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ResearchIn-Press PreviewCOVID-19Inflammation Free access | 10.1172/JCI149236

Group IIA secreted phospholipase A2 is associated with the pathobiology leading to COVID-19 mortality

Justin M. Snider,1 Jeehyun Karen You,2 Xia Wang,3 Ashley J. Snider,1 Brian Hallmark,4 Manja M. Zec,1 Michael C. Seeds,5 Susan Sergeant,6 Laurel Johnstone,7 Qiuming Wang,1 Ryan Sprissler,8 Tara F. Carr,9 Karen Lutrick,10 Sairam Parthasarathy,11 Christian Bime,11 Hao H. Zhang,12 Chiara Luberto,13 Richard R. Kew,14 Yusuf A. Hannun,15 Stefano Guerra,9 Charles E. McCall,16 Guang Yao,3 Maurizio Del Poeta,2 and Floyd H. Chilton1

1Department of Nutritional Sciences, University of Arizona, Tucson, United States of America

2Department of Microbiology and Immunology, Stony Brook University, Stony brook, United States of America

3Department of Molecular and Cellular Biology, University of Arizona, Tucson, United States of America

4BIO5 Institute, University of Arizona, Tucson, United States of America

5Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, United States of America

6Department of Biochemistry, Wake Forest School of Medicine, Tucson, United States of America

7Research Innovation and Impact - Core Facilities, University of Arizona, Tucson, United States of America

8Center for Applied Genetics and Genomic Medicine, University of Arizona, Tucson, United States of America

9Asthma and Airway Disease Research Center, University of Arizona, Tucson, United States of America

10Family and Community Medicine, College of Medicine, University of Arizona, Tucson, United States of America

11Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Arizona, Tucson, United States of America

12Department of Mathematics, University of Arizona, Tucson, United States of America

13Department of Physiology and Biophysics, Stony Brook University, Stony Brook, United States of America

14Department of Pathology, Stony Brook University, Stony Brook, United States of America

15Department of Medicine, Stony Brook University, Stony Brook, United States of America

16Departments of Internal Medicine, Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, United States of America

17Department of Microbiology and Immunology, Stony Brook University, Stony Brook, United States of America

Find articles by Snider, J. in: JCI | PubMed | Google Scholar

1Department of Nutritional Sciences, University of Arizona, Tucson, United States of America

2Department of Microbiology and Immunology, Stony Brook University, Stony brook, United States of America

3Department of Molecular and Cellular Biology, University of Arizona, Tucson, United States of America

4BIO5 Institute, University of Arizona, Tucson, United States of America

5Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, United States of America

6Department of Biochemistry, Wake Forest School of Medicine, Tucson, United States of America

7Research Innovation and Impact - Core Facilities, University of Arizona, Tucson, United States of America

8Center for Applied Genetics and Genomic Medicine, University of Arizona, Tucson, United States of America

9Asthma and Airway Disease Research Center, University of Arizona, Tucson, United States of America

10Family and Community Medicine, College of Medicine, University of Arizona, Tucson, United States of America

11Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Arizona, Tucson, United States of America

12Department of Mathematics, University of Arizona, Tucson, United States of America

13Department of Physiology and Biophysics, Stony Brook University, Stony Brook, United States of America

14Department of Pathology, Stony Brook University, Stony Brook, United States of America

15Department of Medicine, Stony Brook University, Stony Brook, United States of America

16Departments of Internal Medicine, Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, United States of America

17Department of Microbiology and Immunology, Stony Brook University, Stony Brook, United States of America

Find articles by You, J. in: JCI | PubMed | Google Scholar |

1Department of Nutritional Sciences, University of Arizona, Tucson, United States of America

2Department of Microbiology and Immunology, Stony Brook University, Stony brook, United States of America

3Department of Molecular and Cellular Biology, University of Arizona, Tucson, United States of America

4BIO5 Institute, University of Arizona, Tucson, United States of America

5Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, United States of America

6Department of Biochemistry, Wake Forest School of Medicine, Tucson, United States of America

7Research Innovation and Impact - Core Facilities, University of Arizona, Tucson, United States of America

8Center for Applied Genetics and Genomic Medicine, University of Arizona, Tucson, United States of America

9Asthma and Airway Disease Research Center, University of Arizona, Tucson, United States of America

