ABSTRACT
INTRODUCTION: Corticosteroid use in COVID 19 patients has been a much debated topic, and there has been no clear evidence so far supporting it as an effective medication to reduce the inflammatory response and improve mortality rates. We aim to review the data on mortality benefits observed with the use of corticosteroids in COVID-19. METHODS: A comprehensive literature search was conducted across the three largest COVID 19 database provided by WHO, CDC, and LitCovid PubMed Database from inception to July 19th, 2020. We included studies that compared the risk of death among patients with and without use of systemic corticosteroids. We then summarized risk estimates into two random-effect metaanalyses;one with randomized controlled trials and another one with observational studies. We analyzed data in Review Manager Software, version 5.2 (Nordic Cochrane Center, Copenhagen, Denmark), to evaluate combined odds ratio (OR) for RCTs and observational studies with respective 95% confidence intervals (CI) using a random-effects model. RESULTS: Out of total 23 articles, 11 studied were included in final meta-analysis. Among these, 3889 patients were treated with corticosteroids and 5954 were not. The metaanalysis of five clinical trials/prospective studies indicated that administration of corticosteroid significantly reduces the mortality compared to the no corticosteroid use (OR 0.52, 95% CI 0.31-0.87, p-value 0.01;I2=76%). However the meta-analysis of six retrospective observational studies/case series showed summed odds ratio of 2.69;95% CI 0.66 to 10.99, p-value 0.17, I2=94%, suggesting increased risk of mortality with use of systemic steroids. CONCLUSIONS: We observed mortality benefits from metaanalysis on available RCTs. On the contrary, a meta-analysis of observational studies suggested a higher risk of death in similar patients;however, the grade of confidence in this subgroup's results is lower due to inherent methodological limitations.
ABSTRACT
INTRODUCTION: In the current COVID-19 pandemic, as no proven effective treatment is available, the most efficient strategy is to re-purpose existing antiviral drugs. Remdesivir has demonstrated broad spectrum antiviral activity against an array of RNA virus families. Our systematic review and metaanalysis provides a detailed overview of existing literature on remdesivir in COVID-19 to evaluate the benefits and adverse events of this potential drug. METHODS: A systematic search was conducted for articles published between inception and July 31, 2020 focusing on the use of remdesivir in COVID-19. The primary outcomes were defined as mortality rate and median days to recovery and the secondary outcome was pooled adverse events rate and pooled drug discontinuation rate. Statistical analysis was performed using the Comprehensive Meta-Analysis software package (Bio stat, Englewood, NJ, USA). RESULTS: Six studies were included in our meta-analysis. A total of 1858 patients were included. In patients treated with remdesivir, the median recovery time was 15.84 days (95% CI 11.68-20.00, p<0.0001) and the pooled mortality rate was 9.9% (95% CI 7.0%- 13.8%, p <0.0001). The results of three clinical trials indicated that administration of remdesivir significantly reduces the mortality compared to the placebo (OR 0.70, 95% CI 0.58-0.84, p-value 0.000) as well as shortens the recovery time (OR 1.32;95% CI 1.12 to 1.55, p <.001). However, treatment with remdesivir was associated with adverse effects (62.5%, 95% CI 35.9%- 83.3%, p=0.36) eventually warranting the discontinuation of the drug (16.7%, 95% CI 7.2%- 34.3%, p<0.001). CONCLUSIONS: The results of our meta-analysis suggests that pooled mortality rate of patients of COVID-19 with remdesivir is low. The median recovery time was found to be over two weeks. Our meta-analysis suggests that there may be a favorable risk-benefit profile for remdesivir compared with placebo in severe COVID-19 infection.