The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

COVID-19; Mechanical ventilation; Ventilatory ratioCOVID-19; Respiració assistida; Relació ventilatòriaCOVID-19; Ventilación mecánica; Relación ventilatoriaBackground Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0–171.2] to 180.0 [135.4–227.9] mmHg and the ventilatory ratio from 1.73 [1.33–2.25] to 1.96 [1.61–2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01–1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01–1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93–1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation.Financial support was provided by the Instituto de Salud Carlos III de Madrid (COV20/00110, ISCIII), Fondo Europeo de Desarrollo Regional (FEDER), "Una manera de hacer Europa", and by the Centro de Investigación Biomedica En Red – Enfermedades Respiratorias (CIBERES). DdGC has received financial support from Instituto de Salud Carlos III (Miguel Servet 2020: CP20/00041), co-funded by European Social Fund (ESF)/”Investing in your future”

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0–171.2] to 180.0 [135.4–227.9] mmHg and the ventilatory ratio from 1.73 [1.33–2.25] to 1.96 [1.61–2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01–1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01–1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93–1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation.Instituto de Salud Carlos III de Madrid COV20/00110, ISCII

Effects of intubation timing in patients with COVID-19 throughout the four waves of the pandemic: a matched analysis

Background: The primary aim of our study was to investigate the association between intubation timing and hospital mortality in critically ill patients with COVID-19-associated respiratory failure. We also analysed both the impact of such timing throughout the first four pandemic waves and the influence of prior non-invasive respiratory support on outcomes. Methods: This is a secondary analysis of a multicentre, observational and prospective cohort study that included all consecutive patients undergoing invasive mechanical ventilation due to COVID-19 from across 58 Spanish intensive care units (ICU) participating in the CIBERESUCICOVID project. The study period was between 29 February 2020 and 31 August 2021. Early intubation was defined as that occurring within the first 24 h of intensive care unit (ICU) admission. Propensity score (PS) matching was used to achieve balance across baseline variables between the early intubation cohort and those patients who were intubated after the first 24 h of ICU admission. Differences in outcomes between early and delayed intubation were also assessed. We performed sensitivity analyses to consider a different timepoint (48 h from ICU admission) for early and delayed intubation. Results: Of the 2725 patients who received invasive mechanical ventilation, a total of 614 matched patients were included in the analysis (307 for each group). In the unmatched population, there were no differences in mortality between the early and delayed groups. After PS matching, patients with delayed intubation presented higher hospital mortality (27.3% versus 37.1%, p =0.01), ICU mortality (25.7% versus 36.1%, p=0.007) and 90-day mortality (30.9% versus 40.2%, p=0.02) when compared to the early intubation group. Very similar findings were observed when we used a 48-hour timepoint for early or delayed intubation. The use of early intubation decreased after the first wave of the pandemic (72%, 49%, 46% and 45% in the first, second, third and fourth wave, respectively; first versus second, third and fourth waves p<0.001). In both the main and sensitivity analyses, hospital mortality was lower in patients receiving high-flow nasal cannula (n=294) who were intubated earlier. The subgroup of patients undergoing NIV (n=214) before intubation showed higher mortality when delayed intubation was set as that occurring after 48 h from ICU admission, but not when after 24 h. Conclusions: In patients with COVID-19 requiring invasive mechanical ventilation, delayed intubation was associated with a higher risk of hospital mortality. The use of early intubation significantly decreased throughout the course of the pandemic. Benefits of such an approach occurred more notably in patients who had received high-flow nasal cannula.Financial support was provided by the Instituto de Salud Carlos III de Madrid (COV20/00110, ISCIII), Fondo Europeo de Desarrollo Regional (FEDER), "Una manera de hacer Europa", and the Centro de Investigación Biomedica En