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1.
Front Immunol ; 12: 650331, 2021.
Article in English | MEDLINE | ID: covidwho-1156125

ABSTRACT

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection represents a global health crisis. Immune cell activation via pattern recognition receptors has been implicated as a driver of the hyperinflammatory response seen in COVID-19. However, our understanding of the specific immune responses to SARS-CoV-2 remains limited. Mast cells (MCs) and eosinophils are innate immune cells that play pathogenic roles in many inflammatory responses. Here we report MC-derived proteases and eosinophil-associated mediators are elevated in COVID-19 patient sera and lung tissues. Stimulation of viral-sensing toll-like receptors in vitro and administration of synthetic viral RNA in vivo induced features of hyperinflammation, including cytokine elevation, immune cell airway infiltration, and MC-protease production-effects suppressed by an anti-Siglec-8 monoclonal antibody which selectively inhibits MCs and depletes eosinophils. Similarly, anti-Siglec-8 treatment reduced disease severity and airway inflammation in a respiratory viral infection model. These results suggest that MC and eosinophil activation are associated with COVID-19 inflammation and anti-Siglec-8 antibodies are a potential therapeutic approach for attenuating excessive inflammation during viral infections.


Subject(s)
Antigens, CD/immunology , Antigens, Differentiation, B-Lymphocyte/immunology , COVID-19/immunology , Eosinophils/immunology , Lectins/immunology , Mast Cells/immunology , Respiratory Syncytial Virus Infections/immunology , Respiratory Syncytial Viruses/immunology , SARS-CoV-2/immunology , Toll-Like Receptors/immunology , Animals , Antibodies, Monoclonal/pharmacology , Antigens, CD/genetics , Antigens, CD/metabolism , Antigens, Differentiation, B-Lymphocyte/genetics , Antigens, Differentiation, B-Lymphocyte/metabolism , COVID-19/metabolism , COVID-19/prevention & control , COVID-19/virology , Case-Control Studies , Cytokines/metabolism , Disease Models, Animal , Eosinophils/drug effects , Eosinophils/metabolism , Eosinophils/virology , Host-Pathogen Interactions , Humans , Lectins/antagonists & inhibitors , Lectins/genetics , Lectins/metabolism , Mast Cells/drug effects , Mast Cells/metabolism , Mast Cells/virology , Mice, Transgenic , Peptide Hydrolases/metabolism , Respiratory Syncytial Virus Infections/metabolism , Respiratory Syncytial Virus Infections/prevention & control , Respiratory Syncytial Virus Infections/virology , Toll-Like Receptors/metabolism
3.
Microbes Infect ; 22(9): 403-404, 2020 10.
Article in English | MEDLINE | ID: covidwho-618770

Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Respiratory Syncytial Virus Infections/prevention & control , Severe Acute Respiratory Syndrome/prevention & control , Viral Vaccines/administration & dosage , Antibodies, Neutralizing/biosynthesis , Antibodies, Viral/biosynthesis , Betacoronavirus/immunology , COVID-19 , COVID-19 Vaccines , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Eosinophils/drug effects , Eosinophils/immunology , Eosinophils/pathology , Eosinophils/virology , Humans , Lung/drug effects , Lung/immunology , Lung/pathology , Lung/virology , Middle East Respiratory Syndrome Coronavirus/immunology , Middle East Respiratory Syndrome Coronavirus/pathogenicity , Monocytes/drug effects , Monocytes/immunology , Monocytes/pathology , Monocytes/virology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Respiratory Syncytial Virus Infections/epidemiology , Respiratory Syncytial Virus Infections/immunology , Respiratory Syncytial Virus Infections/virology , Respiratory Syncytial Viruses/immunology , Respiratory Syncytial Viruses/pathogenicity , SARS Virus/immunology , SARS Virus/pathogenicity , SARS-CoV-2 , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/immunology , Severe Acute Respiratory Syndrome/virology , Severity of Illness Index , Viral Vaccines/adverse effects
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