Mast cell stabilisers and covid-19
I read with interest the editorial on vaccines and passive immunity (1), which ‘injected’ a note of caution in the expectations of the public. Professor Sewell et al give the triple warnings of vaccines being less effective in those with greatest need (ie older age groups), having likely short term protective immunity or even injurious effect, and the need for careful timing of treatments such as convalescent plasma to avoid progression to a overactive immune-inflammatory response (cytokine storm) with consequent severe organ damage in those predisposed.
While intensive research for effective and safe vaccines continues, in addition to public health measures, we should search widely for ways to ameliorate the underlying pathological processes at an early stage in those affected. Mast cells are known to be the main source of cytokine release that leads to lung damage in SARS-Co-V2. Mast cell stabilisers together with mediator blockers may therefore help to ameliorate the pro-inflammatory effects of covid-19.
Mast cells are the sentinels lining mucosal and connective tissues throughout the body, including the respiratory tract, being located at the junction point of the host and external environment at places of entry of antigen. They are heterogeneous, multifunctional immune master-cells containing an exceptionally large number of granules which store preformed and other inflammatory mediators and equally have a large number of interactions. Their physiological functions include regulation of vasodilation, vascular homeostasis, innate and adaptive immune responses, angiogenesis, and venom detoxification. On activation, mast cells release preformed histamine, proteases, (chymase, tryptase, and carboxypeptidase A type), and later, proinflammatory cytokines including IL-1, IL-6, leukotrienes and TNF α
In the respiratory tract, the immune response to mast cell activation results in airway constriction, increased mucous production, rhinorrhoea, fever and cough. Mast cell degranulation increases vascular permeability and local oedema, which can obstruct nasal airways and lead to congestion. There is increased production of mucus and its accumulation may block off the sinuses and result in a bacterial infection.
Mast cell stabilisers and mediator blockers, such as antihistamines and anti-leukotrienes, are widely used in allergic conditions and mast cell disorders, which may have similar respiratory symptoms, and are therefore logical substances to consider in the fight against SARS-CoV-2. (2)
Mast cell stabilisers include Vitamin D (3), ketotifen (also an antihistamine), sodium cromoglycate, quercetin, luteolin. Vitamin C also has a role in mast cell stabilisation. These could be trialled individually or in combination at an early stage of infection in a patient with moderate symptoms or on admission to assess effect on the subsequent course.
1. Vaccines, convalescent plasma, and monoclonal antibodies for covid-19 https://www.bmj.com/content/370/bmj.m2722
2. Mast cell stabilisers, leukotriene antagonists and antihistamines: A rapid review of the evidence for their use in COVID-19 https://www.cebm.net/covid-19/mast-cell-stabilisers-leukotriene-antagoni...
3. Quercetin and Vitamin C: An Experimental, Synergistic Therapy for the Prevention and Treatment of SARS-CoV-2 Related Disease (COVID-19) https://www.frontiersin.org/articles/10.3389/fimmu.2020.01451/full
Competing interests: No competing interests