Secretory phospholipase A2 in SARS-CoV-2 infection and multisystem inflammatory syndrome in children (MIS-C)

• Type of Material: Article
• Authors: Frans A. Kuypers, University of California San Francisco; Christina Rostad, Emory University; Evan Anderson, Emory University; Ann Chahroudi, Emory University; Preeti Jaggi, Emory University; Jens Wrammert, Emory University; Grace Mantus, Emory University; Rajit Basu, Emory University; Frank Harris, Emory University; Bradley Hanberry, Emory University; Andres Camacho-Gonzalez, Emory University; Shaminy Manoranjithan, Children's Healthcare of Atlanta; Miriam Vos, Emory University; Louann Brown, Emory University; Claudia Morris, Emory University
• Language: English
• Date: 2021-07-13
• Publisher: SAGE PUBLICATIONS LTD
• Publication Version: Final Published Version
• Copyright Statement: © 2021 by the Society for Experimental Biology and Medicine
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1177/15353702211028560
• Title of Journal or Parent Work: EXPERIMENTAL BIOLOGY AND MEDICINE
• Volume: 246
• Issue: 23
• Start Page: 2543
• End Page: 2552
• Grant/Funding Information: This study was funded in part by the Wilbur and Hilda Glenn Family Foundation, a generous donation by Michael and Natalia Beinenson, by the Woodruff Health Sciences Center Synergy Award, an Emory COVID-19 CURE award made possible by philanthropic support from the O. Wayne Rollins Foundation and the William Randolph Hearst Foundation, and by a generous donation by the Scott Hudgens Family Foundation. Sample processing for the Healthcare Worker cohort utilized the Children's Healthcare of Atlanta and Emory University's Children’s Clinical and Translational Discovery Core.
• Keywords: ACUTE CHEST SYNDROME; secretory phospholipase A2; INHIBITOR; multisystem inflammatory syndrome in children; ANNEXIN-V HOMODIMER; Life Sciences & Biomedicine; SICKLE-CELL-DISEASE; A(2); Research & Experimental Medicine; SARS-CoVC-2; REPERFUSION; DIANNEXIN; Science & Technology; PHOSPHATIDYLSERINE; COVID-19; APOPTOSIS; Medicine, Research & Experimental; KAWASAKI-DISEASE
• Research Categories: Biology, Cell; Biology, Virology

Abstract

Secretory phospholipase 2 (sPLA2) acts as a mediator between proximal and distal events of the inflammatory cascade. Its role in SARS-CoV-2 infection is unknown, but could contribute to COVID-19 inflammasome activation and cellular damage. We present the first report of plasma sPLA2 levels in adults and children with COVID-19 compared with controls. Currently asymptomatic adults with a history of recent COVID-19 infection (≥4 weeks before) identified by SARS-CoV-2 IgG antibodies had sPLA2 levels similar to those who were seronegative (9 ± 6 vs.17 ± 28 ng/mL, P = 0.26). In contrast, children hospitalized with severe COVID-19 had significantly elevated sPLA2 compared with those with mild or asymptomatic SARS-CoV-2 infection (269 ± 137 vs. 2 ± 3 ng/mL, P = 0.01). Among children hospitalized with multisystem inflammatory syndrome in children (MIS-C), all had severe disease requiring pediatric intensive care unit (PICU) admission. sPLA2 levels were significantly higher in those with acute illness <10 days versus convalescent disease ≥10 days (540 ± 510 vs. 2 ± 1, P = 0.04). Thus, sPLA2 levels correlated with COVID-19 severity and acute MIS-C in children, implicating a role in inflammasome activation and disease pathogenesis. sPLA2 may be a useful biomarker to stratify risk and guide patient management for children with acute COVID-19 and MIS-C. Therapeutic compounds targeting sPLA2 and inflammasome activation warrant consideration.