Dexamethasone in the management of covid -19BMJ 2020; 370 doi: https://doi.org/10.1136/bmj.m2648 (Published 03 July 2020) Cite this as: BMJ 2020;370:m2648
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Immune modulation as treatment for severe COVID-19: a light at the end of the tunnel, Re: Dexamethasone in the management of covid -19
Johnson and Vinetz recently editorialized on the results of the preprint RECOVERY trial , which showed a clear benefit of dexamethasone (6 mg daily) on all-cause mortality in patients with severe and critical COVID-19.  They highlighted that some gaps still exist regarding the usefulness of dexamethasone in the treatment of patients with this condition, and emphasized that “it is not clear whether corticosteroids are the best option for all patients in the second phase of the illness…” .
Johson and Vinetz did not mention another important study dealing with immune modulation of patients with COVID-19, which showed a clear benefit in the clinical deterioration status (the primary end-point) and in all-cause mortality (a prespecified secondary endpoint) of patients with this condition: the GRECCO study. In that study, clinical deterioration was based on a 7-level ordinal scale ranging from level 1 (ambulatory, normal activities), to level 4 (hospitalized, requiring supplemental oxygen) and to level 7 (death). Clinical deterioration was defined as a 2-level increase on this ordinal scale. 
In GRECCO, Deftereos et al. randomized 105 patients with severe COVID-19 to be treated with either colchicine (n=55) or usual care (n=50); all patients had positive polymerase chain reaction–reverse transcriptase testing. The average time from hospitalization to randomization was 3 days. About 65% of patients had severe (level 4), and 35% moderate COVID-19 (level 3). No patients with critical COVID-19 were enrolled. Background therapy consisted of anticoagulation in 50% of patients, and hydroxychloroquine in 100%. Deterioration in clinical status occurred in 14% of control and in 2% of colchicine group (p=0.02). Furthermore, cumulative 10-day survival was 97% in colchicine x 83% in control group (p=0.03).
Despite the limitation of the sample size, which was much lower in GRECCO than in RECOVERY trial (6425 patients enrolled; 2104 to dexamethasone group x 4321 to usual care), [2,3] the GRECCO trial results suggest that colchicine might be an option when dexamethasone is contraindicated for patients with severe COVID-19, as 61% of patients in RECOVERY had this condition. Furthermore, they also suggest that colchicine might be of benefit to patients with moderate COVID-19. Therefore, we suggest that doctors in the frontline take into account both evidence-based medicine possibilities for treating COVID-19.
No competing interest
1. Horby P, Lim WS, Emberson J, et al. Effect of dexamethasone in hospitalized patients with Covid-19: preliminary report. MedRxiv 2020.06.2220.06137273 (Preprint). https://doi.org10.1101/2020.06.22.20137273
2. Jonhson RM, Vinetz JM. Dexamethasone in the management of COVID-19. BMJ 370: doi 10.1136/bmg.m2648.
3. Deftereos SG, Giannopoulos G, Vrachatis DA, et al. Effect of colchicine vs standard care on cardiac and inflammatory biomarkers and clinical outcomes in patients hospitalized with coronavirus disease 2019. JAMA Network Open. 2020;3(6):e2013136. doi:10.1001/jamanetworkopen.2020.13136
Reinaldo B. Bestetti, MD, PhD* ORCID: 0000-0002-4488-9601/
Rosemary Furlan-Daniel, MD, PhD ORCID: 0000-0002-7375-8205
Competing interests: No competing interests
I read with great interest the editorial by Dr Johnson. At present, the only evidence-based antiviral drug treatment available was remdesivir.1 There is still no vaccine for COVID-19. Vaccines for COVID-19 are under development, and the process may take several years. Thus the RECOVERY press release delivered an inspiring message.
Although interim guidance from WHO advises against the use of corticosteroids,2 corticosteroids were still widely used during the early outbreaks of COVID-19 despite uncertainty over their efficacy. Some scholars commented that corticosteroid treatment should not be used for the treatment of COVID-19 outside of a clinical trial because of insufficient evidence exists to recommend corticosteroid treatment at the time.3 On the contrary, Prevention and Control Protocol for the COVID-19 released by the National Health Commission of the People’s Republic of China recommended corticosteroid treatment4. According to the expert consensus statement,5 corticosteroids should be used when meeting the following basic principles: Firstly, the benefit outweighs the risk. Secondly, only used in critically ill patients with COVID-19. Thirdly, the dosage should be low-to-moderate (≤0.5㎎/㎏ per day methylprednisolone or equivalent). The expert consensus use is consistent with RECOVERY findings to some degree.
Corticosteroid treatment is a double-edged sword. There is a major concerns about the potential risks associated with high-dose corticosteroids in treating COVID-19. More effort should be made to answer unresolved questions in future studies including the optimal type of corticosteroid nor timing, dose, or duration.
1. Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the Treatment of Covid-19 — Preliminary Report. New England Journal of Medicine 2020 doi: 10.1056/NEJMoa2007764
2. WHO. Clinical management of severe acute respiratory infection when novel coronavirus (2019-nCoV) infection is suspected: interim guidance. 2020 [Available from: https://apps.who.int/iris/handle/10665/330893.
3. Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. The Lancet 2020;395(10223):473-75. doi: 10.1016/S0140-6736(20)30317-2
4. PRC NHC. New Coronavirus Pneumonia Prevention and Control Protocol for the novel coronavirus disease 2019 (COVID-19): National Health Commission of the People’s Republic of China; 2020 [Available from: http://www.nhc.gov.cn/yzygj/s7653p/202003/46c9294a7dfe4cef80dc7f5912eb19... accessed July 14.
5. Zhao J, Hu Y, Du R, et al. Expert consensus on the use of corticosteroid in patients with 2019-nCoV pneumonia. Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases 2020;43:183-84. doi: 10.3760/cma.j.issn.1001-0939.2020.03.008
Competing interests: No competing interests