Early corticosteroids are associated with lower mortality in critically ill patients with COVID-19: a cohort study
Authors: Monedero Pablo , Gea Alfredo , Castro Pedro , Candela-Toha Angel M. , Hernández-Sanz María L. , Arruti Egoitz , Villar Jesús , Ferrando Carlos ,   the COVID-19 Spanish ICU Network, Monedero Pablo , Gea Alfredo , Castro Pedro , Candela-Toha Angel M. , Vendrell Marina , Sánchez-Etayo Gerard , Alcón Amalia , Belda Isabel , Agustí Mercé , Carramiñana Albert , Gracia Isabel , Panzeri Miriam , León Irene , Balust Jaume , Navarro Ricard , Arguís María José , Carretero María José , Ibáñez Cristina , Perdomo Juan , López Antonio , López-Baamonde Manuel , Cuñat Tomás , Ubré Marta , Ojeda Antonio , Calvo Andrea , Rivas Eva , Hurtado Paola , Pujol Roger , Martín Nuria , Tercero Javier , Sanahuja Pepe , Magaldi Marta , Coca Miquel , del Rio Elena , Martínez-Ocon Julia , Masgoret Paula , Tio Monserrat , Caballero Angel , Risco Raquel , Bergé Raquel , Gómez Lidia , de Riva Nicolás , Ruiz Ana , Beatriz  , Tena  , Jaramillo Sebastián , Balibrea José María , de Lacy Francisco Borja , Otero Ana , Ibarzabal Ainitze , Bravo Raquel , Carreras Anna , Martín-Barreda Daniel , Alias Alfonso Jesús , Balaguer Mariano , Aliaga Jorge , Almuedo Alex , Alonso Joan Ramón , Andrea Rut , Angelès Gerard Sergi , Arias Marilyn , Aziz Fátima , Badía Joan Ramon , Barbeta Enric , Torres Toni , Batiste Guillem , Benet Pau , Borrat Xavi , Borrell María , Bragulat Ernest , Carmona Inmaculada , Castellà Manuel , Castro Pedro , Ceravalls Joan , Comino Oscar , Cucciniello Claudia , De Deray Clàudia , De Diego Oriol , De la Matta Paula , Farrero Marta , Fernández Javier , Fernández Sara , Fernández Anna , Ferrer Miquel , Fervienza Ana , Forga María Tallo , Forné Daniel , Galán Clàudia , Gómez Andrea , Guasch Eduard , Hernández-Tejero María , Jacas Adriana , Jiménez Beltrán , Leyes Pere , López Teresa , Martínez José Antonio , Martínez-Pallí Graciela , Mercadal Jordi , Muñoz Guido , Muñoz José , Navarro Ricard , Nicolás Josep María , Ortiz José Tomás , Peiró Anna , Pérez Manuel , Poch Esteban , Pujol Margarida , Quintana Eduard , Ramis Bartomeu , Reverter Enric , Rovira Irene , Ruiz Pablo , Sandoval Elena , Schneider Stefan , Sibila Oriol , Solé Carla , Soriano Alex , Soy Dolors , Suárez M. , Téllez Adrián , Toapanta Néstor David , Torres Antoni , Urra Xavier , Aldecoa César , Bordell Alicia , Martín Silvia , Andrés Judith , Ruiz Alberto Martínez , Medel Gonzalo Tamayo , Villasante Iñaki Bilbao , Clavero Fernando Iturri , Álvarez Covadonga Peralta , Díez Julia T. Herrera , Trancho Andrea García , Mandiola Iñaki Sainz , Suarez Carmen Ruano , Bocos Angela Ruiz , Izagirre Eneritz Urrutia , de Urbina Fernández Pablo Ortiz , López Naiara Apodaka , Molano Leire Prieto , Martínez Eunate Ganuza , Hidalgo Iratxe Vallinas , de Orte Sancho Karmele , Paniagua Celia González , Labrador Gemma Ortiz , Larrañaga Mireia Pérez , Miguelez Marta López , Andrés Estíbaliz Bárcena , Laureano Erik Urutxurtu , Boedo Maria Jesús Maroño , Rodríguez Blanca Escontrela , Camiruaga Aitziber Ereñozaga , Aguirre Deiene Lasuen , Maeztu Ainhoa Zabal , Gala Ane Guereca , Korro Iker Castelo , Campo Andrés Álvarez , Viana Alejandro Carcelen , Enríquez Alejandro Alberdi , Rementeria Xabier Ormazábal , Campos Alberto Sánchez , Rico Rosa Gutiérrez , Damborenea Pablo Barbier , Momeñe Marta Guerenabarrena , Ruiz Borja Cuesta , Rico Alejandro López , Polo Ana Rojo , Grijelmo Covadonga García , Reta Mikel Celorrio , Arroyo Eneko Martín , Aparicio Leire Artaza , Aspiazu Iñaki Ituarte , Basabe Ane Igeregi , Julian Itxaso Merino , Rico Isabel Diaz , Martínez Maria Paz , Bartolomé Ramón Adalia , Zattera Luigi , Hernandez Irina Adalid , Altuna Leire Larrañaga , Castells Aina Serrallonga , Garcia Adriana Vílchez , Núñez María , Román Lorena , Delgado Isabel Ramos , Martínez Adela Benítez-Cano , Albert Mireia Chanzá , García Juan Carlos Álvarez , Cuchillo Luis Aguilera , de Heredia Sandra Beltrán , Cordobés Jesús Carazo , Bernedo Carlos Alberto García , Villén Fernando Escolano , Calvo Francisco Javier Redondo , González Rubén Villazala , González Victor Baladron , Faba Patricia , Montenegro Omar , Ramírez Natalia Bejarano , Contreras Sergio Marcos , Rodríguez Alejandro Garcia , Vázquez Saleta Rey , Pérez Cristina Garcia , Miguelez Eva Higuera , Blanco Irene Pérez , Rivera David García , de la Fuente Ane Martín , Pardo Marta , Rodriguez Vanessa , Bengoetxea Unai , Ramasco Fernando , Bernal Sheila Olga Santidrián , Hernando Alvar Santa Cruz , Roca Antonio Planas , Yusta Carlos Figueroa , Villabona Esther García , Lantero Carmen Vallejo , Rodriguez Eva Patiño , Toledo Alvaro Esquivel , Méndez David Arribas , Rodriguez Mar Orts , Hernández Rosa Méndez , Alonso Jesús Nieves , Artazcoz Inés Imaz , Carazo Sonia Expósito , Guerrero Carlos Román , Rodríguez Elena Rojo , González Ricardo Moreno , Santos Julia Hernando , Pérez Jara Torrente , Mena Esperanza Mata , Martínez Manuel José Muñoz , Muñoz Enrique Alday , Serrano Patricia Martin , Muñoz Laura Cotter , Mjertan Amadea , Martínez Diego Gutierrez , García Carmen Rodríguez , Viejo Olaya Alonso , Pereira Juan Alvarez , Bonet Ana Carmona , López Diana Parrado , de Dios Tomas Eva , Celemin Rafael Martín , Paz María Luisa Meilan , Gutiérrez Luis Quecedo , Velasco Noemí Diaz , Hernández Gabriel Martin , del Corral Francisco Garcia , Arias Gloria Hernandez , Cuesta David Rodriguez , Rice Ana Gómez , Sevillano Encarna Mateos , Molpeceres Natalia Olmos , Domínguez Beatriz , Lima Ana Vázquez , Candela Ángel , Bambaren Ismael AAcevedo , Blanco Maria Isabel Albala , Montoiro Paloma Alonso , Utrera Fernando Álvarez , Esteruelas Juan Avellanosa , López Amal Azzam , Balvis Balvis Alberto José , Bardi Tommaso , Martín María Beltrán , Haserfaty Jacobo Benatar , Camacho Alberto Berruezo , Weimer Laura Betolaza , del Mar Carbonell Soto María , Seral Cristina Carrasco , Zaballos Cristina Cerro , Llamas Elizabeth Claros , Orduna Pilar Coleta , Forero Ingrid P. Cortes , Aliseda Pascual Agustín Crespo , de Pablo Pajares María Angélica , Remesal Yolanda Díez , Díaz Trinidad Dorado , Blasco Noemí Echevarría , Martín María Elena Elías , Triviño Javier Felices , López Natalia Fernández , Martín Cristina Fernández , Pozuelo Natalia Ferreiro , Martín Luis Gajate , Santos Clara Gallego , Mayo Diego Gil , Rojo María Gómez , Cibrián Claudia González , López Elena Herrera , Olmedillo Borja Hinojal , Gallego Berta Iglesias , Khonsari Sassan , Ruiz María Nuria Mane , Arroyo María Manzanero , Ortega Ana María Mariscal , Burcio Sara Martín , del Carmen Martín González María , Grande Ascensión Martín , López Jose Juan Martín , Rabes Cecilia Martín , Borja Marcos Martínez , Castro Nilda Martínez , Pérez Adolfo Martínez , Matcan Snejana , Viñas Cristina Medrano , Herrera Lisset Miguel , Betancur Adrián Mira , Carbajo María Montiel , Moradas Javier Moya , Pérez Lorena Muñoz , Murias Mónica Nuñez , González Eva Ordiales , Recio Óscar Ordoñez , Rodriguez Miguel Ángel Palomero , Roux Diego Parise , Torres Lucia Pereira , Lagunas David Pestaña , Corraliza Juana María Pinto , Rodrigo Marian Prieto , Diaz-Regaño Inmaculada Rodriguez , Esteban David Rodriguez , Pernia Víctor Rojas , Saiz Álvaro Ruigómez , Villarino Bárbara Saavedra , Palero Noemí Samaranch , Pérez Gloria Santos , Pérez Jaume Serna , Romero Ana Belén Serrano , López Jesús Tercero , García Carlos Tiscar , de la Torre Concostrina Marta , Mesa Eva María Ureta , Olarte Eva Velasco , Martínez Judith Villahoz , Palacios Raúl Villalaba , García