Signatures of mast cell activation are associated with severe COVID-19
Janessa Y.J. Tana, Danielle E. Andersona, Abhay P. S. Rathoreb, Aled O’Neilla, Chinmay Kumar Mantria, Wilfried A. A. Sarona, Cheryl Q. E. Leec, Chu Wern Cuic, Adrian Kang Eng Zhenga, Randy Fooa, Shirin Kalimuddina d, Jenny Guek Hong Lowa d, Lena Hoc e, Paul Anantharajah Tambyahf g, Thomas W. Burkeh, Christopher W. Woodsh i j, Kuan Rong Chana, Jörn Karhausenb k, Ashley L. St. Johna b l m✉
- aProgram in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore
- bDepartment of Pathology, Duke University Medical Center, Durham, NC, USA
- cDuke-NUS Medical School, Program in Cardiovascular and Metabolic Disorders, Singapore
- dDepartment of Infectious Diseases, Singapore General Hospital, Singapore
- eInstitute of Molecular and Cell Biology, A*STAR, Singapore
- fDepartment of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- gDivision of Infectious Disease, University Medicine Cluster, National University Hospital, Singapore
- hCenter for Applied Genomics and Precision Medicine, Duke University Medical Center, Durham, NC, USA
- iDivision of Infectious Diseases, Duke University Medical Center
- jDurham VA Medical Center, Durham, NC, USA
- kDepartment of Anesthesiology, Duke University Medical Center
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Abstract
Lung inflammation is a hallmark of Coronavirus disease 2019 (COVID-19) in severely ill patients and the pathophysiology of disease is thought to be immune-mediated. Mast cells (MCs) are polyfunctional immune cells present in the airways, where they respond to certain viruses and allergens, often promoting inflammation. We observed widespread degranulation of MCs during acute and unresolved airway inflammation in SARS-CoV-2-infected mice and non-human primates. In humans, transcriptional changes in patients requiring oxygen supplementation also implicated cells with a MC phenotype. MC activation in humans was confirmed, through detection of the MC-specific protease, chymase, levels of which were significantly correlated with disease severity. These results support the association of MC activation with severe COVID-19, suggesting potential strategies for intervention.
TL;DRResults support the association of MC activation with severe COVID-19, suggesting potential strategies for intervention and detection of the MC-specific protease, chymase, levels of which were significantly correlated with disease severity. (Semantic Scholar)