Remdesivir plus Dexamethasone in COVID-19: A cohort study of severe patients requiring high flow oxygen therapy or non-invasive ventilation

Abstract

Introduction: Remdesivir and Dexamethasone represent the cornerstone of therapy for critically ill patients with acute hypoxemic respiratory failure caused by Coronavirus Disease 2019 (COVID-19). However, clinical efficacy and safety of concomitant administration of Remdesivir and Dexamethasone (Rem-Dexa) in severe COVID-19 patients on high flow oxygen therapy (HFOT) or non-invasive ventilation (NIV) remains unknown.

Materials and methods: Prospective cohort study that was performed in two medical Intensive Care Units (ICUs) of a tertiary university hospital. The clinical impact of Rem-Dexa administration in hypoxemic patients with COVID-19, who required NIV or HFOT and selected on the simplified acute physiology score II, the sequential organ failure assessment score and the Charlson Comorbidity Index score, was investigated. The primary outcome was 28-day intubation rate; secondary outcomes were end-of-treatment clinical improvement and PaO2/FiO2 ratio, laboratory abnormalities and clinical complications, ICU and hospital length of stay, 28-day and 90-day mortality.

Results: We included 132 patients and found that 28-day intubation rate was significantly lower among Rem-Dexa group (19.7% vs 48.5%, p<0.01). Although the end-of-treatment clinical improvement was larger among Rem-Dexa group (69.7% vs 51.5%, p = 0.05), the 28-day and 90-day mortalities were similar (4.5% and 10.6% vs. 15.2% and 16.7%; p = 0.08 and p = 0.45, respectively). The logistic regression and Cox-regression models showed that concomitant Rem-Dexa therapy was associated with a reduction of 28-day intubation rate (OR 0.22, CI95% 0.05-0.94, p = 0.04), in absence of laboratory abnormalities and clinical complications (p = ns).

Conclusions: In COVID-19 critically ill patients receiving HFO or NIV, 28-day intubation rate was lower in patients who received Rem-Dexa and this finding corresponded to lower end-of-treatment clinical improvement. The individual contribution of either Remdesevir or Dexamethasone to the observed clinical effect should be further investigated.

Fig 1. Oxygen support on Day 11, 14 and 28 in patients treated with Remdesevir-Dexamethasone and during first wave.

Rem: Remdesevir; Dexa: Dexamethasone; NIV: non-invasive ventilation; HFO: high-flow oxygenation; IMV: invasive mechanical ventilation; ECMO: extracorporealmembrane oxygenation. Oxygen-support status is derived from the clinical status according to the seven-point ordinal scale, as follows: 1, death; 2, receiving invasive mechanical ventilation; 3, receiving high-flow oxygen or non-invasive ventilation; 4, receiving low-flow oxygen; 5 or 6, breathing ambient air; and 7, discharge.

Fig 2. Kaplan-Meier curve showing the impact of Remdesevir-Dexamethasone treatment (grey line) on 28-day intubation rate and mortality.

A: Kaplan-Meier curve showing the impact of Remdesevir-Dexamethasone treatment (grey line) on 28-day intubation rate. The multivariate Cox-regression model showed 28-day ETI rate to be reduced with Remdesevir-Dexamethasone (Rem-Dexa) treatment (HR 0.31, 95% CI 0.16–0.61), and the difference in ETI rate between treatment groups was also found on Kaplan–Meier survival curve analysis (p< 0.001). B: Kaplan-Meier curve showing the impact of Remdesevir-Dexamethasone treatment (grey line) on 28-day mortality. The multivariate Cox-regression model did not show 28-day survival rate to be reduced with Remdesevir-Dexamethasone (Rem-Dexa) treatment (HR 0.33, 95% CI 0.09–1.18), and no significant difference in 28-day mortality rate between treatment groups was found on Kaplan–Meier survival curve analysis (p< 0.07).