Combination therapy of Tocilizumab and steroid for management of COVID-19 associated cytokine release syndrome
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Abstract
Cytokine release syndrome (CRS) or cytokine storm is thought to be the cause of inflammatory lung damage, worsening pneumonia and death in patients with COVID-19. Steroids (Methylprednislone or Dexamethasone) and Tocilizumab (TCZ), an interleukin-6 receptor antagonist, are approved for treatment of CRS in India. The aim of this study was to evaluate the efficacy and safety of combination therapy of TCZ and steroid in COVID-19 associated CRS.
This retrospective cohort study was conducted at Noble hospital and Research Centre (NHRC), Pune, India between April 2 and November 2, 2020. All patients administered TCZ and steroids during this period were included. The primary endpoint was incidence of all cause mortality. Secondary outcomes studied were need for mechanical ventilation and incidence of systemic and infectious complications. Baseline and time dependent risk factors significantly associated with death were identified by Relative risk estimation.
Out of 2831 admitted patients, 515 (24.3% females) were administered TCZ and steroids. There were 135 deaths (26.2%), while 380 patients (73.8%) had clinical improvement. Mechanical ventilation was required in 242 (47%) patients. Of these, 44.2% (107/242) recovered and were weaned off the ventilator. Thirty seven percent patients were managed in wards and did not need intensive care unit (ICU) admission. Infectious complications like hospital acquired pneumonia, blood stream bacterial and fungal infections were observed in 2.13%, 2.13% and 0.06% patients respectively. Age ≥ 60 years ( P = .014), presence of co-morbidities like hypertension ( P = .011), IL-6 ≥ 100 pg/ml ( P = .002), D-dimer ≥ 1000 ng/ml ( P < .0001), CT severity index ≥ 18 ( P < .0001) and systemic complications like lung fibrosis ( P = .019), cardiac arrhythmia ( P < .0001), hypotension ( P < .0001) and encephalopathy ( P < .0001) were associated with increased risk of death.
Combination therapy of TCZ and steroids is likely to be safe and effective in management of COVID-19 associated cytokine release syndrome. Efficacy of this anti-inflammatory combination therapy needs to be validated in randomized controlled trials.
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SciScore for 10.1101/2021.02.04.21249959: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Consent: Patients or their immediate family members signed an informed consent form prior to TCZ administration. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources All data was analyzed by SPSS version 12.0. SPSSsuggested: (SPSS, RRID:SCR_002865)Results from OddPub: Thank you for sharing your data.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Limitations: Our study has several limitations. First, it is not a randomized controlled trial, and therefore unmeasured confounding cannot …
SciScore for 10.1101/2021.02.04.21249959: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Consent: Patients or their immediate family members signed an informed consent form prior to TCZ administration. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources All data was analyzed by SPSS version 12.0. SPSSsuggested: (SPSS, RRID:SCR_002865)Results from OddPub: Thank you for sharing your data.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Limitations: Our study has several limitations. First, it is not a randomized controlled trial, and therefore unmeasured confounding cannot be ruled out. Second, as for all retrospective studies, some individuals administered TCZ and steroids may be unreported leading to measurement bias and overestimation of safety and efficacy of the combination therapy. Third, a comparator arm was not possible in this pandemic setting. Considering the unavailability of observational or RCT data about efficacy of other regimens to tackle hyperinflammation, worsening of respiratory parameters seen in patients despite receiving potent steroids and life threatening nature of the disease characterized by sudden worsening and rapid progression to respiratory failure over few hours, a comparative arm could not be justified. Fourth, concomitant therapies like antiviral drugs, convalescent plasma, anti-fibrotic agents, supplemental oxygen and ventilation strategies (NIV/IMV) can help in reducing disease severity and clinical improvement. The authors acknowledge the fact that individual contribution of each drug is difficult to estimate. However, considering the predefined criteria for introduction of each drug in patient management, strict inclusion and exclusion criteria applied while administering TCZ and steroids, large number of patients enrolled and improvement in symptoms and oxygenation after TCZ administration, the authors are reasonably confident that this study reliably captures the effic...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).
Results from JetFighter: We did not find any issues relating to colormaps.
Results from scite Reference Check: We found no unreliable references.
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