Dear Editor,

Pneumothorax and pneumomediastinum may complicate acute respiratory distress syndrome (ARDS). Early studies in ARDS caused by coronavirus disease 2019 (COVID-19) suggested increased pneumothorax incidence but lacked relevant controls [1, 2]. We investigated whether COVID-19 ARDS is associated with more radiographic pneumothorax and/or pneumomediastinum than pre-pandemic ARDS and whether pneumothorax/pneumomediastinum in COVID-19 ARDS is associated with worse outcomes or differing treatments.

This retrospective cohort study included adult ARDS patients admitted between 2017 and 2021 to a 23-hospital system in the Intermountain West. We abstracted data from the electronic health record and used natural language processing to identify radiographic pneumothorax and/or pneumomediastinum [3, 4]. We performed bivariate and adjusted analyses to compare patients with pre-pandemic ARDS (2017–2020) to patients with a positive SARS-CoV-2 polymerase chain reaction (PCR) result proximate to ARDS (2020–2021) (see also Supplemental Methods).

Comparing 2,211 patients with COVID-19 ARDS and 5522 with pre-pandemic ARDS (Table 1 and Supplemental Fig. 1), unadjusted incidence of pneumothorax/pneumomediastinum was similar (24% vs. 22.5%, p < 0.148). After adjustment, pneumothorax/pneumomediastinum risk was significantly higher in COVID-19 vs. pre-pandemic ARDS (adjusted odds ratio 1.31, 95% CI 1.13–1.52, p < 0.001). COVID-19 ARDS patients had significantly higher rates of pneumomediastinum but not pneumothorax in unadjusted and adjusted analyses (Table 1 and Supplemental Table 2). Compared to COVID-19 ARDS, chest tube placement for pre-pandemic pneumothorax patients was more frequent (52.1% vs. 38.2%, p < 0.001), occurred earlier (− 0.4 vs. 1.3 days, p < 0.001) and remained in place longer (9.9 days vs. 7 days, p < 0.001).

Table 1 Summary demographic and outcome data presented as n (%) or median [IQR]

Mortality rates in COVID-19 ARDS were higher than pre-pandemic ARDS (39.4% vs. 28.5% p < 0.001). Among COVID-19 ARDS patients, we observed higher 30-day mortality rates with pneumothorax/pneumomediastinum (49.5% vs. 36.2%, p < 0.001), while we observed a lower mortality in pre-pandemic ARDS patients with pneumothorax/pneumomediastinum (24.8% vs. 29.5%, p < 0.001). Adjusted analyses yielded similar results (Supplemental Table 3).

Prior to pneumothorax/pneumomediastinum, both COVID-19 and pre-pandemic ARDS cohorts had similar receipt of invasive mechanical ventilation (77% vs. 74%, p = 0.17). COVID-19 patients received higher maximum PEEP (16 vs. 10 mmHg, p < 0.001). The median duration of invasive ventilation prior to pneumothorax/pneumomediastinum was much longer in the COVID-19 patients (2 vs. 0.3 days, p < 0.001; Supplemental Fig. 2), as was time from admission until pneumothorax/pneumomediastinum (7.3 vs. 1.3 days, p < 0.001).

Study strengths include comparison of large, multi-hospital COVID-19 and control ARDS cohorts. Limitations include the possibility of unmeasured confounding and potentially counting radiographic pneumothorax/pneumomediastinum events that were “clinically insignificant” or not due to acute lung injury. We note a substantially higher rate of pneumothorax/pneumomediastinum compared with other published cohorts (Supplemental Table 5). Our detection is more sensitive than clinically reported as all events are included, not just pneumothorax/pneumomediastinum > 2 cm or presence in clinical notes, which may limit generalizability. The relationships between radiographic and clinically significant pneumothorax/pneumomediastinum, pneumothorax/pneumomediastinum risk factors (including use of guideline-endorsed “high positive end-expiratory pressure (PEEP)” ventilation [5]), and pneumothorax management warrant further study.

In conclusion, COVID-19 ARDS patients experienced similar rates of radiographic pneumothorax but more pneumomediastinum. Chest tubes were used less frequently and placed later in COVID-19 ARDS than in pre-pandemic ARDS. Radiographic pneumothorax/pneumomediastinum in COVID-19 ARDS patients is associated with an increased mortality.