One year overview and follow-up in a post-COVID consultation of critically ill patients

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.This study was supported in part by ISCIII (CIBERESUCICOVID, COV20/00110), co-funded by ERDF, “Una manera de hacer Europa,” donation program “Estar Preparados,” UNESPA, Madrid, Spain and Fundación Soria Melguizo (Madrid, Spain). DG-C had received financial support from Instituto de Salud Carlos III (Miguel Servet 2020: CP20/00041), co-funded by the European Social Fund (ESF)/“Investing in your future.” JB acknowledged receiving financial support from Instituto de Salud Carlos III (ISCIII; Miguel Servet 2019: CP19/00108), co-funded by the European Social Fund (ESF), “Investing in your future.”Peer ReviewedArticle signat per 29 autors/es: Jessica González (1,2,3,4), María Zuil (1,2,3,4), Iván D. Benítez (2,3,4), David de Gonzalo-Calvo (2,3,4), María Aguilar (1,2), Sally Santisteve (1,2,3,4), Rafaela Vaca (1,2), Olga Minguez (1,2), Faty Seck (1,2), Gerard Torres (1,2,3,4), Jordi de Batlle (2,3,4), Silvia Gómez (1,2,3,4), Silvia Barril (1,2,3,4), Anna Moncusí-Moix (2,3,4), Aida Monge (1,2,3,4), Clara Gort-Paniello (2,3,4), Ricard Ferrer (4,5), Adrián Ceccato (4), Laia Fernández (4,6), Ana Motos (4,6), Jordi Riera (4,5), Rosario Menéndez (4,7), Darío Garcia-Gasulla (8), Oscar Peñuelas (4,9), Gonzalo Labarca (10,11), Jesús Caballero (12), Carme Barberà (13), Antoni Torres (4,6) and Ferran Barbé (1,2,3,4) * on behalf of the CIBERESUCICOVID Project (COV20/00110, ISCIII) // (1) Department of Pulmonary, Hospital Universitari Arnau de Vilanova and Santa Maria, Lleida, Spain, (2) Translational Research in Respiratory Medicine Group, Lleida, Spain, (3) Lleida Biomedical Research Institute, Lleida, Spain, (4) Centro de Investigación Biomédica en Red (CIBER) of Respiratory Diseases, Institute of Health Carlos III, Madrid, Spain, (5) Intensive Care Department, Vall d’Hebron Hospital Universitari, Shock, Organ Dysfunction and Resuscitation (SODIR) Research Group, Vall d’Hebron Institut de Recerca, Barcelona, Spain, (6) Department of Pulmonary, Hospital Clinic, Universitat de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, (7) Department of Pulmonary, University and Polytechnic Hospital La Fe, Valencia, Spain, (8) Barcelona Supercomputing Center, Barcelona, Spain, (9) Hospital Universitario de Getafe, Madrid, Spain, (10) Faculty of Medicine, University of Concepción, Concepción, Chile, (11) Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, Concepción, Chile, (12) Intensive Care Department, Hospital Universitari Arnau de Vilanova de Lleida, Lleida, Spain, (13) Intensive Care Department, Hospital Universitari Santa Maria de Lleida, Lleida, SpainPostprint (published version

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