Systems Immunology of COVID-19

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications, trials & patents

Abstract

Our goal is to integrate computational approaches and several cutting-edge high-throughput methods to assess changes in the epigenome, transcriptome, and proteome throughout the course of COVID-19 disease. Using CITE-seq, we will simultaneously interrogate the immune cell surface proteome, transcriptome, and B-cell receptor (BCR)/T-cell receptor (TCR) repertoire at the single cell level of peripheral blood mononuclear cells (PBMCs) over the course of infection and convalescence. To complement this experiment, whole-blood RNA-seq will provide information on the transcriptome in neutrophils in addition to PBMCs. To understand the epigenetic and transcriptional network underpinnings of these cellular responses, single cell ATAC-seq will be used and integrated. High-parameter proteomics using a Somalogic panel measuring approximately 5,000 proteins will be used to deeply profile the circulating proteome. In addition, similar approaches will be used to assess the molecular and cellular responses of the immune system over the course of clinical trials to test experimental vaccines and therapeutics including remdesivir. We will also examine if pregnancy affects response to SAR-CoV-2 infection. We will develop and use machine learning and computational modeling approaches to integrate such multi-modal data to better understand the immune systems role in disease and protection. They hope to find predictors of infection response severity, which may help pre-identify patients with increased risk of severe symptoms. Elucidating the molecular and cellular networks that orchestrate the immune response to infection could also serve to identify targets for therapeutic intervention. Furthermore, comparing the new data on COVID-19 to existing data on other respiratory infections such as flu, SARS-CoV, or MERS as well as other immune-mediated diseases may pinpoint reusable drug targets. All results will be integrated with the data from the other Immune Response to COVID-19 research projects, such as host genetics, serology, deep immune repertoires, and clinical measurements. For progress and highlights from October 2020 - September 2021, please see 1) Liu C, Martins AJ, Lau WW, Rachmaninoff N et al. Cell, Apr, 2021 2) Ramaswamy A et al. Immunity, June, 2021 3) Abers MS et al. JCI Insight, 2021 4) Bastard P, Rosen LB et al. Science, 2020 In addition, we have ongoing projects in which we have been analyzing: 1) early B cell correlates (as early as baseline, prior to first vaccination) of antibody responses to mRNA COVID-19 vaccination; these correlates provide hypotheses and predictors on variable responses to the mRNA COVID-19 pandemic vaccine. Paper under revision - please see Kardova L, Rachmaninoff N, and Lau WW et al. medRxiv 2021. 2) Post COVID-19 immune system changes with functional implications; these include changes in both innate and adaptive immune systems. 3) Factors that impact infection and symptom susceptibility.