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 D_{2} (PGD_{2}) is a key meditator of lymphopenia in COVID-19. First, SARS-CoV infection is known to stimulate the production of PGD_{2} in the airways, which inhibits the host dendritic cell response via the DP_{1} receptor signaling. Second, PGD_{2} is known to upregulate monocytic myeloid-derived suppressor cells (MDSC) via the DP_{2} receptor signaling in group 2 innate lymphoid cells (ILC2). We propose targeting PGD_{2}/DP_{2} signaling using a receptor antagonist such as ramatroban as an immunotherapy for immune dysfunction and lymphopenia in COVID-19 disease.
【저자키워드】 COVID-19, SARS-CoV-2, Immunotherapy, Immunosuppression, lymphopenia, Ramatroban, Prostaglandin D(2),