Abstract
There is an ongoing need for new therapeutic modalities against SARS-CoV-2 infection. Mast cell histamine has been implicated in the pathophysiology of COVID-19 as a regulator of proinflammatory, fibrotic, and thrombogenic processes. Consequently, mast cell histamine and its receptors represent promising pharmacological targets. At the same time, nutritional modulation of immune system function has been proposed and is being investigated for the prevention of COVID-19 or as an adjunctive strategy combined with conventional therapy. Several studies indicate that several immunonutrients can regulate mast cell activity to reduce the de novo synthesis and/or release of histamine and other mediators that are considered to mediate, at least in part, the complex pathophysiology present in COVID-19. This review summarizes the effects on mast cell histamine of common immunonutrients that have been investigated for use in COVID-19.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped singlestranded positive-sense ribonucleic acid (RNA) virus that was first detected in China and has caused an ongoing global pandemic [1]
This review summarizes the effects on mast cell and histamine signaling of common immunonutrients that have been investigated for use in COVID-19
Mounting evidence shows that hyper-inflammation is the hallmark of COVID-19 pathophysiology leading to significant morbidity and mortality
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped singlestranded positive-sense ribonucleic acid (RNA) virus that was first detected in China and has caused an ongoing global pandemic [1]. The SARS-CoV-2 infection has been shown to activate mast cells leading to histamine release that increases IL-1 levels, causing hyper-inflammation and cytokine storm [25]. Mast cell degranulation has been reported in alveolar septa of deceased patients with COVID-19 and in SARS-CoV-2-infected mice and non-human primates [23,26] This mast cell activation was associated with interstitial edema and immunothrombosis [27], while the levels of the mast cell-specific protease, chymase, correlated significantly with disease severity [23]. H1 as well as H2 receptor antagonists, such as famotidine, are associated with a reduced risk of infection and deterioration leading to intubation or death from COVID-19 [28,29] These agents are considered to improve pulmonary symptoms of SARS-CoV-2 infection by blocking the histamine-mediated cytokine storm [30]. This review summarizes the effects on mast cell and histamine signaling of common immunonutrients that have been investigated for use in COVID-19
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