individuals, suggesting a post-infection inflammatory stage. Both COVID-19 positive patients and the recovered individuals exhibited a CD40-CD40LG-mediated inflammatory response in the monocytes and T-cell subsets. T-cells, NK-cells, and monocyte-mediated elevation of immunological, stress and antiviral responses were also seen in the COVID-19 positive and the recovered individuals, along with an abnormal T-cell activation, inflammatory response, and faster cellular transition of T cell subtypes in the COVID-19 patients. Importantly, above immune findings were used for a Bayesian network model, which significantly revealed FOS, CXCL8, IL1β, CST3, PSAP, CD45 and CD74 as COVID-19 severity predictors.DiscussionIn conclusion, COVID-19 recovered individuals exhibited a hyper-activated inflammatory response with the loss of B cell maturation, suggesting an impeded post-infection stage, necessitating further research to delineate the dynamic immune response associated with the COVID-19. To our knowledge this is first multi-omic study trying to understand the differential and dynamic immune response underlying the sample subtypes.

No abstract

Erythrosine and tartrazine are common artificial food additives which have become a part of daily human consumption. Advised daily intake values for these agents are set strictly, however, the actual intake is much higher than the recommended ADI. A higher intake of erythrosine and tartrazine is shown to exhibit adverse effects in mammalian models, and is thus a matter of public health concern. In this study we have assessed and compared the dose-dependent effects of erythrosine and tartrazine on inducing oxidative stress in zebrafish embryos. We performed the superoxide dismutase (SOD) enzyme activity assay to test the effect of the two food colorants on reactive oxygen species (ROS) production. Erythrosine and tartrazine treated embryos showed significantly increased SOD activity in an enzyme assay. Additionally SOD mRNA transcripts in the treated embryos were found to be upregulated. Erythrosine and tartrazine treatment specifically altered SOD1 mRNA transcript levels while it had no effect on SOD2 mRNA, the other isoform found in zebrafish. Our study shows that erythrosine at a concentration of 0.05% is embryotoxic in a dose and time dependent manner. Tartrazine treated embryos exhibit similar toxicity at a concentration of 0.5%. Erythrosine treated zebrafish embryos hatch much slower when compared to tartrazine treated embryos and control embryos. While erythrosine affects the yolk utilization, tartrazine exhibits teratogenic effects on early zebrafish embryos. The mRNA expression as well as biochemical analysis indicates that exposure to food colorants induces cytoplasmic SOD transcription to combat the ROS toxicity in zebrafish embryos.

No abstract