The role of Interleukin-6 in the pathogenesis, prognosis and treatment of severe COVID-19.

Giannakodimos, Ilias; Gkountana, Georgia-Vasiliki; Lykouras, Dimosthenis; Karkoulias, Kiriakos; Tsakas, Sotiris

A newly identified virus appeared in Wuhan, China, in December 2019, was named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and causes the coronavirus disease 2019 (COVID-19). SARS-CoV-2 presents similarities with two previous coronavirus pandemics, MERS (Middle East Respiratory Syndrome) and SARS-CoV, concerning phylogenetic origin, structural composition, and clinical symptoms, thus, leading to common pathogenic mechanisms. The purpose of this review is to declare the role of interleukin-6 (IL-6) in the pathogenesis, prognosis, and treatment of COVID-19 by comparing its effect on SARS-CoV and MERS cases. Increased levels of IL-6 comprise the key for the stimulation of cytokine storm and the progression of SARS, MERS, and COVID-19 cases. Especially, in COVID-19 patients, the overactivation of NF-kÎ’, which is caused by the binding of coronavirus spike protein S to alveolar epithelial cells, up-regulates IL-6 and promotes its systematic circulation, causing alveolar damage and extrapulmonary injury. Additionally, IL-6 can be used to evaluate respiratory failure and identify asymptomatic patients. Tocilizumab (TCZ), a monoclonal antibody which blocks IL-6 signaling, comprises a remedial option against COVID-19. TCZ improves oxygenation, reduces fever, and decreases levels of IL-6. IL-6 plays a major role in the pathogenesis of cytokine storm and the progression of COVID-19 and may be used as a therapeutic target against COVID-19. However, further research is needed concerning the relation of IL-6 in COVID-19 cases and more clinical trials are required to declare TCZ as a treatment option.