Background: Non-randomized clinical trials have started shortly after the identification of SARS-CoV-2 as the causative agent for COVID-19. Subsequently, a large number of randomized control trials have been conducted to test several drugs that target every step of the viral life cycle and the dysregulated host immune response. However, even after a 177.4 million cases, 3.8 million deaths, and clinical trials involving more than 100,000 patients, no drug was identified to efficaciously intercept viral infection and reduce mortality. 

Successes and failures: Among the repurposed drugs, chloroquine and hydroxychloroquine (an endosomal fusion inhibitor) with or without macrolides were initially promising candidates based on anecdotal examples and preliminary clinical trials. However, these drugs were uncovered to induce serious cardiac arrhythmia and increase mortality by 2-fold after being tested on over 10,000 patients. Remdesivir (a viral RNA polymerase inhibitor) modestly reduced the length of days in hospital by a median of 4 day and was approved for clinical use. Dexamethasone, a glucocorticosteroid, reduces the mortality of ventilated patients by a third.  Currently, anti-viral (lopinavir/ritonavir), anti-inflammatory (antagonists of IL-6 receptor, ruxolitinib, IFN- β -1A), and adjunctive therapeutic compounds (heparin, surfactant, DNase) are undergoing active clinical trials.

Conclusions: Overall, chloroquine and hydroxychloroquine with or without macrolides represent the failures, while remdesivir and dexamethasone represent the successes. Anti-inflammatories, anti-coagulants, surfactants, and DNases represent potential adjunctive therapies to reduce COVID-19 and mortality in patients. A combination of successful therapeutic drugs, experimental adjunctive therapies and potential vaccines are necessary to mitigate the devastating effects of SARS-CoV-2 on lungs and other organs and to reduce mortality.