Objectives: No specific treatment has been approved for COVID-19. Lopinavir/ritonavir (LPV/r) and hydroxychloroquine (HCQ) have been used with poor results, and a trial showed advantages of combined antiviral therapy vs. single antivirals. The aim of the study was to assess the effectiveness of the combination of antivirals (LPV/r and HCQ) or their single use in COVID-19 hospitalized patients vs. standard of care (SoC). Methods: Patients ≥18 years with SARS-CoV-2 infection, defined as positive RT-PCR from nasal/oropharyngeal (NP/OP) swab or positive serology, admitted at L. Spallanzani Institute (Italy) were included. Primary endpoint: time to invasive ventilation/death. Secondary endpoint: time to two consecutive negative SARS-CoV-2 PCRs in NP/OP swabs. In order to control for measured confounders, a marginal Cox regression model with inverse probability weights was used. Results: A total of 590 patients were included in the analysis: 36.3% female, 64 years (IQR 51–76), and 91% with pneumonia. Cumulative probability of invasive ventilation/death at 14 days was 21.2% (95% CI 17.6, 24.7), without difference between SOC, LPV/r, hydroxychloroquine, HCQ + LPV/r, and SoC. The risk of invasive ventilation/death in the groups appeared to vary by baseline ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2). Overall cumulative probability of confirmed negative nasopharyngeal swabs at 14 days was 44.4% (95% CI 38.9, 49.9), without difference between groups. Conclusion: In this retrospective analysis, we found no difference in the rate of invasive ventilation/death or viral shedding by different strategies, as in randomized trials performed to date. Moreover, even the combination HCQ + LPV/r did not show advantages vs. SoC.
【저자키워드】 Drug repurposing, SARS-CoV-2, antivirals, viral shedding, invasive ventilation, 【초록키워드】 COVID-19, antiviral therapy, Trial, Hydroxychloroquine, Antiviral, Pneumonia, SARS-COV-2 infection, randomized trial, risk, oxygen, Italy, Probability, Nasopharyngeal swab, swabs, female, Patient, Effectiveness, Retrospective analysis, HCQ, Swab, group, positive RT-PCR, Combination, SARS-CoV-2 PCR, Standard of care, Cox regression model, paO2/fiO2, 95% CI, fractional inspired oxygen, no difference, confounders, specific treatment, positive serology, SOC, secondary, invasive, cumulative probability, defined, performed, was used, approved, hospitalized patient, groups, baseline, IQR, 【제목키워드】 Lopinavir/ritonavir, Standard,