Mast Cells in Alveolar Septa of COVID-19 Patients: A Pathogenic Pathway That May Link Interstitial Edema to Immunothrombosis
Jarbas da Silva Motta, Anna Flavia Ribeiro dos Santos Miggiolaro, Seigo Nagashima, Caroline Busatta Vaz de Paula, Cristina Pellegrino Baena, Júlio Scharfstein, Lúcia de Noronha
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.