As most COVID-19 patients show mild to moderate symptoms; 15% suffer from severe respiratory symptoms, and 5% develop acute respiratory distress syndrome which may be associated with multiple organ failure. The highly virulent SARS-CoV-2 affects organs, other than lungs, such as brain, kidney, cardiovascular system and gastrointestinal tract. This review highlights the relation between SARS-CoV-2 and organ involvement. SARS-CoV-2 causes the cytokine storm and damage of the lung cells with activation of NF-κB, hence the damage may reach other organs that leads to death in some cases. The current review discusses the factors affecting COVID-19 severity including the immune response to SARS-CoV-2 with the associated cytokine storm, smoking, gender and blood group. This review discusses also genetic factors associated with severe COVID-19 cases, alongside with comorbid diseases such as diabetes, cardiovascular diseases and obesity. Also, this review focuses on the effect of immunosuppressants and antirheumatic drugs on the protection and treatment of severe COVID-19 cases.

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