10Family and Community Medicine, College of Medicine, University of Arizona, Tucson, United States of America

11Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Arizona, Tucson, United States of America

12Department of Mathematics, University of Arizona, Tucson, United States of America

13Department of Physiology and Biophysics, Stony Brook University, Stony Brook, United States of America

14Department of Pathology, Stony Brook University, Stony Brook, United States of America

15Department of Medicine, Stony Brook University, Stony Brook, United States of America

16Departments of Internal Medicine, Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, United States of America

17Department of Microbiology and Immunology, Stony Brook University, Stony Brook, United States of America

Find articles by Wang, X. in: JCI | PubMed | Google Scholar |

1Department of Nutritional Sciences, University of Arizona, Tucson, United States of America

2Department of Microbiology and Immunology, Stony Brook University, Stony brook, United States of America

3Department of Molecular and Cellular Biology, University of Arizona, Tucson, United States of America

4BIO5 Institute, University of Arizona, Tucson, United States of America

5Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, United States of America

6Department of Biochemistry, Wake Forest School of Medicine, Tucson, United States of America

7Research Innovation and Impact - Core Facilities, University of Arizona, Tucson, United States of America

8Center for Applied Genetics and Genomic Medicine, University of Arizona, Tucson, United States of America

9Asthma and Airway Disease Research Center, University of Arizona, Tucson, United States of America

10Family and Community Medicine, College of Medicine, University of Arizona, Tucson, United States of America

11Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Arizona, Tucson, United States of America

12Department of Mathematics, University of Arizona, Tucson, United States of America

13Department of Physiology and Biophysics, Stony Brook University, Stony Brook, United States of America

14Department of Pathology, Stony Brook University, Stony Brook, United States of America

15Department of Medicine, Stony Brook University, Stony Brook, United States of America

16Departments of Internal Medicine, Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, United States of America

17Department of Microbiology and Immunology, Stony Brook University, Stony Brook, United States of America

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1Department of Nutritional Sciences, University of Arizona, Tucson, United States of America

2Department of Microbiology and Immunology, Stony Brook University, Stony brook, United States of America

3Department of Molecular and Cellular Biology, University of Arizona, Tucson, United States of America

4BIO5 Institute, University of Arizona, Tucson, United States of America

5Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, United States of America

6Department of Biochemistry, Wake Forest School of Medicine, Tucson, United States of America

7Research Innovation and Impact - Core Facilities, University of Arizona, Tucson, United States of America

8Center for Applied Genetics and Genomic Medicine, University of Arizona, Tucson, United States of America

9Asthma and Airway Disease Research Center, University of Arizona, Tucson, United States of America

10Family and Community Medicine, College of Medicine, University of Arizona, Tucson, United States of America

11Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Arizona, Tucson, United States of America

12Department of Mathematics, University of Arizona, Tucson, United States of America

13Department of Physiology and Biophysics, Stony Brook University, Stony Brook, United States of America

14Department of Pathology, Stony Brook University, Stony Brook, United States of America

15Department of Medicine, Stony Brook University, Stony Brook, United States of America

16Departments of Internal Medicine, Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, United States of America

17Department of Microbiology and Immunology, Stony Brook University, Stony Brook, United States of America

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1Department of Nutritional Sciences, University of Arizona, Tucson, United States of America

2Department of Microbiology and Immunology, Stony Brook University, Stony brook, United States of America

3Department of Molecular and Cellular Biology, University of Arizona, Tucson, United States of America

4BIO5 Institute, University of Arizona, Tucson, United States of America

5Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, United States of America

6Department of Biochemistry, Wake Forest School of Medicine, Tucson, United States of America

7Research Innovation and Impact - Core Facilities, University of Arizona, Tucson, United States of America

8Center for Applied Genetics and Genomic Medicine, University of Arizona, Tucson, United States of America

9Asthma and Airway Disease Research Center, University of Arizona, Tucson, United States of America

10Family and Community Medicine, College of Medicine, University of Arizona, Tucson, United States of America

11Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Arizona, Tucson, United States of America

12Department of Mathematics, University of Arizona, Tucson, United States of America

13Department of Physiology and Biophysics, Stony Brook University, Stony Brook, United States of America

