Signatures of mast cell activation are associated with severe COVID-19

Abstract

Lung inflammation is a hallmark of Coronavirus disease 2019 (COVID-19) in severely ill patients and the pathophysiology of disease is thought to be immune-mediated. Mast cells (MCs) are polyfunctional immune cells present in the airways, where they respond to certain viruses and allergens, often promoting inflammation. We observed widespread degranulation of MCs during acute and unresolved airway inflammation in SARS-CoV-2-infected mice and non-human primates. In humans, transcriptional changes in patients requiring oxygen supplementation also implicated cells with a MC phenotype. MC activation in humans was confirmed, through detection of the MC-specific protease, chymase, levels of which were significantly correlated with disease severity. These results support the association of MC activation with severe COVID-19, suggesting potential strategies for intervention.

Pathogenic Mechanisms of Vaccine-Induced Immune Thrombotic Thrombocytopenia in People Receiving Anti-COVID-19 Adenoviral-Based Vaccines: A Proposal

“…Moreover, platelets express high levels of ACE2 and, as a consequence, purified Spike protein may directly activate platelets, potentiating the prothrombotic cascade (9). Finally, since MCAS may be intimately involved in the pathogenesis of both severe form of acute COVID-19 infection and of COVID-19 "long-haul" syndrome through ACE2/Spike protein interactions (50,51), it may be speculated that the interplay of altered mast cells with neosynthesized SARS-CoV-2 spike protein could further contribute to VITT development.…”

Hyper/neuroinflammation in COVID-19 and suicide etiopathogenesis: Hypothesis for a nefarious collision?

“…Mast cells are long-lived innate immune cells that not only provide the first line of host defense against viral and bacterial infections but also participate in the pathogenesis of allergic inflammation and neurological disorders ( Georgin-Lavialle et al, 2016 , Hendrikus et al, 2017 ). Emerging evidence has pointed to an involvement of mast cells in inflammatory syndrome associated with COVID-19 ( Tan et al, 2021 , Conti et al, 2020 ). Mast-cell-enriched mediators, such as carboxypetidase A3, chymase, tryptase, and serotonin, were elevated in sera of SARS-CoV2 infected patients and positively correlated with hyperinflammatory markers ( Soria-Castro et al, 2021 , Gebremeskel et al, 2021 ).…”

Connecting the Dots in Emerging Mast Cell Research: Do Factors Affecting Mast Cell Activation Provide a Missing Link between Adverse COVID-19 Outcomes and the Social Determinants of Health?

“…Inflammatory mediators from mast cell activation are associated with severe COVID-19 [58]). By measuring mast cell-specific protease chymase, [58] Tan et al (2021) observed widespread degranulation of mast cells during airway inflammation in SARS-CoV-2-infected mice.…”

“…Inflammatory mediators from mast cell activation are associated with severe COVID-19 [58]). By measuring mast cell-specific protease chymase, [58] Tan et al (2021) observed widespread degranulation of mast cells during airway inflammation in SARS-CoV-2-infected mice. They also confirmed widespread mast cell activation in COVID-19-infected primates by detecting heparin-containing granules in the lung tissue through fluorescence staining [58].…”

“…By measuring mast cell-specific protease chymase, [58] Tan et al (2021) observed widespread degranulation of mast cells during airway inflammation in SARS-CoV-2-infected mice. They also confirmed widespread mast cell activation in COVID-19-infected primates by detecting heparin-containing granules in the lung tissue through fluorescence staining [58]. Tan et al confirmed mast cell activation in humans by correlating plasma chymase levels with COVID-19 disease severity [58].…”