DEXAMETHASONE IN HOSPITALIZED PATIENTS WITH COVID-19

Abstract

Glucocorticoids have been widely used in various infectious diseases, due to their important anti-inflammatory effect, but there lack powerful data supporting this treatment with potential side effects. Notwithstanding, dexamethasone proved to be beneficial on secondary end-points such as: shorter duration of hospitalisation (2 days vs. 13 days) and a greater chance of home discharge alive in the first 28 days (rate ratio: 1.10; 95% CI, 1.03 to 1.17), successful weaning of invasive ventilation (rate ratio: 1.47; 95% CI, 1.20 to 1.78), lower probability of renal-replacement treatment (risk ratio: 0.61; 95% CI, 0.48 to 0.76). The RECOVERY trial offers evidences that sustain the usage of dexamethasone at a dose of 6 mg once daily for up to 10 days to reduce the 28-day mortality in COVID-19 subjects requiring respiratory support, with or without ventilatory support.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affected, at the beginning of March, almost 140 million people and produced more than 3 million deaths. It emerged in China in late 2019. Even if the majority of the infected subjects remained asymptomatic or mild symptomatic, a percentage evolved towards severe respiratory illness requiring hospitalization for severe hypoxemic respiratory failure. Despite the many therapeutics studies, none showed to reduce mortality.

Glucocorticoids have been widely used in various infectious diseases, due to their important anti-inflammatory effect, but there lack powerful data supporting this treatment with potential side effects.

One drug improving outcomes in patients with Corona Virus Disease 19 (COVID-19) proved to be methylprednisolone in one small trial, but large-scale randomized trials lacked, until Randomized Evaluation of COVID-19 Therapy (RECOVERY) trial, a controlled, open-label trial of dexamethasone in patients hospitalized for COVID-19.

The study recruited 9,355 patients; of these 6,425 received dexamethasone along with usual treatment and 4,321 usual treatments without glucocorticoids. Mortality at 28 days proved to be lower in the dexamethasone group (22.09%) compared with those not receiving glucocorticoids (25.7%, p < 0.001) after age adjustment.

In a sub-analysis, the patients who beneficiated most from dexamethasone were those with invasive mechanical ventilation (1.6 by chi-square test) and those with symptoms for more than 7 days (12.4 by chi-square test). The subjects not requiring mechanical ventilation did not have an advantage on mortality.

Patients who did not receive invasive mechanical ventilation initially, but progressed afterwards to mechanical ventilation were fewer in the dexamethasone group. Notwithstanding, dexamethasone proved to be beneficial on secondary end-points such as: shorter duration of hospitalisation (2 days vs. 13 days) and a greater chance of home discharge alive in the first 28 days (rate ratio: 1.10; 95% CI, 1.03 to 1.17), successful weaning of invasive ventilation (rate ratio: 1.47; 95% CI, 1.20 to 1.78), lower probability of renal-replacement treatment (risk ratio: 0.61; 95% CI, 0.48 to 0.76). Several adverse reactions were noted from the trialists, four in total: two severe hyperglycaemias, one episode of gastro-intestinal haemorrhage, and one case of psychosis, but all these seem insignificant compared with the benefits of using dexamethasone.

Unfortunately, there were no specific measures evaluating laboratory variables in order to correlate the virologic data with the outcome of subjects. This was mainly due to the rapid evolution of the pandemic that required practice guidelines in real time, driving to rapid progression of the study, in the detriment of more solid data that would have combined virologic and other laboratory information with the evolution of the infection.

The RECOVERY trial offers evidences that sustain the usage of dexamethasone at a dose of 6 mg once daily for up to 10 days to reduce the 28-day mortality in COVID-19 subjects requiring respiratory support, with or without ventilatory support. This trial was the cornerstone of the changes made by the European Medicines Agency and the World Health Organization in Covid-19 treatment guidelines recommending glucocorticoids in hospitalized subjects infected with SARS-CoV-2 requiring oxygen. Those who did not require oxygen do not beneficiate from glucocorticoids, furthermore exposing them to the adverse reactions.

This trial is only one of the many others that investigate the effects of particular drugs on SARS-CoV-2 infection, mainly on those with moderate to severe forms requiring hospitalisation and many others wait the ethical committees' approval for launching.

Sidebar

* The RECOVERY Collaborative Group. Dexa-methasone in Hospitalized Patients with Cov-id-19. N Engl J Med. 2021;384:693-704.