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=11

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=<p>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 histopathology data obtained in post-mortem lung biopsies of COVID-19, showing the increased density of perivascular and septal mast cells (MCs) and IL-4-expressing cells (<italic>n</italic> = 6), in contrast to the numbers found in pandemic H1N1-induced pneumonia (<italic>n</italic> = 10) or Control specimens (<italic>n</italic> = 10). Noteworthy, COVID-19 lung biopsies showed a higher density of CD117<sup>+</sup> cells, suggesting that c-kit positive MCs progenitors were recruited earlier to the alveolar septa. These findings suggest that MC proliferation/differentiation in the alveolar septa might be harnessed by the shift toward IL-4 expression in the inflamed alveolar septa. Future studies may clarify whether the fibrin-dependent generation of the hyaline membrane, processes that require the diffusion of procoagulative plasma factors into the alveolar lumen and the endothelial dysfunction, are preceded by MC-driven formation of interstitial edema in the alveolar septa.</p>