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Abstract Background Characteristics of COVID-19 patients have mainly been reported within confirmed COVID-19 cohorts. By analyzing patients with respiratory infections in the emergency department during the first pandemic wave, we aim to assess differences in the characteristics of COVID-19 vs. Non-COVID-19 patients. This is particularly important regarding the second COVID-19 wave and the approaching influenza season. Methods We prospectively included 219 patients with suspected COVID-19 who received radiological imaging and RT-PCR for SARS-CoV-2. Demographic, clinical and laboratory parameters as well as RT-PCR results were used for subgroup analysis. Imaging data were reassessed using the following scoring system: 0 – not typical, 1 – possible, 2 – highly suspicious for COVID-19. Results COVID-19 was diagnosed in 72 (32,9%) patients. In three of them (4,2%) the initial RT-PCR was negative while initial CT scan revealed pneumonic findings. 111 (50,7%) patients, 61 of them (55,0%) COVID-19 positive, had evidence of pneumonia. Patients with COVID-19 pneumonia showed higher body temperature (37,7 ± 0,1 vs. 37,1 ± 0,1 °C; p = 0.0001) and LDH values (386,3 ± 27,1 vs. 310,4 ± 17,5 U/l; p = 0.012) as well as lower leukocytes (7,6 ± 0,5 vs. 10,1 ± 0,6G/l; p = 0.0003) than patients with other pneumonia. Among abnormal CT findings in COVID-19 patients, 57 (93,4%) were evaluated as highly suspicious or possible for COVID-19. In patients with negative RT-PCR and pneumonia, another third was evaluated as highly suspicious or possible for COVID-19 (14 out of 50; 28,0%). The sensitivity in the detection of patients requiring isolation was higher with initial chest CT than with initial RT-PCR (90,4% vs. 79,5%). Conclusions COVID-19 patients show typical clinical, laboratory and imaging parameters which enable a sensitive detection of patients who demand isolation measures due to COVID-19.