Red – Enfermedades Respiratorias (CIBERES). DdGC has received financial support from the Instituto de Salud Carlos III (Miguel Servet 2020: CP20/00041), co-funded by European Social Fund (ESF)/”Investing in your future”.Peer ReviewedArticle signat per 70 autors/es: Jordi Riera*1,2; Enric Barbeta*2,3,4; Adrián Tormos5; Ricard Mellado-Artigas2,3; Adrián Ceccato6; Anna Motos4; Laia Fernández-Barat4; Ricard Ferrer1; Darío García-Gasulla5; Oscar Peñuelas7; José Ángel Lorente7; Rosario Menéndez8; Oriol Roca1,2; Andrea Palomeque4,9; Carlos Ferrando2,3; Jordi SoléViolán10; Mariana Novo11; María Victoria Boado12; Luis Tamayo13; Ángel Estella14, Cristóbal Galban15; Josep Trenado16; Arturo Huerta17; Ana Loza18; Luciano Aguilera19; José Luís García Garmendia20; Carme Barberà21; Víctor Gumucio22; Lorenzo Socias23; Nieves Franco24; Luis Jorge Valdivia25; Pablo Vidal26; Víctor Sagredo27; Ángela Leonor Ruiz-García28; Ignacio Martínez Varela29; Juan López30; Juan Carlos Pozo31; Maite Nieto32; José M Gómez33; Aaron Blandino34; Manuel Valledor35; Elena Bustamante-Munguira36; Ángel Sánchez-Miralles37; Yhivian Peñasco38; José Barberán39; Alejandro Ubeda40; Rosario Amaya-Villar41; María Cruz Martín42; Ruth Jorge43; Jesús Caballero44; Judith Marin45; José Manuel Añón46; Fernando Suárez Sipmann47; Guillermo Muñiz2,48;Álvaro Castellanos-Ortega49; Berta Adell-Serrano50; Mercedes Catalán51; Amalia Martínez de la Gándara52; Pilar Ricart53; Cristina Carbajales54; Alejandro Rodríguez55; Emili Díaz6; Mari C de la Torre56; Elena Gallego57; Luisa Cantón-Bulnes58; Nieves Carbonell59, Jessica González60, David de Gonzalo-Calvo60, Ferran Barbé60 and Antoni Torres2,4,9 on behalf of the CiberesUCICOVID Consortium. // 1. Critical Care Department, Hospital Universitari Vall d’Hebron; SODIR, Vall d’Hebron Institut de Recerca, Barcelona, Spain. 2. CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain. 3.Surgical Intensive Care Unit, Hospital Clínic de Barcelona, Barcelona, Spain. 4. Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona (UB), Barcelona, Spain. 5. Barcelona Supercomputing Center (BSC), Barcelona, Spain. 6. Critical Care Center, Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí I3PT, Sabadell, Spain. Universitat Autonoma de Barcelona (UAB), Spain. 7. Hospital Universitario de Getafe, Universidad Europea, Madrid, Spain. 8. Pneumology Department, Hospital Universitario y Politécnico La Fe/Instituto de Investigación Sanitaria (IIS) La Fe, 46026 Valencia, Spain; Pneumology Department, Hospital Universitario y Politécnico La Fe, Avda, Fernando Abril Martorell 106, 46026 Valencia, Spain. 9.Respiratory Intensive Care Unit, Hospital Clínic de Barcelona, Barcelona, Spain. 10. Critical Care Department, Hospital Dr. Negrín Gran Canaria. Universidad Fernando Pessoa. Las Palmas, Gran Canaria, Spain. 11. Servei de Medicina Intensiva, Hospital Universitari Son Espases, Palma de Mallorca, Illes Balears, Spain. 12. Hospital Universitario de Cruces, Barakaldo, Spain. 13. Critical Care Department, Hospital Universitario Río Hortega de Valladolid, Valladolid, Spain. 14. Departamento Medicina Facultad Medicina Universidad de Cádiz. Hospital Universitario de Jerez, Jerez de la Frontera, Spain. 15. Department of Medicine, CHUS, Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain. 16. Servicio de Medicina Intensiva, Hospital Universitario Mútua de Terrassa, Terrassa, Barcelona, Spain. 17. Pulmonary and Critical Care Division; Emergency Department, Clínica Sagrada Família, Barcelona, Spain. 18. Hospital Virgen de Valme, Sevilla, Spain. 19. Hospital de Basurto, Bilbao, Spain. 20. Intensive Care Unit, Hospital San Juan de Dios del Aljarafe, Bormujos, Sevilla, Spain. 21. Hospital Santa Maria; IRBLleida, Lleida, Spain. 22. Department of Intensive Care. Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain. Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain. 23. Intensive Care Unit, Hospital Son Llàtzer, Palma de Mallorca, Illes Balears, Spain. 24. Hospital Universitario de Móstoles, Madrid, Spain. 25. Hospital Universitario de León, León, Spain. 26. Complexo Hospitalario Universitario de Ourense, Ourense, Spain. 27. Hospital Universitario de Salamanca, Salamanca, Spain. 28. Servicio de Microbiología Clínica, Hospital Universitario Príncipe de Asturias – Departamento de Biomedicina y Biotecnología, Universidad de Alcalá de Henares, Madrid, Spain. 29. Critical Care Department, Hospital Universitario Lucus Augusti, Lugo, Spain. 30. Complejo Asistencial Universitario de Palencia, Palencia, Spain. 31. UGC-Medicina Intensiva, Hospital Universitario Reina Sofia, Instituto Maimonides IMIBIC, Córdoba, Spain. 