Mast cell activation in lungs during SARS-CoV-2 infection associated with lung pathology and severe COVID-19
Janessa Y.J. Tan, … , Jörn Karhausen, Ashley L. St. John
Janessa Y.J. Tan, … , Jörn Karhausen, Ashley L. St. John
Published August 10, 2023
Citation Information: J Clin Invest. 2023;133(19):e149834. https://doi.org/10.1172/JCI149834.
View: Text | PDF
Research Article

Mast cell activation in lungs during SARS-CoV-2 infection associated with lung pathology and severe COVID-19

Abstract

Lung inflammation is a hallmark of Coronavirus disease 2019 (COVID-19) in patients who are severely ill, 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 and often promote inflammation. We observed widespread degranulation of MCs during acute and unresolved airway inflammation in SARS-CoV-2-infected mice and nonhuman primates. Using a mouse model of MC deficiency, MC-dependent interstitial pneumonitis, hemorrhaging, and edema in the lung were observed during SARS-CoV-2 infection. In humans, transcriptional changes in patients requiring oxygen supplementation also implicated cells with a MC phenotype in severe disease. MC activation in humans was confirmed through detection of MC-specific proteases, including chymase, the levels of which were significantly correlated with disease severity and with biomarkers of vascular dysregulation. These results support the involvement of MCs in lung tissue damage during SARS-CoV-2 infection in animal models and the association of MC activation with severe COVID-19 in humans, suggesting potential strategies for intervention.

Authors

Janessa Y.J. Tan, Danielle E. Anderson, Abhay P.S. Rathore, Aled O’Neill, Chinmay Kumar Mantri, Wilfried A.A. Saron, Cheryl Q.E. Lee, Chu Wern Cui, Adrian E.Z. Kang, Randy Foo, Shirin Kalimuddin, Jenny G. Low, Lena Ho, Paul Tambyah, Thomas W. Burke, Christopher W. Woods, Kuan Rong Chan, Jörn Karhausen, Ashley L. St. John

×

Figure 5

Serum chymase and MC activation pathways associated with severe COVID-19.

Options: View larger image (or click on image) Download as PowerPoint
Serum chymase and MC activation pathways associated with severe COVID-19...
(A) Pathway analysis indicates a significant perturbation of pathways associated with host responses to characteristic MC products. Ingenuity software was used to generate P values. (B) Strategy for grouping of patients by WHO score (34) for analysis. (C) Plasma chymase levels were increased in patients with COVID-19 compared with CABG controls and correlate with disease severity (Supplemental Figure 7A). (D) Chymase levels were also increased in patients who later required intubation, compared with nonintubated patients from multiple groups (WHO-1, WHO-2, and WHO-3). (E) Serum tryptase levels were significantly increased in all patients with COVID-19 and were undetectable in CABG controls. (F) Significantly increased plasma Ang2/Ang1 ratios in patients in group WHO-3 compared with other groups and CABG controls. 1-way ANOVA (C, E, and F) or Student’s unpaired t test (D) were performed; *P <0.05; ***P <0.001; ***P <0.0001. Nonsignificant P values are indicated on the graphs; significant P values are indicated with asterisks. For panels (C–F), CABG patients, n = 20; For WHO-1, n = 13; for WHO-2, n = 13; for WHO-3, n = 12.