14Department of Pathology, Stony Brook University, Stony Brook, United States of America

15Department of Medicine, Stony Brook University, Stony Brook, United States of America

16Departments of Internal Medicine, Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, United States of America

17Department of Microbiology and Immunology, Stony Brook University, Stony Brook, United States of America

Find articles by Zec, M. in: JCI | PubMed | Google Scholar |

1Department of Nutritional Sciences, University of Arizona, Tucson, United States of America

2Department of Microbiology and Immunology, Stony Brook University, Stony brook, United States of America

3Department of Molecular and Cellular Biology, University of Arizona, Tucson, United States of America

4BIO5 Institute, University of Arizona, Tucson, United States of America

5Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, United States of America

6Department of Biochemistry, Wake Forest School of Medicine, Tucson, United States of America

7Research Innovation and Impact - Core Facilities, University of Arizona, Tucson, United States of America

8Center for Applied Genetics and Genomic Medicine, University of Arizona, Tucson, United States of America

9Asthma and Airway Disease Research Center, University of Arizona, Tucson, United States of America

10Family and Community Medicine, College of Medicine, University of Arizona, Tucson, United States of America

11Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Arizona, Tucson, United States of America

12Department of Mathematics, University of Arizona, Tucson, United States of America

13Department of Physiology and Biophysics, Stony Brook University, Stony Brook, United States of America

14Department of Pathology, Stony Brook University, Stony Brook, United States of America

15Department of Medicine, Stony Brook University, Stony Brook, United States of America

16Departments of Internal Medicine, Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, United States of America

17Department of Microbiology and Immunology, Stony Brook University, Stony Brook, United States of America

Find articles by Seeds, M. in: JCI | PubMed | Google Scholar

1Department of Nutritional Sciences, University of Arizona, Tucson, United States of America

2Department of Microbiology and Immunology, Stony Brook University, Stony brook, United States of America

3Department of Molecular and Cellular Biology, University of Arizona, Tucson, United States of America

4BIO5 Institute, University of Arizona, Tucson, United States of America

5Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, United States of America

6Department of Biochemistry, Wake Forest School of Medicine, Tucson, United States of America

7Research Innovation and Impact - Core Facilities, University of Arizona, Tucson, United States of America

8Center for Applied Genetics and Genomic Medicine, University of Arizona, Tucson, United States of America

9Asthma and Airway Disease Research Center, University of Arizona, Tucson, United States of America

10Family and Community Medicine, College of Medicine, University of Arizona, Tucson, United States of America

11Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Arizona, Tucson, United States of America

12Department of Mathematics, University of Arizona, Tucson, United States of America

13Department of Physiology and Biophysics, Stony Brook University, Stony Brook, United States of America

14Department of Pathology, Stony Brook University, Stony Brook, United States of America

15Department of Medicine, Stony Brook University, Stony Brook, United States of America

16Departments of Internal Medicine, Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, United States of America

17Department of Microbiology and Immunology, Stony Brook University, Stony Brook, United States of America

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1Department of Nutritional Sciences, University of Arizona, Tucson, United States of America

2Department of Microbiology and Immunology, Stony Brook University, Stony brook, United States of America

3Department of Molecular and Cellular Biology, University of Arizona, Tucson, United States of America

4BIO5 Institute, University of Arizona, Tucson, United States of America

5Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, United States of America

6Department of Biochemistry, Wake Forest School of Medicine, Tucson, United States of America

7Research Innovation and Impact - Core Facilities, University of Arizona, Tucson, United States of America

8Center for Applied Genetics and Genomic Medicine, University of Arizona, Tucson, United States of America

9Asthma and Airway Disease Research Center, University of Arizona, Tucson, United States of America

10Family and Community Medicine, College of Medicine, University of Arizona, Tucson, United States of America

11Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Arizona, Tucson, United States of America

12Department of Mathematics, University of Arizona, Tucson, United States of America

13Department of Physiology and Biophysics, Stony Brook University, Stony Brook, United States of America

14Department of Pathology, Stony Brook University, Stony Brook, United States of America

15Department of Medicine, Stony Brook University, Stony Brook, United States of America

16Departments of Internal Medicine, Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, United States of America

17Department of Microbiology and Immunology, Stony Brook University, Stony Brook, United States of America

