Background The impacts of chronic airway diseases on coronavirus disease 2019 (COVID-19) are far from understood. Objective To explore the influence of asthma and chronic obstructive pulmonary disease (COPD) comorbidity on disease expression and outcomes, and the potential underlying mechanisms in COVID-19 patients. Methods A total of 961 hospitalized COVID-19 patients with a definite clinical outcome (death or discharge) were retrospectively enrolled. Demographic and clinical information were extracted from the medical records. Lung tissue sections from patients suffering from lung cancer were used for immunohistochemistry study of angiotensin-converting enzyme II (ACE2) expression. BEAS-2B cell line was stimulated with various cytokines. Results In this cohort, 21 subjects (2.2%) had COPD and 22 (2.3%) had asthma. After adjusting for confounding factors, COPD patients had higher risk of developing severe illness (OR: 23.433; 95% CI 1.525-360.135;P < .01) and acute respiratory distress syndrome (OR: 19.762; 95% CI 1.461-267.369;P = .025) than asthmatics. COPD patients, particularly those with severe COVID-19, had lower counts of CD4(+)T and CD8(+)T cells and B cells and higher levels of TNF-alpha, IL-2 receptor, IL-10, IL-8, and IL-6 than asthmatics. COPD patients had increased, whereas asthmatics had decreased ACE2 protein expression in lower airways, compared with that in control subjects without asthma and COPD. IL-4 and IL-13 downregulated, but TNF-alpha, IL-12, and IL-17A upregulated ACE2 expression in BEAS-2B cells. Conclusion Patients with asthma and COPD likely have different risk of severe COVID-19, which may be associated with different ACE2 expression.