The Cytokine Storm in COVID-19: The Strongest Link to Morbidity and Mortality in the Current Epidemic

ABSTRACT

COVID-19 is an infectious disease caused by the SARS-CoV-2 virus. The clinical presentations of the SARS-CoV-2 infection are widely variable and treatment strategies for COVID-19 are dependent on the infection phase. Timing the right treatment for the right phase of this disease is paramount, with correlations detected between the phase of the infection and the type of drug used to treat. The immune system activation following COVID-19 infection can further develop to a fulminant cytokine storm which can progress to acute respiratory distress syndrome. The inflammatory phase, or the hyperinflammation phase, is a later stage when patients develop acute respiratory distress syndrome (ARDS), sepsis, and kidney and other organ failure. In this stage, the virus is probably not necessary and all the damage is due to the immune system's cytokine storm. Immunosuppressive or immunomodulatory agent administration is the major strategy in treating COVID-19 patients at this stage. On the other hand, immunodeficient patients who are treated with immunomodulator agents have attenuated immune systems that do not produce enough cytokines. Current data do not show an increased risk of severe COVID-19 in patients taking biologic therapies or targeted disease-modifying antirheumatic drugs. However, more comprehensive studies are needed to assess the effect of these medications, and whether they may actually be protective of the severe type of disease. Although medications for COVID-19 and for the cytokine storm are important, the main breakthrough in slowing down the pandemic was developing effective vaccines. These vaccines showed a dramatic result in reducing morbidity and mortality up to the Delta variant's spread. However, the emergence of the new variant, Omicron, influenced the successful results we had before. This variant is more contagious but less dangerous than Delta. The aim now is to develop vaccines based on the Omicron and Delta immunogens in the future for broad protection against different variants.