Find articles by Johnstone, L. in: JCI | PubMed | Google Scholar |

1Department of Nutritional Sciences, University of Arizona, Tucson, United States of America

2Department of Microbiology and Immunology, Stony Brook University, Stony brook, United States of America

3Department of Molecular and Cellular Biology, University of Arizona, Tucson, United States of America

4BIO5 Institute, University of Arizona, Tucson, United States of America

5Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, United States of America

6Department of Biochemistry, Wake Forest School of Medicine, Tucson, United States of America

7Research Innovation and Impact - Core Facilities, University of Arizona, Tucson, United States of America

8Center for Applied Genetics and Genomic Medicine, University of Arizona, Tucson, United States of America

9Asthma and Airway Disease Research Center, University of Arizona, Tucson, United States of America

10Family and Community Medicine, College of Medicine, University of Arizona, Tucson, United States of America

11Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Arizona, Tucson, United States of America

12Department of Mathematics, University of Arizona, Tucson, United States of America

13Department of Physiology and Biophysics, Stony Brook University, Stony Brook, United States of America

14Department of Pathology, Stony Brook University, Stony Brook, United States of America

15Department of Medicine, Stony Brook University, Stony Brook, United States of America

16Departments of Internal Medicine, Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, United States of America

17Department of Microbiology and Immunology, Stony Brook University, Stony Brook, United States of America

Find articles by Wang, Q. in: JCI | PubMed | Google Scholar

1Department of Nutritional Sciences, University of Arizona, Tucson, United States of America

2Department of Microbiology and Immunology, Stony Brook University, Stony brook, United States of America

3Department of Molecular and Cellular Biology, University of Arizona, Tucson, United States of America

4BIO5 Institute, University of Arizona, Tucson, United States of America

5Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, United States of America

6Department of Biochemistry, Wake Forest School of Medicine, Tucson, United States of America

7Research Innovation and Impact - Core Facilities, University of Arizona, Tucson, United States of America

8Center for Applied Genetics and Genomic Medicine, University of Arizona, Tucson, United States of America

9Asthma and Airway Disease Research Center, University of Arizona, Tucson, United States of America

10Family and Community Medicine, College of Medicine, University of Arizona, Tucson, United States of America

11Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Arizona, Tucson, United States of America

12Department of Mathematics, University of Arizona, Tucson, United States of America

13Department of Physiology and Biophysics, Stony Brook University, Stony Brook, United States of America

14Department of Pathology, Stony Brook University, Stony Brook, United States of America

15Department of Medicine, Stony Brook University, Stony Brook, United States of America

16Departments of Internal Medicine, Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, United States of America

17Department of Microbiology and Immunology, Stony Brook University, Stony Brook, United States of America

Find articles by Sprissler, R. in: JCI | PubMed | Google Scholar

1Department of Nutritional Sciences, University of Arizona, Tucson, United States of America

2Department of Microbiology and Immunology, Stony Brook University, Stony brook, United States of America

3Department of Molecular and Cellular Biology, University of Arizona, Tucson, United States of America

4BIO5 Institute, University of Arizona, Tucson, United States of America

5Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, United States of America

6Department of Biochemistry, Wake Forest School of Medicine, Tucson, United States of America

7Research Innovation and Impact - Core Facilities, University of Arizona, Tucson, United States of America

8Center for Applied Genetics and Genomic Medicine, University of Arizona, Tucson, United States of America

9Asthma and Airway Disease Research Center, University of Arizona, Tucson, United States of America

10Family and Community Medicine, College of Medicine, University of Arizona, Tucson, United States of America

11Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Arizona, Tucson, United States of America

12Department of Mathematics, University of Arizona, Tucson, United States of America

13Department of Physiology and Biophysics, Stony Brook University, Stony Brook, United States of America

14Department of Pathology, Stony Brook University, Stony Brook, United States of America

15Department of Medicine, Stony Brook University, Stony Brook, United States of America

16Departments of Internal Medicine, Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, United States of America

17Department of Microbiology and Immunology, Stony Brook University, Stony Brook, United States of America

Find articles by Carr, T. in: JCI | PubMed | Google Scholar |

1Department of Nutritional Sciences, University of Arizona, Tucson, United States of America

2Department of Microbiology and Immunology, Stony Brook University, Stony brook, United States of America

