Andiappan, A. | Search bioRxiv

bioRxiv2020

Whole blood immunophenotyping uncovers immature neutrophil-to-VD2 T-cell ratio as an early prognostic marker for severe COVID-19

SARS-CoV-2 is the novel coronavirus responsible for the current COVID-19 pandemic. Severe complications are observed only in a small proportion of infected patients but the cellular mechanisms underlying this progression are still unknown. Comprehensive flow cytometry of whole blood samples from 54 COVID-19 patients revealed a dramatic increase in the number of immature neutrophils. This increase strongly correlated with disease severity and was associated with elevated IL-6 and IP-10 levels, two key players in the cytokine storm. The most pronounced decrease in cell counts was observed for CD8 T-cells and VD2 {gamma}{delta} T-cells, which both exhibited increased differentiation and activation. ROC analysis revealed that the count ratio of immature neutrophils to CD8 or VD2 T-cells predicts pneumonia onset (0.9071) as well as hypoxia onset (0.8908) with high sensitivity and specificity. It would thus be a useful prognostic marker for preventive patient management and improved healthcare resource management.

immunology↗

bioRxiv2017

Analysis of archaic human haplotypes suggest 5-hmC to act as epigenetic guide for meiotic point recombination

Meiotic \"point recombination\" refers to homologue recombination events affecting only individual SNPs. Driven mostly by gene conversion, it is common process that allows for a gradual adaptation and maturation of haplotypes during genetic evolution. In contrast to crossover recombination it is not tied to predetermined recombination sites and therefore assumed to occur largely randomly. Our analysis of archaic human haplotypes however revealed striking differences in the local point recombination rate. A linkage-study of 1.9 million SNPs defined by the sequence of denisovan hominids revealed low rates in introns and quiescent intergenic regions but high rates in splice sites, exons, 5- and 3-UTRs, and CpG islands. Correlations with ChIP-Seq tracks from ENCODE and other public sources identified a number of epigenetic modifications, that associated directly with these recombination events. A particularly tight association was observed for 5-hydroxymethylcytosine marks (5hmC). The mark was enriched in virtually all of the functional regions associated with elevated point recombination rates, including CpG islands and poised bivalent regions. As intermediate of oxidative demethylation, 5hmC is also a marker of recently opened gene loci. The data, thus, supports a model of guided evolution, in which point recombination is directed by 5hmC marks towards the functionally relevant regions.

evolutionary biology↗