COVID-19, microthromboses, inflammation, and platelet activating factor
Abstract
Recent articles report elevated markers of coagulation, endothelial injury, and microthromboses in lungs from deceased COVID-19 patients. However, there has been no discussion of what may induce intravascular coagulation. Platelets are critical in the formation of thrombi and their most potent trigger is platelet activating factor (PAF), first characterized by Demopoulos and colleagues in 1979. PAF is produced by cells involved in host defense and its biological actions bear similarities with COVID-19 disease manifestations. PAF can also stimulate perivascular mast cell activation, leading to inflammation implicated in severe acute respiratory syndrome (SARS). Mast cells are plentiful in the lungs and are a rich source of PAF and of inflammatory cytokines, such as IL-1β and IL-6, which may contribute to COVID-19 and especially SARS. The histamine-1 receptor antagonist rupatadine was developed to have anti-PAF activity, and also inhibits activation of human mast cells in response to PAF. Rupatadine could be repurposed for COVID-19 prophylaxis alone or together with other PAF-inhibitors of natural origin such as the flavonoids quercetin and luteolin, which have antiviral, anti-inflammatory, and anti-PAF actions.
Keywords: COVID-19; PAF; coagulation; flavonoids; inflammation; mast cells; rupatadine
Coronavirus 2019, Microthromboses, and Platelet Activating Factor. Theoharides TC, et al.Clin Ther. 2020.PMID: 32883529Free PMC article.
Rupatadine inhibits inflammatory mediator release from human laboratory of allergic diseases 2 cultured mast cells stimulated by platelet-activating factor. Alevizos M, et al.Ann Allergy Asthma Immunol. 2013.PMID: 24267366
Rupatadine protects against pulmonary fibrosis by attenuating PAF-mediated senescence in rodents. Lv XX, et al.PLoS One. 2013.PMID: 23869224Free PMC article.
Effects of Rupatadine on Platelet- Activating Factor-Induced Human Mast Cell Degranulation Compared With Desloratadine and Levocetirizine (The MASPAF Study). Munoz-Cano R, et al.J Investig Allergol Clin Immunol. 2017.PMID: 27758758
Clotting disorder in severe acute respiratory syndrome coronavirus 2. Pujhari S, et al.Rev Med Virol. 2021.PMID: 33022790Free PMC article.Review.
Cited by 10articles
Ultramicronized Palmitoylethanolamide in the Management of Sepsis-Induced Coagulopathy and Disseminated Intravascular Coagulation. D'Amico R, et al.Int J Mol Sci. 2021.PMID: 34768820Free PMC article.
The relevance of magnesium homeostasis in COVID-19. Trapani V, et al.Eur J Nutr. 2021.PMID: 34687321Free PMC article.Review.
The serum amino acid profile in COVID-19. Atila A, et al.Amino Acids. 2021.PMID: 34605988Free PMC article.Clinical Trial.
Ways to Address Perinatal Mast Cell Activation and Focal Brain Inflammation, including Response to SARS-CoV-2, in Autism Spectrum Disorder. Theoharides TC.J Pers Med. 2021.PMID: 34575637Free PMC article.Review.
Mast cells: Therapeutic targets for COVID-19 and beyond. Lam HY, et al.IUBMB Life. 2021.PMID: 34467628Free PMC article.Review.