Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has challenged medicine and health care 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 patients who are severely ill, 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. Objective The aim of this paper is to study the cytokine storm response in SARS-CoV-2 and to explore the early treatment options for patients who are critically ill with the coronavirus disease (COVID-19) in the early stages of the pandemic by reviewing the literature. Methods A literature review was performed from December 1, 2000, to April 4, 2020, to explore and compare therapies that target cytokine storm among SARS-CoV-2 and prior coronavirus cases. Results A total of 38 eligible studies including 24 systematic reviews, 5 meta-analyses, 5 experimental model studies, 7 cohort studies, and 4 case reports matched the criteria. Conclusions The severity of the cytokine storm, measured by elevated levels of interleukin-1B, interferon-γ, interferon-inducible protein 10, and monocyte chemoattractant protein 1, was associated with COVID-19 disease severity. Many treatment options with different targets have been proposed during the early stages of the COVID-19 pandemic, ranging from targeting the virus itself to managing the systemic inflammation caused by the virus and the excessive cytokine response. Among the different agents to manage cytokine storm in patients with COVID-19, there is developing support for convalescent plasma therapy particularly for patients who are critically ill or mechanically ventilated and resistant to antivirals and supportive care. Treatment options that were proposed in the beginning phases of the pandemic were multidimensional, and further research is needed to develop a more established treatment guideline.
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.
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