Recently, evaluation of the diaphragm by means of ultrasound has become popular.1 The increase in diaphragm thickness during inspiration (thickening fraction) has been proposed as a noninvasive bedside measure of diaphragm function,2,3 although previous studies have reported wide variability between thickening, inspiratory effort, and transdiaphragmatic pressure.4–6 We hypothesized that the force-length and force-generating relationship in the diaphragm is altered by different positive end-expiratory pressure (PEEP) levels in patients with SARS-CoV-2.7We investigated the relationship between diaphragm thickening fraction and transdiaphragmatic pressure swing during noninvasive helmet continuous positive airway pressure. From March to December 2021, a total of 26 consecutive patients with laboratory-confirmed SARS-CoV-2 infection admitted to the intensive care unit of Santa Chiara Hospital (Trento, Italy) were prospectively enrolled. The study was approved by the ethics committee (Rep. Int. 282/2022), and written informed consent was obtained. At intensive care unit admission, according to the local protocol, noninvasive respiratory assistance with helmet continuous positive airway pressure was started, and a nasogastric tube provided with two balloons for registering the esophageal and gastric pressures was inserted.8 Intragastric positioning of the tube was checked with standard methods; both balloons were inflated with manufacturer- recommended volume. Intragastric position of the lower balloon was confirmed by positive pressure deflections during gentle abdominal compressions; the mid-lower third esophageal position of the proximal balloon was confirmed by inspiratory negative deflections and the presence of cardiac artifacts. In vivo calibration of the filling volume was performed. Patients underwent a trial with three increasing levels of PEEP, lasting 30 min each. The first level was set at 0 cm H2O. PEEP was then increased to 5 and 10 cm H2O; fractional expired oxygen tension was left unchanged. An average of three measurements was made, with careful attention to select the same breaths for the diaphragm ultrasound and for esophageal/gastric pressure measurements. During the last 5 min of each step, esophageal and transdiaphragmatic pressure swing and diaphragmatic ultrasound were recorded. The right hemidiaphragm was identified in the zone of apposition as a three-layered structure by B-mode ultrasonography, with the probe at the mid-axillary line at the 10th intercostal space.1 Thickness was measured from frozen M-mode images as the distance from the pleural to the peritoneal line. All the examinations were performed by the same expert physician and recorded for a subsequent offline analysis.The study population had a median age of 67.5 [62.3–72.5 interquartile range] yr, 16 (61.5%) were male, body mass index was 27 [24–33 interquartile range] kg/m2, and Pao2/fractional expired oxygen tension ratio and Paco2 at admission were 122 [103–139 interquartile range] and 39 [37–44 interquartile range] mmHg, respectively. No association was found between diaphragm thickening fraction and transdiaphragmatic pressure swings or esophageal pressure swings, at 0 cm H2O, 5 cm H2O, and 10 cm H2O (fig. 1).In a previous investigation, Steinberg et al.9 found that neither thickening fraction nor diaphragmatic excursion was able to estimate esophageal pressure swings in patients with SARS-CoV-2. We sought to extend these findings by investigating the relationship between diaphragm ultrasound and the transdiaphragmatic pressure swing, which should be more representative of the contribution of the diaphragm to the total inspiratory effort. Similar to other authors,4 we confirm the lack of association between diaphragm thickening and the transdiaphragmatic pressure. Despite that it may lie on the nonlinear pressure–volume relationship of the diaphragm, during a single breath, the diaphragm inspiratory thickening and the transdiaphragmatic pressure generated depend on the specific pattern of thoracoabdominal motion (i.e., a descent of the diaphragm rather than expansion of the rib cage). The application of PEEP also causes changes in the diaphragm geometry also modifying the force generated by the diaphragm that may not be uniform across the muscle.The different position of the diaphragm muscle over its force or length relationship is likely explained by changes in end-expiratory lung volume during the PEEP trial. Although not directly measured, diaphragm dysfunction can also be a contributing factor; COVID-19 is associated with a viral myositis,10 which might have affected diaphragm force-generating capacity.However, the impact of the small sample size on any statistical inference must be considered, and the lack of Gilbert index and pressure-time product of diaphragmatic pressure calculation reduces the interpretation of our results.In summary, despite being promising for its feasibility and noninvasive characteristics, the assessment of diaphragm thickening should not be used as a surrogate for inspiratory effort. In SARS-CoV-2 patients during helmet continuous positive airway pressure in the acute setting, an increase in inspiratory effort, as measured by transdiaphragmatic pressure swings, is not related to diaphragm thickening fraction. We suggest caution against using this tool to inform clinical choices about respiratory support, at least until more robust data will be available.Support was provided solely from institutional and/or departmental sources.The authors declare no competing interests.