3Department of Molecular and Cellular Biology, University of Arizona, Tucson, United States of America

4BIO5 Institute, University of Arizona, Tucson, United States of America

5Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, United States of America

6Department of Biochemistry, Wake Forest School of Medicine, Tucson, United States of America

7Research Innovation and Impact - Core Facilities, University of Arizona, Tucson, United States of America

8Center for Applied Genetics and Genomic Medicine, University of Arizona, Tucson, United States of America

9Asthma and Airway Disease Research Center, University of Arizona, Tucson, United States of America

10Family and Community Medicine, College of Medicine, University of Arizona, Tucson, United States of America

11Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Arizona, Tucson, United States of America

12Department of Mathematics, University of Arizona, Tucson, United States of America

13Department of Physiology and Biophysics, Stony Brook University, Stony Brook, United States of America

14Department of Pathology, Stony Brook University, Stony Brook, United States of America

15Department of Medicine, Stony Brook University, Stony Brook, United States of America

16Departments of Internal Medicine, Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, United States of America

17Department of Microbiology and Immunology, Stony Brook University, Stony Brook, United States of America

Find articles by Lutrick, K. in: JCI | PubMed | Google Scholar |

1Department of Nutritional Sciences, University of Arizona, Tucson, United States of America

2Department of Microbiology and Immunology, Stony Brook University, Stony brook, United States of America

3Department of Molecular and Cellular Biology, University of Arizona, Tucson, United States of America

4BIO5 Institute, University of Arizona, Tucson, United States of America

5Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, United States of America

6Department of Biochemistry, Wake Forest School of Medicine, Tucson, United States of America

7Research Innovation and Impact - Core Facilities, University of Arizona, Tucson, United States of America

8Center for Applied Genetics and Genomic Medicine, University of Arizona, Tucson, United States of America

9Asthma and Airway Disease Research Center, University of Arizona, Tucson, United States of America

10Family and Community Medicine, College of Medicine, University of Arizona, Tucson, United States of America

11Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Arizona, Tucson, United States of America

12Department of Mathematics, University of Arizona, Tucson, United States of America

13Department of Physiology and Biophysics, Stony Brook University, Stony Brook, United States of America

14Department of Pathology, Stony Brook University, Stony Brook, United States of America

15Department of Medicine, Stony Brook University, Stony Brook, United States of America

16Departments of Internal Medicine, Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, United States of America

17Department of Microbiology and Immunology, Stony Brook University, Stony Brook, United States of America

Find articles by Parthasarathy, S. in: JCI | PubMed | Google Scholar

1Department of Nutritional Sciences, University of Arizona, Tucson, United States of America

2Department of Microbiology and Immunology, Stony Brook University, Stony brook, United States of America

3Department of Molecular and Cellular Biology, University of Arizona, Tucson, United States of America

4BIO5 Institute, University of Arizona, Tucson, United States of America

5Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, United States of America

6Department of Biochemistry, Wake Forest School of Medicine, Tucson, United States of America

7Research Innovation and Impact - Core Facilities, University of Arizona, Tucson, United States of America

8Center for Applied Genetics and Genomic Medicine, University of Arizona, Tucson, United States of America

9Asthma and Airway Disease Research Center, University of Arizona, Tucson, United States of America

10Family and Community Medicine, College of Medicine, University of Arizona, Tucson, United States of America

11Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Arizona, Tucson, United States of America

12Department of Mathematics, University of Arizona, Tucson, United States of America

13Department of Physiology and Biophysics, Stony Brook University, Stony Brook, United States of America

14Department of Pathology, Stony Brook University, Stony Brook, United States of America

15Department of Medicine, Stony Brook University, Stony Brook, United States of America

16Departments of Internal Medicine, Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, United States of America

17Department of Microbiology and Immunology, Stony Brook University, Stony Brook, United States of America

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1Department of Nutritional Sciences, University of Arizona, Tucson, United States of America

2Department of Microbiology and Immunology, Stony Brook University, Stony brook, United States of America

3Department of Molecular and Cellular Biology, University of Arizona, Tucson, United States of America

4BIO5 Institute, University of Arizona, Tucson, United States of America

5Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, United States of America

6Department of Biochemistry, Wake Forest School of Medicine, Tucson, United States of America

