Timing of corticosteroids impacts mortality in hospitalized COVID-19 patients

Abstract

The optimal timing of initiating corticosteroid treatment in hospitalized patients is unknown. We aimed to assess the relationship between timing of initial corticosteroid treatment and in-hospital mortality in COVID-19 patients. In this observational study through medical record analysis, we quantified the mortality benefit of corticosteroids in two equally matched groups of hospitalized COVID-19 patients. We subsequently evaluated the timing of initiating corticosteroids and its effect on mortality in all patients receiving corticosteroids. Demographic, clinical, and laboratory variables were collected and employed for multivariable regression analyses. 1461 hospitalized patients with confirmed COVID-19 were analyzed. Of these, 760 were also matched into two equal groups based on having received corticosteroid therapy. Patients receiving corticosteroids had a lower risk of death than those who did not (HR 0.67, 95% CI 0.67-0.90; p = 0.01). Timing of corticosteroids was assessed for all 615 patients receiving corticosteroids during admission. Patients receiving first dose of corticosteroids > 72 h into hospitalization had a lower risk of death compared to patients with first dose at earlier time intervals (HR 0.56, 95% CI 0.38-0.82; p = 0.003). There was a mortality benefit in patients with > 7 days of symptom onset to initiation of corticosteroids (HR 0.56, 95% CI 0.33-0.95; p = 0.03). In patients receiving oxygen therapy, corticosteroids reduced risk of death in mechanically ventilated patients (HR 0.38, 95% CI 0.24-0.60; p < 0.001) but not in patients on high-flow or other oxygen therapy (HR 0.46, 95% CI 0.20-1.07; p = 0.07) and (HR 0.84, 95% CI 0.35-2.00; p = 0.69), respectively. Timing of corticosteroids initiation was related to in-hospital mortality for COVID-19 patients. Time from symptom onset > 7 days should trigger initiation of corticosteroids. In the absence of invasive mechanical ventilation, corticosteroids should be initiated if the patient remains hospitalized at 72 h. Hypoxia requiring supplemental oxygen therapy should not be a trigger for initiation of corticosteroids unless the timing is appropriate.

Keywords: COVID-19; Coronavirus; Corticosteroids; Mortality; Timing; Treatment.

Figure 1.

Kaplan-Meier survival curve for corticosteroids treatment. Figure shows overall survival for propensity score-matched patients treated with or without corticosteroids. The estimated survival curves were pooled from 20 imputed datasets

Figure 2.

Survival curve for the timing of corticosteroids treatment. Figure shows overall survival of study patients associated with the initial receipt of corticosteroids treatment during the hospitalization. The direct adjusted survival curves were estimated based on a multivariable analysis and pooled from 20 imputed datasets

Figure 3.

Survival curve for receipt of corticosteroids treatment by oxygen therapy. Figure shows overall survival of study patients associated with receipt of corticosteroids treatment for patients receiving oxygen therapy with different levels of oxygen requirement. The direct adjusted survival curves were estimated based on the inverse probability weighting of propensity score analyses and pooled from 20 imputed datasets