To analyse susceptibility/risk of suffering COVID-19 among adults with distinct underlying medical conditions.Population-based cohort study involving 79,083 individuals ≥50 years old in Tarragona (Southern Catalonia, Spain). Baseline cohort characteristics (demographic, pre-existing comorbidities, chronic medications and vaccinations history) were established at study start (01/03/2020) and primary outcome was laboratory-confirmed COVID-19 occurred among cohort members throughout 01/03/2020-30/06/2020. Risk of suffering COVID-19 was evaluated by Cox regression, estimating multivariable hazard ratios (HRs) adjusted for age/sex and pre-existing comorbidities.Across study period, 536 laboratory-confirmed COVID-19 cases were observed (mean incidence: 39.5 cases per 100,000 persons-week). In multivariable-analysis, increasing age/years (HR: 1.01; 95% CI: 1.00-1.02), nursing-home (HR: 20.19; 95% CI: 15.98-25.51), neurological disease (HR: 1.35; 95% CI: 1.03-1.77), taking diuretics (HR: 1.39; 95% CI: 1.10-1.75), antiplatelet (HR: 1.36; 95% CI: 1.05-1.76) and benzodiazepines (HR: 1.24; 95% CI: 1.00-1.53) increased risk; conversely, taking angiotensin-converting-enzyme inhibitors (HR: 0.78; 95% CI: 0.61-1.00), angiotensin-receptor-blockers (HR: 0.70; 95%CI: 0.51-0.96) and statins (HR: 0.75; 95% CI: 0.58-0.96) were associated with reduced risk. Among community-dwelling individuals, pre-existing cancer, renal and cardiac disease appeared also related with an increased risk, whereas influenza vaccination was associated with reduced risk.In a setting with relatively low incidence of COVID-19 across the first wave of pandemic period, increasing age, nursing-home residence and multiple comorbidities appear predisposing for COVID-19 among middle-aged/older adults. Conversely, statins, angiotensin-receptor blockers/inhibitors and influenza vaccination were related with decreased risk.