This study investigated the clinical characteristics and risk factors of coronavirus disease 2019 (COVID-19) in patients in designated hospitals (Port Hospital) in the Henan province. A total of 391 COVID-19 patients with complete case information from August 6, 2021 to February 26, 2022 were selected. Logistic regression was used to analyze the differences between the clinical types, ages, and sex of the patients. Multivariate regression analysis of the severe group indicated that underlying diseases [odds ratio (OR):6.76, 95% confidence interval (CI):1.83–24.93], increased urea levels (OR: 1.41, 95% CI: 1.04–1.91), old age (OR: 1.05, 95% CI: 1.00–1.10), and increased lactic dehydrogenase (OR: 1.02, 95% CI: 1.01–1.03) levels and decreased hemoglobin (OR: 0.95, 95% CI: 0.91–1.00) levels were predictors of illness severity. Multivariate regression analysis for those > 50 years of age showed that underlying diseases (OR: 7.06, 95% CI: 2.79–17.89) and increased urea (OR: 1.91, 95% CI: 1.47–2.48), total bilirubin (OR: 1.14, 95% CI: 1.08–1.21), total protein (OR: 1.08, 95% CI: 1.00–1.17), and lactic dehydrogenase (OR: 1.01, 95% CI: 1.00–1.02) levels and decreased albumin (OR: 0.66, 95% CI: 0.58–0.76) levels were characteristics of COVID-19. Multivariate regression analysis stratified by sex showed that the characteristics of COVID-19 patients were increased white blood cell count in males (OR: 0.66, 95% CI: 0.55–0.78) as well as increased creatinine levels (OR: 0.89, 95% CI: 0.87–0.91). This retrospective analysis provides useful information to support the clinical management of patients with COVID-19.