Subjects and study design
The research protocol of this single-center, retrospective cohort study conformed to the principles of the Declaration of Helsinki and was approved by the institutional ethics board of West China Hospital of Sichuan University (No.2020-126). Written informed consent was collected from all patients. Patients diagnosed with laboratory-confirmed COVID-19 infection in Wuhan Red Cross hospital during the period from January 23, 2020 to March 19, 2020 were included. Nasopharyngeal swabs of upper respiratory tract were collected from all patients by two investigators (Tao Liu and Yanbin Liu), and patients enrolled in this study were diagnosed according to the following criteria based on WHO recommendation: isolation of COVID-19 or at least two positive results by reverse-transcription-polymerase-chain-reaction (RT-PCR) assay for COVID-19 or a genetic sequence that matched COVID-19 . Eligible patients were those aged 18 years or older. Patients who were intubated, who died, or who were transferred to another hospital within 24 hours after admission were excluded. Patients receiving oral LPV/r were classified as LPV/r group, while those given LPV/r and subcutaneous injection of IFN alpha-2b were assigned into combination group.
Treatments during the epidemic were empirical. All eligible patients rested in bed in the isolation wards and daily sufficient caloric intake, balance of water-electrolyte and stability of internal environment were ensured. Oxygen therapy was given according to each patient’s oxygen saturation. Antibiotics were only administered in patients with combined bacterial infection. For anti-viral treatment, LPV/r group were given oral lopinavir/ritonavir tablets (Abb-Vie Ltd, North Chicago, IL, USA; 200mg/50mg/ pill), 400 mg/ time, twice a day, and combination group were supplemented with subcutaneous injection of IFN alpha-2b (3SBIO Inc, Shenyang, China; 3 million IU/ dose), 3 million IU/time, qod, in addition to LPV/r treatment. The course of LPV/r treatment was 10 days, while IFN was used until the virus was detected negative by RT-PCR in two consecutive respiratory specimens (≥1 day apart). In addition to regular clinical monitoring (body temperature, respiratory rate, blood pressure, pulse, symptoms and signs), blood count, liver enzymes and renal function were assessed at baseline and throughout the treatment course. Two investigators (Bo Wang and Yanbin Liu) obtained all clinical information, including demographic data, medical history, co-morbidities symptoms, signs, laboratory findings and management from electronic medical records of Wuhan Red-cross Hospital.
The primary outcomes were the length of hospitalization and the time to viral clearance of SARS-CoV-2 in the upper respiratory tract from hospital admission. The secondary outcomes included adverse effects, ICU admission rate, and hospital mortality during the treatment.
Continuous variables were presented as mean ± standard deviation (SD), while categorical variables were presented as counts and percentages. Means for continuous variables were compared using independent t test when the data were normally distributed; otherwise, the Mann-Whitney test was used. Proportions for categorical variables were compared using the χ2 test or Fisher-Exact test when appropriate. Time to viral clearance, defined as the days from hospital admission to the first negative PCR of two negative consecutive PCR tests, was portrayed by Kaplan-Meier plot and compared with a log-rank test. P <0.05 was considered statistically significant. All statistical analyses were performed by SPSS 25.0 for Windows (IBM, Chicago, IL, USA).