COVID-19, microthromboses, inflammation, and platelet activating factor

Constantinos Demopoulos; Smaragdi Antonopoulou; Theoharis C Theoharides

doi:10.1002/biof.1696

COVID-19, microthromboses, inflammation, and platelet activating factor

Biofactors. 2020 Nov;46(6):927-933. doi: 10.1002/biof.1696. Epub 2020 Dec 9.

Authors

Constantinos Demopoulos¹, Smaragdi Antonopoulou², Theoharis C Theoharides^{3

4

5}

Affiliations

¹ Laboratory of Biochemistry, Faculty of Chemistry, National & Kapodistrian University, Athens, Greece.
² Laboratory of Biology, Biochemistry and Microbiology, Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece.
³ Laboratory of Molecular Immunopharmacology and Drug Discovery, Department of Immunology, Tufts University School of Medicine, Boston, Massachusetts, USA.
⁴ School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, Massachusetts, USA.
⁵ Department of Internal Medicine, Tufts University School of Medicine and Tufts Medical Center, Boston, Massachusetts, USA.

PMID: 33296106
DOI: 10.1002/biof.1696

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.

Publication types

Review

MeSH terms

Antiviral Agents / therapeutic use
Blood Platelets / drug effects
Blood Platelets / pathology
Blood Platelets / virology
COVID-19 / blood
COVID-19 / pathology
COVID-19 / prevention & control*
COVID-19 / virology
Cyproheptadine / analogs & derivatives*
Cyproheptadine / therapeutic use
Disseminated Intravascular Coagulation / blood
Disseminated Intravascular Coagulation / pathology
Disseminated Intravascular Coagulation / prevention & control*
Disseminated Intravascular Coagulation / virology
Gene Expression Regulation
Humans
Inflammation
Interleukin-1beta / genetics
Interleukin-1beta / metabolism
Interleukin-6 / genetics
Interleukin-6 / metabolism
Lung / drug effects
Lung / pathology
Lung / virology
Luteolin / therapeutic use
Mast Cells / drug effects
Mast Cells / pathology
Mast Cells / virology
Platelet Activating Factor / antagonists & inhibitors*
Platelet Activating Factor / genetics
Platelet Activating Factor / metabolism
Pulmonary Embolism / blood
Pulmonary Embolism / pathology
Pulmonary Embolism / prevention & control*
Pulmonary Embolism / virology
Quercetin / therapeutic use
SARS-CoV-2 / drug effects
SARS-CoV-2 / pathogenicity*
Severe Acute Respiratory Syndrome / blood
Severe Acute Respiratory Syndrome / pathology
Severe Acute Respiratory Syndrome / prevention & control*
Severe Acute Respiratory Syndrome / virology

Substances

Antiviral Agents
IL1B protein, human
IL6 protein, human
Interleukin-1beta
Interleukin-6
Platelet Activating Factor
rupatadine
Cyproheptadine
Quercetin
Luteolin