Identification of Suitable Drug Combinations for Treating COVID-19 Using a Novel Machine Learning Approach: The RAIN Method

SIMPLE SUMMARY: This study follows an improved approach to systematic reviews, called the Systematic Review and Artificial Intelligence Network Meta-Analysis (RAIN), registered within PROSPERO (CRD42021256797), in which, the PRISMA criterion is still considered. Drugs used in the treatment of COVID-19 were searched in the databases of ScienceDirect, Web of Science (WoS), ProQuest, Embase, Medline (PubMed), and Scopus. In addition, using artificial intelligence and the measurement of the p-value between human genes affected by COVID-19 and drugs that have been suggested by clinical experts, and reported within the identified research papers, suitable drug combinations are proposed for the treatment of COVID-19. During the systematic review process, 39 studies were selected. Our analysis shows that most of the reported drugs, such as azithromycin and hydroxyl-chloroquine on their own, do not have much of an effect on the recovery of COVID-19 patients. Based on the result of the new artificial intelligence, on the other hand, at a significance level of less than 0.05, the combination of the two drugs therapeutic corticosteroid + camostat with a significance level of 0.02, remdesivir + azithromycin with a significance level of 0.03, and interleukin 1 receptor antagonist protein + camostat with a significance level 0.02 are considered far more effective for the treatment of COVID-19 and are therefore recommended. ABSTRACT: COVID-19 affects several human genes, each with its own p-value. The combination of drugs associated with these genes with small p-values may lead to an estimation of the combined p-value between COVID-19 and some drug combinations, thereby increasing the effectiveness of these combinations in defeating the disease. Based on human genes, we introduced a new machine learning method that offers an effective drug combination with low combined p-values between them and COVID-19. This study follows an improved approach to systematic reviews, called the Systematic Review and Artificial Intelligence Network Meta-Analysis (RAIN), registered within PROSPERO (CRD42021256797), in which, the PRISMA criterion is still considered. Drugs used in the treatment of COVID-19 were searched in the databases of ScienceDirect, Web of Science (WoS), ProQuest, Embase, Medline (PubMed), and Scopus. In addition, using artificial intelligence and the measurement of the p-value between human genes affected by COVID-19 and drugs that have been suggested by clinical experts, and reported within the identified research papers, suitable drug combinations are proposed for the treatment of COVID-19. During the systematic review process, 39 studies were selected. Our analysis shows that most of the reported drugs, such as azithromycin and hydroxyl-chloroquine on their own, do not have much of an effect on the recovery of COVID-19 patients. Based on the result of the new artificial intelligence, on the other hand, at a significance level of less than 0.05, the combination of the two drugs therapeutic corticosteroid + camostat with a significance level of 0.02, remdesivir + azithromycin with a significance level of 0.03, and interleukin 1 receptor antagonist protein + camostat with a significance level 0.02 are considered far more effective for the treatment of COVID-19 and are therefore recommended. Additionally, at a significance level of less than 0.01, the combination of interleukin 1 receptor antagonist protein + camostat + azithromycin + tocilizumab + oseltamivir with a significance level of 0.006, and the combination of interleukin 1 receptor antagonist protein + camostat + chloroquine + favipiravir + tocilizumab7 with corticosteroid + camostat + oseltamivir + remdesivir + tocilizumab at a significant level of 0.009 are effective in the treatment of patients with COVID-19 and are also recommended. The results of this study provide sets of effective drug combinations for the treatment of patients with COVID-19. In addition, the new artificial intelligence used in the RAIN method could provide a forward-looking approach to clinical trial studies, which could also be used effectively in the treatment of diseases such as cancer.