Identification of Biomarkers for COVID-19 Associated Secondary Hemophagocytic Lymphohistiocytosis

Overview

Journal bioRxiv

Date 2024 Aug 26

PMID 39185173

Authors

Susan P Canny

Ian B Stanaway

Sarah E Holton

Mallorie Mitchem

Allison R ORourke

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

Affiliations

Soon will be listed here.

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 and in , suggesting that genetic alterations in immune-related genes may contribute to hyperinflammation and fatal outcomes in COVID-19.

Conclusions: Biomarkers of COVID-19 associated sHLH, such as soluble PD-L1, and pathways, such as the syntaxin pathway, and variants in immune genes in these individuals, suggest critical roles for the immune response in driving sHLH in the context of COVID-19.

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