摘要INTRODUCTION: Radiological phenotypes are observable radiological patterns or characteristics. Robust data are available regarding the role of high?resolution computed tomography (HRCT) in coronavirus disease 2019 (COVID?19) pneumonia. We evaluated the role of radiological phenotyping in assessing severity and predicting the response to therapy, as well as its association with outcomes in COVID?19 pneumonia. METHODS: This prospective observational study included 3000 COVID?19 reverse transcription polymerase chain reaction?confirmed cases with lung involvement who underwent thoracic HRCT on hospital admission and were categorized as mild, moderate, or severe according to lung segment bilateral involvement (mild 1–7, moderate 8–15, and severe 16–25). Follow?up thoracic CT imaging was also conducted 6 months after hospital discharge. Response to treatment phenotypes was categorized as "easy to treat" or "difficult to treat" based on the response and interventions required in indoor settings, including ventilatory support. Age, gender, comorbidities, laboratory parameters, the use of bilevel?positive airway pressure/noninvasive ventilation, and outcomes (with or without lung fibrosis) were key observations. The Chi?square test was used for statistical analysis. RESULTS: Easy?to?treat and difficult?to?treat radiological response phenotypes were observed in 20％ and 80％ of the cases, respectively. There were significant associations between the radiological phenotypes and the duration of illness at hospital admission. The duration of illness (＜7 days, 7–14 days, and ＞14 days) could predict the radiological phenotype (P ＜ 0.00001). Laboratory parameters at hospital admission (C?reactive protein, interleukin?6, ferritin, lactate dehydrogenase, and D?dimer) were significantly associated with the radiological phenotypes (P ＜ 0.00001), as were interventions required in indoor units (P ＜ 0.00001). The HRCT severity score at admission was significantly correlated with the radiological phenotype (P ＜ 0.00001). Post?COVID lung fibrosis or sequelae were also significantly associated with the radiological phenotype (P ＜ 0.00001). CONCLUSION: Easy?to?treat and difficult?to?treat phenotypic differentiation had a crucial role during the initial assessment of COVID?19 cases on hospitalization and was used for planning targeted intervention treatments in intensive care units. In addition, phenotypic differentiation had an important role in analyzing the radiological sequelae and predicting final treatment outcomes.