Medium and Long-Term Respiratory Sequelae of Acute Respiratory Distress Syndrome in Patients with COVID-19

Aim: To describe the medium- and long-term respiratory sequelae in survivors of severe acute respiratory distress syndrome (ARDS) associated with COVID-19 and their impact on the disability degree.Methods: We studied consecutive subjects with severe COVID-19-associated ARDS, who remained alive 6 months after ICU discharge. Lung morphology was assessed with chest non-contrast CT scans and CT angiography. The functional evaluation included spirometry, plethysmography, respiratory and limb muscle strength, and diffusion capacity, with assessment of gas exchange components through diffusing capacity of nitric oxide. Disability was evaluated by an incremental exercise test, and measurements were repeated 12 and 24 months later in patients with functional alterations.Findings: Out of 108 evaluated patients, only 19% remained asymptomatic 6 months after ICU discharge, and 10% had a normal CT scan. Restrictive impairment was observed in 57% of patients, whereas impaired gas exchange was present in 28% due to involvement of a membrane component. In patients with restrictive impairment, total lung capacity increased in the following 2 years, while recovery of diffusion capacity was more modest. A dissociation between morphological and clinical-functional sequelae was identified. Maintained moderate-severe disability affected 47% of patients and was independently associated with female sex, hypothyroidism, reduced membrane diffusion component, lower functional residual capacity, and high-attenuation lung volume.Interpretation: While restrictive disorder is relatively frequent in the medium-term and partially reversible at long-term among survivors of severe COVID-19-associated ARDS, gas exchange impairment is less frequent, but also less reversible. Both contribute to moderate-severe disability in almost half of the patients.Funding: This study was supported by grants from Sociedad Madrileña de Neumología y Cirugía Torácica (NEUMOMADRID), Spain PE20/0001 to F. García-Río, Comunidad de Madrid, Spain SPACE 2-CV-COVID-CM to F. García-Río and Instituto de Salud Carlos III-Fondos FEDER, Spain COV20/00207 to C. Cubillos-Zapata. Declaration of Interest: We declare no competing interests.Ethical Approval: Participants provided their written consent, and the study was approved by the institutional Ethics Committee (PI-4189).