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

Rania M Sarhan, Hadeer S Harb, Ahmed E Abou Warda, Mounir M Salem-Bekhit, Faiyaz Shakeel, Sami Ali Alzahrani, Yasmin M Madney, Marian S Boshra, Rania M Sarhan, Hadeer S Harb, Ahmed E Abou Warda, Mounir M Salem-Bekhit, Faiyaz Shakeel, Sami Ali Alzahrani, Yasmin M Madney, Marian S Boshra

Abstract

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 confirmed 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/FiO2 (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).

Keywords: Anti-inflammatory; Antiviral; COVID-19; Cytokine storm; Hydroxychloroquine; Remdesivir; Tocilizumab.

Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

Figures

Fig. 1
Fig. 1
C-reactive protein (CRP) level (mg/dl) before and after receiving therapy (data are expressed as mean ± SE. TCZ-HCQ; tocilizumab plus hydroxychloroquine treatment group, TCZ-RMV; tocilizumab plus remdesivir treatment group. (*) significantly different when compared with baseline CRP level before receiving TCZ-HCQ at p

Fig. 2

PaO 2 /FiO 2 (P/F)…

Fig. 2

PaO 2 /FiO 2 (P/F) ratio before and after receiving therapy (data are…

Fig. 2
PaO2/FiO2 (P/F) ratio before and after receiving therapy (data are expressed as mean ± SE. TCZ-HCQ; tocilizumab plus hydroxychloroquine treatment group, TCZ-RMV; tocilizumab plus remdesivir treatment group. (*) significantly different when compared with baseline P/F ratio before receiving TCZ-HCQ at p

Fig. 3

Ferritin level (ng/mL) before and…

Fig. 3

Ferritin level (ng/mL) before and after receiving therapy (data are expressed as mean…

Fig. 3
Ferritin level (ng/mL) before and after receiving therapy (data are expressed as mean ± SE. TCZ-HCQ; tocilizumab plus hydroxychloroquine treatment group, TCZ-RMV; tocilizumab plus remdesivir treatment group. (*) significantly different when compared with baseline ferritin level before receiving TCZ-HCQ at p

Fig. 4

Total leucocyte count (×10 9…

Fig. 4

Total leucocyte count (×10 9 /L) before and after receiving therapy (data are…

Fig. 4
Total leucocyte count (×109/L) before and after receiving therapy (data are expressed as mean ± SE. TCZ-HCQ; tocilizumab plus hydroxychloroquine treatment group, TCZ-RMV; tocilizumab plus remdesivir treatment group. (#) significantly different when compared with baseline TLC before receiving TCZ-RMV at p

Fig. 5

Absolute lymphocyte count before and…

Fig. 5

Absolute lymphocyte count before and after receiving therapy (data are expressed as mean…

Fig. 5
Absolute lymphocyte count before and after receiving therapy (data are expressed as mean ± SE. TCZ-HCQ; tocilizumab plus hydroxychloroquine treatment group, TCZ-RMV; tocilizumab plus remdesivir treatment group. (*) significantly different when compared with baseline lymphocyte count before receiving TCZ-HCQ at p = 0.013. (#) significantly different when compared with baseline lymphocyte count before receiving TCZ-RMV at p = 0.025. ($) significantly different when compared with endpoint lymphocyte count after receiving TCZ-HCQ at p = 0.002.
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References
    1. Zhou F., Yu T., Du R., Fan G., Liu Y., Liu Z., et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 - PMC - PubMed
    1. Klopfenstein T., Zayet S., Lohse A., Balblanc J.-C., Badie J., Royer P.-Y., et al. Tocilizumab therapy reduced intensive care unit admissions and/or mortality in COVID-19 patients. Médecine Mal Infect. 2020;50(5):397–400. - PMC - PubMed
    1. Ziaie S., Koucheck M., Miri M., Salarian S., Shojaei S., Haghighi M., et al. Review of therapeutic agents for the treatment of COVID-19. J Cell Mol Anesth. 2020;5(1):32–36.
    1. Wang M., Cao R., Zhang L., Yang X., Liu J., Xu M., et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30(3):269–271. - PMC - PubMed
    1. Savarino A., Boelaert J.R., Cassone A., Majori G., Cauda R. Effects of chloroquine on viral infections: an old drug against today’s diseases. Lancet Infect Dis. 2003;3(11):722–727. - PMC - PubMed
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Fig. 2
Fig. 2
PaO2/FiO2 (P/F) ratio before and after receiving therapy (data are expressed as mean ± SE. TCZ-HCQ; tocilizumab plus hydroxychloroquine treatment group, TCZ-RMV; tocilizumab plus remdesivir treatment group. (*) significantly different when compared with baseline P/F ratio before receiving TCZ-HCQ at p

