Correspondence
Does the RECOVERY dexamethasone improve COVID-19 mortality?
Mina T. Kelleni, MD, PhD
Assistant Professor of Pharmacology, College of Medicine, Minia
University, Egypt.
+201200382422
mina.kelleni@mu.edu.eg,
drthabetpharm@yahoo.com
The randomized open-label evaluation of COVID-19 therapy (RECOVERY) collaborative group showed a small mortality benefit to dexamethasone therapy among patients who were receiving invasive mechanical ventilation; 482/2104 patients (22.9%) in the dexamethasone group and 1110/4321 patients (25.7%) in the usual care group 1, yet several concerns regarding the study design, the data and its interpretation were raised2,3. Moreover, the RECOVERY results showing a potential benefit of dexamethasone in SRAS CoV-2 complicated patients contradicts the conclusive outcomes of several previous studies showing evidence of a possible harmful effect when corticosteroids were used to manage SARS, MERS and influenza pneumonia patients 4-6. On the same day the results of the RECOVERY study were published; July 17, 2020, we have submitted a letter to New England Journal of Medicine (NEJM, ID 20-25534) representing some concerns about this study. Unfortunately, its status remained with editor until November 29, 2020 on which a withdrawal request has been sent to NEJM and was promptly accepted on the following day. Notably, four emails were sent to NEJM, once every month wondering about this unprecedent delay in publishing a short letter and the response was that the editor has been contacted on multiple occasions but he/she is busy because of the large number of COVID-19 related submissions. Our concerns were a wonder about the reason that the RECOVERY group chose 2:1 randomization though dexamethasone is a cheap drug and a 1:1 randomization maximizes the statistical power to detect the same difference7,8. Further, in Table 2, the death ratio included in secondary outcomes was similar in both groups; 21.7% in dexamethasone group and 22.7% in the usual care group, and we encouraged the authors to explain the potential reasons and to provide a more clarification to the included numbers e.g. the number of living patients who have not been discharged from hospital within 28 days doesn’t match the subsequent subgroups. Furthermore, a second randomization of 4.5% of patients, complaining of hypoxia and inflammation, performed in the dexamethasone arm to compare the addition of tocilizumab on top of dexamethasone has not been excluded in interpretation of the small mortality benefit assumed to be attributed only to dexamethasone. Finally, we would like to restress our previous agreement with the clinical recommendation against the routine use of glucocorticoids in the management of COVID-19 especially after important concerns were raised regarding the interpretation of data as well as the limitations of several studies showing potential benefit of glucocorticoids in COVID-199. Moreover, a potential real benefit from the RECOVERY dexamethasone as well as to assess its optimal dose and duration of administration in selected COVID-19 critical cases should be confirmed, or denied, by other well designed and interpreted large randomized and controlled clinical trials 10-12. Finally, an ethical call for all journals, which publish any COVID-19 clinical trial, to adhere to a transparent policy that obligates an urgent handling of any related criticism in order avoid encountering another short letter remaining more than four months with a busy editor.
Acknowledgment
The author would like to acknowledge NEJM and its editor in Chief; Dr. Eric Rubin for the prompt rejection to publish the main bulk of this manuscript (NEJM ID: 20-34248).