Aim Pneumomediastinum (PM) is associated with several etiologies and mechanisms. Although it has been described more than 100 years ago, the literature is limited to small retrospective studies. This study aimed to follow patients with coronavirus disease (COVID-19) that developed PM during hospitalization and describe their clinical and radiological evolution. Methods A prospective cohort was developed with patients with PM, excluding those with aerodigestive trauma, inside a hospital COVID-19 dedicated hospital. Clinical variables including onset of symptoms, hemodynamic instability, associated complications, the need of interventions, and disease course were all recorded. Also, radiological findings such as the presence of the Macklin effect, extension of lung involvement by COVID-19, and characteristics of the PM were analyzed. Results Twenty-one patients with non-traumatic PM were followed, resulting in an overall incidence of 0.5% during the study period. Seven (33%) patients had associated pneumothorax and malignant/tension PM was observed in three (14%) cases. The Macklin effect could be found in 11 patients (52%) and the majority of them had more than 50% of lung involvement due to COVID-19. The mortality rate was 49%; however, no deaths were directly related to the PM. Conclusions PM incidence is probably increased in the severe acute respiratory syndrome caused by COVID-19, especially in those with greater involvement of the lungs, and the Macklin effect may be an important underlying mechanism of this complication. Usually, PM has a benign course, but complications like tension/malignant PM may occur requiring prompt detection and intervention.

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