CYP3A4 and COVID-19: For example, in patients with moderate to severe COVID-19, the activity of CYP2C19 and CYP3A4 decreased by 75% and 23%, respectively, whereas the activity of CYP2C9 increased by 56%.19 The extent of the change in the AUC of a victim drug in the presence of inflammation and a DDI can be difficult to predict.