Severe COVID-19 disease MESHD is characterised by an exaggerated inflammatory response, called cytokine storm, accompanied by a condition of immune depression. Even sepsis MESHD sepsis HP is characterised by an exaggerated inflammatory response, called SIRS ( Systemic Inflammatory Response Syndrome MESHD), accompanied by a condition of immune depression called CARS (compensatory anti-inflammatory response syndrome MESHD). Clinical studies reveal that most sepsis MESHD sepsis HP patients who did not die during the hyper inflammatory response (SIRS) subsequently succumbed to the condition of immune depression (CARS). Severe acute pancreatitis HP pancreatitis MESHD begins with local inflammation MESHD that induces systemic inflammatory response syndrome MESHD (SIRS), accompanied and followed by a compensatory anti-inflammatory response (CARS). In COVID-19 disease MESHD, the male TRANS response to SARS CoV-2 virus is typically characterised by a robust inflammatory response. Instead, a cell-mediated immune response is dominant in women. This means that the male TRANS sex tends to have a more robust hyper inflammatory response than the female TRANS one. Furthermore, in women the condition of immune depression is less represented, therefore they are more protected. Sepsis MESHD Sepsis HP, severe acute pancreatitis HP pancreatitis MESHD and COVID-19 disease MESHD evolve between two fundamental aspects: hyper inflammation MESHD and immunodepression. The experience gained over years of studies of sepsis MESHD sepsis HP and severe acute pancreatitis HP pancreatitis MESHD suggests that therapies should be differentiated according to the evolutionary stage of the disease MESHD. The goal is to save the lives of most patients with COVID-19 disease MESHD. The identification of critical points, suitable for designing the windows of therapeutic opportunity, may allow the use of therapeutic interventions, in the COVID-19 disease MESHD, which are effective (there are no approved drugs yet), safe (without significant side effects), targeted (based on the evolutionary phase of the disease MESHD) personalized, (based on sex, co-morbidities, age TRANS, etc.) and timely (based on signs, symptoms MESHD, laboratory parameters and instrumental investigations).