COVID-19 exhibits both variability and rapid progression, particularly in patients with comorbidities such as diabetes, hypertension or cancer. To determine how these underlying disorders exacerbate pneumonia in COVID-19, we evaluated 79 patients with severe COVID-19 and grouped them according to whether or not they had comorbidities. Clinical information, laboratory examinations, immunological function, and treatment outcomes were retrospectively analyzed. Our study revealed that severe COVID-19 patients with comorbidities had higher levels of inflammatory indices, including blood interferon-γ, interleukin (IL)-6 and c-reactive protein levels as well as the erythrocyte sedimentation rate. These were accompanied by lymphopenia, hypokalemia, hypoalbuminemia, a decrease in either CD4+ T cells or lymphocyte count, and coagulation disorders, which were closely related to poor prognosis. Patients with comorbidities also had longer disease remission times (27 ± 6.7 days) than those without comorbidities (20 ± 6.5 days). Cox multivariate analysis indicated that glucocorticoid therapy and IL-6 were independent prognostic factors. Our findings suggest that coexisting comorbidities aggravate COVID-19 through the excessive release of inflammatory factors and that glucocorticoid therapy may be beneficial.