32. Hospital Universitario de Segovia, Segovia, Spain. 33. Hospital General Universitario Gregorio Marañón, Madrid, Spain. 34. Servicio de Medicina Intensiva, Hospital Universitario Ramón y Cajal, Madrid, Spain. 35. Hospital Universitario "San Agustín", Avilés, Spain. 36. Department of Intensive Care Medicine, Hospital Clínico Universitario Valladolid, Valladolid, Spain. 37. Servicio de Medicina Intensiva. Hospital Universitario Sant Joan d´Alacant, Alicante, Spain. 38. Servicio de Medicina Intensiva, Hospital Universitario Marqués de Valdecilla, Santander, Spain. 39. Hospital Universitario HM Montepríncipe, Universidad San Pablo-CEU, Madrid, Spain. 40. Servicio de Medicina Intensiva, Hospital Punta de Europa, Algeciras, Spain. 41. Intensive Care Clinical Unit, Hospital Universitario Virgen de Rocío, Sevilla, Spain. 42. Hospital Universitario Torrejón- Universidad Francisco de Vitoria, Madrid, Spain. 43. Intensive Care Department, Hospital Nuestra Señora de Gracia, Zaragoza, Spain. 44. Critical Care Department, Hospital Universitari Arnau de Vilanova; IRBLleida, Lleida, Spain. 45. Critical Care Department, Hospital del Mar-IMIM, Barcelona, Spain. 46. Hospital Universitario la Paz, Madrid, Spain. 47. Intensive Care Unit, Hospital Universitario La Princesa, Madrid, Spain. 48. Departamento de Biología Funcional. Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo; Instituto de Investigación Sanitaria del Principado de Asturias, Hospital Central de Asturias, Oviedo, Spain. 49. Hospital Universitario y Politécnico la Fe, Valencia, Spain. 50. Hospital de Tortosa Verge de la Cinta, Tortosa, Tarragona, Spain. 51. Department of Intensive Care Medicine, Hospital Universitario 12 de Octubre, Madrid, Spain. 52. Hospital Universitario Infanta Leonor, Madrid, Spain. 53. Servei de Medicina Intensiva, Hospital Universitari Germans Trias, Badalona, Spain. 54. Intensive Care Unit, Hospital Álvaro Cunqueiro, Vigo, Spain. 55. Hospital Universitari Joan XXIII de Tarragona, Tarragona, Spain. 56. Hospital de Mataró de Barcelona, Spain. 57. Unidad de Cuidados Intensivos, Hospital Universitario San Pedro de Alcántara, Cáceres, Spain. 58. Unidad de Cuidados Intensivos, Hospital Virgen Macarena, Sevilla, Spain. 59. Intensive Care Unit, Hospital Clínico y Universitario de Valencia, Valencia, Spain. 60. Translational Research in Respiratory Medicine, Respiratory Department, Hospital Universitari Aranu de Vilanova and Santa Maria, IRBLleida, Lleida, Spain.Postprint (published version

Higher frequency of comorbidities in fully vaccinated patients admitted to the ICU due to severe COVID-19: a prospective, multicentre, observational study

Severe COVID-19 disease requiring ICU admission is possible in the fully vaccinated population, especially in those with immunocompromised status and other comorbidities. Interventions to improve vaccine response might be necessary in this population.Peer ReviewedArticle signat per 23 autors/es: Anna Motos, Alexandre López-Gavín, Jordi Riera, Adrián Ceccato, Laia Fernández-Barat, Jesús F. Bermejo-Martin, Ricard Ferrer, David de Gonzalo-Calvo, Rosario Menéndez, Raquel Pérez-Arnal, Dario García-Gasulla, Alejandro Rodriguez, Oscar Peñuelas, José Ángel Lorente, Raquel Almansa, Albert Gabarrus, Judith Marin-Corral, Pilar Ricart, Ferran Roche-Campo, Susana Sancho Chinesta, Lorenzo Socias, Ferran Barbé, Antoni Torres on behalf of the CIBERESUCICOVID Project (COV20/00110, ISCIII).Postprint (published version

ICU-acquired pneumonia is associated with poor health post-COVID-19 syndrome

Some patients previously presenting with COVID-19 have been reported to develop persistent COVID-19 symptoms. While this information has been adequately recognised and extensively published with respect to non-critically ill patients, less is known about the incidence and factors associated with the characteristics of persistent COVID-19. On the other hand, these patients very often have intensive care unit-acquired pneumonia (ICUAP). A second infectious hit after COVID increases the length of ICU stay and mechanical ventilation and could have an influence on poor health post-COVID 19 syndrome in ICU-discharged patients. Methods: This prospective, multicentre, and observational study was carrid out across 40 selected ICUs in Spain. Consecutive patients with COVID-19 requiring ICU admission were recruited and evaluated three months after hospital discharge. Results: A total of 1255 ICU patients were scheduled to be followed up at 3 months; however, the final cohort comprised 991 (78.9%) patients. A