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Severity of SARS-CoV-2 infection is associated with high numbers of alveolar mast cells and their degranulation.
Krysko, Olga; Bourne, Joshua H; Kondakova, Elena; Galova, Elena A; Whitworth, Katharine; Newby, Maddy L; Bachert, Claus; Hill, Harriet; Crispin, Max; Stamataki, Zania; Cunningham, Adam F; Pugh, Matthew; Khan, Abdullah O; Rayes, Julie; Vedunova, Maria; Krysko, Dmitri V; Brill, Alexander.
  • Krysko O; Upper Airways Research Laboratory, Department of Head and Skin, Ghent University, Ghent, Belgium.
  • Bourne JH; Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
  • Kondakova E; Institute of Biology and Biomedicine, Department of Basic and Medical Genetics, National Research Lobachevsky State University of Nizhniy Novgorod, Nizhniy Novgorod, Russia.
  • Galova EA; University Clinic of Privolzhsky Research Medical University, Nizhny Novgorod, Russia.
  • Whitworth K; Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
  • Newby ML; School of Biological Sciences, University of Southampton, Southampton, United Kingdom.
  • Bachert C; Upper Airways Research Laboratory, Department of Head and Skin, Ghent University, Ghent, Belgium.
  • Hill H; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.
  • Crispin M; School of Biological Sciences, University of Southampton, Southampton, United Kingdom.
  • Stamataki Z; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.
  • Cunningham AF; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.
  • Pugh M; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.
  • Khan AO; Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
  • Rayes J; Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
  • Vedunova M; Institute of Biology and Biomedicine, Department of Basic and Medical Genetics, National Research Lobachevsky State University of Nizhniy Novgorod, Nizhniy Novgorod, Russia.
  • Krysko DV; Institute of Biology and Biomedicine, Department of Basic and Medical Genetics, National Research Lobachevsky State University of Nizhniy Novgorod, Nizhniy Novgorod, Russia.
  • Brill A; Department of Pathophysiology, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.
Front Immunol ; 13: 968981, 2022.
Article in English | MEDLINE | ID: covidwho-2114656
ABSTRACT

Background:

The systemic inflammatory response post-SARS-CoV-2 infection increases pro-inflammatory cytokine production, multi-organ damage, and mortality rates. Mast cells (MC) modulate thrombo-inflammatory disease progression (e.g., deep vein thrombosis) and the inflammatory response post-infection.

Objective:

To enhance our understanding of the contribution of MC and their proteases in SARS-CoV-2 infection and the pathogenesis of the disease, which might help to identify novel therapeutic targets.

Methods:

MC proteases chymase (CMA1), carboxypeptidase A3 (CPA3), and tryptase beta 2 (TPSB2), as well as cytokine levels, were measured in the serum of 60 patients with SARS-CoV-2 infection (30 moderate and 30 severe; severity of the disease assessed by chest CT) and 17 healthy controls by ELISA. MC number and degranulation were quantified by immunofluorescent staining for tryptase in lung autopsies of patients deceased from either SARS-CoV-2 infection or unrelated reasons (control). Immortalized human FcεR1+c-Kit+ LUVA MC were infected with SARS-CoV-2, or treated with its viral proteins, to assess direct MC activation by flow cytometry.

Results:

The levels of all three proteases were increased in the serum of patients with COVID-19, and strongly correlated with clinical severity. The density of degranulated MC in COVID-19 lung autopsies was increased compared to control lungs. The total number of released granules and the number of granules per each MC were elevated and positively correlated with von Willebrand factor levels in the lung. SARS-CoV-2 or its viral proteins spike and nucleocapsid did not induce activation or degranulation of LUVA MC in vitro.

Conclusion:

In this study, we demonstrate that SARS-CoV-2 is strongly associated with activation of MC, which likely occurs indirectly, driven by the inflammatory response. The results suggest that plasma MC protease levels could predict the disease course, and that severe COVID-19 patients might benefit from including MC-stabilizing drugs in the treatment scheme.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Prognostic study Limits: Humans Language: English Journal: Front Immunol Year: 2022 Document Type: Article Affiliation country: Fimmu.2022.968981

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Prognostic study Limits: Humans Language: English Journal: Front Immunol Year: 2022 Document Type: Article Affiliation country: Fimmu.2022.968981