AUTHOR=Motta Junior Jarbas da Silva , Miggiolaro Anna Flavia Ribeiro dos Santos , Nagashima Seigo , de Paula Caroline Busatta Vaz , Baena Cristina Pellegrino , Scharfstein Julio , de Noronha Lucia 

TITLE=Mast Cells in Alveolar Septa of COVID-19 Patients: A Pathogenic Pathway That May Link Interstitial Edema to Immunothrombosis

JOURNAL=Frontiers in Immunology

VOLUME=Volume 11 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.574862

DOI=10.3389/fimmu.2020.574862

ISSN=1664-3224

ABSTRACT=It is currently believed that innate immunity is unable to prevent the spread of SARS-CoV-2 from the upper airways to the alveoli of high-risk groups of patients. SARS-CoV-2 replication in ACE-2-expressing pneumocytes can drive the diffuse alveolar injury through the cytokine storm and immunothrombosis by upregulating the transcription of chemokine/cytokines, unlike several other respiratory viruses. Here we report histopathological data showing that mast cell density and IL-4 tissue expression are markedly increased in post-mortem biopsies of COVID-19 patients (n=6). In contrast, we detected fewer mast cells and lower IL-4 tissue expression in the alveolar septa of H1N1-induced pneumonia (n=10) or control specimens (n=10).  Although conceding that cytokine storms may also influence the dynamics of recruitment and maturation of mast cells in the injured alveolar micro-environment, our histopathological data raise the possibility that mast cells-driven microvascular leakage and IL-4-mediated vascular injury may reinforce the intra-alveolar hyaline membranes and alveolar-capillary immunothrombosis by enhancing the influx of plasma coagulative factors to the alveolar lumen and promoting endothelial cell's pro-inflammatory response.