7Research Innovation and Impact - Core Facilities, University of Arizona, Tucson, United States of America

8Center for Applied Genetics and Genomic Medicine, University of Arizona, Tucson, United States of America

9Asthma and Airway Disease Research Center, University of Arizona, Tucson, United States of America

10Family and Community Medicine, College of Medicine, University of Arizona, Tucson, United States of America

11Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Arizona, Tucson, United States of America

12Department of Mathematics, University of Arizona, Tucson, United States of America

13Department of Physiology and Biophysics, Stony Brook University, Stony Brook, United States of America

14Department of Pathology, Stony Brook University, Stony Brook, United States of America

15Department of Medicine, Stony Brook University, Stony Brook, United States of America

16Departments of Internal Medicine, Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, United States of America

17Department of Microbiology and Immunology, Stony Brook University, Stony Brook, United States of America

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1Department of Nutritional Sciences, University of Arizona, Tucson, United States of America

2Department of Microbiology and Immunology, Stony Brook University, Stony brook, United States of America

3Department of Molecular and Cellular Biology, University of Arizona, Tucson, United States of America

4BIO5 Institute, University of Arizona, Tucson, United States of America

5Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, United States of America

6Department of Biochemistry, Wake Forest School of Medicine, Tucson, United States of America

7Research Innovation and Impact - Core Facilities, University of Arizona, Tucson, United States of America

8Center for Applied Genetics and Genomic Medicine, University of Arizona, Tucson, United States of America

9Asthma and Airway Disease Research Center, University of Arizona, Tucson, United States of America

10Family and Community Medicine, College of Medicine, University of Arizona, Tucson, United States of America

11Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Arizona, Tucson, United States of America

12Department of Mathematics, University of Arizona, Tucson, United States of America

13Department of Physiology and Biophysics, Stony Brook University, Stony Brook, United States of America

14Department of Pathology, Stony Brook University, Stony Brook, United States of America

15Department of Medicine, Stony Brook University, Stony Brook, United States of America

16Departments of Internal Medicine, Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, United States of America

17Department of Microbiology and Immunology, Stony Brook University, Stony Brook, United States of America

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1Department of Nutritional Sciences, University of Arizona, Tucson, United States of America

2Department of Microbiology and Immunology, Stony Brook University, Stony brook, United States of America

3Department of Molecular and Cellular Biology, University of Arizona, Tucson, United States of America

4BIO5 Institute, University of Arizona, Tucson, United States of America

5Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, United States of America

6Department of Biochemistry, Wake Forest School of Medicine, Tucson, United States of America

7Research Innovation and Impact - Core Facilities, University of Arizona, Tucson, United States of America

8Center for Applied Genetics and Genomic Medicine, University of Arizona, Tucson, United States of America

9Asthma and Airway Disease Research Center, University of Arizona, Tucson, United States of America

10Family and Community Medicine, College of Medicine, University of Arizona, Tucson, United States of America

11Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Arizona, Tucson, United States of America

12Department of Mathematics, University of Arizona, Tucson, United States of America

13Department of Physiology and Biophysics, Stony Brook University, Stony Brook, United States of America

14Department of Pathology, Stony Brook University, Stony Brook, United States of America

15Department of Medicine, Stony Brook University, Stony Brook, United States of America

16Departments of Internal Medicine, Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, United States of America

17Department of Microbiology and Immunology, Stony Brook University, Stony Brook, United States of America

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1Department of Nutritional Sciences, University of Arizona, Tucson, United States of America

2Department of Microbiology and Immunology, Stony Brook University, Stony brook, United States of America

3Department of Molecular and Cellular Biology, University of Arizona, Tucson, United States of America

4BIO5 Institute, University of Arizona, Tucson, United States of America

5Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, United States of America

6Department of Biochemistry, Wake Forest School of Medicine, Tucson, United States of America

7Research Innovation and Impact - Core Facilities, University of Arizona, Tucson, United States of America

8Center for Applied Genetics and Genomic Medicine, University of Arizona, Tucson, United States of America

9Asthma and Airway Disease Research Center, University of Arizona, Tucson, United States of America

10Family and Community Medicine, College of Medicine, University of Arizona, Tucson, United States of America

11Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Arizona, Tucson, United States of America

