Study design and patient populations
This retrospective analysis was conducted using data collected between Jan 21, 2020 and Feb 25, 2020 from Ningbo First Hospital (Zhejiang Province, China) and Jingzhou Central Hospital (Hubei Province, China). Patients with laboratory confirmed diagnoses of SARS-CoV-2 and had been admitted to one of the above medical centers were included. All patients were identified by positive results of reverse transcriptase polymerase chain reaction (RT-PCR) on SARS-CoV-2 in lower respiratory specimens. Patients enrolled presented with mild to moderate SARS-CoV-2 pneumonia at baseline. To avoid potential effects of antiviral drugs, the largest cohort of patients were selected for analysis; all were initiated on combination therapy of arbidol and Kaletra. Ethical approvals for this study were obtained from the Ethics Commission of Ningbo First Hospital (2020 - R017) and the Ethics Commission of Jingzhou Central Hospital (2020–2 - 19). Written informed consent was waived due to the rapid emergence of this disease and approved by the local ethics committee.
Patients’ electronic medical records were reviewed to extract the following information retrospectively. The following data were collected: Demographic characteristics: age, gender and history of chronic disease; Symptoms: temperature, cough, dyspnea, score throat, muscle soreness, fatigue, anorexic, nausea and diarrhea; Laboratory assessments on admission: white blood cell count, peripheral blood lymphocyte (PBL), D-dimer, Alanine aminotransferase (ALT), Aspartate Aminotransferase (AST) and C-reactive protein (CRP); Dates of important events: onset of symptoms, onset of antiviral therapy, admission to hospital time, discharge or death and the date of negative result of viral nucleic acid test; Details of therapeutic regimen: antiviral medicines and use of corticosteroids.
The severity scores were calculated within 48 h of hospital admission. Patients were divided into two cohorts according to the version of Diagnosis and Treatment of Pneumonia Caused by COVID-19 (version 6) issued by National Health Commission of the People’s Republic of China . Cohort 1, patients who did not convert to severe cases; Cohort 2, patients who converted to severe cases. Patients who met at least one of the following criteria were defined as the severe cases : (1). Respiratory rate ≥ 33/min; (2). Oxygen saturation ≤ 94% in resting state; (3). PO2/FiO2 ≤ 300 mmHg; (4). Developed respiratory failure and require mechanical ventilation; (5). Developed shock; (6). Multiple organ dysfunction and requiring ICU care. The duration (in days) from the start of antiviral therapy to clinical recovery was selected as the primary outcome measure. Clinical recovery is defined as the remission of clinical symptoms for at least 72 h, including normalization of respiratory rate (≤ 24/min on room air), oxygen saturation (> 94% on room air), fever (≤ 37 °C of axilla, ≤ 37·2 °C of oral) and cough (no cough or mild cough).
Continuous variables were expressed as mean (SD) or median (IQR) and categorical variables as quantity (proportion). The t-test or Mann-Whitney U test was used for comparison of continuous variables. The chi-squared (χ2) test was used to compare categorical variables. Logistic regression was performed to assess the usefulness of risk factors in predicting the patients with mild to moderate SARS-CoV-2 pneumonia who would convert to severe cases. The following factors were analyzed to determine their effects: age, sex, fever, time from onset of symptoms to antiviral treatment, comorbidities, CRP, PBL, and use of corticosteroids. Odds Ratios (ORs) and 95% confidence intervals (CIs) were estimated. A 2-sided α of < 0·05 was considered statistically significant. Statistical analyses were conducted using SPSS version 18·0 (SPSS, Chicago, IL, USA) and SAS version 9·4 (SAS Institute, Cary, North Carolina).