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?

Abstract

Evidence continues to emerge that the social determinants of health play a role in adverse outcomes related to COVID-19, including increased morbidity and mortality, increased risk of long COVID, and vaccine adverse effects. Therefore, a more nuanced understanding of the biochemical and cellular pathways of illnesses commonly associated with adverse social determinants of health is urgently needed. We contend that a commitment to understanding adverse outcomes in historically marginalized communities will increase community-level confidence in public health measures. Here, we synthesize emerging literature on mast cell disease, and the role of mast cells in chronic illness, alongside emerging research on mechanisms of COVID illness and vaccines. We propose that a focus on aberrant and/or hyperactive mast cell behavior associated with chronic underlying health conditions can elucidate adverse COVID-related outcomes and contribute to the pandemic recovery. Standards of care for mast cell activation syndrome (MCAS), as well as clinical reviews, experimental research, and case reports, suggest that effective and cost-efficient remedies are available, including antihistamines, vitamin C, and quercetin, among others. Primary care physicians, specialists, and public health workers should consider new and emerging evidence from the biomedical literature in tackling COVID-19. Specialists and researchers note that MCAS is likely grossly under-diagnosed; therefore, public health agencies and policy makers should urgently attend to community-based experiences of adverse COVID outcomes. It is essential that we extract and examine experiential evidence of marginalized communities from the broader political–ideological discourse.

Aging and long COVID-19 syndrome: what’s new in 2023?

“…44 5) Social determinants, marginalization, and deficient mast cell behavior. 45 6) Endocannabinoid-like mediators. 46…”

Neurological post‐acute sequelae of SARS‐CoV‐2 infection

“…58,76 Neuroinflammation in association with mast cells may be the cause of brain fog. 77 Although this condition is associated with mast cell activation syndrome, 78,79 mast cell activation syndrome itself is not a wellestablished concept. It is speculated that neurogenesis disorders, myelin damage, and inflammation may be a possible cause of PASC.…”

Biological mechanisms underpinning the development of long COVID

“…The role of the latter three mediators has been implicated in the pathogenesis of LC. 105 , 106 , 107 , 108 Mucosa and connective tissue MC-derived tryptase can trigger eosinophils to secrete IL-6 and -8 for neutrophil recruitment to affected sites. This enzyme may also stimulate inflammatory cytokine release from endothelial cells, such as IL-8 and -1β.…”

“…Tryptase may contribute to cognitive impairments such as brain fog symptoms due to the induction of vascular leakage, thus causing increased blood-brain barrier permeability. 99 , 106 , 109 In addition, tryptase may contribute to post-infection fibrosis of the lungs by inciting the movement and division of pulmonary fibroblasts leading to the reorganization and upregulation of fibroblastic collagen synthesis. 106 Chymases are members of a large serine protease family whose expression is unique to MCs.…”