Pandemic, epidemic, endemic: B cell repertoire analysis reveals unique anti-viral responses to SARS-CoV-2, Ebola and Respiratory Syncytial Virus

Immunoglobulin gene heterogeneity reflects the diversity and focus of the humoral immune response towards different infections, enabling inference of B cell development processes. Detailed compositional and lineage analysis of long read IGH repertoire sequencing, combining examples of pandemic, epidemic and endemic viral infections with control and vaccination samples, demonstrates general responses including increased use of IGHV4-39 in both EBOV and COVID-19 infection cohorts. We also show unique characteristics absent in RSV infection or yellow fever vaccine samples: EBOV survivors show unprecedented high levels of class switching events while COVID-19 repertoires from acute disease appear underdeveloped. Despite the high levels of clonal expansion in COVID-19 IgG1 repertoires there is a striking lack of evidence of germinal centre mutation and selection. Given the differences in COVID-19 morbidity and mortality with age, it is also pertinent that we find significant differences in repertoire characteristics between young and old patients. Our data supports the hypothesis that a primary viral challenge can result in a strong but immature humoral response where failures in selection of the repertoire risks off-target effects.

Changes to the sebum lipidome upon COVID-19 infection observed via non-invasive and rapid sampling from the skin

The COVID-19 pandemic has led to an urgent and unprecedented demand for testing - both for diagnosis and prognosis. Here we explore the potential for using sebum, collected via swabbing of a patients skin, as a novel sampling matrix to fulfil these requirements. In this pilot study, sebum samples were collected from 67 hospitalised patients (30 PCR positive and 37 PCR negative). Lipidomics analysis was carried out using liquid chromatography mass spectrometry. Lipid levels were found to be depressed in COVID-19 positive participants, indicative of dyslipidemia. Partial Least Squares-Discriminant Analysis (PLS-DA) modelling showed promising separation of COVID-19 positive and negative participants when comorbidities and medication were controlled for, with sensitivity of 75% and specificity of 81% in stratified subsets. Given that sebum sampling is rapid and non-invasive, this work highlights the potential of this alternative matrix for testing for COVID-19.