Multi-omics identify falling LRRC15 as a COVID-19 severity marker and persistent pro-thrombotic signals in convalescence

• Published in: Nature communications Vol. 13; no. 1; p. 7775
• Main Authors: Gisby, Jack S., Buang, Norzawani B., Papadaki, Artemis, Clarke, Candice L., Malik, Talat H., Medjeral-Thomas, Nicholas, Pinheiro, Damiola, Mortimer, Paige M., Lewis, Shanice, Sandhu, Eleanor, McAdoo, Stephen P., Prendecki, Maria F., Willicombe, Michelle, Pickering, Matthew C., Botto, Marina, Thomas, David C., Peters, James E.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.12.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 45/91; 631/1647/2017; 631/1647/2067; 631/326/596/4130; 692/308/53; 82/79; Coagulation; Convalescence; Coronaviruses; COVID-19; End-stage renal disease; Flow cytometry; Gene expression; Gene sequencing; Hemodialysis; Humanities and Social Sciences; Humans; Immune system; Infections; Kidney diseases; Kidneys; Leukocytes, Mononuclear; Membrane Proteins; multidisciplinary; Multiomics; Peripheral blood mononuclear cells; Plasma; Platelet factor 4; Platelets; Proteomes; Proteomics; Ribonucleic acid; Risk; RNA; SARS-CoV-2; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; Thrombosis; Transcriptomes; Transcriptomics; Viral diseases
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-35454-4

Patients with end-stage kidney disease (ESKD) are at high risk of severe COVID-19. Here, we perform longitudinal blood sampling of ESKD haemodialysis patients with COVID-19, collecting samples pre-infection, serially during infection, and after clinical recovery. Using plasma proteomics, and RNA-sequencing and flow cytometry of immune cells, we identify transcriptomic and proteomic signatures of COVID-19 severity, and find distinct temporal molecular profiles in patients with severe disease. Supervised learning reveals that the plasma proteome is a superior indicator of clinical severity than the PBMC transcriptome. We show that a decreasing trajectory of plasma LRRC15, a proposed co-receptor for SARS-CoV-2, is associated with a more severe clinical course. We observe that two months after the acute infection, patients still display dysregulated gene expression related to vascular, platelet and coagulation pathways, including PF4 (platelet factor 4), which may explain the prolonged thrombotic risk following COVID-19. End-stage kidney disease confers a high risk for severe COVID-19 infection. Using an at-risk group (end-stage kidney disease patients with COVID-19), authors using RNA-sequencing of immune cells and plasma proteomic profiling to investigate the host response to viral infection.