Biology subjects

Lye, D. C.

Publications and source records attributed to Lye, D. C..

5 recordsLinked to original sources

bioRxiv2021

Data-driven analysis of COVID-19 reveals specific severity patterns distinct from the temporal immune response

Key immune signatures of SARS-CoV-2 infection may associate with either adverse immune reactions (severity) or simply an ongoing anti-viral response (temporality); how immune signatures contribute to severe manifestations and/or temporal progression of disease and whether longer disease duration correlates with severity remain unknown. Patient blood was comprehensively immunophenotyped via mass cytometry and multiplex cytokine arrays, leading to the identification of 327 basic subsets that were further stratified into more than 5000 immunotypes and correlated with 28 plasma cytokines. Low-density neutrophil abundance was closely correlated with hepatocyte growth factor levels, which in turn correlated with disease severity. Deep analysis also revealed additional players, namely conventional type 2 dendritic cells, natural killer T cells, plasmablasts and CD16+ monocytes, that can influence COVID-19 severity independent of temporal progression. Herein, we provide interactive network analysis and data visualization tools to facilitate data mining and hypothesis generation for elucidating COVID-19 pathogenesis.

immunology↗

bioRxiv2020

Highly functional virus-specific cellular immune response in asymptomatic SARS-CoV-2 infection

The efficacy of virus-specific T cells in clearing pathogens involves a fine balance between their antiviral and inflammatory features. SARS-CoV-2-specific T cells in individuals who clear SARS-CoV-2 infection without symptoms or disease could reveal non-pathological yet protective characteristics. We therefore compared the quantity and function of SARS-CoV-2-specific T cells in a cohort of asymptomatic individuals (n=85) with that of symptomatic COVID-19 patients (n=76), at different time points after antibody seroconversion. We quantified T cells reactive to structural proteins (M, NP and Spike) using ELISpot assays, and measured the magnitude of cytokine secretion (IL-2, IFN-{gamma}, IL-4, IL-6, IL-1{beta}, TNF- and IL-10) in whole blood following T cell activation with SARS-CoV-2 peptide pools as a functional readout. Frequencies of T cells specific for the different SARS-CoV-2 proteins in the early phases of recovery were similar between asymptomatic and symptomatic individuals. However, we detected an increased IFN-{gamma} and IL-2 production in asymptomatic compared to symptomatic individuals after activation of SARS-CoV-2-specific T cells in blood. This was associated with a proportional secretion of IL-10 and pro-inflammatory cytokines (IL-6, TNF- and IL-1{beta}) only in asymptomatic infection, while a disproportionate secretion of inflammatory cytokines was triggered by SARS-CoV-2-specific T cell activation in symptomatic individuals. Thus, asymptomatic SARS-CoV-2 infected individuals are not characterized by a weak antiviral immunity; on the contrary, they mount a robust and highly functional virus-specific cellular immune response. Their ability to induce a proportionate production of IL-10 might help to reduce inflammatory events during viral clearance.

immunology↗

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↗

bioRxiv2020

Potent neutralizing antibodies in the sera of convalescent COVID-19 patients are directed against conserved linear epitopes on the SARS-CoV-2 spike protein

The ongoing SARS-CoV-2 pandemic demands rapid identification of immunogenic targets for the design of efficient vaccines and serological detection tools. In this report, using pools of overlapping linear peptides and functional assays, we present two immunodominant regions on the spike glycoprotein that were highly recognized by neutralizing antibodies in the sera of COVID-19 convalescent patients. One is highly specific to SARS-CoV-2, and the other is a potential pan-coronavirus target.

immunology↗

bioRxiv2017

Dominance of ST131 Escherichia coli carrying blaCTX-M in patients with bloodstream infections caused by cephalosporin-resistant strains in Australia, New Zealand and Singapore: whole genome analysis of isolates from a randomised trial

Synopsis/AbstractO_ST_ABSObjectivesC_ST_ABSTo characterise multi-drug resistant Escherichia coli isolated from patients in Australia, New Zealand and Singapore with bloodstream infection (BSI).\n\nMethodsWe prospectively collected third-generation cephalosporin resistant (3GC-R) E. coli from blood cultures obtained from patients enrolled in a randomised controlled trial. Whole genome sequencing was used to characterise antibiotic resistance genes, sequence types (STs), plasmids and phylogenetic relationships. Antibiotic susceptibility was determined using disk diffusion and Etest.\n\nResultsA total of 70 E. coli were included, of which the majority were ST131 (61.4%). BSI was most frequently from a urinary source (69.6%), community-associated (62.9%) and in older patients (median age 71 years [IQR 64-81]). The median Pitt bacteraemia score at presentation was 1 (IQR 0-2, range 0-3) and ICU admission was infrequent (3.1%). ST131 possessed significantly more acquired resistance genes than non-ST131 (p=0.003). Clade C1/C2 ST131 predominated (30.2% and 53.5% of all ST131 respectively) and these were all resistant to ciprofloxacin. All clade A ST131 were community-associated. The predominant ESBL types were blaCTX-M (78.6% of isolates) and were strongly associated with ST131, with the majority blaCTX-M-15. Clade C1 was associated with blaCTX-M-14 and blaCTX-M-27, whereas blaCTX-M-15 predominated in clade C2. Plasmid-mediated AmpC (p-AmpC) genes (mainly blaCMY-2) were also frequent (17.1%) but were more common with non-ST131 strains (p< 0.001). The majority of plasmid replicon types were IncF.\n\nConclusionsIn a prospective collection of 3GC-R E. coli causing BSI in the Australasian region, community-associated Clade C1/C2 ST131 predominate in association with blaCTX-M ESBLs, although a significant proportion of non-ST131 strains carried blaCMY-2.

microbiology↗