To the editor Currently, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global health threat leading to more than 300,000 deaths [1] . SARS-CoV-2 primarily targets the pulmonary system resulting in hypoxemic respiratory failure and acute respiratory distress syndrome (ARDS). Pneumomediastinum is a well-known life-threatening complication related to the use of mechanical ventilation, especially in ARDS patients. However, publications highlighting the characteristics and outcomes of COVID-19 patients who developed pneumomediastinum following intubation and mechanical ventilation are very limited. Herein, we present our institutions' experience with four patients [ Table 1 ]. The median age of our patients was 56 years (range, 41-74 years). Two were male, and two were female. All patients had significant risk factors for developing severe COVID-19, including comorbidities, obesity and the elevation of inflammatory markers. None was a smoker nor had any underlying lung diseases. All patients were intubated due to acute hypoxemic respiratory failure from COVID-19 pneumonia, using direct laryngoscopy. Assist volume control ventilation was implemented in all cases. The positive end-expiratory pressure (PEEP) values and tidal volume before developing pneumomediastinum ranged from 16 -20 cmH 2 O, and 350-520 ml, respectively.
One patient underwent prone intervention for six days on and off.. The diagnosis of pneumomediastinum was confirmed by chest X-ray ( Figure 1 ). Due to patients' persistent hypoxemia from severe ARDS, we could not decrease ventilator setting of any patients after they had developed pneumomediastinum. All patients ultimately expired due to septic shock and multi-organ failure from severe COVID-19. We did not perform autopsy.
We searched the MEDLINE database for pneumomediastinum in mechanically ventilated COVID-19 patients and discovered one previously reported case series from the UK [2] . Wali A et al. (2020) described five COVID-19 patients, who developed pneumomediastinum after tracheal intubation and mechanically ventilated and proposed that the pneumomediastinum is at least partly due to the large bore tracheal tubes (initially used size 9 in all patients) leading to tracheobronchial injury. However, our patients were intubated with smaller size of tracheal tubes (median 7.5, ranges 7-8). We hypothesize that the primary mechanism of pneumomediastinum in these patients was barotrauma as evident by the high requirement of PEEP in all patients. The positive correlations of high PEEP values, barotrauma, and the risks of developing pneumomediastinum were well-recognized [3] . None of our patients nor Wali A et al. (2020) cases have underlying lung pathology. All our patients had never been smoking. The lack of pre-existing pulmonary abnormalities may support the hypothesis that the destruction of alveoli from cytokine storm in patients with severe COVID-19 is a significant predisposing factor of developing barotrauma and pneumomediastinum. We also found substantially high inflammatory markers in all patients validating the occurrence of the cytokine storm. However, whether immunosuppressive agents will help in decreasing the destruction of alveoli and the risks of developing pneumomediastinum need to be determined.
Prone positioning has shown proven benefits in patients with acute respiratory distress syndromes [4, 5] . Recent evidences also suggested that prone positioning improves oxygenation in non-mechanically ventilated COVID-19 patients [6] . In contrast, the risks and Endotracheal tube (ETT), positive end-expiratory pressure (PEEP), Chest x-ray (CXR), C-reactive protein (CRP (mg/dl), normal <0.4 mg/dl), D-dimer (DD (ng/ml) normal < 230 ng/ml), interleukin-6 (IL6 (pg/mL), normal < 15.5 pg/mL), length of stay (LOS)