Fig. 3

Ferritin level (ng/mL) before and…

Fig. 3

Ferritin level (ng/mL) before and after receiving therapy (data are expressed as mean…

Fig. 3
Ferritin level (ng/mL) before and after receiving therapy (data are expressed as mean ± SE. TCZ-HCQ; tocilizumab plus hydroxychloroquine treatment group, TCZ-RMV; tocilizumab plus remdesivir treatment group. (*) significantly different when compared with baseline ferritin level before receiving TCZ-HCQ at p

Fig. 4

Total leucocyte count (×10 9…

Fig. 4

Total leucocyte count (×10 9 /L) before and after receiving therapy (data are…

Fig. 4
Total leucocyte count (×109/L) before and after receiving therapy (data are expressed as mean ± SE. TCZ-HCQ; tocilizumab plus hydroxychloroquine treatment group, TCZ-RMV; tocilizumab plus remdesivir treatment group. (#) significantly different when compared with baseline TLC before receiving TCZ-RMV at p

Fig. 5

Absolute lymphocyte count before and…

Fig. 5

Absolute lymphocyte count before and after receiving therapy (data are expressed as mean…

Fig. 5
Absolute lymphocyte count before and after receiving therapy (data are expressed as mean ± SE. TCZ-HCQ; tocilizumab plus hydroxychloroquine treatment group, TCZ-RMV; tocilizumab plus remdesivir treatment group. (*) significantly different when compared with baseline lymphocyte count before receiving TCZ-HCQ at p = 0.013. (#) significantly different when compared with baseline lymphocyte count before receiving TCZ-RMV at p = 0.025. ($) significantly different when compared with endpoint lymphocyte count after receiving TCZ-HCQ at p = 0.002.
Similar articles
Cited by
References
    1. Zhou F., Yu T., Du R., Fan G., Liu Y., Liu Z., et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 - PMC - PubMed
    1. Klopfenstein T., Zayet S., Lohse A., Balblanc J.-C., Badie J., Royer P.-Y., et al. Tocilizumab therapy reduced intensive care unit admissions and/or mortality in COVID-19 patients. Médecine Mal Infect. 2020;50(5):397–400. - PMC - PubMed
    1. Ziaie S., Koucheck M., Miri M., Salarian S., Shojaei S., Haghighi M., et al. Review of therapeutic agents for the treatment of COVID-19. J Cell Mol Anesth. 2020;5(1):32–36.
    1. Wang M., Cao R., Zhang L., Yang X., Liu J., Xu M., et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30(3):269–271. - PMC - PubMed
    1. Savarino A., Boelaert J.R., Cassone A., Majori G., Cauda R. Effects of chloroquine on viral infections: an old drug against today’s diseases. Lancet Infect Dis. 2003;3(11):722–727. - PMC - PubMed
Show all 56 references
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MeSH terms
Associated data
[x]
Cite
Copy Download .nbib
Format: AMA APA MLA NLM

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The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

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Fig. 3
Fig. 3
Ferritin level (ng/mL) before and after receiving therapy (data are expressed as mean ± SE. TCZ-HCQ; tocilizumab plus hydroxychloroquine treatment group, TCZ-RMV; tocilizumab plus remdesivir treatment group. (*) significantly different when compared with baseline ferritin level before receiving TCZ-HCQ at p

