Résumé
BACKGROUND: Early antiviral therapy was effective in the treatment of COVID-19. We assessed the efficacy and safety of combined interferon beta-1b and remdesivir treatment in hospitalized COVID-19 patients. METHODS: We conducted a multicentre, prospective open-label, randomized-controlled trial involving high-risk adults hospitalized for COVID-19. Patients were randomly assigned to a 5-day interferon beta-1b 16 million units daily and remdesivir 200mg loading on day 1 followed by 100mg daily on day 2 to 5 (combination-group), or to remdesivir only of similar regimen (control-group) (1:1). The primary end-point was the time to complete alleviation of symptoms (NEWS2 = 0). RESULTS: Two-hundred and twelve patients were enrolled. The median days of starting treatment from symptom-onset was 3 days. The median age was 65 years and 159 patients (75%) had chronic disease. The baseline demographics were similar. There was no mortality. For the primary-endpoint, the combination-group was significantly quicker to NEWS2 = 0 (4 versus 6.5 days; hazard-ratio [HR],6.59; 95% confidence-interval [CI],6.1-7.09; p < 0.0001) when compared to the control-group. For the secondary endpoints, the combination-group was quicker to negative NPS VL (6 versus 8 days; HR,8.16; 95% CI,7.79-8.52; p < 0.0001) and develop seropositive IgG (8 versus 10 days; HR,10.78; 95% CI,9.98-11.58; p < 0.0001). All adverse events resolved upon follow-up. Combination group (HR,4.1 95%CI,1.9-8.6, p < 0.0001), was the most significant independent factor associated with NEWS2 = 0 on day 4. CONCLUSIONS: Early treatment with interferon beta-1b and remdesivir was safe and better than remdesivir only in alleviating symptoms, shorten viral shedding and hospitalization with earlier seropositivity in high-risk COVID-19 patients.
Résumé
Introduction:Significant ventilator-associated pneumonia and mortality were found in COVID-19 patients who required mechanical ventilation which calls for non-invasive means in managing respiratory failure.Methods:We retrospectively reviewed patients admitted to the intensive care unit of Pamela Youde Nethersole Eastern Hospital in Hong Kong with severe acute respiratory syndrome coronavirus 2 infection from 28 November to 15 December 2020. Patients? laboratory, respiratory parameters and outcome data were recorded and analysed.Results:Eleven received prone ventilation. The median age was 67 (inter-quartile range: 59?72)?years, and median COVID-19 GRAM score was 151 (inter-quartile range: 133?181), representing a high-risk group. There were significant improvements 1?h after awake proning in SpO2 (95% vs 92%, p = 0.008), FiO2 (0.4 vs 0.5, p = 0.003), SpO2/FiO2 (240 vs 184, p = 0.005), respiratory rate (19 vs 26, p = 0.006) and respiratory rate ? oxygenation index (13.22 vs 7.67, p = 0.003;Table 1). Although not reaching statistical significance, the median PaO2, PaCO2 and PaO2/FiO2 improved after proning. The overall intubation rate was 22% and intensive care unit mortality was 22%, which is in contrast to 65.5% and 27.6%, respectively, in the first three waves. Although did not reach statistical significance, those received prone ventilation tend to have a lower ICU mortality (9.1% vs 42.9%, p = 0.245) and hospital mortality (18.2% vs 42.9%, p = 0.326).Conclusion:Awake proning potentially minimizes complications from invasive ventilation and provides a low-cost low-risk treatment option in COVID-19 patients with respiratory failure. This is particularly important when healthcare resources are strained at times of a pandemic.
Résumé
BACKGROUND: Effective antiviral therapy is important for tackling the coronavirus disease 2019 (COVID-19) pandemic. We assessed the efficacy and safety of combined interferon beta-1b, lopinavir-ritonavir, and ribavirin for treating patients with COVID-19. METHODS: This was a multicentre, prospective, open-label, randomised, phase 2 trial in adults with COVID-19 who were admitted to six hospitals in Hong Kong. Patients were randomly assigned (2:1) to a 14-day combination of lopinavir 400 mg and ritonavir 100 mg every 12 h, ribavirin 400 mg every 12 h, and three doses of 8 million international units of interferon beta-1b on alternate days (combination group) or to 14 days of lopinavir 400 mg and ritonavir 100 mg every 12 h (control group). The primary endpoint was the time to providing a nasopharyngeal swab negative for severe acute respiratory syndrome coronavirus 2 RT-PCR, and was done in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT04276688. FINDINGS: Between Feb 10 and March 20, 2020, 127 patients were recruited; 86 were randomly assigned to the combination group and 41 were assigned to the control group. The median number of days from symptom onset to start of study treatment was 5 days (IQR 3-7). The combination group had a significantly shorter median time from start of study treatment to negative nasopharyngeal swab (7 days [IQR 5-11]) than the control group (12 days [8-15]; hazard ratio 4·37 [95% CI 1·86-10·24], p=0·0010). Adverse events included self-limited nausea and diarrhoea with no difference between the two groups. One patient in the control group discontinued lopinavir-ritonavir because of biochemical hepatitis. No patients died during the study. INTERPRETATION: Early triple antiviral therapy was safe and superior to lopinavir-ritonavir alone in alleviating symptoms and shortening the duration of viral shedding and hospital stay in patients with mild to moderate COVID-19. Future clinical study of a double antiviral therapy with interferon beta-1b as a backbone is warranted. FUNDING: The Shaw-Foundation, Richard and Carol Yu, May Tam Mak Mei Yin, and Sanming Project of Medicine.