COVID-19, Mast Cells, Cytokine Storm, Psychological Stress, and Neuroinflammation

Abstract

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new pandemic infectious disease that originated in China. COVID-19 is a global public health emergency of international concern. COVID-19 causes mild to severe illness with high morbidity and mortality, especially in preexisting risk groups. Therapeutic options are now limited to COVID-19. The hallmark of COVID-19 pathogenesis is the cytokine storm with elevated levels of interleukin-6 (IL-6), IL-1β, tumor necrosis factor-alpha (TNF-α), chemokine (C-C-motif) ligand 2 (CCL2), and granulocyte-macrophage colony-stimulating factor (GM-CSF). COVID-19 can cause severe pneumonia, and neurological disorders, including stroke, the damage to the neurovascular unit, blood-brain barrier disruption, high intracranial proinflammatory cytokines, and endothelial cell damage in the brain. Mast cells are innate immune cells and also implicated in adaptive immune response, systemic inflammatory diseases, neuroinflammatory diseases, traumatic brain injury and stroke, and stress disorders. SARS-CoV-2 can activate monocytes/macrophages, dendritic cells, T cells, mast cells, neutrophils, and induce cytokine storm in the lung. COVID-19 can activate mast cells, neurons, glial cells, and endothelial cells. SARS-CoV-2 infection can cause psychological stress and neuroinflammation. In conclusion, COVID-19 can induce mast cell activation, psychological stress, cytokine storm, and neuroinflammation.

Mast cell changes the phenotype of microglia via histamine

“…On the other hand, an inhibition of microglial phagocytosis was also reported through H3R at concentrations above 10 µM of histamine [37]. Despite contradictory data in relation to the concentrations required to promote or inhibit phagocytic activity in microglia (which may be due to the different types of cells used and experimental protocols), our results reveal a dual role of histamine; evidence that, by the way, has already been described on microglia-induced neurodegeneration [38] The role of MCs in determining the microglial phenotype in Alzheimer and other pathologies can be crucial [40] [41]. MCs are among the first brain cells to sense amyloid beta peptides [42] and MCs treated with A enhanced histamine release [43] that, according to our data, could decide the microglial phagocytotic response.…”

Acute Traumatic Brain Injury-Induced Neuroinflammatory Response and Neurovascular Disorders in the Brain

“…Moreover, both pro and anti-inflammatory cytokines and chemokines can act on mast cells. Viral activation of mast cells can release IL-1, IL-6, and IL-33 and exacerbate inflammation and endothelial functions in the lung and central nervous system in Coronavirus disease 2019 (COVID-19) (Kempuraj et al 2020b;Kritas et al 2020). We have previously shown that IL-1 can activate mast cells and selective release of IL-6, which is implicated in COVID-19 (Kandere-Grzybowska et al 2003;Kempuraj et al 2020b).…”

“…Viral activation of mast cells can release IL-1, IL-6, and IL-33 and exacerbate inflammation and endothelial functions in the lung and central nervous system in Coronavirus disease 2019 (COVID-19) (Kempuraj et al 2020b;Kritas et al 2020). We have previously shown that IL-1 can activate mast cells and selective release of IL-6, which is implicated in COVID-19 (Kandere-Grzybowska et al 2003;Kempuraj et al 2020b). IL-1 enhances endothelial cell-leukocyte adhesion, causes inflammation, and the formation of microthrombi through thromboxane A1 production in COVID-19 patients (Conti et al 2020).…”

Molecular and cellular mechanisms of central nervous system alteration in COVID-19

“…Неврологические симптомы при инфицировании SARS-CoV-2 регистрируются у 30-40% пациентов [2,36,55,63]. Дисфункция ЦНС при COVID-19 увеличивает неблагоприятный исход у пациентов [42].…”

“…В головном мозге АПФ2 экспрессируется глией, нейронами и эндотелиоцитами кровеносных сосудов, что делает мозг более уязвимым для инфекции COVID-19 [5,29]. Экспрессия АПФ2 отмечается в ядре одиночного пути, паравентрикулярном ядре и ростральном вентролатеральном сером веществе [42,79].…”