Fig. 4

Total leucocyte count (×10 9…

Fig. 4

Total leucocyte count (×10 9 /L) before and after receiving therapy (data are…

Fig. 4
Total leucocyte count (×109/L) before and after receiving therapy (data are expressed as mean ± SE. TCZ-HCQ; tocilizumab plus hydroxychloroquine treatment group, TCZ-RMV; tocilizumab plus remdesivir treatment group. (#) significantly different when compared with baseline TLC before receiving TCZ-RMV at p

Fig. 5

Absolute lymphocyte count before and…

Fig. 5

Absolute lymphocyte count before and after receiving therapy (data are expressed as mean…

Fig. 5
Absolute lymphocyte count before and after receiving therapy (data are expressed as mean ± SE. TCZ-HCQ; tocilizumab plus hydroxychloroquine treatment group, TCZ-RMV; tocilizumab plus remdesivir treatment group. (*) significantly different when compared with baseline lymphocyte count before receiving TCZ-HCQ at p = 0.013. (#) significantly different when compared with baseline lymphocyte count before receiving TCZ-RMV at p = 0.025. ($) significantly different when compared with endpoint lymphocyte count after receiving TCZ-HCQ at p = 0.002.
Similar articles
Cited by
References
    1. Zhou F., Yu T., Du R., Fan G., Liu Y., Liu Z., et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 - PMC - PubMed
    1. Klopfenstein T., Zayet S., Lohse A., Balblanc J.-C., Badie J., Royer P.-Y., et al. Tocilizumab therapy reduced intensive care unit admissions and/or mortality in COVID-19 patients. Médecine Mal Infect. 2020;50(5):397–400. - PMC - PubMed
    1. Ziaie S., Koucheck M., Miri M., Salarian S., Shojaei S., Haghighi M., et al. Review of therapeutic agents for the treatment of COVID-19. J Cell Mol Anesth. 2020;5(1):32–36.
    1. Wang M., Cao R., Zhang L., Yang X., Liu J., Xu M., et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30(3):269–271. - PMC - PubMed
    1. Savarino A., Boelaert J.R., Cassone A., Majori G., Cauda R. Effects of chloroquine on viral infections: an old drug against today’s diseases. Lancet Infect Dis. 2003;3(11):722–727. - PMC - PubMed
Show all 56 references
Publication types
MeSH terms
Associated data
[x]
Cite
Copy Download .nbib
Format: AMA APA MLA NLM
Fig. 4
Fig. 4
Total leucocyte count (×109/L) before and after receiving therapy (data are expressed as mean ± SE. TCZ-HCQ; tocilizumab plus hydroxychloroquine treatment group, TCZ-RMV; tocilizumab plus remdesivir treatment group. (#) significantly different when compared with baseline TLC before receiving TCZ-RMV at p

Fig. 5

Absolute lymphocyte count before and…

Fig. 5

Absolute lymphocyte count before and after receiving therapy (data are expressed as mean…

Fig. 5
Absolute lymphocyte count before and after receiving therapy (data are expressed as mean ± SE. TCZ-HCQ; tocilizumab plus hydroxychloroquine treatment group, TCZ-RMV; tocilizumab plus remdesivir treatment group. (*) significantly different when compared with baseline lymphocyte count before receiving TCZ-HCQ at p = 0.013. (#) significantly different when compared with baseline lymphocyte count before receiving TCZ-RMV at p = 0.025. ($) significantly different when compared with endpoint lymphocyte count after receiving TCZ-HCQ at p = 0.002.
Fig. 5
Fig. 5
Absolute lymphocyte count before and after receiving therapy (data are expressed as mean ± SE. TCZ-HCQ; tocilizumab plus hydroxychloroquine treatment group, TCZ-RMV; tocilizumab plus remdesivir treatment group. (*) significantly different when compared with baseline lymphocyte count before receiving TCZ-HCQ at p = 0.013. (#) significantly different when compared with baseline lymphocyte count before receiving TCZ-RMV at p = 0.025. ($) significantly different when compared with endpoint lymphocyte count after receiving TCZ-HCQ at p = 0.002.

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