12Department of Mathematics, University of Arizona, Tucson, United States of America

13Department of Physiology and Biophysics, Stony Brook University, Stony Brook, United States of America

14Department of Pathology, Stony Brook University, Stony Brook, United States of America

15Department of Medicine, Stony Brook University, Stony Brook, United States of America

16Departments of Internal Medicine, Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, United States of America

17Department of Microbiology and Immunology, Stony Brook University, Stony Brook, United States of America

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1Department of Nutritional Sciences, University of Arizona, Tucson, United States of America

2Department of Microbiology and Immunology, Stony Brook University, Stony brook, United States of America

3Department of Molecular and Cellular Biology, University of Arizona, Tucson, United States of America

4BIO5 Institute, University of Arizona, Tucson, United States of America

5Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, United States of America

6Department of Biochemistry, Wake Forest School of Medicine, Tucson, United States of America

7Research Innovation and Impact - Core Facilities, University of Arizona, Tucson, United States of America

8Center for Applied Genetics and Genomic Medicine, University of Arizona, Tucson, United States of America

9Asthma and Airway Disease Research Center, University of Arizona, Tucson, United States of America

10Family and Community Medicine, College of Medicine, University of Arizona, Tucson, United States of America

11Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Arizona, Tucson, United States of America

12Department of Mathematics, University of Arizona, Tucson, United States of America

13Department of Physiology and Biophysics, Stony Brook University, Stony Brook, United States of America

14Department of Pathology, Stony Brook University, Stony Brook, United States of America

15Department of Medicine, Stony Brook University, Stony Brook, United States of America

16Departments of Internal Medicine, Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, United States of America

17Department of Microbiology and Immunology, Stony Brook University, Stony Brook, United States of America

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1Department of Nutritional Sciences, University of Arizona, Tucson, United States of America

2Department of Microbiology and Immunology, Stony Brook University, Stony brook, United States of America

3Department of Molecular and Cellular Biology, University of Arizona, Tucson, United States of America

4BIO5 Institute, University of Arizona, Tucson, United States of America

5Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, United States of America

6Department of Biochemistry, Wake Forest School of Medicine, Tucson, United States of America

7Research Innovation and Impact - Core Facilities, University of Arizona, Tucson, United States of America

8Center for Applied Genetics and Genomic Medicine, University of Arizona, Tucson, United States of America

9Asthma and Airway Disease Research Center, University of Arizona, Tucson, United States of America

10Family and Community Medicine, College of Medicine, University of Arizona, Tucson, United States of America

11Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Arizona, Tucson, United States of America

12Department of Mathematics, University of Arizona, Tucson, United States of America

13Department of Physiology and Biophysics, Stony Brook University, Stony Brook, United States of America

14Department of Pathology, Stony Brook University, Stony Brook, United States of America

15Department of Medicine, Stony Brook University, Stony Brook, United States of America

16Departments of Internal Medicine, Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, United States of America

17Department of Microbiology and Immunology, Stony Brook University, Stony Brook, United States of America

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1Department of Nutritional Sciences, University of Arizona, Tucson, United States of America

2Department of Microbiology and Immunology, Stony Brook University, Stony brook, United States of America

3Department of Molecular and Cellular Biology, University of Arizona, Tucson, United States of America

4BIO5 Institute, University of Arizona, Tucson, United States of America

5Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, United States of America

6Department of Biochemistry, Wake Forest School of Medicine, Tucson, United States of America

7Research Innovation and Impact - Core Facilities, University of Arizona, Tucson, United States of America

8Center for Applied Genetics and Genomic Medicine, University of Arizona, Tucson, United States of America

9Asthma and Airway Disease Research Center, University of Arizona, Tucson, United States of America

10Family and Community Medicine, College of Medicine, University of Arizona, Tucson, United States of America

11Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Arizona, Tucson, United States of America

12Department of Mathematics, University of Arizona, Tucson, United States of America

13Department of Physiology and Biophysics, Stony Brook University, Stony Brook, United States of America

14Department of Pathology, Stony Brook University, Stony Brook, United States of America

15Department of Medicine, Stony Brook University, Stony Brook, United States of America

16Departments of Internal Medicine, Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, United States of America

17Department of Microbiology and Immunology, Stony Brook University, Stony Brook, United States of America

