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Covid-19: Low dose steroid cuts death in ventilated patients by one third, trial finds

BMJ 2020; 369 doi: https://doi.org/10.1136/bmj.m2422 (Published 16 June 2020) Cite this as: BMJ 2020;369:m2422

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Dexamethasone and CoViD-19: RECOVERY trial provided invaluable clinical evidence but costed precious lives!

Dear Editor

The recent findings from the RECOVERY trial provided invaluable clinical evidence to support the use of systemic corticosteroids in severely ill CoViD-19 patients with acute respiratory distress syndrome (ARDS) on respiratory support [1]. The trial reported a significant benefit of dexamethasone to prevent deaths; a reduction in mortality of around a third in ventilated CoViD-19 patients. To many, this was overwhelmingly shocking but was this really surprising, perhaps not.

The corticosteroids were widely used during the 2002-2003 outbreak of severe acute respiratory syndrome (SARS) [2]. It was then believed that the corticosteroid treatment improves tissue injury associated with the uncontrolled release of proinflammatory cytokines in response to the viral infection [3,4]. A similar cytokine storm was evident in CoViD-19 as a dysregulated host immune response to the virus in severely ill CoViD-19 patients and was believed to be a major reason for high mortality among severely ill patients [5]. Consequently, various therapeutic strategies to target cytokine release syndrome in CoViD-19 were proposed [5,6], and corticosteroids have been an obvious choice by many clinicians across the world at the front line fight against CoViD-19 to save lives. The clinical records from China also provided an early evidence of significantly reduced risk of mortality in severely ill CoViD-19 patients receiving systemic corticosteroids. The use of corticosteroids in severely ill CoViD-19 patients was also supported by the clinical guidance in different countries, such as the Australian and New Zealand Intensive Care Society (ANZICS) [7], the Sciensano Belgium [8], the Canadian government [9] and the Society of Critical Care Medicine [10]. This may also explain, in part, the low CoViD-19 associated mortality observed in some countries.

Due to the perceived risk of delayed virus clearance and lack of evidence for corticosteroids use in CoViD-19, the World Health Organisation (WHO) advised against the routine use of corticosteroids in severely ill CoViD-19 patients in their March 2020 recommendations [11], in contrary to the clinical evidence and recommendations from various societies [7-10] that favoured the use of corticosteroids in patients with COVID-19 associated ARDS.

The United Kingdom government admitted the knowledge of the potential benefits of corticosteroids in reducing CoViD-19 associated mortality in March 2020 in a public statement following the press release on dexamethasone results from RECOVERY trial on 16th June 2020. The government started to stockpile the drug back in March 2020 but did not use it when thousands of precious lives were lost due to CoViD-19 across the world. In particular, the death toll was at its peak in the UK during April 2020, the government kept stockpiling the drug instead of using it to save lives.

A randomised controlled trial was inevitable to confirm the beneficial role of corticosteroids amid the controversy surrounding steroid use in CoViD-19, particularly after the WHO advisory note in March 2020. Indeed, the RECOVERY trial provided the most needed evidence but costed thousands of precious lives. Perhaps, it is the time to reflect on the decisions made instead of celebrating a mere victory against the virus!

References:
[1] https://www.medrxiv.org/content/10.1101/2020.06.22.20137273v1.full.pdf
[2] http://dx.doi.org/10.1136/thx.2003.017665
[3] https://doi.org/10.1089/088282402320914520
[4] https://doi.org/10.1016/s0140-6736(02)11772-7
[5] https://doi.org/10.1016/j.ijantimicag.2020.105954
[6] https://doi.org/10.1007/s10067-020-05190-5
[7] https://www.health.nsw.gov.au/Infectious/diseases/Documents/anzics-covid...
[8] https://covid-19.sciensano.be/sites/default/files/Covid19/COVID-19_Inter...
[9] https://www.canada.ca/en/public-health/services/diseases/2019-novel-coro...
[10] https://www.sccm.org/getattachment/Disaster/SSC-CoViD19-Critical-Care-Gu...
[11] https://www.who.int/publicationsdetail/clinical-management-of-severe-acu...(ncov)-infection-is-suspected

Competing interests: No competing interests

26 June 2020
Hamid A. Merchant
Subject Leader in Pharmacy, University of Huddersfield
Chia Siang Kow; Syed Shahzad Hasan
International Medical University, Malaysia
University of Huddersfield, UK