•Chest CT patterns in COVID-19 may be divided into three main phenotypes with different characteristics o In phenotype 1, respiratory mechanics are consistent with high pulmonary compliance and severe hypoxemia.•In phenotype 2, moderate to high PEEP as well as lateral and/or prone positioning may help recruit collapsed areas.•Phenotype 3 resembles typical ARDS and should be managed as such.•Attention should be paid to the risk of pulmonary embolism, regardless of phenotype. Coronavirus disease 2019 (COVID-19) can cause severe respiratory failure requiring mechanical ventilation. The abnormalities observed on chest computed tomography (CT) and the clinical presentation of COVID-19 patients are not always like those of typical acute respiratory distress syndrome (ARDS) and can change over time. This manuscript aimed to provide brief guidance for respiratory management of COVID-19 patients before, during, and after mechanical ventilation, based on the recent literature and on our direct experience with this population. We identify that chest CT patterns in COVID-19 may be divided into three main phenotypes: 1) multiple, focal, possibly overperfused ground-glass opacities; 2) inhomogeneously distributed atelectasis; and 3) a patchy, ARDS-like pattern. Each phenotype can benefit from different treatments and ventilator settings. Also, peripheral macro- and microemboli are common, and attention should be paid to the risk of pulmonary embolism. We suggest use of personalized mechanical ventilation strategies based on respiratory mechanics and chest CT patterns. Further research is warranted to confirm our hypothesis.