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1Department of Nutritional Sciences, University of Arizona, Tucson, United States of America

2Department of Microbiology and Immunology, Stony Brook University, Stony brook, United States of America

3Department of Molecular and Cellular Biology, University of Arizona, Tucson, United States of America

4BIO5 Institute, University of Arizona, Tucson, United States of America

5Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, United States of America

6Department of Biochemistry, Wake Forest School of Medicine, Tucson, United States of America

7Research Innovation and Impact - Core Facilities, University of Arizona, Tucson, United States of America

8Center for Applied Genetics and Genomic Medicine, University of Arizona, Tucson, United States of America

9Asthma and Airway Disease Research Center, University of Arizona, Tucson, United States of America

10Family and Community Medicine, College of Medicine, University of Arizona, Tucson, United States of America

11Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Arizona, Tucson, United States of America

12Department of Mathematics, University of Arizona, Tucson, United States of America

13Department of Physiology and Biophysics, Stony Brook University, Stony Brook, United States of America

14Department of Pathology, Stony Brook University, Stony Brook, United States of America

15Department of Medicine, Stony Brook University, Stony Brook, United States of America

16Departments of Internal Medicine, Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, United States of America

17Department of Microbiology and Immunology, Stony Brook University, Stony Brook, United States of America

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1Department of Nutritional Sciences, University of Arizona, Tucson, United States of America

2Department of Microbiology and Immunology, Stony Brook University, Stony brook, United States of America

3Department of Molecular and Cellular Biology, University of Arizona, Tucson, United States of America

4BIO5 Institute, University of Arizona, Tucson, United States of America

5Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, United States of America

6Department of Biochemistry, Wake Forest School of Medicine, Tucson, United States of America

7Research Innovation and Impact - Core Facilities, University of Arizona, Tucson, United States of America

8Center for Applied Genetics and Genomic Medicine, University of Arizona, Tucson, United States of America

9Asthma and Airway Disease Research Center, University of Arizona, Tucson, United States of America

10Family and Community Medicine, College of Medicine, University of Arizona, Tucson, United States of America

11Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Arizona, Tucson, United States of America

12Department of Mathematics, University of Arizona, Tucson, United States of America

13Department of Physiology and Biophysics, Stony Brook University, Stony Brook, United States of America

14Department of Pathology, Stony Brook University, Stony Brook, United States of America

15Department of Medicine, Stony Brook University, Stony Brook, United States of America

16Departments of Internal Medicine, Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, United States of America

17Department of Microbiology and Immunology, Stony Brook University, Stony Brook, United States of America

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Published August 24, 2021 - More info

J Clin Invest. https://doi.org/10.1172/JCI149236.
Copyright © 2021, American Society for Clinical Investigation
Published August 24, 2021 - Version history
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Abstract

There is an urgent need to identify cellular/molecular mechanisms responsible for severe COVID-19 progressing to mortality. We initially performed untargeted/targeted lipidomics and focused biochemistry on 127 plasma samples and found elevated metabolites associated with secreted phospholipase A2 (sPLA2) activity and mitochondrial dysfunction in severe COVID-19 patients. Deceased COVID-19 patients had higher levels of circulating, catalytically active sPLA2 Group IIA (sPLA2-IIA), with a median value 9.6-fold higher than mild patients and 5.0-fold higher than severe COVID-19 survivors. Elevated sPLA2-IIA levels paralleled several indices of COVID-19 disease severity (e.g., kidney dysfunction, hypoxia, multiple organ dysfunction). A decision tree generated by machine learning identified sPLA2-IIA levels as a central node in stratifying patients that succumbed to COVID-19. Random forest analysis and LASSO-based regression analysis additionally identified sPLA2-IIA and blood urea nitrogen (BUN) as the key variables among 80 clinical indices in predicting COVID-19 mortality. The combined PLA-BUN index performed significantly better than either alone. An independent cohort (n=154) confirmed higher plasma sPLA2-IIA levels in deceased patients vs. severe or mild COVID-19, with the PLA-BUN index-based decision tree satisfactorily stratifying mild, severe, and deceased COVID-19 patients. With clinically tested inhibitors available, this study supports sPLA2-IIA as a therapeutic target to reduce COVID-19 mortality.

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