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OBJECTIVE To explore the different clinical and CT features distinguishing COVID-19 from H1N1 influenza pneumonia. PATIENTS AND METHODS We compared two independent cohorts of COVID-19 pneumonia (n=405) and H1N1 influenza pneumonia (n=78), retrospectively. All patients were confirmed by RT-PCR. Four hundred and five cases of COVID-19 pneumonia were confirmed in nine hospitals of Zhejiang province, China from January 21 to February 20, 2020. Seventy-eight cases of H1N1 influenza pneumonia were confirmed in our hospital from January 1, 2017 to February 29, 2020. Their clinical manifestations, laboratory test results, and CT imaging characteristics were compared. RESULTS COVID-19 pneumonia patients showed less proportions of underlying diseases, fever and respiratory symptoms than those of H1N1 pneumonia patients (p<0.01). White blood cell count, neutrophilic granulocyte percentage, C-reactive protein, procalcitonin, D-Dimer, and lactate dehydrogenase in H1N1 pneumonia patients were higher than those of COVID-19 pneumonia patients (p<0.05). H1N1 pneumonia was often symmetrically located in the dorsal part of inferior lung lobes, while COVID-19 pneumonia was unusually showed as a peripheral but non-specific lobe distribution. Ground glass opacity was more common in COVID-19 pneumonia and consolidation lesions were more common in H1N1 pneumonia (p<0.01). COVID-19 pneumonia lesions showed a relatively clear margin compared with H1N1 pneumonia. Crazy-paving pattern, thickening vessels, reversed halo sign and early fibrotic lesions were more common in COVID-19 pneumonia than H1N1 pneumonia (p<0.05). Pleural effusion in COVID-19 pneumonia was significantly less common than H1N1 pneumonia (p<0.01). CONCLUSIONS Compared with H1N1 pneumonia in Zhejiang, China, the clinical manifestations of COVID-19 pneumonia were more concealed with less underlying diseases and slighter respiratory symptoms. The more common CT manifestations of COVID-19 pneumonia included ground-glass opacity with a relatively clear margin, crazy-paving pattern, thickening vessels, reversed halo sign, and early fibrotic lesions, while the less common CT manifestations of COVID-19 pneumonia included consolidation and pleural effusion.