total of 315 patients developed ICUAP (97% of them had ventilated ICUAP). Patients requiring invasive mechanical ventilation had more persistent post-COVID-19 symptoms than those who did not require mechanical ventilation. Female sex, duration of ICU stay, development of ICUAP, and ARDS were independent factors for persistent poor health post-COVID-19. Conclusions: Persistent post-COVID-19 symptoms occurred in more than two-thirds of patients. Female sex, duration of ICU stay, development of ICUAP, and ARDS all comprised independent factors for persistent poor health post-COVID-19. Prevention of ICUAP could have beneficial effects in poor health post-COVID-19.Financial support was provided by the Instituto Carlos III de Madrid (COV20/00110, ISCIII) and by the Centro de Investigación Biomedica En Red—Enfermedades Respiratorias (CIBERES). DdGC has received financial support from Instituto de Salud Carlos III (Miguel Servet 2020: CP20/00041), co-funded by European Social Fund (ESF)/ “Investing in your future”Peer ReviewedArticle signat per 53 autors/es: Ignacio Martin-Loeches (1,2,3), Anna Motos (1,3), Rosario Menéndez (1,4), Albert Gabarrús (1,4), Jessica González (5,6), Laia Fernández-Barat (1,3), Adrián Ceccato (1,3), Raquel Pérez-Arnal (7), Dario García-Gasulla (7), Ricard Ferrer (1,8), Jordi Riera (1,8), José Ángel Lorente (1,9), Óscar Peñuelas (1,9), Jesús F. Bermejo-Martin (1,10,11), David de Gonzalo-Calvo (5,6), Alejandro Rodríguez (12), Ferran Barbé (5,6), Luciano Aguilera (13), Rosario Amaya-Villar (14), Carme Barberà (15), José Barberán (16), Aaron Blandino Ortiz (17), Elena Bustamante-Munguira (18), Jesús Caballero (19), Cristina Carbajales (20), Nieves Carbonell (21),Mercedes Catalán-González (22), Cristóbal Galbán (23), Víctor D. Gumucio-Sanguino (24), Maria del Carmen de la Torre (25), Emili Díaz (26), Elena Gallego (27), José Luis García Garmendia (28), José Garnacho-Montero (29), José M. Gómez (30), Ruth Noemí Jorge García (31), Ana Loza-Vázquez (32), Judith Marín-Corral (33), Amalia Martínez de la Gándara (34), Ignacio Martínez Varela (35), Juan Lopez Messa (36), Guillermo M. Albaiceta (37,38), Mariana Andrea Novo (39), Yhivian Peñasco (40), Pilar Ricart (41), Luis Urrelo-Cerrón (42), Angel Sánchez-Miralles (43), Susana Sancho Chinesta (44), Lorenzo Socias (45), Jordi Solé-Violan (1,46), Luis Tamayo Lomas (47), Pablo Vidal (48) and Antoni Torres (1,3)*, on behalf of CIBERESUCICOVID Project (COV20/00110 and ISCIII) // (1) CIBER of Respiratory Diseases (CIBERES), Institute of Health Carlos III, 28029 Madrid, Spain; (2) Pulmonary Department, Hospital Clinic, Universitat de Barcelona, IDIBAPS, 08036 Barcelona, Spain; (3) Department of Intensive Care Medicine, St. James’s Hospital, Multidisciplinary Intensive Care Research Organization (MICRO), James’s Street, D08 NHY1 Dublin, Ireland; (4) Pulmonary Department, University and Polytechnic Hospital La Fe, 46026 Valencia, Spain; (5) Translational Research in Respiratory Medicine Group (TRRM), Lleida Biomedical Research Institute (IRBLleida), 25198 Lleida, Spain; (6) Pulmonary Department, Hospital Universitari Arnau de Vilanova and Santa Maria, 25198 Lleida, Spain; (7) Barcelona Supercomputing Centre (BSC), 08034 Barcelona, Spain; (8) Intensive Care Department, Vall d’Hebron Hospital Universitari, SODIR Research Group, Vall d’Hebron Institut de Recerca (VHIR), 08035 Barcelona, Spain; (9) Hospital Universitario de Getafe, 28905 Madrid, Spain; (10) Hospital Universitario Río Hortega de Valladolid, 47012 Valladolid, Spain; (11) Instituto de Investigación Biomédica de Salamanca (IBSAL), Gerencia Regional de Salud de Castilla y León, 47007 Valladolid, Spain; (12) Critical Care Department, Hospital Joan XXIII, 43005 Tarragona, Spain; (13) Anestesia, Reanimación y Terapia del Dolor, Hospital Universitario de Basurto, 48013 Bilbao, Spain; (14) Intensive Care Clinical Unit, Hospital Universitario Virgen de Rocío, 41013 Sevilla, Spain; (15) Hospital Santa Maria, IRBLleida, 25198 Lleida, Spain; (16) Critical Care Department, Hospital Universitario HM Montepríncipe, Universidad San Pablo-CEU, 28660 Madrid, Spain; (17) Servicio de Medicina Intensiva, Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain; (18) Department of Intensive Care Medicine, Hospital Clínico Universitario Valladolid, 47003 Valladolid, Spain; (19) Critical Care Department, Hospital Universitari Arnau de Vilanova, IRBLleida, 25198 Lleida, Spain; (20) Hospital Álvaro Cunqueiro, 36213 Vigo, Spain; (21) Intensive Care Unit, Hospital Clínico y Universitario de Valencia, 46010 Valencia, Spain; (22) Department of