Abstract
Cytokine storm is an acute hyperinflammatory response that may be responsible for critical illness in many conditions including viral infections, cancer, sepsis, and multi-organ failure. The phenomenon has been implicated in critically ill patients infected with SARS-CoV-2, the novel coronavirus implicated in COVID-19. Critically ill COVID-19 patients experiencing cytokine storm are believed to have a worse prognosis and increased fatality rate. In SARS-CoV-2 infected patients, cytokine storm appears important to the pathogenesis of several severe manifestations of COVID-19: acute respiratory distress syndrome, thromboembolic diseases such as acute ischemic strokes caused by large vessel occlusion and myocardial infarction, encephalitis, acute kidney injury, and vasculitis (Kawasaki-like syndrome in children and renal vasculitis in adult). Understanding the pathogenesis of cytokine storm will help unravel not only risk factors for the condition but also therapeutic strategies to modulate the immune response and deliver improved outcomes in COVID-19 patients at high risk for severe disease. In this article, we present an overview of the cytokine storm and its implications in COVID-19 settings and identify potential pathways or biomarkers that could be targeted for therapy. Leveraging expert opinion, emerging evidence, and a case-based approach, this position paper provides critical insights on cytokine storm from both a prognostic and therapeutic standpoint.
Highlights
The coronavirus disease 2019 (COVID-19) pandemic has caused a public health crisis with profound long-term socioeconomic fallout
Therapy should be changed in stable patients only if they are at a higher risk for exposure to COVID-19 or if they become infected with the disease
Our proposed algorithm may be used as a possible approach (Figure 5) [120,121,122]; clinical decision should be based on individual patient profile and disease severity
Summary
The coronavirus disease 2019 (COVID-19) pandemic has caused a public health crisis with profound long-term socioeconomic fallout. This article discusses the implications of hypercytokinemia for COVID-19 patients, including the risk factors for cytokine storm, potential therapeutic strategies [6], and clinical considerations, with special emphasis on patients with cancer, autoimmune diseases, and those undergoing immunosuppressive therapies. Special considerations must guide management of patients at high risk of severe COVID-19 disease and cytokine storm, including patients with underlying coronary artery disease, obesity, cancer, primary immunoglobulin deficiencies, autoimmune conditions, as well as those receiving immunosuppressive therapies. Therapy should be changed in stable patients only if they are at a higher risk for exposure to COVID-19 or if they become infected with the disease In this situation treatment should gradually be reduced and halted consistent with the guidelines from the American College of Rheumatology [80] and the German Society of Rheumatology [81]. Drug interactions with medications used for SARS-CoV2 therapy as well as strategies targeting cytokine storm with antivirals, antiretrovirals, antimalarials (e.g., chloroquine and hydroxychloroquine), or immunomodulators (e.g., tocilizumab) may be considered on a case-by- case basis
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