The ongoing coronavirus disease 2019 (COVID-19) pandemic outbreak, which has seemingly emerged in Wuhan (China) at the end of 2019, has now spread all around the world, causing dramatic clinical consequences (in terms of morbidity, disability or mortality), a collapse of worldwide economies, raising also serious threats to human society [1]. Although several pathogenic features of this infectious disorder still need to be unraveled, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a respiratory pathogen, whose virulence extends far beyond what is commonly seen in patients with infections caused by other similar microorganisms. The evidence garnered so far allows us to conclude that COVID-19 is not a narrow respiratory disorder, though it principally manifests with low respiratory tract infection (ie, bilateral interstitial pneumonia, eventually progressing to acute respiratory distress syndrome; ARDS), but shall rather be considered an evolving systemic pathology, which may affect many organs and tissues, characterized also by relevant risk of developing capillary, venous and arterial thrombosis, inside and outside the lung tissue [2].

Beside evidence of systemic dissemination of SARS-CoV-2 in patients with severe and especially critical forms of illness [3], an abnormal, often exaggerated inflammatory response has been reported, since the beginning of this outbreak, in patients at risk of unfavorable disease progression. This phenomenon, defined “cytokine storm”[4], resembles that seen in other hyperinflammation syndromes, falling into the broader definition of cytokine release syndrome (CRS)(Table 1)[5]. Irrespective of the specific causes, the underlying mechanisms leading to CRS have usually been identified with an abnormal, supraphysiologic response to specific (immune) triggers, then accompanied by exaggerated activation and/or engagement of lymphocytes, monocytes/macrophages, dendritic and other immune effector cells, culminating with development and persistence of a self-reinforcing inflammatory loop.