Safety and Efficacy of Imatinib, Nilotinib, and Artesunate in COVID-19 Patients: A Systematic Review of Current Evidence

Introduction: There is a need for better treatment options against COVID-19. This systematic review aimed to assess the safety and efficacy of imatinib and nilotinib, two tyrosine kinase inhibitors (TKIs), as well as artesunate (an anti-malarial agent), whose multilayer activities against SARS, MERS, and SARS-CoV-2 pathogenesis have been suggested in laboratory and observational studies. Methods: A comprehensive search strategy targeting relevant literature on PubMed, Scopus, and Web of Science online databases was constructed. The retrieved records were reviewed and screened by title/abstract and full text with eligibility criteria, and the most pertinent articles were included in the final qualitative synthesis. This review adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) to ensure the reliability of the results. Results: This systematic review assessed the safety and applicability of imatinib, nilotinib, and artesunate in COVID-19 patients. The results showed not only possible anti-COVID-19 effects but also acceptable safety for both generic users with comorbidities with COVID-19 and offlabel use in other COVID-19 patients. Promising results were also reported enhancing the survival of COVID-19 patients. Conclusion: A double-blinded multicenter randomized controlled trial found survival benefits for imatinib with no significant treatment-related adverse events. However, no clinical trials or large observational studies exist for artesunate and nilotinib, and the evidence relies only on case reports and case series. Molecular mechanisms revealed in preclinical studies support the possible benefits of these medications in COVID-19 treatment. However, the scarcity of reliable evidence requires further studies on possible COVID-19 treatments, including but not limited to artesunate, nilotinib, and imatinib. Nevertheless, these drugs' lack of serious adverse events suggests their safe use for other indications during the COVID-19 pandemic.