Demographic and Clinical Characteristics
A total of 208 severe patients with COVID-19 were included in this study. Based on whether treated with ribavirin, patients were divided into two groups. The ribavirin group has 68 patients. Among them, 29 patients were treated with the regimen of ribavirin and interferon, and 26 patients received the regimen of ribavirin and lopinavir/ritonavir. There were 140 patients without ribavirin treatment.
The median age of patients was 62 years (IQR, 52-70 years), and 51.4% of the patients were men. 121 (58.2%) patients had chronic illness: 66 (31.7%) had hypertension, 53 (25.5%) had diabetes, 34 (16.4%) had heart disease, 19 (9.1%) had cancer. A few patients had liver or kidney disease. The most common symptoms before admission were fever (78.4%), cough (70.2%), expectoration (30.8%) and dyspnea (58.2%), and diarrhea (13.5%). Demographic and clinical features are shown in Table 1 and Supplementary Table 1. The median interval time between symptom onset and admission was 12 days (IQR, 7 to 15 days). There were no significant between-group differences in demographic characteristics, baseline laboratory test results, distribution of ordinal scale scores at enrollment, except coexisting diseases especially cancer (ribavirin group vs no ribavirin group, P = 0.014). In terms of treatment approaches, most of them received the treatment of arbidol, respiratory support, antibiotic agents, expectorants, and immunopotentiators. Some were given with chloroquine, Lianhua Qingwen, XUE BI JING injection, and glucocorticoid. There were no between-group differences in treatment (Table 2).
Outcome
The time to clinical improvement, defined as the time from admission to an improvement of two points on the seven-category ordinal scale, was used as the primary endpoint to assess the primary outcome of treatments [9]. Patients with failure to reach clinical improvement or death before day 28 were considered as right-censored at day 28. The median time to clinical improvement was 22 days in the ribavirin group, 23 days in the ribavirin and lopinavir/ritonavir group, 27 days in the ribavirin and interferon group, as compared with 22 days in the no ribavirin group (P = 0.483; P = 0.562; P = 0.483) (Table 3). There were no differences in the cumulative improvement rate between-group (ribavirin group vs no ribavirin group: P = 0.483, HR = 0.884, 95% CI = 0.627-1.247; ribavirin and lopinavir/ritonavir group vs no ribavirin group: P = 0.560, HR = 0.862, 95% CI = 0.522-1.421; ribavirin and interferon group vs no ribavirin group: P = 0.483, HR = 0.239, 95% CI= 0.457-1.216) (Figure 1). No significant differences were observed in the score on a seven-category scale at day 7, 14 (Table 3).
The time from admission to throat swab SARS-CoV-2 nucleic acid negative conversion was used to assess the secondary outcome of different treatments. A total of 167 patients reached a negative conversion of the SARS-CoV-2 virus.The median duration for a patient with positive SARS-CoV-2 from admission was 10 days in the ribavirin group, 13 days in the ribavirin and lopinavir/ritonavir group, 13 days in the ribavirin and interferon group, as compared with 10 days in the no ribavirin group (P = 0.533; P = 0.764; P = 0.255) (Table 3). There were no differences in the cumulative conversion of SARS-CoV-2 nucleic acid between-group (ribavirin group vs no ribavirin group: P = 0.533, HR = 1.111, 95% CI = 0.797-1.549; ribavirin and lopinavir/ritonavir group vs no ribavirin group: P = 0.764, HR = 1.080, 95% CI = 0.653-1.786; ribavirin and interferon group vs no ribavirin group: P = 0.255, HR = 0.766, 95% CI = 0.484-1.212) (Figure 2). No significant differences were observed between-group in the number of patients with SARS-CoV-2 nucleic acid negative conversion at day 7, 14 and 28 (Table 3).
There were 16 (23.53%) deaths in the ribavirin group, 8 (30.77%) deaths in the ribavirin and lopinavir/ritonavir group, 6 (20.69%) deaths in the ribavirin and interferon group, and 25 (17.86%) deaths in the no ribavirin group. There were no differences in the survival rate (ribavirin group vs no ribavirin group: P = 0.437, HR = 1.282, 95% CI = 0.685-2.402; ribavirin and lopinavir/ritonavir group vs no ribavirin group: P = 0.196, HR = 1.692, 95% CI = 0.763-3.751; ribavirin and interferon group vs no ribavirin group: P = 0.794, HR = 1.126, 95% CI = 0.462-2.745) (Figure 3). The mortality at day 7, 14 and 28, duration of hospitalization and clinical symptoms during inpatient were no differences between-group (Table 3).