Hazards of the Cytokine Storm and Cytokine-Targeted Therapy in Patients With COVID-19: Review (Preprint)

Abstract

UNSTRUCTURED Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has challenged medicine and healthcare on a global scale. Its impact and frightening mortality rate are in large part attributable to the fact that there is a lack of available treatments. It has been shown that in severely-ill patients, SARS-CoV-2 can lead to an inflammatory response known as cytokine storm, which involves activation and release of inflammatory cytokines in a positive feedback loop of pathogen-triggered inflammation. Currently, cytokine storm is one of the leading causes of morbidity and mortality in SARS-CoV-2, but there is no proven treatment to combat this systemic response. We performed a literature review from December 1, 2000 to April 4, 2020 to explore and compare different treatments that have been proposed to manage cytokine storm among coronavirus disease 2019 (COVID-19) patients. Our review found 38 eligible studies including 24 systematic reviews, 5 meta-analysis, 5 experimental model studies, 7 cohort studies, and 4 case reports that matched criteria. One of the innovative treatments that is being studied is convalescent plasma, which has been used in previous Coronavirus pandemics. Prior use of the interleukin-6 antibody Tocilizumab led to the inference of interleukin-6 and interleukin-1 antibodies as possible therapies. Given its role in the pathway of cytokine storm, the JAK2 pathway was found to be a potential target for treatment. More common agents such as melatonin and Vitamin C provide the same anti-inflammatory effect with a lower side-effect profile. Such agents that are non-traditional in an intensive care unit (ICU) setting but have shown positive results. Interestingly, there is a lack of promising data toward the use of one of the most commonly used therapies, glucocorticoids. Many studies report poorer outcomes with glucocorticoid use, particularly in the setting of severe COVID-19 cases. Among the different agents and therapies to manage cytokine storm in COVID-19 patients, there is strong data for convalescent plasma therapy. The promising data from prior studies indicate that research into its use may prove beneficial to critically-ill patients. Currently, there are many different agents to fight SARS-CoV-2 ranging from targeting the virus itself to managing the systemic inflammation caused by the virus. While plasma therapy is quickly becoming one of the frontline therapies, there are many other agents with potential to treat the severely-ill and those who have been let down by traditional agents.