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Authors: Malgorzata Mikulska et al. 

Journal/ Pre-Print:MedRχiv Pre Print 

Tags: Clinical, Drug discovery/Drug repurpose, Therapeutics 

Research Highlights 

  1. Methylprednisolone and / or tocilizumab may be beneficial in reducing requirement for intubation and preventing mortality in patients with COVID-19 compared with standard care. 

  1. Either agent used alone, has better overall survival at 14 and 30 day follow up compared to standard treatment.  

  1. The non-randomised nature of the study and a number of other critical biases significantly diminish the impact of the study. 

Summary

This is a single centre non-randomised, non-blinded study comparing treatment with IV methylprednisolone and / or IV/SC tocilizumab to standard of care (supportive treatment and hydroxychloroquine +/- darunavir/ritonavir). 196 patients in the treatment group were compared to 66 in the control group for overall mortality and treatment failure, defined as intubation or death at 30 days following admission. Correction was made based on propensity score of baseline differences in the treatment and control groups. The treatment group had significantly better outcomes than the control group both in terms of the failure criteria and in overall survival.   

Impact for SARS-CoV2/COVID19 research efforts  

Treat of SARS-CoV2/COVID19 positive individuals: Treatment with corticosteroids and/or IL-6 receptor blockers may be beneficial. 

Study Type  

  • Clinical Cohort study (e.g. drug trials) 

Strengths and limitations of the paper 

Novelty: This paper is one of a number suggesting benefit to corticosteroids and IL-6 receptor blockers in COVID-19.  

Standing in the field: These results support those of other studies of corticosteroids and IL-6 receptor blockers against SARS Co-V2. Cohort used in this study were comparable to real world patients.  

Appropriate statistics: No power calculation for group size was made, but statistical tests of outcomes have been made. Comparison of adverse events between groups were not tested statistically. First noted use of overlap weighting, allowing propensity score matching of smaller populations, but there is no comparable group, to evaluate if this is appropriate. Use a landmark point at day 3 is suboptimal and may be related to a need to include more patients in the control group. A number of patients may have died/been intubated before day 3 

Viral model used: Clinical study of patients infected with circulating SARS-CoV2 

Translatability: This is a clinical study. The study used routine parameters for assessment. Drugs are commercially available. Follows standard WHO assessment procedure for swabbing.  

Main limitations: This was a non-randomisednon-blinded single centre observational study with a number of inherent biases and no power analysis. The control group receiving standard care received hydroxychloroquine, which is not routine in all centres. Patients on combined therapy were younger and fewer comorbidities. Some patients were switched from IV to SC but these were not assessed for bioequivalence. Other confounders include changes in SOC such as darunavir and ritanvoir in some patients, administration of LMW heparin, the latter implicated in disease progression. Other changes in treatment over the course of the pandemic are possible, and given that control patients appear to have been treated in the early stages of the pandemic, these patients did not benefit from the enhanced clinical experience as the pandemic evolved. It is possible that those not receiving tocilizumab/steroids were thought to be less severe at admission. More details on the regression analysis are required.