Intensive Care Medicine, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain, (23) Department of Medicine, CHUS, Complejo Hospitalario Universitario de Santiago, 15076 Santiago de Compostela, Spain; (24) Department of Intensive Care, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, 08907 Barcelona, Spain; (25) Hospital de Mataró de Barcelona, 08301 Mataró, Spain; (26) Department of Medicine, Universitat Autònoma de Barcelona (UAB), Critical Care Department, Corpo-Ració Sanitària Parc Taulí, Sabadell, 08208 Barcelona, Spain; (27) Unidad de Cuidados Intensivos, Hospital San Pedro de Alcántara, 10003 Cáceres, Spain; (28) Intensive Care Unit, Hospital San Juan de Dios del Aljarafe, 41930 Sevilla, Spain; (29) Intensive Care Clinical Unit, Hospital Universitario Virgen Macarena, 41009 Seville, Spain; (30) Hospital General Universitario Gregorio Marañón, 28009 Madrid, Spain; (31) Intensive Care Department, Hospital Nuestra Señora de Gracia, 50009 Zaragoza, Spain; (32) Unidad de Medicina Intensiva, Hospital Universitario Virgen de Valme, 41014 Sevilla, Spain; (33) Critical Care Department, Hospital del Mar-IMIM, 08003 Barcelona, Spain; (34) Department of Intensive Medicine, Hospital Universitario Infanta Leonor, 28031 Madrid, Spain; (35) Critical Care Department, Hospital Universitario Lucus Augusti, 27003 Lugo, Spain; (36) Critical Care Department, Complejo Asistencial Universitario de Palencia, 34005 Palencia, Spain; (37) Departamento de Biología Funcional, Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo, 33011 Oviedo, Spain; (38) Instituto de Investigación Sanitaria del Principado de Asturias, Hospital Central de Asturias, 33011 Oviedo, Spain; (39) Servei de Medicina Intensiva, Hospital Universitari Son Espases, Palma de Mallorca, 07120 Illes Balears, Spain; (40) Servicio de Medicina Intensiva, Hospital Universitario Marqués de Valdecilla, 39008 Santander, Spain; (41) Servei de Medicina Intensiva, Hospital Universitari Germans Trias, 08916 Badalona, Spain; (42) Hospital Verge de la Cinta, 08916 Tortosa, Spain; (43) Hospital de Sant Joan d’Alacant, 03550 Alacant, Spain; (44) Servicio de Medicina Intensiva, Hospital Universitario y Politécnico La Fe, 46026 Valencia, Spain; (45) Intensive Care Unit, Hospital Son Llàtzer, Palma de Mallorca, 07198 Illes Balears, Spain; (46) Critical Care Department, Hospital Dr. Negrín., 35019 Las Palmas de GC, Spain; (47) Critical Care Department, Hospital Universitario Río Hortega de Valladolid, 47102 Valladolid, Spain; (48) Intensive Care Unit, Complexo Hospitalario Universitario de Ourense, 32005 Ourense, Spain.Postprint (published version

Major candidate variables to guide personalised treatment with steroids in critically ill patients with COVID-19: CIBERESUCICOVID study

Purpose: Although there is evidence supporting the benefits of corticosteroids in patients affected with severe coronavirus disease 2019 (COVID-19), there is little information related to their potential benefits or harm in some subgroups of patients admitted to the intensive care unit (ICU) with COVID-19. We aim to investigate to find candidate variables to guide personalized treatment with steroids in critically ill patients with COVID-19. Methods: Multicentre, observational cohort study including consecutive COVID-19 patients admitted to 55 Spanish ICUs. The primary outcome was 90-day mortality. Subsequent analyses in clinically relevant subgroups by age, ICU baseline illness severity, organ damage, laboratory findings and mechanical ventilation were performed. High doses of corticosteroids (≥ 12 mg/day equivalent dexamethasone dose), early administration of corticosteroid treatment (< 7 days since symptom onset) and long term of corticosteroids (≥ 10 days) were also investigated. Results: Between February 2020 and October 2021, 4226 patients were included. Of these, 3592 (85%) patients had received systemic corticosteroids during hospitalisation. In the propensity-adjusted multivariable analysis, the use of corticosteroids was protective for 90-day mortality in the overall population (HR 0.77 [0.65–0.92], p = 0.003) and in-hospital mortality (SHR 0.70 [0.58–0.84], p < 0.001). Significant effect modification was found after adjustment for covariates using propensity score for age (p = 0.001 interaction term), Sequential Organ Failure Assessment (SOFA) score (p = 0.014 interaction term), and mechanical ventilation (p = 0.001 interaction term). We observed a beneficial effect of corticosteroids on 90-day mortality in various patient subgroups, including those patients aged ≥ 60 years; those with higher baseline