Tocilizumab in the Treatment of Coronavirus Induced Disease (COVID-19)

Background and Rationale The Acute Respiratory Syndrome by Corona Virus 2 (SARS-CoV-2), first discovered in December 2019 in Wuhan/China, is causing a worldwide pandemic with potentially lethal implications on an individual basis, and, on the large scale bringing the health care systems and the economy to its limits. The mortality rate of this COronaVIrus induced Disease, COVID-19, has been estimated by the World Health Organization (WHO) to be 3.7%, which is more than 10-fold higher than the mortality of influenza. An infection with SARS-CoV-2 may cause an excessive host immune response, leading to an Acute Respiratory Distress Syndrome (ARDS) and death. Reports from China and from Italy describe an overwhelming inflammation which is triggered by the virus, causing a cytokine storm with features of Cytokine-Release Syndrome (CRS) and/or Macrophage Activation Syndrome (MAS). Pro-inflammatory cytokines such as Interleukin-6 (IL-6) are elevated in the plasma of patients and features of MAS in COVID-19 include elevated levels of ferritin, d-dimer and low platelets. There is increasing evidence, that cytokine-targeted biological therapies can improve outcomes in CRS or MAS and even in sepsis. In recognition of the dramatic development of the COVID-19 pandemic, and in a pragmatic manner, already approved and safe therapies should be evaluated for the use in severe COVID-19. Tocilizumab (TCZ), an anti-IL-6R biological therapy, has been approved for the treatment of CRS and is used in patients with MAS (and in other rheumatologic conditions like Rheumatoid Arthritis (RA) or Giant Cell Arteritis (GCA), with a good safety profile also in the elderly). Collectively, the data strongly suggest that neutralization of the inflammatory pathway induced by IL-6 may reduce mortality in patients with severe COVID-19 prone to CRS and ARDS.