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(1) Background: Data on COVID-19 outcomes and disease course as a function of different medications used to treat cardiovascular disease and chronic kidney disease (CKD), as well as the presence of different comorbidities in primarily Black cohorts, are lacking. (2) Methods: We conducted a retrospective medical chart review on 327 patients (62.6% Black race) who were admitted to the Detroit Medical Center, Detroit, MI. Group differences (CKD vs. non-CKD) were compared using the Pearson χ2 test. We conducted univariate and multivariate regression analyses for factors contributing to death during hospitalization due to COVID-19 (primary outcome) and ICU admission (secondary outcome), adjusting for age, sex, different medications, and comorbidities. A sub-analysis was also completed for CKD patients. (3) Results: In the fully adjusted model, a protective effect of ACEi alone, but not in combination with ARB or CCB, for ICU admission was found (OR = 0.400, 95% CI [0.183–0.874]). Heart failure was significantly associated with the primary outcome (OR = 4.088, 95% CI [1.1661–14.387]), as was COPD (OR = 3.747, 95% CI [1.591–8.828]). (4) Conclusions: Therapeutic strategies for cardiovascular disease and CKD in the milieu of different comorbidities may need to be tailored more prudently for individuals with COVID-19, especially Black individuals.