Although the medium- and long-term sequelae of survivor of acute respiratory distress syndrome (ARDS) of any cause have been documented, little is known about the way in which COVID-19-induced ARDS affects functional disability and exercise components. Our aims were to examine the medium-term disability in severe COVID-19-associated ARDS survivors, delineate pathophysiological changes contributing to their exercise intolerance, and explore its utility in predicting long-term functional impairment persistence.

We studied 108 consecutive subjects with severe COVID-19 ARDS who remained alive 6 months after intensive care unit (ICU) discharge. Lung morphology was assessed with chest non-contrast CT scans and CT angiography. Functional evaluation included spirometry, plethysmography, muscle strength, and diffusion capacity, with assessment of gas exchange components through diffusing capacity of nitric oxide. Disability was assessed through an incremental exercise test, and measurements were repeated 12 and 24 months later in patients with functional impairments.

At 6 months after ICU discharge, a notable dissociation between morphological and clinical-functional sequelae was identified. Moderate-severe disability was present in 47% of patients and these subjects had greater limitation of ventilatory mechanics and gas exchange, as well as greater symptomatic perception during exercise and a probable associated cardiac limitation. Female sex, hypothyroidism, reduced membrane diffusion component, lower functional residual capacity, and high-attenuation lung volume were independently associated with the presence of moderate-severe functional disability, which in turn was related to higher frequency and greater intensity of dyspnea and worse quality of life. Out of the 71 patients with reduced lung volumes or diffusion capacity at 6 months post-ICU discharge, only 19 maintained a restrictive disorder associated with gas exchange impairment at 24 months post-discharge. In these patients, 6-month values for diffusion membrane component, maximal oxygen uptake, ventilatory equivalent for CO2, and dead space to tidal volume ratio were identified as independent risk factors for persistence of long-term functional sequelae.

Less than half of survivors of COVID-19 ARDS have moderate-severe disability in the medium term, identifying several risk factors. In turn, diffusion membrane component and exercise tolerance at 6-month ICU discharge are independently associated with the persistence of long-term functional sequelae.