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The long-term clinical management and evolution of a cohort of critical COVID-19 survivors have not been described in detail. We report a prospective observational study of COVID-19 patients admitted to the ICU between March and August 2020. The follow-up in a post-COVID consultation comprised symptoms, pulmonary function tests, the 6-minute walking test (6MWT), and chest computed tomography (CT). Additionally, questionnaires to evaluate the prevalence of post-COVID-19 syndrome were administered at 1 year. A total of 181 patients were admitted to the ICU during the study period. They were middle-aged (median [IQR] of 61 [52;67]) and male (66.9%), with a median ICU stay of 9 (5-24.2) days. 20% died in the hospital, and 39 were not able to be included. A cohort of 105 patients initiated the follow-up. At 1 year, 32.2% persisted with respiratory alterations and needed to continue the follow-up. Ten percent still had moderate/severe lung diffusion (DLCO) involvement (<60%), and 53.7% had a fibrotic pattern on CT. Moreover, patients had a mean (SD) number of symptoms of 5.7 ± 4.6, and 61.3% met the criteria for post-COVID syndrome at 1 year. During the follow-up, 46 patients were discharged, and 16 were transferred to other consultations. Other conditions, such as emphysema (21.6%), COPD (8.2%), severe neurocognitive disorders (4.1%), and lung cancer (1%) were identified. A high use of health care resources is observed in the first year. In conclusion, one-third of critically ill COVID-19 patients need to continue follow-up beyond 1 year, due to abnormalities on DLCO, chest CT, or persistent symptoms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 González, Zuil, Benítez, de Gonzalo-Calvo, Aguilar, Santisteve, Vaca, Minguez, Seck, Torres, de Batlle, Gómez, Barril, Moncusí-Moix, Monge, Gort-Paniello, Ferrer, Ceccato, Fernández, Motos, Riera, Menéndez, Garcia-Gasulla, Peñuelas, Labarca, Caballero, Barberà, Torres and Barbé.)

Background: The pathophysiology of COVID-19-related critical illness is not completely understood. Here, we analyzed the microRNA (miRNA) profile of bronchial aspirate (BAS) samples from COVID-19 and non-COVID-19 patients admitted to the ICU to identify prognostic biomarkers of fatal outcomes and to define molecular pathways involved in the disease and adverse events., Methods: Two patient populations were included ( n = 89): (i) a study population composed of critically ill COVID-19 and non-COVID-19 patients; (ii) a prospective study cohort composed of COVID-19 survivors and non-survivors among patients assisted by invasive mechanical ventilation (IMV). BAS samples were obtained by bronchoaspiration during the ICU stay. The miRNA profile was analyzed using RT-qPCR. Detailed biomarker and bioinformatics analyses were performed., Results: The deregulation in five miRNA ratios (miR-122-5p/miR-199a-5p, miR-125a-5p/miR-133a-3p, miR-155-5p/miR-486-5p, miR-214-3p/miR-222-3p, and miR-221-3p/miR-27a-3p) was observed when COVID-19 and non-COVID-19 patients were compared. In addition, five miRNA ratios segregated between ICU survivors and nonsurvivors (miR-1-3p/miR-124-3p, miR-125b-5p/miR-34a-5p, miR-126-3p/miR-16-5p, miR-199a-5p/miR-9-5p, and miR-221-3p/miR-491-5p). Through multivariable analysis, we constructed a miRNA ratio-based prediction model for ICU mortality that optimized the best combination of miRNA ratios (miR-125b-5p/miR-34a-5p, miR-199a-5p/miR-9-5p, and miR-221-3p/miR-491-5p). The model (AUC 0.85) and the miR-199a-5p/miR-9-5p ratio (AUC 0.80) showed an optimal discrimination value and outperformed the best clinical predictor for ICU mortality (days from first symptoms to IMV initiation, AUC 0.73). The survival analysis confirmed the usefulness of the miRNA ratio model and the individual ratio to identify patients at high risk of fatal outcomes following IMV initiation. Functional enrichment analyses identified pathological mechanisms implicated in fibrosis, coagulation, viral infections, immune responses and inflammation., Conclusions: COVID-19 induces a specific miRNA signature in BAS from critically ill patients. In addition, specific miRNA ratios in BAS samples hold individual and collective potential to improve risk-based patient stratification following IMV initiation in COVID-19-related critical illness. The biological role of the host miRNA profiles may allow a better understanding of the different pathological axes of the disease., Competing Interests: DdG-C holds patents on microRNAs as biomarkers. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Molinero, Benítez, González, Gort-Paniello, Moncusí-Moix, Rodríguez-Jara, García-Hidalgo, Torres, Vengoechea, Gómez, Cabo, Caballero, Bermejo-Martin, Ceccato, Fernández-Barat, Ferrer, Garcia-Gasulla, Menéndez, Motos, Peñuelas, Riera, Torres, Barbé and de Gonzalo-Calvo.)