JMIR Publications

ABSTRACT

Background:

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.

Objective:

To study the cytokine storm response in SARS-CoV-2 and to explore the available treatment options for critically-ill coronavirus disease 2019 (COVID-19) patients in the early stages of the pandemic by reviewing literature.

Methods:

A literature review was performed from December 1, 2000 to April 4, 2020, to explore and compare different treatments that have been proposed to manage cytokine storm among COVID-19 patients. Thirty-eight eligible studies including 24 systematic reviews, 5 meta-analysis, 5 experimental model studies, 7 cohort studies, and 4 case reports matched criteria.

Results:

Severity of the cytokine storm, measured by elevated levels of IL1B, IFNγ, IP10, and MCP1, was associated with the COVID-19 disease severity. Tocilizumab, an IL-6 monoclonal antibody, showed improvement in lung lesions, oxygenation, and lymphocytopenia. One of earliest proposed treatments, chloroquine and hydroxychloroquine demonstrated efficacy in viral load reduction but have not been studied extensively among critically-ill COVID-19 patients. The anti-oxidative properties of melatonin and Vitamin C showed decreased mortality rate among patients with acute respiratory distress syndrome (ARDS) secondary to COVID-19. Glucocorticoids, on the other hand, delayed clearance of the COVID-19 viral RNA from respiratory tract secretions. Plasma therapy in treatment-resistant patients who required mechanical ventilation showed improvement in viral load, inflammatory markers, and ventilation needs.

Conclusions:

Many treatment options with different targets have been proposed from the early stages of the COVID-19 pandemic, ranging from targeting the virus itself to managing the systemic inflammation caused by the virus. Among the different agents to manage cytokine storm in COVID-19 patients, there is developing support for convalescent plasma therapy particularly for critically-ill and mechanically ventilated patients who are resistant to antivirals and supportive care. Treatment options that were proposed in the beginning phases of the pandemic were multi-dimensional, and further research is needed to establish treatment guidelines.