For September 2020, we have selected: The RECOVERY Collaborative Group. Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report.
N Engl J Med. 2020 Jul 17;NEJMoa2021436. doi: 10.1056/NEJMoa2021436.
By Antonella Macerollo
The spread of the COVID-19 infection in Europe has highlighted a typical presentation of the disease: the diffuse lung damage. For this month only, we have chosen to highlight a general medical rather than neurological paper, because of the wide general impact on our patients.
Our Covid-19 paper of the month reports a controlled, open-label trial comparing 2104 hospitalised Covid-19 patients treated within the Covid-19 Therapy (RECOVERY) trial with oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days with 4321 those receiving usual care alone. Patients were recruited from 176 National Health Service organisations in the United Kingdom. The study was supported by the National Institute for Health Research Clinical Research Network.
Selection criteria were: clinically suspected or laboratory confirmed SARS-CoV-2 infection; and no medical history that might put patients at substantial risk if they were to participate in the trial.
Exclusion criteria were: dexamethasone was unavailable at the hospital at the time of enrolment; dexamethasone was considered by the managing physician
to be either definitely indicated or definitely contraindicated.
The data was collected using a web-based case-report form. Randomisation was performed with the use of a web-based system with concealment of the trial-group assignment. Eligible and consenting patients were assigned in a 2:1 ratio to
receive either the usual standard of care alone or the usual standard of care plus oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days (or until hospital discharge if sooner) or to receive one of the other suitable and available treatments. The randomly assigned treatment was prescribed by the treating clinician.
The primary outcome was all-cause mortality within 28 days after randomisation.
482 patients (22.9%) in the dexamethasone group and 1110 patients (25.7%) in the usual care group died within 28 days after randomisation (age-adjusted rate ratio, 0.83; 95% confidence interval [CI], 0.75 to 0.93; P<0.001).
Of note, the difference in mortality between the two groups varied considerably according to the level of respiratory support at the time of randomisation.
In the dexamethasone group, the incidence of death was lower than that in the usual care group among patients receiving invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64; 95% CI, 0.51 to 0.81) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%; rate ratio, 0.82; 95% CI, 0.72 to 0.94) but not among those who were receiving no respiratory support at randomisation (17.8% vs. 14.0%; rate ratio, 1.19; 95% CI, 0.91 to 1.55).
Of note, dexamethasone therapy was associated with a reduction in 28-day mortality among those with symptoms for more than 7 days but not among those with a more recent symptom onset. This result is very likely related to the presence of inflammatory lung damage, which is most common after 7 days of symptoms that earlier.
In conclusion, our Covid-19 paper of the month reported positive results on the treatment of this fatal syndrome with dexamethasone, which is on the list of essential medicines of the World Health Organisation and is readily available worldwide at low cost, whilst more specific treatments as well as vaccines are developed.