severity; and those receiving invasive mechanical ventilation at ICU admission. Early administration was associated with a higher risk of 90-day mortality in the overall population (HR 1.32 [1.14–1.53], p < 0.001). Long-term use was associated with a lower risk of 90-day mortality in the overall population (HR 0.71 [0.61–0.82], p < 0.001). No effect was found regarding the dosage of corticosteroids. Moreover, the use of corticosteroids was associated with an increased risk of nosocomial bacterial pneumonia and hyperglycaemia. Conclusion: Corticosteroid in ICU-admitted patients with COVID-19 may be administered based on age, severity, baseline inflammation, and invasive mechanical ventilation. Early administration since symptom onset may prove harmful.15 página

Prognostic implications of comorbidity patterns in critically ill COVID-19 patients: A multicenter, observational study

Background: The clinical heterogeneity of COVID-19 suggests the existence of different phenotypes with prognostic implications. We aimed to analyze comorbidity patterns in critically ill COVID-19 patients and assess their impact on in-hospital outcomes, response to treatment and sequelae. Methods: Multicenter prospective/retrospective observational study in intensive care units of 55 Spanish hospitals. 5866 PCR-confirmed COVID-19 patients had comorbidities recorded at hospital admission; clinical and biological parameters, in-hospital procedures and complications throughout the stay; and, clinical complications, persistent symptoms and sequelae at 3 and 6 months. Findings: Latent class analysis identified 3 phenotypes using training and test subcohorts: low-morbidity (n=3385; 58%), younger and with few comorbidities; high-morbidity (n=2074; 35%), with high comorbid burden; and renal-morbidity (n=407; 7%), with chronic kidney disease (CKD), high comorbidity burden and the worst oxygenation profile. Renal-morbidity and high-morbidity had more in-hospital complications and higher mortality risk than low-morbidity (adjusted HR (95% CI): 1.57 (1.34-1.84) and 1.16 (1.05-1.28), respectively). Corticosteroids, but not tocilizumab, were associated with lower mortality risk (HR (95% CI) 0.76 (0.63-0.93)), especially in renal-morbidity and high-morbidity. Renal-morbidity and high-morbidity showed the worst lung function throughout the follow-up, with renal-morbidity having the highest risk of infectious complications (6%), emergency visits (29%) or hospital readmissions (14%) at 6 months (p<0.01). Interpretation: Comorbidity-based phenotypes were identified and associated with different expression of in-hospital complications, mortality, treatment response, and sequelae, with CKD playing a major role. This could help clinicians in day-to-day decision making including the management of post-discharge COVID-19 sequelae.Financial support was provided by Instituto de Salud Carlos III (CIBERESUCICOVID, COV20/00110), co-funded by Fondo Europeo de Desarrollo Regional (FEDER), “Una manera de hacer Europa”, Centro de Investigación Biomédica en Red − Enfermedades Respiratorias (CIBERES) and Donation Program “estar preparados”, UNESPA, Madrid, Spain. JdB acknowledges receiving financial support from Instituto de Salud Carlos III (ISCIII; Miguel Servet 2019: CP19/00108), cofunded by the European Social Fund (ESF), “Investing in your future”. DdGC acknowledges receiving financial support from Instituto de Salud Carlos III (ISCIII; Miguel Servet 2019: CP20/00041), co-funded by the European Social Fund (ESF), “Investing in your future”. AC acknowledges receiving financial support from Instituto de Salud Carlos III (ISCIII; Sara Borrell 2021: CD21/00087).Peer ReviewedArticle signat per 71 autors/es: Iván D. Benítez (a,b,1), Jordi de Batlle (a,b,1), Gerard Torres (a,b), Jessica Gonzáalez (a,b), David de Gonzalo-Calvo (a,b), Adriano D.S. Targa (a,b), Clara Gort-Paniello (a,b), Anna Moncusí-Moix (a,b), Adrián Ceccato (b,c), Laia Fernández-Barat (b,d), Ricard Ferrer (b,e), Dario Garcia-Gasulla (f), Rosario Menéndez (b,g), Anna Motos (b,d), Oscar Peñuelas (b,h), Jordi Riera (b,e), Jesús F. Bermejo-Martin (b,i), Yhivian Peñasco (j), Pilar Ricart (k), María Cruz Martin Delgado(l), Luciano Aguilera(m), Alejandro Rodríguez(n), Maria Victoria Boado Varela (o), Fernando Suarez-Sipmann (p), Juan Carlos Pozo-Laderas (q), Jordi Solé-Violan (r), Maite Nieto (s), Mariana Andrea Novo (t), José Barberán (u), Rosario Amaya Villar (v), José Garnacho-Montero (w), Jose Luis García-Garmendia (x), José M. Gómez (y), José Ángel Lorente (b,h), Aaron Blandino Ortiz (z), Luis Tamayo Lomas (aa), Esther