Early Stage Combination Treatment with Methylprednisolone Pulse and Remdesivir for Severe COVID-19 Pneumonia.

BACKGROUND: This study evaluated the clinical outcomes of patients with severe COVID-19 pneumonia treated with remdesivir plus standard corticosteroid treatment (SCT) or with remdesivir plus high-dose corticosteroid pulse therapy (HDCPT). METHODS: One hundred and two patients with severe COVID-19 pneumonia and respiratory failure were included. The patients were divided into two cohorts. The first comprised patients who received remdesivir and SCT, consisting of 6 mg dexamethasone daily for up to 10 days or until hospital discharge. The second included patients who received remdesivir and HDCPT, composed of 250 mg iv of methylprednisolone for three days, followed by a slow reduction in the dose of steroids. The severity of hypoxemia was assessed using the SaO2/FiO2 peripheral oxygen saturation index. RESULTS: 55 received remdesivir plus HDCPT, and 47 received remdesivir plus SCT. Mortality at 30 days was significantly lower among patients who received remdesivir plus HDCPT (4/55) than among those who did not (15/47). In patients who received remdesivir plus HDCPT, 7.3% required invasive mechanical ventilation and admission to the ICU and 36.4% non-invasive ventilation versus 29.8% and 61.7%, respectively, among those treated with remdesivir plus SCT. Remdesivir plus HDCPT induced a significantly faster improvement in the SaO2/FiO2 index. CONCLUSION: Early combination treatment with remdesivir plus HDCPT reduced in-hospital mortality and the need for admission to the ICU. Furthermore, it improved the SaO2/FiO2 index faster in patients with severe COVID-19 pneumonia.

The impact of obesity and dyslipidemia on Remdesivir effectiveness in hospitalized patients with SARS-CoV-2-related pneumonia: An observational study.

BACKGROUND AND AIMS: Remdesivir (GS-5734), an inhibitor of the viral RNA-dependent, RNA polymerase was early identified as a promising therapeutic candidate against COVID-19. Our aim was to evaluate the impact of several metabolic parameters on Remdesivir effectiveness among hospitalized COVID-19 patients. METHODS AND RESULTS: We conducted an observational study on patients with SARS-CoV-2-related pneumonia admitted between May 2020 and September 2021 to the COVID-19 Units of Internal Medicine, Pneumology and Intensive Care of Garibaldi Hospital, Catania, Italy, and treated with Remdesivir. The "Ordinal Scale For Clinical Improvement" was used to assess patients' clinical improvement within 28 days of hospitalization. Short-term mortality rate was also evaluated. A total of 142 patients with SARS-CoV-2-related pneumonia were studied. The prevalence of obesity (20.7% vs. 41.9%, p = 0.03), the average BMI (27.1 ± 4.4 vs. 31.1 ± 6.1, p < 0.01) and the mean LDL-C levels (78 ± 19 mg/dl vs. 103 ± 18 mg/dl, p = 0.03) were significantly lower in early-improved (EI) compared to not-improved (NI) individuals. Obesity was negatively associated to clinical improvement after Remdesivir (OR 0.48, 95%CI 0.17-0.97, p = 0.04). Both obesity (OR 2.82, 95% CI 1.05-7.71, p = 0.04) and dyslipidemia (OR 2.78, 95%CI 1.17-7.16, p = 0.03) were significantly related to patients' mortality. Dyslipidemic subjects experienced a slower clinical improvement than non-dyslipidemic ones (Long-Rank p = 0.04). CONCLUSION: Our study showed that unfavorable metabolic conditions such as obesity and dyslipidemia could predict a worse clinical response to Remdesivir as well as the mortality in hospitalized COVID-19 patients. Further prospective and larger-scale studies are needed to confirm these preliminary findings.