Risk factors for developing ventilator-associated lower respiratory tract infection in patients with severe COVID-19: a multinational, multicentre study, prospective, observational study
Authors: Reyes Luis Felipe , Rodriguez Alejandro , Fuentes Yuli V. , Duque Sara , García-Gallo Esteban , Bastidas Alirio , Serrano-Mayorga Cristian C. , Ibáñez-Prada Elsa D. , Moreno Gerard , Ramirez-Valbuena Paula C. , Ospina-Tascon Gustavo , Hernandez Glenn , Silva Edwin , Díaz Ana Maria , Jibaja Manuel , Vera-Alarcon Magdalena , Díaz Emili , Bodí María , Solé-Violán Jordi , Ferrer Ricard , Albaya-Moreno Antonio , Socias Lorenzo , Figueroa William , Lozano-Villanueva Jose L. , Varón-Vega Fabio , Estella Ángel , Loza-Vazquez Ana , Jorge-García Ruth , Sancho Isabel , Shankar-Hari Manu , Martin-Loeches Ignacio ,   LIVEN-Covid-19, Gorordo Luis Antonio , Buitrago Ricardo , Poveda Marcela , Saucedo Lina Maria , Estenssoro Elisa , Ortiz Guillermo , Nin Nicolas , Arango Alfonso Jose , Aguilar Alvaro , Ayala Andrea Lizeth , Bayona Andrea Viviana , Ayala Andrea Lizeth , Rodriguez Angelica , Aponte Carol Viviana , Forero-Carreño Carolina , Muñoz Conny Stefanny , Estrada Cristian Augusto , Romero Cristopher , Trujillo Danilo , Holguin Diego , Chavez-Villegas Jesus , Rodriguez Faure , Franco Francisco , Sánchez Hernan , Moncayo Janett Vanessa , Pinedo Jennifer A. , Bravo Jesica Valeria , Cruz Jose David , Angel Jose Miguel , Castro-Lara Jovany , Mantilla Karen Andrea , Garcia Lorena , Pabón Lorena , Lopez Luis Arturo , Mamani Luis Fernando , Yupa Marisa Lucrecia , Quevedo Valeria Catalina ,   SEMICYUC Study Group,   Andalucía, Loza Ana , Zapata Diego Matallana , Torres Isabel Díaz , Cuadros Sonia Ibañez , Nuñez María Recuerda , Pérez Maria Luz Carmona , Ramos Jorge Gómez , Casas Alba Villares , Cantón María Luisa , Contreras José Javier González , Chomón Helena Pérez , Chicote Nerissa Alvarez , González Alberto Sousa , De Alba Aparicio María ,   Aragón, García Ruth Jorge , Montori Laura Sánchez , García Sandra Herrero , Moreno Paula Abanses , García Carlos Mayordomo , Bonet Tomás Mallor , Bonafonte Paula Omedas , Gonzalez Enric Franquesa , Vidales Nestor Bueno , Buil Paula Ocabo , Arbeloa Carlos Serón , Sancho Isabel , Ibañez Pablo Guerrero , Gutierrez Pablo , Valdovinos María Concepción , Canto Raquel , García Ruth Jorge , Montori Laura Sánchez , García Sandra Herrero , Moreno Paula Abanses , García Carlos Mayordomo , Bonet Tomás Mallor , Bonafonte Paula Omedas , Gonzalez Enric Franquesa , Vidales Nestor Bueno , Buil Paula Ocabo , Arbeloa Carlos Serón , Sancho Isabel , Ibañez Pablo Guerrero , Gutierrez Pablo , Valdovinos María Concepción , Canto Raquel ,   Asturias, Mariño Ana Luz Balán , Fernández María José Gutiérrez , Cuadrado Marta Martín , Arias Belén García , Espina Lorena Forcelledo , Soria Lucía Viña , Iglesias Lorena Martín , Amor Lucía López , Rey Elisabet Fernández , Prieto Emilio García , Ruíz Débora Fernández , González Carla Martínez ,   Baleares, Socias Lorenzo , Borges‐Sá Marcio , Pérez María Aranda , Socias Antonia , Goytisolo José Ma Bonell , Mayayo Inmaculada Alcalde , Corradini Carlos , Ceniceros Isabel , Rodríguez Edwin , Rota Jose Ignacio Ayestarán , Novo Mariana Andrea , Climent Joaquim Colomina , Castilla Albert Figueras , Rullan