Efficacy of the early treatment with tocilizumab-hydroxychloroquine and tocilizumab-remdesivir in severe COVID-19 Patients

Background: The effectiveness of the best combination between different antiviral and anti-inflammatory drugs stills an interest in the treatment of COVID19 infection.Patients and methods: A prospective randomized cohort study comprised 108 adult patients with con-firmed PCR COVID 19 infection with systemic hyper inflammation state, divided into two groups according to the treatment regimen, 56 in the tocilizumab-hydroxychloroquine (TCZ-HCQ) treatment, and 52 in the tocilizumab-remdesivir (TCZ-RMV) treatment. The first group received a combination of I.V. TCZ (400-800 mg every 24 h for only two doses) and HCQ (400 mg twice in the first day then 200 mg twice for 5 days) while the second group of patients received I.V. RMV of 200 mg on day 1 followed by 100 mg once daily infused over 60 min for 5 days with the same TCZ regimen used in the first group. All clinical parameters and laboratory investigations were assessed before and after treatment.Results: The CRP was significantly decreased while PaO2/FiO(2) (P/F) ratio post-treatment was significantly improved in both treatment groups. TCZ-HCQ group showed a significant decrease in the ferritin, LDH, and D. Dimer levels. The median days of hospitalization with interquartile range (IQR) were 10 (6-16) and 8 (5-12) for TCZ-HCQ and TCZ-RMV groups, respectively. The numbers of mechanically ventilated patients were 25 and 43 for TCZ-HCQ and TCZ-RMV groups, respectively. Therapeutic failure was about 26.8% in the TCZ-HCQ group and 30.8% in the TCZ-RMV group but there was no significant difference between both groups. Some complications were recognized only in TCZ-RMV following treatment including secondary bacterial infections (42.3%), myocarditis (15.4%), and finally pulmonary embolism (7.7%).Conclusion: Efficacy of both TCZ-RMV and TCZ-HCQ combinations are observed in the treatment of severe COVID-19 patients; however the increased need for ICU or mechanical ventilation in the TCZ-RMV arm contributed to the appearance of cardiac and thrombotic events.The study was registered at the Clinical Trials registry (ClinicalTrials.gov; NCT04779047).(c) 2021 The Authors. Published by Elsevier Ltd on behalf of King Saud Bin Abdulaziz University for Health Sciences. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).

Automated summary

The effectiveness of tocilizumab-hydroxychloroquine (TCZ-HCQ) and tocilizumab-remdesivir (TCZ-RMV) combinations were observed in the treatment of severe COVID-19 patients. However, the TCZ-RMV group had a higher incidence of ICU or mechanical ventilation and a greater risk of cardiac and thrombotic events.