A 39-year-old vaccinated woman was admitted to our emergency department with dyspnea and respiratory failure with a positive nasopharyngeal molecular swab test for SARS-CoV-2 infection. After 6 days of O2 therapy, the patient was transferred to the intensive care for respiratory worsening requiring non-invasive ventilation (NIV) with a helmet (FiO2 60%, PS 8 cmH2O, PEEP 12 cmH2O). For the further 6 days, the patient alternated NIV and high flow nasal oxygen (HFNO) (FiO2 50%, flow 60 L/min) until, after an episode of desaturation and respiratory distress with visual analogic scale (VAS) for dyspnea of 6 (on a 0-10 scale), required tracheal intubation, and she was transferred to intensive care for invasive mechanical ventilation. The respiratory gas exchange and chest x-ray slowly improved in the following 7 days (arterial blood gas on the 7th day: pH 7.38, PaO2 231 mmHg, PaCO2 47 mmHg, HCO3 28.1 mmol/L, BE 2.6 mmol/L, Lactate 1.20 mmol/L), and we attempted to wean the patient from the ventilator reducing the pressure support to 8 cmH20 with 5 cmH2O of PEEP, however, without success. Clinically, the patient showed increased accessory respiratory muscles’ fatigue, and the PaCO2 increased > 100 mmHg; tidal volume (Vt) was less than 300 mL with respiratory rate (RR) of 26/min. After 2 unsuccessful attempts of reducing pressure support, she was tracheostomized [1, 2]. Just after the second weaning attempt and before performing the tracheostomy, point-of-care ultrasonography (POCUS) with low-frequency probe (Hitachi, Arietta 65, Tokyo 110-0015 Japan) revealed a lung ultrasound score (LUS) of 8 and with high-frequency probe diaphragmatic weakness with a thickening fraction (TF) < 20% (normal value between 20 and 30%). TF was measured as the maximal diaphragm thickness during inspiration (Tdi, pi) minus the diaphragm thickness at end-expiration (Tdi, ee) divided by the Tdi, ee, and multiplied by 100. Ultrasonographic diaphragm assessment was performed while the patient was ventilated with pressure support ventilation of 8 cmH20 and 5 cmH2O of PEEP; in the supine position, the diaphragmatic excursion was < 1.3 cm (normal value > 1.8 cm) [3] (Fig. 1 and supplemental video 1). Supplemental video 2 showed TF measurement.