Prostaglandin D2 as a mediator of lymphopenia and a therapeutic target in COVID-19 disease

Med Hypotheses. 2020 Oct:143:110122. doi: 10.1016/j.mehy.2020.110122. Epub 2020 Jul 21.

Abstract

A characteristic feature of COVID-19 disease is lymphopenia. Lymphopenia occurs early in the clinical course and is a predictor of disease severity and outcomes. The mechanism of lymphopenia in COVID-19 is uncertain. It has been variously attributed to the release of inflammatory cytokines including IL-6 and TNF-α; direct infection of the lymphocytes by the virus; and rapid sequestration of lymphocytes in the tissues. Additionally, we postulate that prostaglandin D2 (PGD2) is a key meditator of lymphopenia in COVID-19. First, SARS-CoV infection is known to stimulate the production of PGD2 in the airways, which inhibits the host dendritic cell response via the DP1 receptor signaling. Second, PGD2 is known to upregulate monocytic myeloid-derived suppressor cells (MDSC) via the DP2 receptor signaling in group 2 innate lymphoid cells (ILC2). We propose targeting PGD2/DP2 signaling using a receptor antagonist such as ramatroban as an immunotherapy for immune dysfunction and lymphopenia in COVID-19 disease.

Keywords: COVID-19; Immunosuppression; Immunotherapy; Lymphopenia; Prostaglandin D(2); Ramatroban; SARS-CoV-2.

Publication types

  • Letter

MeSH terms

  • Adult
  • Betacoronavirus*
  • COVID-19
  • Carbazoles / pharmacology
  • Carbazoles / therapeutic use
  • Child
  • Coronavirus Infections / complications
  • Coronavirus Infections / immunology
  • Coronavirus Infections / physiopathology*
  • Dendritic Cells / immunology
  • Humans
  • Lymphopenia / etiology
  • Lymphopenia / physiopathology*
  • Models, Immunological*
  • Molecular Targeted Therapy*
  • Myeloid Cells / immunology
  • Pandemics*
  • Pneumonia, Viral / complications
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / physiopathology*
  • Prostaglandin D2 / biosynthesis
  • Prostaglandin D2 / physiology*
  • Receptors, Immunologic / antagonists & inhibitors
  • Receptors, Immunologic / metabolism
  • Receptors, Prostaglandin / antagonists & inhibitors
  • Receptors, Prostaglandin / metabolism
  • Receptors, Prostaglandin / physiology
  • Respiratory System / metabolism*
  • SARS-CoV-2
  • Sulfonamides / pharmacology
  • Sulfonamides / therapeutic use
  • T-Lymphocytes / immunology
  • Thromboxane A2 / antagonists & inhibitors

Substances

  • Carbazoles
  • Receptors, Immunologic
  • Receptors, Prostaglandin
  • Sulfonamides
  • prostanoid D receptor 1, human
  • Thromboxane A2
  • ramatroban
  • Prostaglandin D2
  • prostaglandin D2 receptor