Background The use of chest CT for COVID-19 diagnosis or triage in healthcare settings with limited SARS-CoV-2 PCR capacity is controversial. CO-RADS categorization of the level of COVID-19 suspicion might improve diagnostic performance. Purpose To investigate the value of chest CT with CO-RADS classification to screen for asymptomatic SARS-CoV-2 infections and to determine its diagnostic performance in individuals with COVID-19 symptoms during the exponential phase of viral spread. Materials and Methods In this secondary analysis of a prospective trial (Clinical Trial Number: IRB B1172020000008), from March 2020 to April 2020, we performed parallel SARS-CoV-2 PCR and CT with categorization of COVID-19 suspicion by CO-RADS, for individuals with COVID-19 symptoms and controls without COVID-19 symptoms admitted to the hospital for medical urgencies unrelated to COVID-19. CT-CORADS was categorized on a 5-point scale from 1 (very low suspicion) to 5 (very high suspicion). AUC were calculated in symptomatic versus asymptomatic individuals to predict positive SARS-CoV-2 positive PCR and likelihood ratios for each CO-RADS score were used for rational selection of diagnostic thresholds. Results 859 individuals (median 70 years, IQR 52-81, 443 men) with COVID-19 symptoms and 1138 controls (median 68 years, IQR 52-81, 588 men) were evaluated. CT-CORADS had good diagnostic performance (P<.001) in both symptomatic (AUC=.89) and asymptomatic (AUC=.70) individuals. In symptomatic individuals (41.7% PCR+), CO-RADS ≥ 3 detected positive PCR with high sensitivity (89%, 319/358) and 73% specificity. In asymptomatic individuals (5.3% PCR+), a CO-RADS score ≥ 3 detected SARS-CoV-2 infection with low sensitivity (45%, 27/60) but high specificity (89%). Conclusion CT-CORADS had good diagnostic performance in symptomatic individuals, supporting its application for triage. Sensitivity in asymptomatic individuals was insufficient to justify its use as first-line screening approach. Incidental detection of CO-RADS ≥ 3 in asymptomatic individuals should trigger testing for respiratory pathogens.