Optimized combinatorial strategy for Age- and Obese-dependent Treatments COVID-19 Recurrence

Introduction: Various medical treatments for COVID-19 are attempted at the beginning of COVID-19 emerging. After patients are discharged, SARS-CoV-2 recurring cases are reported and the recurrence could profoundly impact patient healthcare and social economics. The specific treatment plan for individuals is essential for patient recovery and public safety. We retrospectively analyzed real-world data from a major hospital in China using a machine-learning approach and revealed optimized age- and obesity-dependent methods that can provide novel strategy for precision medicine for treating infectious diseases in the future.

Materials and

Methods: We analyzed the treatment data of combinations of ten different drugs for the COVID-19 patients recurring cases and followed up for recurrence for 28 days quarantine after being discharged from the medical center between February and May, 2020 in a single medical center, Shenzhen, China. We applied the Synthetic Minority Oversampling Technique (SMOTE) to overcome the rare recurring events in certain age groups and performed Virtual Twins (VT) analysis facilitated by random forest regression for medical treatment-recurrence classification.

Results, Conclusions, and Discussions: There were a total of 113 recurring cases from 414 patients. There is no significant difference between recurrence and non-recurrence groups in terms of sex, disease conditions, comorbidity, imaging features, biochemical parameters and most of medical symptoms, except cough and sputum. Among ten different drugs used for the treatments, no individual drug showed significant impact on the recurrence. The ages of patients range from 3 to 78 years old. The drug combination of Methylprednisolone/Interferon/Lopinavir/Ritonavir/Arbidol led to the lowest recurring rate (0.133) as compared to the average recurring rate (0.203). For the younger group (age 20-27) or the older group (age 60-70), the optimal drug combinations are different, but the above combination is still the second best. For obese patients, the combination of Ribavirin/Interferon/Lopinavir/Ritonavir/Arbidol led to the lowest recurring rate for age group of 20-50, whereas the combination of Interferon/Lopinavir/Ritonavir/Arbidol led to lowest recurring rate for age group of 50-70.
Our findings suggest that different combinatorial therapies could lead to various COVID-19 recurrence. The age and obese status are important factors for the choices of combinatorial therapy.

Acknowledgements (Optional): We would like to thank Dr.Jia Huang at the Second Affiliated Hospital of the Southern University of Science and Technology for the original data.