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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2543-2552 |
| Number of pages | 10 |
| Journal | Experimental Biology and Medicine |
| Volume | 246 |
| Issue number | 23 |
| DOIs | |
| State | Published - Dec 2021 |
Funding
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. The authors like to thank Merrill Chandler, MD, for helpful discussions regarding patient evaluation. The authors also acknowledge Deb Leake, NP; Rashika Mendis, MBBS; Patricia Bush, MS; Christie Chen, MD,; Rachel Krieger, MD; Laila Hussaini, MPH; Lisa Macoy, MSN; Stacy Heilman, PhD; Patrick Sullivan, PhD; and Rebecca Cleeton, MS for excellent assistance with patient enrollment. We thank Stacey A Lapp, MS, MPH, and the laboratories of CHOA and the Emory Hope Clinic for specimen handling and processing. Sample processing for the Healthcare Worker Cohort utilized the CHOA and Emory University's Children?s Clinical and Translational Discovery Core. The authors dedicate this article to Bertram Lubin, MD, the former president and chief executive officer of UCSF-Benioff Children?s Hospital Oakland, who passed away on 27 June 2020. Dr Lubin was an ardent supporter of children?s health, an advocate for children with SCD, and an inspiration to countless clinician-scientists. The scientific community mourns the loss of a hero. 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
- COVID-19
- SARS-CoVC-2
- multisystem inflammatory syndrome in children
- secretory phospholipase A2
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology