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

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 Investigaci on Biom edica en Red − Enfermedades Res- piratorias (CIBERES) and Donation Program “estar pre- parados”, UNESPA, Madrid, Spain. JdB acknowledges receiving financial support from Instituto de Salud Car- los III (ISCIII; Miguel Servet 2019: CP19/00108), co- funded 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).Benítez ID, de Batlle J, Torres G, González J, de Gonzalo-Calvo D, Targa ADS, Gort-Paniello C, Moncusí-Moix A, Ceccato A, Fernández-Barat L, Ferrer R, Garcia-Gasulla D, Menéndez R, Motos A, Peñuelas O, Riera J, Bermejo-Martin JF, Peñasco Y, Ricart P, Martin Delgado MC, Aguilera L, Rodríguez A, Boado Varela MV, Suarez-Sipmann F, Pozo-Laderas JC, Solé-Violan J, Nieto M, Novo MA, Barberán J, Amaya Villar R, Garnacho-Montero J, García-Garmendia JL, Gómez JM, Lorente JÁ, Blandino Ortiz A, Tamayo Lomas L, López-Ramos E, Úbeda A, Catalán-González M, Sánchez-Miralles A, Martínez Varela I, Jorge García RN, Franco N, Gumucio-Sanguino VD, Huerta Garcia A, Bustamante-Munguira E, Valdivia LJ, Caballero J, Gallego E, Martínez de la Gándara A, Castellanos-Ortega Á, Trenado J, Marin-Corral J, Albaiceta GM, de la Torre MDC, Loza-Vázquez A, Vidal P, Lopez Messa J, Añón JM, Carbajales Pérez C, Sagredo V, Bofill N, Carbonell N, Socias L, Barberà C, Estella A, Valledor Mendez M, Diaz E, López Lago A, Torres A, Barbé F; CIBERESUCICOVID Project (COV20/00110, ISCIII

ICU-Acquired Pneumonia Is Associated with Poor Health Post-COVID-19 Syndrome

Background: 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

Risk factors associated with mortality among elderly patients with COVID-19: Data from 55 intensive care units in Spain

On behalf of CIBERESUCICOVID Project (COV20/00110ISCIII).Introduction and objectives: Critically-ill elderly ICU patients with COVID-19 have poor outcomes. We aimed to compare the rates of in-hospital mortality between non-elderly and elderly critically-ill COVID-19 ventilated patients, as well as to analyze the characteristics, secondary outcomes and independent risk factors associated with in-hospital mortality of elderly ventilated patients. Patients and Methods: We conducted a multicentre, observational cohort study including consecutive critically-ill patients admitted to 55 Spanish ICUs due to severe COVID-19 requiring mechanical ventilation (non-invasive respiratory support [NIRS; include non-invasive mechanical ventilation and high-flow nasal cannula] and invasive mechanical ventilation [IMV]) between February 2020 and October 2021. Results: Out of 5,090 critically-ill ventilated patients, 1,525 (27%) were aged =70 years (554 [36%] received NIRS and 971 [64%] received IMV. In the elderly group, median age was 74 years (interquartile range 72–77) and 68% were male. Overall in-hospital mortality was 31% (23% in patients <70 years and 50% in those =70 years; p<0.001). In-hospital mortality in the group =70 years significantly varied according to the modality of ventilation (40% in NIRS vs. 55% in IMV group; p<0.001). Factors independently associated with in-hospital mortality in elderly ventilated patients were age (sHR 1.07 [95%CI 1.05–1.10], p<0.001); previous admission within the last 30 days (sHR 1.40 [95%CI 1.04–1.89], p = 0.027); chronic heart disease (sHR 1.21 [95%CI 1.01–1.44], p = 0.041); chronic renal failure (sHR 1.43 [95%CI 1.12- 1.82], p = 0.005); platelet count (sHR 0.98 [95% CI 0.98–0.99], p<0.001); IMV at ICU admission (sHR 1.41 [95% CI 1.16- 1.73], p<0.001); and systemic steroids (sHR 0.61 [95%CI 0.48- 0.77], p<0.001). Conclusions: Amongst critically-ill COVID-19 ventilated patients, those aged =70 years presented significantly higher rates of in-hospital mortality than younger patients. Increasing age, previous admission within the last 30 days, chronic heart disease, chronic renal failure, platelet count, IMV at ICU admission and systemic steroids (protective) all comprised independent factors for in-hospital mortality in elderly patientsThis study was supported by the Instituto de Salud Carlos III de Madrid (COV20/00110, ISCIII); Fondo Europeo de Desarrollo Regional (FEDER); "Una manera de hacer Europa"; and Centro de Investigacion Biomédica 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”. CC received a grant from the Fondo de Investigacion Sanitaria ( PI19/00207), Instituto de Salud Carlos III, co-funded by the European Union.Peer ReviewedCIBERESUCICOVID Project Investigators: Víctor D. Gumucio- Sanguino, Rafael Manez: Hospital Universitario de Bellvitge, Barcelona. Jordi Sole-Violan, Felipe Rodríguez de Castro: Hospital Dr. Negrín, Las Palmas. Fernando SuarezSipmann: Hospital Universitario La Princesa, Madrid. Ruth Noemí Jorge García, María Mora Aznar: Hospital Nuestra Senora de Gracia, Zaragoza. Mateu Torres, María Martinez, Cynthia Alegre, Jordi Riera, Sofía Contreras: Hospital Universitari Vall d’Hebron, Barcelona. Jesus Caballero, Javier Trujillano, Montse Vallverdu, Miguel Leon, Mariona Badía, Begona Balsera, Lluís Servia, Judit Vilanova, Silvia Rodríguez, Neus Montserrat, Silvia Iglesias, Javier Prados, Sula Carvalho, Mar Miralbes, Josman Monclou, Gabriel Jimenez, Jordi Codina, Estela Val, Pablo Pagliarani, Jorge Rubio, Dulce Morales, Andres Pujol, Angels Furro, Beatriz García, Gerard Torres, Javier Vengoechea, David de Gonzalo-Calvo, Jessica Gonzalez, Silvia Gomez: Hospital Universitari Arnau de Vilanova, Lleida. Jose M. Gomez: Hospital General Universitario Gregorio Marañon, Madrid. Nieves Franco: Hospital Universitario de Mostoles, Madrid. Jose Barberan: Hospital Universitario HM Montepríncipe. Guillermo M Albaiceta, Lorena Forcelledo Espina, Emilio García Prieto, Paula Martín Vicente, Cecilia del Busto Martínez: Hospital Universitario Central de Asturias, Oviedo. Pablo Vidal: Complexo Hospitalario Universitario de Ourense, Ourense. Jose Luis García Garmendia, María Aguilar Cabello, Carmen Eulalia Martínez Fernandez: Hospital San Juan de Dios del Aljarafe, Sevilla. Nieves Carbonell, María Luisa Blasco Cortes, Ainhoa Serrano Lazaro, Mar Juan Díaz: Hospital Clínic Universitari de Valencia, Valencia. Aaron Blandino Ortiz:Hospital Universitario Ramon y Cajal, Madrid. Rosario Menendez: Hospital La Fe de Valencia. Luis Jorge Valdivia: Hospital Universitario de Leon, Leon. María Victoria Boado: Hospital Universitario de Cruces, Barakaldo. Susana Sancho Chinesta: Hospital Universitario y Politecnico La Fe, Valencia. Maria del Carmen de la Torre: Hospital de Mataro. Ignacio Martínez Varela, María Teresa Bouza Vieiro, Ines Esmorís Arij on: Hospital Universitario Lucus Augusti, Lugo. David Campi Hermoso., Rafaela Nogueras Salinas., Teresa Farre Monjo., Ramon Nogue Bou., Gregorio Marco Naya., Carme Barbera, Nuria Ramon Coll: Hospital Universitari de Santa Maria, Lleida. Mercedes Catalan-Gonzalez, Juan Carlos Montejo-Gonzalez: Hospital Universitario 12 de Octubre, Madrid. Gloria Renedo SanchezGiron, Juan Bustamante-Munguira, Elena Bustamante-Munguira, Ramon Cicuendez Avila, Nuria Mamolar Herrera: Hospital Clínico Universitario, Valladolid. Raquel Almansa: Instituto de Investigacion Biomedica de Salamanca (IBSAL). Víctor Sagredo: Hospital Universitario de Salamanca, Salamanca. Jose Anon, Alexander Agrifoglio, Lucia Cachafeiro, Emilio Maseda: Hospital Universitario La Paz-Carlos III, Madrid. Lorenzo Socias, Mariana Andrea Novo, Albert Figueras, Maria Teresa Janer, Laura Soliva, Marta Ocon, Luisa Clar, J Ignacio Ayestaran: Hospital Universitario Son Espases, Palma de Mallorca. Yhivian Penasco, Sandra Campos Fernandez: Hospital Universitario Marques de Valdecilla, Santander. Mireia Serra-Fortuny, Eva Forcadell-Ferreres, Immaculada Salvador-Adell, Neus Bofill, Berta Adell-Serrano, Josep Pedregosa Díaz, Nuria Casacuberta-Barbera, Luis Urrelo-Cerron, Angels Piñol-Tena, Ferran Roche-Campo: Hospital Verge de la Cinta de Tortosa, Tortosa. Amalia Martínez de la Gandara, Pablo Ryan Murua, Covadonga Rodríguez Ruíz, Laura Carrion García, Juan I Lazo Alvarez: Hospital Universitario Infanta Leonor, Madrid. Jose Angel Lorente: Hospital Universitario de Getafe. Ana Loza-Vazquez, Desire Macias Guerrero: Hospital Universitario Virgen de Valme, Sevilla. Arturo Huerta, Daniel Tognetti: Clinica Sagrada Familia, Barcelona. Carlos García Redruello, David Mosquera Rodríguez, Eva María Menor Fernandez, Sabela Vara Adrio, Vanesa Gomez Casal, Marta Segura Pensado, María Digna Rivas Vilas, Amaia García Sagastume: Hospital de Vigo, Vigo. Raul de Pablo Sanchez, David Pesta na Laguna, Tommaso Bardi: Hospital Universitario Ramon y Cajal, Madrid. Rosario Amaya Villar, Carmen Gomez Gonzalez, Maria Luisa Gascon Castillo: Hospital Universitario Virgen del Rocio, Sevilla. Jose Garnacho-Montero, María Luisa Canton-Bulnes: Hospital Universitario Virgen Macarena, Sevilla. Judith Marin-Corral, Cristina Carbajales Perez: Hospital Alvaro Cunqueiro, Vigo. Joan Ramon Masclans, Ana Salazar Degracia, Judit Bigas, Rosana Munoz-Bermudez, Clara Vila-Vilardel, Francisco Parrilla, Irene Dot, Ana Zapatero, Yolanda Díaz, María Pilar Gracia, Purificacion Perez, Andrea Castellví, Cristina Climent: Hospital del Mar, Barcelona. Lidia Serra, Laura Barbena, Iosune Cano: Consorci Sanitari del Maresme, Barcelona. Pilar Ricart, Alba Herraiz, Pilar Marcos, Laura Rodríguez, Maria Teresa Sarinena, Ana Sanchez: Hospital Universitari Germans Trias i Pujol, Badalona. Alejandro Ubeda: Hospital Punta de Europa, Algeciras. María Cruz Martin Delgado: Hospital Universitario Torrejon-Universidad Francisco de Vitoria, Madrid. Elena Gallego, Juan Fernando Masa Jimenez: Hospital Universitario San Pedro de Alcantara, Caceres. Gemma Goma, Emi Díaz: Hospital Parc Taulí, Sabadell. Mercedes Ibarz, Diego De Mendoza: Hospital Universitari Sagrat Cor, Bacelona. Enric Barbeta, Victoria Alcaraz-Serrano, Joan Ramon Badia, Manuel Castella, Leticia Bueno, Adrian Ceccato, Andrea Palomeque, Laia Fernandez Barat, Catia Cilloniz, Pamela Conde, Javier Fernandez, Albert Gabarrus, Karsa Kiarostami, Alexandre Lopez- Gavín, Cecilia L Mantellini, Carla Speziale, Nil Vazquez, Hua Yang, Minlan Yang, Carlos Ferrando, Pedro Castro, Marta Arrieta, Jose Maria Nicolas, Rut Andrea: Hospital Clinic, Barcelona. Marta Barroso, Raquel Perez, Sergio Alvarez, Dario Garcia-Gasulla, Adrian Tormos: Barcelona supercomputing Center, Barcelona. Luis Tamayo Lomas, Cesar Aldecoa, Ruben Herran-Monge, Jose Angel Berezo García, Pedro Enríquez Giraudo: Hospital Rio Hortega, Valladolid. Pablo Cardinal Fernandez, Alberto Rubio Lopez, Orville Baez Pravia: Hospitales HM, Madrid. Juan Lopez Messa, Leire Perez Bastida, Antonjo Alvarez Ruiz: Complejo Asistencial Universitario de Palencia, Palencia. Jose Trenado, Anna Parera Pous: Hospital Universitari MutuaTerrassa, Terrassa. Cristobal Galban, Ana Lopez Lago, Eva Saborido Paz, Patricia Barral Segade: Hospital de Santiago de Compostela, Santiago. Ana Balan Marino, Manuel Valledor Mendez: Hospital San Agustin, Aviles. Raul de Frutos, Luciano Aguilera: Hospital Basurto, Basurto. Felipe Perez-García, Esther Lopez-Ramos, Angela Leonor Ruiz-García, Belen Betere: Hospital Universitario Principe Asturias, Alcala de Henares. Rafael Blancas: Hospital Universitario del Tajo, Aranjuez. Cristina Dolera, Gloria Perez Planelles, Enrique Marmol Peis, Maria Dolores Martinez Juan, Miriam Ruiz Miralles, Eva Perez Rubio, Maria Van der Hofstadt MartinMontalvo, Angel Sanchez-Miralles, Tatiana Villada Warrington: Hospital Universitario Sant Joan d’Alacant, Alicante. Juan Carlos Pozo-Laderas: Hospital Universitario Reina Sofia. Angel Estella, Sara Guadalupe Moreno Cano: Hospital de Jerez, Jerez. Federico Gordo: Hospital Universitario del Henares, Coslada. Basilisa Martinez Palacios: Hospital Universitario Infanta Cristina, Parla. Maite Nieto, Maria Teresa Nieto: Hospital de Segovia, Segovia. Sergio Ossa: Hospital de Burgos, Burgos. Ana Ortega: Hospital Montecelo, Pontevedra. Miguel Sanchez: Hospital Clinico, Madrid. Bitor Santacoloma: Hospital Galdakao, Galdakao.Postprint (published version

Procalcitonin and C-reactive protein to rule out early bacterial coinfection in COVID-19 critically ill patients

PurposeAlthough the prevalence of community-acquired respiratory bacterial coinfection upon hospital admission in patients with coronavirus disease 2019 (COVID-19) has been reported to be < 5%, almost three-quarters of patients received antibiotics. We aim to investigate whether procalcitonin (PCT) or C-reactive protein (CRP) upon admission could be helpful biomarkers to identify bacterial coinfection among patients with COVID-19 pneumonia.MethodsWe carried out a multicentre, observational cohort study including consecutive COVID-19 patients admitted to 55 Spanish intensive care units (ICUs). The primary outcome was to explore whether PCT or CRP serum levels upon hospital admission could predict bacterial coinfection among patients with COVID-19 pneumonia. The secondary outcome was the evaluation of their association with mortality. We also conducted subgroups analyses in higher risk profile populations.ResultsBetween 5 February 2020 and 21 December 2021, 4076 patients were included, 133 (3%) of whom presented bacterial coinfection. PCT and CRP had low area under curve (AUC) scores at the receiver operating characteristic (ROC) curve analysis [0.57 (95% confidence interval (CI) 0.51-0.61) and 0.6 (95% CI, 0.55-0.64), respectively], but high negative predictive values (NPV) [97.5% (95% CI 96.5-98.5) and 98.2% (95% CI 97.5-98.9) for PCT and CRP, respectively]. CRP alone was associated with bacterial coinfection (OR 2, 95% CI 1.25-3.19; p = 0.004). The overall 15, 30 and 90 days mortality had a higher trend in the bacterial coinfection group, but without significant difference. PCT & GE; 0.12 ng/mL was associated with higher 90 days mortality.ConclusionOur study suggests that measurements of PCT and CRP, alone and at a single time point, are not useful for ruling in or out bacterial coinfection in viral pneumonia by COVID-19

Multiplex protein profiling of bronchial aspirates reveals disease-, mortality- and respiratory sequelae-associated signatures in critically ill patients with ARDS secondary to SARS-CoV-2 infection

Introduction: Bronchial aspirates (BAS) obtained during invasive mechanical ventilation (IMV) constitutes a useful tool for molecular phenotyping and decision making. Aim: To identify the proteomic determinants associated with disease pathogenesis, all-cause mortality and respiratory sequelae in BAS samples from critically ill patients with SARS-CoV-2-induced ARDS. Methods: Multicenter study including 74 critically ill patients with COVID-19 and non-COVID-19 ARDS. BAS were obtained by bronchoaspiration after IMV initiation. Three hundred sixty-four proteins were quantified using proximity extension assay (PEA) technology. Random forest models were used to assess predictor importance. Results: After adjusting for confounding factors, CST5, NADK, SRPK2 and TGFa were differentially detected in COVID-19 and non-COVID-19 patients. In random forest models for COVID-19, CST5, DPP7, NADK, KYAT1 and TYMP showed the highest variable importance. In COVID-19 patients, reduced levels of ENTPD2 and PTN were observed in nonsurvivors of ICU stay, even after adjustment. AGR2, NQO2, IL-1a, OSM and TRAIL showed the strongest associations with in-ICU mortality and were used to construct a proteinbased prediction model. Kaplan-Meier curves revealed a clear separation in mortality risk between subgroups of PTN, ENTPD2 and the prediction model. Cox regression models supported these findings. In survivors, the levels of FCRL1, NTF4 and THOP1 in BAS samples obtained during the ICU stay correlated with lung function (i.e., DLCO levels) 3 months after hospital discharge. Similarly, Flt3L and THOP1 levels were correlated with radiological features (i.e., TSS). These proteins are expressed in immune and nonimmune lung cells. Poor host response to viral infectivity and an inappropriate reparative mechanism seem to be linked with the pathogenesis of the disease and fatal outcomes, respectively. Conclusion: BAS proteomics identified novel factors associated with the pathology of SARS-CoV-2-induced ARDS and its adverse outcomes. BASbased protein testing emerges as a novel tool for risk assessment in the ICU

Impact of time to intubation on mortality and pulmonary sequelae in critically ill patients with COVID-19: a prospective cohort study

Question: We evaluated whether the time between first respiratory support and intubation of patients receiving invasive mechanical ventilation (IMV) due to COVID-19 was associated with mortality or pulmonary sequelae. Materials and methods: Prospective cohort of critical COVID-19 patients on IMV. Patients were classified as early intubation if they were intubated within the first 48 h from the first respiratory support or delayed intubation if they were intubated later. Surviving patients were evaluated after hospital discharge. Results: We included 205 patients (140 with early IMV and 65 with delayed IMV). The median [p25;p75] age was 63 [56.0; 70.0] years, and 74.1% were male. The survival analysis showed a significant increase in the risk of mortality in the delayed group with an adjusted hazard ratio (HR) of 2.45 (95% CI 1.29-4.65). The continuous predictor time to IMV showed a nonlinear association with the risk of in-hospital mortality. A multivariate mortality model showed that delay of IMV was a factor associated with mortality (HR of 2.40; 95% CI 1.42-4.1). During follow-up, patients in the delayed group showed a worse DLCO (mean difference of - 10.77 (95% CI - 18.40 to - 3.15), with a greater number of affected lobes (+ 1.51 [95% CI 0.89-2.13]) and a greater TSS (+ 4.35 [95% CI 2.41-6.27]) in the chest CT scan. Conclusions: Among critically ill patients with COVID-19 who required IMV, the delay in intubation from the first respiratory support was associated with an increase in hospital mortality and worse pulmonary sequelae during follow-up.The study was supported in part by ISCIII (CIBERESUCICOVID, COV20/00110), co‑funded by ERDF, “Una manera de hacer Europa” and Donation pro‑gram "estar preparados". UNESPA. Madrid. Spain David de Gonzalo Calvo acknowledges receiving financial support from Instituto de Salud Carlos III (ISCIII); Miguel Servet 2020: CP20/00041), co‑funded by the European Social Fund (ESF), “Investing in your future”. JdB acknowledges receiving financial support from Instituto de Salud Carlos III (Miguel Servet 2019: CP19/00108), co‑funded by European Regional European Social Fund (ESF), “Investing in your future

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. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd

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

Clustering COVID-19 ARDS patients through the first days of ICU admission. An analysis of the CIBERESUCICOVID Cohort

Background Acute respiratory distress syndrome (ARDS) can be classified into sub-phenotypes according to different inflammatory/clinical status. Prognostic enrichment was achieved by grouping patients into hypoinflammatory or hyperinflammatory sub-phenotypes, even though the time of analysis may change the classification according to treatment response or disease evolution. We aimed to evaluate when patients can be clustered in more than 1 group, and how they may change the clustering of patients using data of baseline or day 3, and the prognosis of patients according to their evolution by changing or not the cluster.Methods Multicenter, observational prospective, and retrospective study of patients admitted due to ARDS related to COVID-19 infection in Spain. Patients were grouped according to a clustering mixed-type data algorithm (k-prototypes) using continuous and categorical readily available variables at baseline and day 3.Results Of 6205 patients, 3743 (60%) were included in the study. According to silhouette analysis, patients were grouped in two clusters. At baseline, 1402 (37%) patients were included in cluster 1 and 2341(63%) in cluster 2. On day 3, 1557(42%) patients were included in cluster 1 and 2086 (57%) in cluster 2. The patients included in cluster 2 were older and more frequently hypertensive and had a higher prevalence of shock, organ dysfunction, inflammatory biomarkers, and worst respiratory indexes at both time points. The 90-day mortality was higher in cluster 2 at both clustering processes (43.8% [n = 1025] versus 27.3% [n = 383] at baseline, and 49% [n = 1023] versus 20.6% [n = 321] on day 3). Four hundred and fifty-eight (33%) patients clustered in the first group were clustered in the second group on day 3. In contrast, 638 (27%) patients clustered in the second group were clustered in the first group on day 3.Conclusions During the first days, patients can be clustered into two groups and the process of clustering patients may change as they continue to evolve. This means that despite a vast majority of patients remaining in the same cluster, a minority reaching 33% of patients analyzed may be re-categorized into different clusters based on their progress. Such changes can significantly impact their prognosis

Mechanical power is not associated with mortality in COVID-19 mechanically ventilated patients

Publisher Copyright: © The Author(s) 2025.Background: The relative contribution of the different components of mechanical power to mortality is a subject of debate and has not been studied in COVID-19. The aim of this study is to evaluate both the total and the relative impact of each of the components of mechanical power on mortality in a well-characterized cohort of patients with COVID-19-induced acute respiratory failure undergoing invasive mechanical ventilation. This is a secondary analysis of the CIBERESUCICOVID project, a multicenter observational cohort study including fifty Spanish intensive care units that included COVID-19 mechanically ventilated patients between February 2020 and December 2021. We examined the association between mechanical power and its components (elastic static, elastic dynamic, total elastic and resistive power) with 90-day mortality after adjusting for confounders in seven hundred ninety-nine patients with COVID-19-induced respiratory failure undergoing invasive mechanical ventilation. Results: At the initiation of mechanical ventilation, the PaO2/FiO2 ratio was 106 (78; 150), ventilatory ratio was 1.69 (1.40; 2.05), and respiratory system compliance was 35.7 (29.2; 44.5) ml/cmH2O. Mechanical power at the initiation of mechanical ventilation was 24.3 (18.9; 29.6) J/min, showing no significant changes after three days. In multivariable regression analyses, mechanical power and its components were not associated with 90-day mortality at the start of mechanical ventilation. After three days, total elastic and elastic static power were associated with higher 90-day mortality, but this relationship was also found for positive end-expiratory pressure. Conclusions: Neither mechanical power nor its components were independently associated with mortality in COVID-19-induced acute respiratory failure at the start of MV. Nevertheless, after three days, static elastic power and total elastic power were associated with lower odds of survival. Positive end-expiratory pressure and plateau pressure, however, captured this risk in a similar manner.Peer reviewe