BackgroundCOVID-19 cases were first detected in the UK in January 2020 and vulnerable patients were asked to shield from March to reduce their risk of COVID-19 infection.AimTo determine the risk and determinants of COVID-19 diagnosis in shielded versus non-shielded groups, adjusted for key comorbidities not explained by shielding.Design & settingRetrospective cohort study of adults with COVID-19 infection between 1 February 2020 and 15 May 2020 in west London.MethodIndividuals diagnosed with COVID-19 were identified in SystmOne records using clinical codes. Infection risks were adjusted for sociodemographic factors, nursing home status, and comorbidities.ResultsOf 57 713 adults, 573 (1%) individuals were identified as shielded and 1074 adults had documented COVID-19 infections (1.9%). COVID-19 infection rate in the shielded group individuals compared with non-shielded adult individuals was 6.5% (n = 37/573) versus 1.8% (n = 1037/57 140), P<0.001. A multivariable fully adjusted Cox proportional hazards (CPH) regression identified that COVID-19 infection was increased with shielding status (adjusted hazard ratio [aHR] 1.52; 95% confidence interval [CI] = 1.00 to 2.30; P = 0.048). Other determinants of COVID-19 infection included nursing home residency (aHR 7.05; 95% CI = 4.22 to 11.77; P<0.001); Black African (aHR 2.52; 95% CI = 1.99 to 3.18; P<0.001), Other (aHR 1.74; 95% CI = 1.42 to 2.13; P<0.001), Non-stated (aHR 1.70; 95% CI = 1.02 to 2.84; P = 0.04), or South Asian ethnic group (aHR 1.46; 95% CI = 1.10 to 1.93; P = 0.01); history of respiratory disease (aHR 1.51; 95% CI = 1.06 to 2.16; P = 0.02); deprivation (third versus least deprived Index of Multiple Deprivation [IMD] quintile) (aHR 1.25 ; 95% CI = 1.01 to 1.56; P = 0.05); obesity (body mass index [BMI] >30 kg/m²) (aHR 1.39; 95% CI = 1.18 to 1.63; P<0.001); and age (aHR 1.02; 95% CI = 1.01 to 1.02; P<0.001. Male sex was associated with lower risk of COVID-19 infection (aHR 0.71; 95% CI = 0.62 to 0.82; P<0.001).ConclusionShielded individuals had a higher COVID-19 infection rate compared with non-shielded individuals, after adjusting for sociodemographic factors, nursing home status, and comorbidities.