López-Ramos (ab), Alejandro Úbeda (ac), Mercedes Catalán-González (ad), Angel Sánchez-Miralles (ae), Ignacio Martínez Varela (af), Ruth Noemí Jorge García (ag), Nieves Franco (ah), Víctor D. Gumucio-Sanguino (ai), Arturo Huerta Garcia (aj), Elena Bustamante-Munguira (ak), Luis Jorge Valdivia (al), Jesús Caballero (am), Elena Gallego (an), Amalia Martínez de la Gándara (ao), Álvaro Castellanos-Ortega (ap), Josep Trenado (aq), Judith Marin-Corral (ar), Guillermo M Albaiceta (b,as), Maria del Carmen de la Torre (at), Ana Loza-Vázquez (au), Pablo Vidal (av), Juan Lopez Messa (aw), Jose M. Añon (b,ax), Cristina Carbajales Pérez (ay), Victor Sagredo (az), Neus Bofill (ba), Nieves Carbonell (bb), Lorenzo Socias(bc), Carme Barberá (bd), Angel Estella (be), Manuel Valledor Mendez (bf), Emili Diaz (bg), Ana López Lago (bh), Antoni Torres (b,d) and Ferran Barbé (a,b*), on behalf of the CIBERESUCICOVID Project (COV20/00110, ISCIII)2 // (a) Translational Research in Respiratory Medicine, University Hospital Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Spain; (b) CIBER of Respiratory Diseases (CIBERES), Institute of Health Carlos III, Madrid, Spain; (c) Critical Care Center, ParcTaulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí I3PT, Sabadell, Spain; (d) Department of Pneumology, Hospital Clinic of Barcelona; August Pi i Sunyer Biomedical Research Institute−IDIBAPS, University of Barcelona, Barcelona, Spain; (e) Intensive Care Department, Vall d’Hebron Hospital Universitari. SODIR Research Group, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain; (f) Barcelona Supercomputing Center (BSC), Barcelona, Spain; (g) Pulmonology Service, University and Polytechnic Hospital La Fe, Valencia, Spain; (h) Hospital Universitario de Getafe, Madrid, Spain; Universidad Europea, Madrid, Spain; (i) Hospital Universitario Río Hortega de Valladolid, Valladolid, Spain; Group for Biomedical Research in Sepsis (BioSepsis), Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain; (j) Servicio de Medicina Intensiva, Hospital Universitario Marqués de Valdecilla, Santander, Spain; (k) Servei de Medicina Intensiva, Hospital Universitari Germans Trias, Badalona, Spain; (l) Hospital Universitario Torrejón-Universidad Francisco de Vitoria, Madrid, Spain; (m) Servicio de Anestesiología y Reanimación, Hospital Universitario Basurto, Bilbao, Spain; (n) Critical Care Department, Hospital Joan XXIII, Tarragona, Spain; (o) Servicio de Medicina Intensiva, Hospital de Cruces, Baracaldo, Vizcaya, Spain; (p) Intensive Care Unit, Hospital Universitario La Princesa, Madrid, Spain; (q) UGC-Medicina Intensiva, Hospital Universitario Reina Sofia, Instituto Maimonides IMIBIC, Córdoba, Spain; (r) Critical Care Department, Hospital Dr. Negrín Gran Canaria, Las Palmas, Gran Canaria, Spain. Universidad Fernando Pessoa, Canarias, Spain; (s) Hospital Universitario de Segovia, Segovia, Spain; (t) Servei de Medicina Intensiva, Hospital Universitari Son Espases, Palma de Mallorca, Illes Balears, Spain; (u) Hospital Universitario HM Montepríncipe, Universidad San Pablo-CEU, Madrid, Spain; vIntensive Care Clinical Unit, Hospital Universitario Virgen de Rocío, Sevilla, Spain; (w) Intensive Care Clinical Unit, Hospital Universitario Virgen Macarena, Seville, Spain; (x) Intensive Care Unit, Hospital San Juan de Dios del Aljarafe, Bormujos, Sevilla, Spain; (y) Hospital General Universitario Gregorio Marañon, Madrid, Spain; (z) Servicio de Medicina Intensiva, Hospital Universitario Ramón y Cajal, Madrid, Spain; (aa) Critical Care Department, Hospital Universitario Río Hortega de Valladolid, Valladolid, Spain; (ab) Servicio de Medicina Intensiva, Hospital Universitario Príncipe de Asturias, Madrid, Spain; (ac) Servicio de Medicina Intensiva, Hospital Punta de Europa, Algeciras, Spain; (ad) Department of Intensive Care Medicine, Hospital Universitario 12 de Octubre, Madrid, Spain; (ae) Hospital de Sant Joan d’Alacant, Alacant, Spain; (af) Critical Care Department, Hospital Universitario Lucus Augusti, Lugo, Spain; (ag) Intensive Care Department, Hospital Nuestra Señora de Gracia, Zaragoza, Spain; (ah) Hospital Universitario de Móstoles, Madrid, Spain; (ai) Department of Intensive Care. Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain. Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; (aj) Pulmonary and Critical Care Division; Emergency Department, Clínica Sagrada Família, Barcelona, Spain; (ak) Department of Intensive Care Medicine, Hospital Clínico Universitario Valladolid, Valladolid, Spain; (al) Hospital Universitario de León, León, Spain; (am) Critical Care Department, Hospital Universitari Arnau de Vilanova; IRBLleida, Lleida, Spain; (an) Unidad de Cuidados Intensivos, Hospital Universitario San Pedro de Alcántara, Cáceres, Spain; (ao) Department of Intensive Medicine, Hospital Universitario Infanta Leonor, Madrid, Spain; (ap) Servicio de medicina intensiva. Hospital Universitario y Politécnico La Fe, Valencia, Spain; (aq) Servicio de Medicina Intensiva, Hospital Universitario Mútua de Terrassa, Terrassa, Barcelona, Spain; (ar) Critical Care Department, Hospital del Mar-IMIM, Barcelona, Spain; (as) Departamento de Biología Funcional. Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo; Instituto de Investigación Sanitaria del Principado de Asturias, Hospital Central de Asturias, Oviedo, Spain; (at) Hospital de Mataró de Barcelona, Spain; (au) Unidad de Medicina Intensiva, Hospital Universitario Virgen de Valme, Sevilla, Spain; (av) Complexo Hospitalario Universitario de Ourense, Ourense, Spain; (aw) Complejo Asistencial Universitario de Palencia, Palencia, Spain; (ax) Servicio de Medicina Intensiva. Hospital Universitario La Paz, IdiPAZ, Madrid, Spain; (ay) Intensive Care Unit, Hospital Álvaro Cunqueiro, Vigo, Spain; (az) Hospital Universitario de Salamanca, Salamanca, Spain; (ba) Department of Physical Medicine and Rehabilitation, Hospital Verge de la Cinta, Tortosa, Tarragona, Spain; (bb) Intensive Care Unit, Hospital Clínico y Universitario de Valencia, Valencia, Spain; (bc) Intensive Care Unit, Hospital Son Llàtzer, Palma de Mallorca, Illes Balears, Spain; (bd) Hospital Santa Maria; IRBLleida, Lleida, Spain; (be) Intensive Care Unit, University Hospital of Jerez. Medicine Department University of Cadiz. INiBICA, Spain; (bf) Hospital Universitario San Agustín, Asturias, Spain; (bg) Department of Medicine, Universitat Autónoma de Barcelona (UAB); Critical Care Department, Corporació Sanitària Parc Taulí, Sabadell, Barcelona, Spain; (bh) Department of Intensive care Medicine, Complejo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, SpainPostprint (published version

Pulmonary function and radiologic features in survivors of critical COVID-19: a 3-month prospective cohort

© 2021 Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/BACKGROUND: More than 20% of hospitalized patients with COVID-19 demonstrate ARDS requiring ICU admission. The long-term respiratory sequelae in such patients remain unclear. RESEARCH QUESTION: What are the major long-term pulmonary sequelae in critical patients who survive COVID-19? STUDY DESIGN AND METHODS: Consecutive patients with COVID-19 requiring ICU admission were recruited and evaluated 3 months after hospitalization discharge. The follow-up comprised symptom and quality of life, anxiety and depression questionnaires, pulmonary function tests, exercise test (6-min walking test [6MWT]), and chest CT imaging. RESULTS: One hundred twenty-five patients admitted to the ICU with ARDS secondary to COVID- 19 were recruited between March and June 2020. At the 3-month follow-up, 62 patients were available for pulmonary evaluation. The most frequent symptoms were dyspnea (46.7%) and cough (34.4%). Eighty-two percent of patients showed a lung diffusing capacity of less than 80%. The median distance in the 6MWT was 400 m (interquartile range, 362-440 m). CT scans showed abnormal results in 70.2% of patients, demonstrating reticular lesions in 49.1% and fibrotic patterns in 21.1%. Patients with more severe alterations on chest CT scan showed worse pulmonary function and presented more degrees of desaturation in the 6MWT. Factors associated with the severity of lung damage on chest CT scan were age and length of invasive mechanical ventilation during the ICU stay. INTERPRETATION: Three months after hospital discharge, pulmonary structural abnormalities and functional impairment are highly prevalent in patients with ARDS secondary to COVID- 19 who required an ICU stay. Pulmonary evaluation should be considered for all critical COVID-19 survivors 3 months after discharge.This study was supported in part by the Instituto de Salud Carlos III [Grant CIBERESUCICOVID, COV20/00110] and was cofunded by European Regional Development Funds, “Una manera de hacer Europa.” D. d. G.-C. has received financial support from the Instituto de Salud Carlos III [Grant Miguel Servet 2020: CP20/00041], co-funded by the European Social Fund “Investing in Your Future.” L. P. acknowledges receiving financial support from the Ministry of Science, Innovation and Universities for the Training of University Lecturers (FPU19 / 03526).Peer ReviewedPostprint (author's final draft