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Urgent avenues in the treatment of COVID-19: Targeting downstream inflammation to prevent catastrophic syndrome

2020; Elsevier BV; Volume: 87; Issue: 3 Linguagem: Inglês

10.1016/j.jbspin.2020.03.011

1778-7254

Luca Quartuccio, Luca Semerano, Maurizio Benucci, Marie‐Christophe Boissier, Salvatore De Vita,

Inflammasome and immune disorders

At present, healthcare systems all over the world are coping with the new coronavirus infection [1]. In particular, tremendous efforts are are being made in order to support governments in the policy of infection spread containment and early detection, and researchers are working on causal treatment and the treatment of the severe and critical manifestations downstream from the viral infection [2]. As largely known, coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with droplets and contact as the main way of transmission. Since the first case reported in Wuhan, China, in December 2019, the outbreak has gradually spread nationwide and then abroad, rapidly becoming a pandemic infection. Now, coronaviruses (CoVs) have come back into the limelight after the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 and Middle East Respiratory Syndrome (MERS-CoV) outbreak in Saudi Arabia and South Korea. The Rheumatology scientific community has been involved in the management of this pandemic infection, since some treatments, usually employed in patients with inflammatory rheumatic diseases, might be useful to directly counteract the virus, as suggested for antimalarials [3], and more recently for baricitinib, or be effective in downregulating the dangerous inflammatory pathways triggered by the virus itself [4]. A first and crucial issue to address is whether and when it is important to target the viral infection or the downstream inflammatory events as a priority for clinical purposes. Our past experience in hepatitis C virus infection (HCV) and cryoglobulinemic vasculitis (i.e., an autoimmune and lymphoproliferative disease driven by a treatable infection) may be of value to this end, as it shows that, for life-threatening and severe disease manifestations, the immediate targeting of the events downstream of infection is mandatory [5]. Currently, the humanized monoclonal antibody anti-interleukin-6 receptor (anti-IL-6R), namely tocilizumab, appears as a promising tool to turn off the cytokine storm, which dramatically complicates the course of the infection in some patients, causing a rapidly fatal acute respiratory distress syndrome. The rationale for the use of anti-cytokine drugs is to play for time, by decreasing the dangerous inflammatory peak, while the immune system is building the adaptive response to the virus. As we write this paper, several protocols using anti-IL6R treatments are starting to recruit COVID-19 patients in different countries to build an evidence-based support for this treatment. Tocilizumab is an effective and safe treatment for rheumatoid arthritis, for systemic and polyarticular juvenile chronic arthritis and for the most frequent systemic vasculitis in adults, i.e., giant-cell arteritis. Moreover, it has been recently licensed for the treatment of cytokine storm syndrome in CAR-T protocols [6]. Interleukin-1 (IL-1) is another proinflammatory cytokine involved in the early phases of cytokine release syndrome and clinical protocols involving IL-1 blockade are being adopted in several countries. A second important open and urgent question is, however, at which stage of the infection this treatment approach has to be best applied. To answer this question, it is important to carefully consider what we already know about coronaviruses from the lessons of previous epidemic infections, and to compare with COVID-19 outbreak.