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Evaluation of Microparticulate Cytokine Inhibitors for their Potential Use for the Treatment of COVID-19 Cytokine Storm

Mohammad N. Uddin, Priyal Bagwe, Carl Oettinger, Martin J. D'Souza

COVID-19 pandemic has claimed millions of lives and resulted in an economic slowdown worldwide. The mortality rate is approximately 2% in the United States, with many individuals requiring prolonged hospitalization. At least 10% of patients with severe COVID-19 will eventually have respiratory failure. The recent deployment of a vaccine will hopefully ease and ultimately deter the spread of this highly contagious virus. However, newer virulent strains continue to emerge since most people in different parts of the world have little or no access to vaccines. The virus is associated with the cytokine storm in its severe form. This manifestation is highly lethal, resulting in acute respiratory distress syndrome and multi-organ failure. Since only a few therapeutic drugs can treat severe COVID-19, it is essential to focus on therapeutic strategies to increase the COVID-19 survival rate and preventive vaccination. This review describes microparticulate cytokine inhibiting agents such as antisense oligonucleotides to Nuclear Factor kappa B (NF-kB), antioxidant, catalase, Tumor necrosis factor (TNF) and Interleukin-1 (IL-1) neutralizing antibodies, CNI-1493 and dexamethasone. These microparticulate cytokine inhibiting agents have demonstrated remarkable effectiveness in cytokine suppression intracellularly compared to equivalent drug doses in solution. Much of this work was published before the emergence of COVID-19 and its subsequent variants. Moreover, these microparticles might effectively moderate cytokine storms and requires additional review and investigation.