Factors associated with dexamethasone efficacy in COVID-19. A retrospective investigative cohort study

Abstract

Dexamethasone has demonstrated efficacy in reducing mortality in COVID-19. However, its practical use is badly defined. We aimed to investigate factors associated with dexamethasone efficacy in real life. Our retrospective study was conducted in two university hospitals between September and November 2020 and included all the consecutive hospitalized patients with a laboratory-confirmed SARS-CoV-2 infection assessed by RT-PCR, treated with intravenous dexamethasone (6 mg/day). Among 111 patients, 10.6% necessitated a transfer into the intensive care unit (ICU) and the 28-day mortality rate was 17.1%. The 28-day mortality rate was significantly lower in patients who demonstrated improvement at 48 h (hazard ratio [HR]: 0.17, 95% confidence interval [CI]: 0.04-0.78, p = 0.02) and 96 h (HR: 0.07, 95% CI: 0.02-0.31, p = 0.0005) after dexamethasone initiation. Apart from well-known risk factors (age, hypertension, active cancer, severe lesions on chest computed tomography [CT] scan), we found that a high viral load in nasopharyngeal swab (Cycle threshold <30) at dexamethasone initiation was associated with higher 28-day mortality (66.6% vs. 36.7%, p = 0.03). Patients who did not receive antibiotics at dexamethasone initiation had a higher rate of transfer into the ICU (55.6% vs. 23.5%, p = 0.045) with a trend towards higher mortality in case of severe or critical lesions on CT scan (75.0% vs. 25.0%, p = 0.053). Patients who did not improve within 2-4 days after steroid initiation have a bad prognosis and should receive additional anti-inflammatory drugs. Our data suggest better efficacy of dexamethasone in patients with a low or negative viral load, receiving broad-spectrum antibiotics.

Keywords: COVID-19; antibiotics; dexamethasone; intensive care unit; mortality.

Figure 1

Kaplan–Meier survival curve for 28‐day cumulative survival rates. Comparison (using stratified log‐rank tests) between patients with a good and a poor response 48 h (A) and 96 h (B) after dexamethasone initiation

Figure 2

Kaplan–Meier survival curve for 28‐day cumulative survival or transfer into ICU. Comparison (using stratified log‐rank tests) between patients with a good and a poor response 48 h (A) and 96 h (B) after dexamethasone initiation. ICU, intensive care unit

Figure 3

Viral load at dexamethasone initiation as a predictor of 28‐day mortality. Kaplan–Meier survival curve for 28‐day cumulative survival rates. Comparison (using stratified log‐rank tests) between patients with a cycle threshold ≥ or <30 on nasopharyngeal SARS‐CoV2 RT‐PCR at dexamethasone initiation

Figure 4

Large‐spectrum antibiotic treatment at the time of dexamethasone initiation as a predictor of transfer into the ICU. Kaplan‐Meier survival curve for 28‐day transfer into the ICU rates. Comparison (using stratified log‐rank tests) between patients receiving large‐spectrum antibiotics or not at dexamethasone initiation. ICU, intensive care unit