Role of mast cells in the pathogenesis of severe lung damage in COVID-19 patients

Abstract

Background There is still insufficient knowledge with regard to the potential involvement of mast cells (MCs) and their mediators in the pathology of coronavirus disease-2019 (COVID-19). Therefore, our study aimed to investigate the role of MCs, their activation and protease profiles in the pathogenesis of early and late lung damage in COVID-19 patients. Methods Formalin-fixed and paraffin embedded lung specimens from 30 patients who died from COVID-19 and 9 controls were used for histological detection of MCs and their proteases (tryptase, chymase) followed by morphometric quantification. Results Our results demonstrated increased numbers of MCs at early stage and further augmentation of MCs number during the late stage of alveolar damage in COVID-19 patients, as compared to the control group. Importantly, the percentage of degranulated (activated) MCs was higher during both stages of alveolar lesions in comparison to the controls. While there was no prominent alteration in the profile of tryptase-positive MCs, our data revealed a significant elevation in the number of chymase-positive MCs in the lungs of COVID-19 patients, compared to the controls. Conclusions MCs are characterized by dysregulated accumulation and increased activation in the lungs of patients suffering from COVID-19. However, future profound studies are needed for precise analysis of the role of these immune cells in the context of novel coronavirus disease.

Increase in venous thromboembolism in SARS‐CoV‐2 infected lung tissue: proteome analysis of lung parenchyma, isolated endothelium, and thrombi

“…Histamine has been found to induce proinflammatory cytokines and provoking endothelial damage in COVID19 51–53 . Our results are in line with these findings and imply increased mast cell activity, which may contribute to pulmonary fibrosis and thrombosis in COVID‐19 54,55 . Upregulation of arginase ( ARG1 ) in COVID‐19 patients may also contribute to organ failure and pulmonary fibrosis.…”

“…[51][52][53] Our results are in line with these findings and imply increased mast cell activity, which may contribute to pulmonary fibrosis and thrombosis in COVID-19. 54,55 Upregulation of arginase (ARG1) in COVID-19 patients may also contribute to organ failure and pulmonary fibrosis. Arginase was also found to be increased in blood samples of intubated COVID-19 patients, [56][57][58] which is able to induce (pulmonary) fibrosis by indirectly promoting fibroblast proliferation and collagen production.…”

Mechanisms of COVID-19 Associated Pulmonary Thrombosis: A Narrative Review

“…Clusters of degranulating MCs expressing chymase and tryptase are seen in the lung areas with hemorrhagic phenomena, and it could be connected to local histamine production, stored endogenously within the secretory granules of MCs, and released into the vessels after cell stimulation [ 64 , 65 ]. Resident phagocyte alveolar macrophages activated by SARS-CoV-2-TLR interaction produce IL-1 which further stimulates MCs to produce IL-6 [ 65 ].…”

“…Immune cells, such as macrophages, monocytes, MCs, T cells, DCs, NK cells, and neutrophils, “orchestrate” the crosstalk between proinflammatory and procoagulative networks [ 4 , 18 , 43 , 44 , 45 , 46 , 47 , 48 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 113 , 114 , 115 , 129 , 131 ].…”

Mast cell degranulation-triggered by SARS-CoV-2 induces tracheal-bronchial epithelial inflammation and injury

“…In addition to being the main effector cells in type I allergic reactions, MCs are increasingly recognized for their regulatory roles in various pathophysiological processes ( Elieh Ali Komi et al., 2020 ; Lam et al., 2021 ). In SARS-CoV-2 infection, MCs are massively recruited to the alveolar septa and pulmonary parenchyma in postmortem lung biopsies of COVID-19 patients or infected monkeys ( Motta Junior et al., 2020 ; Ribeiro Dos Santos Miggiolaro et al., 2020 ; Malone et al., 2021 ; Budnevsky et al., 2022 ; Schaller et al., 2022 ). The severity of SARS-CoV-2 infection is associated with higher numbers of alveolar MCs and greater degranulation ( Krysko et al., 2022 ).…”