Corticosteroids do not avert mortality in severe, critical COVID-19 patients

Use of systemic corticosteroids does not reduce in-hospital mortality for patients with severe or critical coronavirus disease (COVID-19), which is in stark contrast to that observed in the RECOVERY clinical trial, according to a study in Wuhan, China.

“Absence of the beneficial effect in our study in contrast to that was observed in the clinical trial may be due to biases in observational data, in particular confounding by indication bias, differences in clinical characteristics of patients, choice of corticosteroid used, or timing of initiation of treatment and duration of treatment,” the researchers said.

A total of 1,514 severe and 249 critical hospitalized COVID-19 patients from two medical centres in Wuhan were included in this study. The researchers assessed the association of corticosteroid use with the risk of in-hospital mortality in severe and critical cases using multivariable Cox models, Cox model with time-varying exposure and propensity score analysis (inverse-probability-of-treatment-weighting [IPTW] and propensity score matching [PSM]).

Among hospitalized patients, 531 (35.1 percent) with severe and 159 (63.9 percent) with critical COVID-19 received corticosteroids. Compared to nonuse, use of systemic corticosteroid was not associated with reductions in in-hospital mortality in either severe (hazard ratio [HR], 1.77, 95 percent confidence interval [CI], 1.08–2.89; p=0.023) or critical cases (HR, 2.07, 95 percent CI, 1.08–3.98; p=0.028). [J Clin Endocrinol Metab 2020;105:dgaa627]

Time-varying Cox analysis showed similar results. Furthermore, corticosteroid use in patients with severe COVID-19 at admission resulted in neither improved nor harmful outcome in either PSM or IPTW analysis. Findings for critical patients at admission were consistent in multivariable Cox model analysis.

Several reasons explain why these results conflict with those from the RECOVERY trial, according to the researchers. First, the baseline conditions of patients were different between treated and untreated cases due to the retrospective and nonrandomized nature of the current study.

Second, prednisone was used by most patients in this study as opposed to dexamethasone. Although both agents are glucocorticoids, dexamethasone is four to five times more potent than prednisone and >20 times more potent than naturally occurring hormone cortisol. [N Engl J Med 2005;353:1711-1723]

Finally, durations and doses of corticosteroid therapy were different between the two studies. In the current analysis, dexamethasone 7.5 mg was initiated at the onset of severe illness for a median of 5 days. In the RECOVERY trial, dexamethasone 6 mg was administered for 7 days.

“The rationale for corticosteroid use includes its potential role in suppressing inflammatory storm, reducing inflammatory exudation, and preventing multiple organ injuries in acute respiratory failure,” the researchers said. “However, its multifaceted negative impacts on prognosis should not be overlooked.”

In other recent studies, the viral load of SARS-CoV-2, the causative agent of COVID-19, significantly exacerbated the severity of the disease. Corticosteroids may suppress immunity and promote virus replication, further worsening prognosis. [Sci China Life Sci 2020;63:364-374; BMJ 2014;348:g1721]

“Our results showed that median lymphocyte count remained low during the use of systemic corticosteroids, which might lead to a higher risk of superinfections,” the researchers said. “Systemic corticosteroids could also induce hyperglycaemia, which was shown to be an independent risk factor for the prognosis of infection and critically ill patients.” [J Clin Endocrinol Metab 2015;100:4490-4497; Crit Care Med 2020;48:e115-e122; Diabetes Metab J 2013;37:385-390]

Use of corticosteroids was also associated with complications in the elderly population. In the present cohort, the median age of severe and critical COVID-19 patients was 61.0 and 68.0 years, respectively. [Gastroenterology 2014;147:784-792.e9; Ann Intern Med 2004;141:764-770]