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

Frans A Kuypers, Christina A Rostad, Evan J Anderson, Ann Chahroudi, Preeti Jaggi, Jens Wrammert, Grace Mantus, Rajit Basu, Frank Harris, Bradley Hanberry, Andres Camacho-Gonzalez, Shaminy Manoranjithan, Miriam Vos, Lou Ann Brown, Claudia R Morris

Journal: Experimental biology and medicine (Maywood, N.J.) 2021;246(23):2543-2552

PMID: 34255566

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,  = 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,  = 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,  = 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.

Address: Division of Hematology, Department of Pediatrics, University of California, San Francisco, CA 94609, USA.; Department of Pediatrics1371, School of Medicine, Emory University, Atlanta, GA 30322, USA.; Children's Healthcare of Atlanta, Atlanta, GA 30322, USA.; Center for Childhood Infections and Vaccines of Children's Healthcare of Atlanta and Emory University, Atlanta, GA 30322, USA.; Department of Medicine, School of Medicine, Emory University, Atlanta, GA 30322, USA.; Center for Clinical and Translational Research, Children's Healthcare of Atlanta and Emory University, Atlanta, GA 30322, USA.
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