Identification of biomarkers for COVID-19 associated secondary hemophagocytic lymphohistiocytosis

作者：Susan Canny, Ian B. Stanaway, Sarah E. Holton, Mallorie Mitchem, Allison R. O’Rourke, Stephan Pribitzer, Sarah K. Baxter, Mark M. Wurfel, Uma Malhotra, Jane H. Buckner, Pavan K. Bhatraju, Eric D. Morrell, Cate Speake, Carmen Mikacenic, Jessica A. Hamerman · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2024 · DOI：10.1101/2024.08.13.607855 · 被引用次数：3 · 研究领域：Autoimmune and Inflammatory Disorders Research、Long-Term Effects of COVID-19、Kawasaki Disease and Coronary Complications

Abstract OBJECTIVES We aimed to define and validate novel biomarkers that could identify individuals with COVID-19 associated secondary hemophagocytic lymphohistiocytosis (sHLH) and to test whether fatalities due to COVID-19 in the presence of sHLH were associated with specific defects in the immune system. DESIGN In two cohorts of adult patients presenting with COVID-19 in 2020 and 2021, clinical lab values and serum proteomics were assessed. Subjects identified as having sHLH were compared to those with COVID-19 without sHLH. Eight deceased patients defined as COVID-sHLH underwent genomic sequencing in order to identify variants in immune-related genes. SETTING Two tertiary care hospitals in Seattle, Washington (Virginia Mason Medical Center and Harborview Medical Center). PATIENTS 186 patients with COVID-19 INTERVENTIONS None MEASUREMENTS AND MAIN RESULTS Nine percent of enrolled COVID-19 subjects met our defined criteria for sHLH. Using broad serum proteomic approaches (O-link and SomaScan), we identified three biomarkers for COVID-19 associated sHLH (soluble PD-L1, TNF-R1, and IL-18BP), supporting a role for proteins previously associated with other forms of sHLH (IL-18BP and sTNF-R1). We also identified novel biomarkers and pathways of COVID-sHLH, including sPD-L1 and the syntaxin pathway. We detected variants in several genes involved in immune responses in individuals with COVID-sHLH, including in DOCK8 and in TMPRSS15 , suggesting that genetic alterations in immune-r...