A combination of remdesivir plus dexamethasone was associated with a significant reduction in mortality compared with dexamethasone alone among people hospitalized with COVID-19 across all baseline oxygen requirements, according to a large retrospective study.

Findings from the study of more than 33 000 individuals hospitalized with COVID-19 when Omicron was the most dominant variant in the US showed that the combination therapy was associated with lower mortality risk at 14 and 28 days across all levels of baseline respiratory support ranging from no supplemental oxygen to invasive mechanical ventilation/extracorporeal membrane oxygen (IMV/ECMO) compared to monotherapy with dexamethasone.

“Much of the more commonly cited evidence regarding effectiveness of COVID-19 therapies and clinical treatment decisions is based on data obtained in the early stages of the pandemic even though the evidence has evolved considerably,” researchers wrote in the study published online in Clinical Infectious Diseases.

To better understand more recent trends, investigators analyzed data from the PINC AI Healthcare Database, which represents approximately 25% of yearly inpatient hospitalizations in the US, according to the study. They identified adults hospitalized with COVID-19 who received either remdesivir plus dexamethasone or dexamethasone alone between December 2021 and April 2023.

Using propensity score matching, 33 037 individuals who received remdesivir plus dexamethasone were matched in a 1:1 ratio to those who received dexamethasone monotherapy and stratified by baseline oxygen requirements. For both groups, most participants (72%) were aged 65 years and older and White (78%), and 45% did not receive supplemental oxygen at baseline. Among people who did receive supplemental oxygen, 37% received low-flow oxygen (LFO), 16% had high-flow oxygen/noninvasive mechanical ventilation (HFO/NIV), and 2% got IMV/ECMO, according to researchers.

Findings

Results showed that, at 14 days, treatment with remdesivir plus dexamethasone was associated with a lower mortality risk compared with dexamethasone monotherapy overall (adjusted HR [aHR] 0.74, 95% CI 0.69-0.79) and across all baseline oxygen requirements: no supplemental oxygen (aHR 0.79, 95% CI 0.72-0.87), LFO (aHR 0.70, 95% CI 0.64-0.77), HFO/NIV (aHR 0.69, 95% CI 0.62-0.76), and IMV/ECMO (aHR 0.78, 95% CI 0.64-0.94).

Investigators observed similar results at 28 days:

• Overall: aHR 0.76 (95% CI 0.72-0.81)
• No supplemental oxygen: aHR 0.80 (95% CI 0.74-0.88)
• LFO: aHR 0.74 (95% CI 0.68-0.81)
• HFO/NIV: aHR 0.71 (95% CI 0.65-0.78)
• IMV/ECMO: aHR 0.81 (95% CI 0.69-0.97)

Investigators also compared guideline recommendations for the use of remdesivir plus dexamethasone and dexamethasone monotherapy to use observed in this real-world clinical practice setting. They found that 35% did not received remdesivir or dexamethasone in the first 2 days of hospitalization despite guidelines that recommend the combination therapy in the majority of individuals hospitalized. Among people who did not receive supplemental oxygen at baseline, 63% received remdesivir plus dexamethasone and 37% received dexamethasone monotherapy, despite recommendations against dexamethasone use in these patients.

These findings, researchers reported, “reinforce the recent evidence from [real-world data] supporting the use of antiviral treatment for hospitalized COVID-19 patients across all oxygen levels and the need to update and clarify clinical treatment guidelines.”

Reference: Mozaffari E, Chandak A, Gottlieb RL, et al. Lower mortality risk associated with remdesivir + dexamethasone versus dexamethasone alone for the treatment of patients hospitalized for COVID-19. Clin Infect Dis. Published online September 20, 2024. doi:10.1093/cid/ciae477