Clinical Characteristics of COVID-19 Patients at Different Epidemic Stages in Zhejiang, China

Background: At present, COVID-19 is the most serious threat to global public health. It is important to understand COVID-19 from different perspectives. Evidence is needed to determine whether there are differences in the clinical characteristics of COVID-19 patients as the SARS-CoV-2 virus continues to circulate in the population.Methods: This is a retrospective, multi-center cohort study. All adult cases with laboratory-confirmed COVID-19 from four hospitals in Zhejiang, China were enrolled in this study. Based on epidemiological history, patients were clustered into 3 groups. They included first-generation patients who had a clear travel history to Hubei within 14 days before disease onset; second generation patients who had a clear contact history with first-generation patients; third-generation patients who had a clear contact history with second-generation patients. Demographic, clinical characteristics, radiological features, laboratory data, clinical outcomes, and duration of viral shedding were then analyzed.Findings: Total of 171 patients with COVID-19 (aged 50.5±15.2 years, 92 males (53.8)) were enrolled. Third generation patients were older ( P <0.001), had more coexisting conditions ( P =0.013), a higher level of urea nitrogen ( P <0.05) and significantly higher CURB-65 scores ( P =0.004) compared to the other two groups. At 7±1 days from illness onset, white blood cell counts decreased in 26.9% of patients, lymphocyte counts decreased in 50.3% of patients, and platelet counts decreased in 11.4% of patients. Lung CT scans indicated that 66.1% of patients had a wide range of lesions that involved 4-5 pulmonary lobes. Third generation patients had lower lymphocyte and platelet levels ( P =0.007), higher C-reactive protein ( P =0.007) and D-dimer levels ( P =0.002), and more lesions involving the pulmonary lobes as determined by lung CT scans ( P <0.001). The proportion of third-generation patients who developed severe illness ( P <0.001), critical illness ( P <0.001) and received endotracheal intubation ( P =0.002) were significantly higher compared to the other two groups. No significant differences were observed between the three groups for the mean time from onset to severe or critical illness, distribution of endotracheal intubation and ECMO treatment, SARS-CoV-2 RNA negative conversion in the respiratory tract.Interpretation: Third generation patients were older, had more underlying comorbidities and had a higher proportion of severe or critical illness compared to first and second-generation patients. Baseline characteristics and clinical procedures in first- and second-generation patients were similar. We did not observe evidence of decreased virulence after the SARS-CoV-2 virus had passed through the population in Zhejiang, China.Funding Statement: This work was supported by a grant for COVID-19 from Jiaxing Science and Technology Bureau (2020GZ30001) and a grant from the National Natural Science Foundation of China (81971897). The research funding was provided to Dr. Hua Zhou.Declaration of Interests: All authors declare no conflicts of interest.Ethics Approval Statement: The study was approved by the Research Ethics Commission of The First Affiliated Hospital, School of Medicine, Zhejiang University (IIT20200129A), and supported by the Research Ethics Commissions of the other three hospitals. Due to the urgency to collect data on this emerging pathogen, the requirement for informed consent was waived by the Ethics Commission.