Cytokine Release Syndrome in COVID-19 Patients, A New Scenario for an Old Concern: The Fragile Balance between Infections and Autoimmunity

Abstract

On 7 January 2020, researchers isolated and sequenced in China from patients with severe pneumonitis a novel coronavirus, then called SARS-CoV-2, which rapidly spread worldwide, becoming a global health emergency. Typical manifestations consist of flu-like symptoms such as fever, cough, fatigue, and dyspnea. However, in about 20% of patients, the infection progresses to severe interstitial pneumonia and can induce an uncontrolled host-immune response, leading to a life-threatening condition called cytokine release syndrome (CRS). CRS represents an emergency scenario of a frequent challenge, which is the complex and interwoven link between infections and autoimmunity. Indeed, treatment of CRS involves the use of both antivirals to control the underlying infection and immunosuppressive agents to dampen the aberrant pro-inflammatory response of the host. Several trials, evaluating the safety and effectiveness of immunosuppressants commonly used in rheumatic diseases, are ongoing in patients with COVID-19 and CRS, some of which are achieving promising results. However, such a use should follow a multidisciplinary approach, be accompanied by close monitoring, be tailored to patient's clinical and serological features, and be initiated at the right time to reach the best results. Autoimmune patients receiving immunosuppressants could be prone to SARS-CoV-2 infections; however, suspension of the ongoing therapy is contraindicated to avoid disease flares and a consequent increase in the infection risk.

Keywords: COVID-19; SARS-CoV-2; autoimmunity; baricitinib; cytokine release syndrome; hydroxychloroquine; immunomodulation; rheumatoid arthritis; tocilizumab.

Figure 1

Use of anti-rheumatic immunosuppressive agents in COVID-19 patients, targeted to their immunomodulatory/antiviral activity and disease severity. Tocilizumab, sarilumab, and anakinra have the strongest immunosuppressive effect and have been already tested in cytokine release syndrome (CRS) (with tocilizumab being the only scheduled); thus, they should be administered in severe COVID-19 patients at the first manifestations of hyperinflammation. Baricitinib has both immunosuppressive effects (however, no data are available for CRS) and antiviral activity; thus, it could be adopted in the moderate/severe form of COVID-19. Hydroxychloroquine (HIQ) has antiviral properties and milder immunosuppressive activity than the other drugs; thus, it could be used in the moderate/severe form of COVID-19.