Tomàs Leal , Sastre Maria Magdalena Garcias , Senoff Rossana Pérez , Fernández Ramón ,   Canarias, González Juan Carlos Martín , Ortiz Carmen Pérez , Santana José Luciano Cabrera , Agra Juan José Cáceres , Romero Domingo González , Ortega Ana Casamitjana , Gómez Luis Alberto Ramos , Ojeda Carolina Montelongo , Solé-Violán Jordi ,   Cataluña, Rodríguez Alejandro , Bodí María , Moreno Gerard , Trefler Sandra , Claverias Laura , Carbonell Raquel , Esteve Erika , Olona Montserrat , Teixidó Xavier , Vidal Monserrat Vallverdú , Garrido Begoña Balsera , Gallofré Elisabeth Papiol , Martell Raquel Albertos , Peñarrocha Rosa Alcaráz , Casals Xavier Nuvials , Roca Ricard Ferrer , Vázquez Eric Adrián Mayor , Campo Ferrán Roche , Martínez Pablo Concha , Llasat Diego Franch , Masclanz Joan Ramón , Corral Judith Marín‐ , Pérez Purificación , Muñoz Rosana , Vila Clara , de Molina Francisco Javier González , Moya Elisabeth Navas , Trenado Josep , Vallverdú Imma , Castañé Eric , Santos Emili Díaz , Goma Gemma , Edg  ,   Cantabria, Suberviola Borja ,   Castilla La Mancha, Moreno Antonio Albaya , Crespo Carlos Marian , Pérez Carmen Carolina Sena , Linde Francisca Arbol ,   Castilla y León, Donaire Diana Monge , Martínez Vega Losada , Castroviejo Nuria Rodrigo , Ferrigno Gerardo , Beltrán Reyes , Sanmartino Carolina , Maján Concepción Tarancón , Gutiérrez Alfredo Marcos , Valverde Virginia Hidalgo , López Caridad Martín , Badallo Oihane , del Valle Ortiz María , Arlanzón Rebeca Vara , Posadilla David Iglesias , Recio María Teresa , Ballesteros Juan Carlos ,   Ceuta, Laza Enrique ,   Extremadura, Curto Elena Gallego , García Ma Car‐men Sánchez , Díaz‐Tavora Miguel , Mancha Rosa ,   Galicia, Montes Ana Ortega , Barbachano Isabel Gallego , Mantiñán Eva Sanmartín , Cordero María Lourdes , García Raquel María Rodríguez , Zapata Jorge Gámez , Vázquez María Gestal , Orjales María José Castro , Diéguez María Isabel Álvarez , Velasco Carmen Rivero , Massa Beatriz Lence , Vázquez María Gestal , Martí Ignacio ,   Huelva, Zapata Diego Matallana ,   Madrid, Tejedor Alberto Hernández , Ramos Esther Ma López , Elvira Laura Alcázar Sánchez , Montero Rocío Molina , Delgado Ma Consuelo Pintado , de la Peña María Trascasa Muñoz , de Zárate Ansotegui Yaiza Betania Ortiz , Aranda Alejandra Acha , Lucas Juan Higuera , Giralt Juan Antonio Sanchez , Llano Marta Chicot , Fernández Nuria Arevalillo , Galindo Marta Sánchez , Ruiz Ricardo Andino , Berlanga Alfonso Canabal , Sánchez Miguel , Nieto Mercedes , Sarmiento Eduardo Arias , Blázquez Adoración Bueno , de la Casa Rosa María , Martín Fátima , González Samuel ,   Murcia, Quintana Elena Martínez , Rueda Bernardo Gil , Cañigral Áurea Higon , Gómez Laura López , Delis Pablo Safwat Bayoumi , Muore Augusto Montenegro , Luengas Ángel Andrés Agamez , Soler Enriqueta Andreu , Pérez Ana Beatriz , de Gea García José Higinio , Rubio Rubén Jara , Cámara Silvia Sánchez , Flores Alba Moreno , Sánchez José Moya , Martínez Daniel Fran‐cisco Pérez , del Rey Carrión Ma Desamparados , Lledó María José Rico , Navarro Juana María Serrano , Ruíz Juan Fran‐cisco Martín , Hidalgo Julián Triviño , Ferrer África López , Navalón Isabel Cremades , Payá Josefa Murcia , Gallego J. M. Allegre , del Carmen Lorente María ,   Navarra, Natera Ruth González , de Murillo Raquel Garrido López , Gros Tania Ojuel , Viguera Raquel Flecha , González Isabel López , Herrera Adriana García ,   País Vasco, Tello Loreto Vidaur , Aseguinolaza Maialen , Eguibar Itziar ,   Valencia, Parra Asunción Marqués , Marti Sergio García , Aguilar Alberto Lorenzo , Bosch Laura Bellver , Sanchez Victor Gascón , De la Guía Ortega Sonia , Montell Martín Parejo , Muncharaz Alberto Belenguer , Garces Hector Hernández , Montero Victor Ramírez , Gómez Mónica Crespo , Algarra Verónica Martí , Chinesta Susana Sancho , Cervera Joaquin Arguedas , Cebrian Faustino Álvarez , Pérez Begoña Balerdi , Fores Rosa Jannone , de Maglia Javier Botella , Monleón Nieves Carbonell , Franco Jose Ferreres , Lazaro Ainhoa Serrano , Díaz Mar Juan , Cortés María Luisa Blasco , Fayos Laura , Giménez Julia , Soriano Gaspar , Navarro Ricardo , Mas Sonia , Bisbal Elena , Albert Laura , Romero Johncard , Cabreara Juan Fernández , Ortíz Andrea ,   Principado de Andorra, Ribas Antonio Margarit , Guasch Neus 
Published: April 2023

Around one-third of patients diagnosed with COVID-19 develop a severe illness that requires admission to the Intensive Care Unit (ICU). In clinical practice, clinicians have learned that patients admitted to the ICU due to severe COVID-19 frequently develop ventilator-associated lower respiratory tract infections (VA-LRTI). This study aims to describe the clinical characteristics, the factors associated with VA-LRTI, and its impact on clinical outcomes in patients with severe COVID-19. This was a multicentre, observational cohort study conducted in ten countries in Latin America and Europe. We included patients with confirmed rtPCR for SARS-CoV-2 requiring ICU admission and endotracheal intubation. Only patients with a microbiological and clinical diagnosis of VA-LRTI were included. Multivariate Logistic regression analyses and Random Forest were conducted to determine the risk factors for VA-LRTI and its clinical impact in patients with severe COVID-19. In our study cohort of 3287 patients, VA-LRTI was diagnosed in 28.8% [948/3287]. The cumulative incidence of ventilator-associated pneumonia (VAP) was 18.6% [610/3287], followed by ventilator-associated tracheobronchitis (VAT) 10.3% [338/3287]. A total of 1252 bacteria species were isolated. The most frequently isolated pathogens werePseudomonas aeruginosa(21.2% [266/1252]), followed byKlebsiella pneumoniae(19.1% [239/1252]) andStaphylococcus aureus(15.5% [194/1,252]). The factors independently associated with the development of VA-LRTI were prolonged stay under invasive mechanical ventilation, AKI during ICU stay, and the number of comorbidities. Regarding the clinical impact of VA-LRTI, patients with VAP had an increased risk of hospital mortality (OR [95% CI] of 1.81 [1.40–2.34]), while VAT was not associated with increased hospital mortality (OR [95% CI] of 1.34 [0.98–1.83]). VA-LRTI, often with difficult-to-treat bacteria, is frequent in patients admitted to the ICU due to severe COVID-19 and is associated with worse clinical outcomes, including higher mortality. Identifying risk factors for VA-LRTI might allow the early patient diagnosis to improve clinical outcomes.

Trial registration:This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable.