A Real-World Retrospective Study on the Efficacy and Safety of Four Antiviral Drugs for Hospitalized COVID-19 Patients: Nirmatrelvir/Ritonavir, Simnotrelvir/Ritonavir, Molnupiravir and Azvudine

Ximiao Yu,1,&ast; Ruiqi Luo,2,&ast; Guijuan Xie,2 Jiali Ji,3,4 Jiehong Wang,1 Xiyue Li,3 Xiaojun Qian,2 Xun Wang1,2,5 1Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu Province, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Jiangnan University Medical Center, Jiangnan University (Wuxi No.2 People’s Hospital), Wuxi, Jiangsu Province, People’s Republic of China; 3Department of Pulmonary and Critical Care Medicine, The Affiliated Wuxi No. 2 People’s Hospital of Nanjing Medical University, Wuxi, Jiangsu Province, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, The First People’s Hospital of Changzhou, Changzhou, Jiangsu Province, People’s Republic of China; 5Department of Medicine, Nantong University, Nantong, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xun Wang, Department of Pulmonary and Critical Care Medicine, Jiangnan University Medical Center, Jiangnan University (Wuxi No.2 People’s Hospital), Wuxi, Jiangsu Province, 214126, People’s Republic of China, Email 081104125@fudan.edu.cnPurpose: This retrospective study aims to compare the effectiveness and safety of four oral antiviral drugs including Simnotrelvir/Ritonavir, Nirmatrelvir/Ritonavir, Azvudine and Molnupiravir in hospitalized patients with Coronavirus Disease 2019 (COVID-19) in a real-world setting, providing evidence to guide clinical practice against COVID-19.Patients and Methods: Patients with mild or moderate COVID-19 hospitalized at Wuxi City’s Second People’s Hospital during December 2022 to June 2023 were included in this study. Patients were grouped by the antiviral drug received. The primary endpoint was the length of hospital stay. Patients were further divided into subgroups for stratified analysis, considering age, timing of medication, and drug mechanisms, to explore whether these factors could influence the treatment efficacy.Results: Of the enrolled 195 patients receiving any treatment, 42 received Nirmatrelvir/Ritonavir, 33 received Molnupiravir, 81 received Simnotrelvir/Ritonavir, and 39 received Azvudine. Patients in Nirmatrelvir/Ritonavir and Simnotrelvir/Ritonavir groups had significantly shorter hospital stays compared to those in Azvudine group (P < 0.05). No significant difference was observed in hospital stays between those initiating antiviral therapy within or more than five days after symptom onset (P = 0.1109). Among patients with comorbidities, the Nirmatrelvir/Ritonavir and Simnotrelvir/Ritonavir group showed shorter hospital stays than the Azvudine group (P < 0.05). No serious treatment-related adverse events were observed across the groups.Conclusion: In this retrospective study, Nirmatrelvir/Ritonavir and Simnotrelvir/Ritonavir exerts stronger potency on reducing duration of hospital stays in hospitalized patient with COVID-19, suggestive of a better choice for antiviral therapy. Patients who fail to take antiviral drugs in time after symptom onset would still benefit from these antiviral regimens. Additional well-designed clinical trials with large sample size are still needed to further confirm the effectiveness of these antivirals.Keywords: antivirals, COVID-19, molnupiravir, simnotrelvir/ritonavir, azvudine, nirmatrelvir/ritonavir