Patients
This was a retrospective observational study carried out in Optics Valley Branch of Tongji Hospital. Consecutive discharged patients in Optics Valley Branch of Tongji Hospital treated by Fujian Medical Team aiding Hubei province were enrolled in the study between January 28, 2020 and March 30, 2020. Inclusion criteria were as follows: 1. COVID-19 patients who had clinical symptoms were confirmed by positive SARS-CoV-2 real-time RT-PCR results. 2. Patients had completed laboratory data of cytokines. Patients with age less than 18 years old were excluded. This retrospective study was approved by the Ethics Committee of Zhongshan Hospital, Xiamen University. Informed consent was obtained from patients involved before data were collected retrospectively.
Data collection
The medical records of all COVID-19 patients with positive SARS-CoV-2 real-time RT-PCR results were reviewed. The demographic data, comorbidities, clinical symptoms, signs, first time of laboratory findings during hospitalization, chest CT findings were collected. All data were checked by a team of trained physicians.
Grouping criteria
COVID-19 patients were classified as mild cases, moderate cases, severe cases, and critical ill cases according to the guidelines for diagnosis and management of COVID-19 (7th edition, in Chinese) released by National Health Commission of China. Mild cases: the clinical symptoms are mild and no pneumonia manifestation can be found in imaging. Moderate cases: patients have symptoms such as fever and respiratory tract symptoms, etc., and pneumonia manifestation can be seen in imaging. Severe cases: adults who meet any of the following criteria: respiratory rate ≥ 30 breaths/min; SpO2 ≤ 93% at rest; PaO2/FiO2 ≤ 300. Patients with greater than 50% lesion progression wihin 24 to 48 hours in pulmonary imaging were also defined as severe cases. Critically ill cases: patients who meet any of the following criteria: occurrence of respiratory failure requiring mechanical ventilation; presence of shock; other organ failure that requires monitoring and treatment in the ICU. We further group mild cases as COVID-19 without pneumonia and moderate cases, severe cases, critical ill cases as COVID-19 with pneumonia.
CT severity score
CT images were reviewed and scored independently by two respiratory and critical care physicians who were blinded to the clinical information in a consistent manner. CT severity score was evaluated based on the criteria as previously described [6, 7]. Briefly, each of the five lung lobes was assessed for percentage of the area involved. It was defined as none (0%), minimal (1–25%), mild (26–50%), moderate (51–75%), or severe (76–100%), with corresponded lobe score of 0, 1, 2, 3, 4, respectively. A CT severity score was calculated by summing the five lobe scores. The total score ranges from 0 to 20.
Cytokine measurement
Blood samples were collected from the patients on admission or the second day after admission. Serum cytokines including IL-1β, IL-2R, IL-6, IL-8, IL-10, and TNF-α were measured using chemiluminescent immunoassay (CLIA) by Siemens Immulite 1000 analyzer according to the manufacturer’s instructions.
Statistical analysis
Data analyses were performed using SPSS v 22.0 (SPSS Inc., Chicago, IL). Normally distributed, skewed, and categorical data were described using mean ± SD, median (interquartile range), and number (percentage), respectively. Student’s t test was conducted for two group comparison when variables were normally distributed; otherwise, the Mann–Whitney test was used. One-way ANOVA test was conducted for multiple group comparison when variables were normally distributed; otherwise, the Kruskal–Wallis H(K) test was used. Chi-square test or Fisher exact test were used to compare categorical variables. Spearman rank test was performed to test correlations between variables. In order to determine the independent predictors of lung injury, stepwise multiple linear regression analysis was performed. All descriptive data not in normal distribution were log-transformed before multivariate analysis. Statistical significance was determined as p < 0.05.
