A vaccine against COVID-19 has been developed; however, COVID-19 transmission continues. Although there have been many studies of comorbidities that have important roles in COVID-19, some studies have reported contradictory results. This study was conducted using real-world data from COVID-19 patients in South Korea and aimed to investigate the impact of patient demographics and comorbidities on the infection rate and severity of COVID-19. Data were derived from a nationwide South Korean COVID-19 cohort study with propensity score (PS) matching. We included infected individuals who were COVID-19-positive between January 1, 2020, and May 30, 2020, and PS-matched uninfected controls. PS matching was performed to balance the baseline characteristics of each comorbidity and to adjust for potential confounders, such as age, sex, Charlson Comorbidity Index, medication, and other comorbidities, that were matched with binary variables. The outcomes were the confirmed comorbidities affecting the infection rate and severity of COVID-19. The endpoints were COVID-19 positivity and severe clinical outcomes of COVID-19 (such as tracheostomy, continuous renal replacement therapy, intensive care unit admission, ventilator use, cardiopulmonary resuscitation, and death). The COVID-19 cohort with PS matching included 8070 individuals with positive COVID-19 test results and 8070 matched controls. The proportions of patients in the severe group were higher for individuals 60 years or older (severe clinical outcomes for those 60 years or older, 16.52%; severe clinical outcomes for those of other ages, 2.12%), those insured with Medicaid (Medicaid, 10.81%; other insurance, 5.61%), and those with disabilities (with disabilities, 18.26%; without disabilities, 5.07%). The COVID-19 infection rate was high for patients with pulmonary disease (odds ratio [OR] 1.88; 95% CI 1.70-2.03), dementia (OR 1.75; 95% CI 1.40-2.20), gastrointestinal disease (OR 1.74; 95% CI 1.62-1.88), stroke (OR 1.67; 95% CI 1.23-2.27), hepatobiliary disease (OR 1.31; 95% CI 1.19-1.44), diabetes mellitus (OR 1.28; 95% CI 1.16-1.43), and cardiovascular disease (OR 1.20; 95% CI 1.07-1.35). In contrast, it was lower for individuals with hyperlipidemia (OR 0.73; 95% CI 0.67-0.80), autoimmune disease (OR 0.73; 95% CI 0.60-0.89), and cancer (OR 0.73; 95% CI 0.62-0.86). The severity of COVID-19 was high for individuals with kidney disease (OR 5.59; 95% CI 2.48-12.63), hypertension (OR 2.92; 95% CI 1.91-4.47), dementia (OR 2.92; 95% CI 1.91-4.47), cancer (OR 1.84; 95% CI 1.15-2.94), pulmonary disease (OR 1.72; 95% CI 1.35-2.19), cardiovascular disease (OR 1.54; 95% CI 1.17-2.04), diabetes mellitus (OR 1.43; 95% CI 1.09-1.87), and psychotic disorders (OR 1.29; 95% CI 1.01-6.52). However, it was low for those with hyperlipidemia (OR 0.78; 95% CI 0.60-1.00). Upon PS matching considering the use of statins, it was concluded that people with hyperlipidemia could have lower infection rates and disease severity of COVID-19.