Gema Villanueva , de Medeiros Cristina Vogel , Ovejero Soraya Gholamian , Orgaz Marta Vicente , Herradon Patricia Lloreda , Gómez Cristina Crespo , Sarmiento-Trujillo Tatiana , Medina Noemí García , García María Martínez , Ramírez Carles Espinós , Rivero Nabil Mouhaffel , Gil Jose Antonio Bernia , Martín Sonsoles , Moral María Victoria , Galán Josefina , Paniagua Pilar , Pérez Sergio , Bainac Albert , Arias Ana , Ramil Elsa , Escudero Jorge , Monedero Pablo , Cara Carmen , Lara Andrea , Martínez Elena Mendez , Mendoza Jorge , Baines Íñigo Rubio , Trull Carmen Sala , López Pablo Montero , Gea Alfredo , Montero Alejandro , Ibañez Rocío Armero , Pitarch Juan Vicente Llau , Alcóver Fernando Rauer , Herreros Cristina Álvarez , Martín Cyntia Sánchez , Olmos Lucía López Ocáriz , Moruno Marta Navas , Montoto Fernando García , Rodriguez M. F. Mirón , Coco Laura Fuentes , Gamito Cristina Hernández , Orejudo Antonio Barba , Vielma Luis Gerardo Smith , Marín Yasmina González , de Borja Amador Penco Francisco , Domínguez Marta Donoso , Ramírez Silvia Esquivel , Carbonell José Antonio , López Berta Monleón , Martínez-Castro Sara , Aguilar Gerardo , Gestal María , Casas Pablo , Rosato Angel Outeiro , Pan Andrea Naveiro , Portela María Alonso , Romar Adrián García , Rodríguez Eva Mosquera , Seijo Diego Ruanova , Maceiras Pablo Rama , Castro-Ceoane Francisco , López Esther Moreno , Gil Sergio , Antón Julia Guillén , Tirado Patricia García-Consuegra , Calvo Aurora Callau , Lisbona Laura Forés , Romero María Carbonell , Gil Belén Albericio , Jarne Laura Pradal , Lozano María Soria , López Diego Loscos , Abarca Andrea Patiño , Pérez-Asenjo Javier , Díez-Domínguez Ángel , Zubizarreta Ion , Ramos Jon , Fernández Iosu , Maseda Emilio , de la Rica Alejandro Suárez , Veganzones Javier , Insausti Itziar , Sagra Javier , Carrasco Sofía Díaz , Feijoo Ana Montero , Yagüe Julio , Garutti Ignacio , Hortal Javier , Piñeiro Patricia , Piñeiro Matilde , Zaballos Matilde , cedeño Jamil , García-Olivares Pablo , Garriido Alberto , Guerrero Jose Eugenioi , Parga Eva Bassas , Garcia Carmen Deiros , Rosa Elisenda Pujol , Navarro Ana Tejedor , Gabernet Roser Font , Bernat Maria José , Valls Meritxell Serra , Garcia-Bernalt Cristina Cobaleda , Fernanz Anton Jesus , Sierra Adriana Aponte , Gomez Lucia Gil , Vaqueiro Olaia Guenaga , Marin Susana Hernandez , Pinzon Laura Pardo , Garcia Aranda Sira , Orejuela Carlos Briones , Sánchez Edgar Cortes , Fernández Alejandro Romero , SanJosé Esther Fernández , Garsabal Patricia Iglesias , Lopez Guillermo Isidro , Vicol Ana , Malagon Sara Espejo , Sanabra Loewe María , Torradeflo Laura Grau , Alcaide Lourdes Blanco , Buenaventura Sanclemente Gloria , Serra Pujol Pere , Mendoza Gustavo Cuadros , Konarska Miroslawa , Bachs Almenara Fedra , Golska Agnieszka , Carmona Blesa Aleix , Serra Arantxa Mas , Melchor Javier Ripolles , Moreno Ana Nieto , Novo Káteri Chao , López Sandra Gadín , Moreno Elena Nieto , Tonal Bérénice Gutiérrez , de Pablo Elena Lucena , Yañez Barbara Algar , Rivero Beatriz Vázquez , Mateo Beatriz Nozal , de Retes Marina , Escoda Norma Aracil , Mayo Cristina Gallardo , González Rosa Sanz , Escobar Alicia Ruiz , López Maria Laura Pelegrina , Peña Marina Valenzuela , Dueñas David Stolle , Motos Ane Abad , Abad-Gurumeta Alfredo , Errazquin Ana Tirado , Ruiz Elena Sáez , Pérez Nerea Gómez , de Borja Bau González Francisco , Serra Cesar Morcillo , Higueras Jessica Souto , Vicente Rosario , Ferrandis Raquel , Martín Silvia Polo , Moncho Azucena Pajares , Puigdollers Ignacio Moreno , Cortés Juan Pérez Artacho , Calvo Ana Moret , Peña Ana Pi , Fernández María Catalán , Varela Marina , Parada Pilar Díaz , Carlín Raquel Rey , Aragunde Sarra Barreiro , Chiva María Isabel Forés , Agulló A. Javier , Ferrer Antonio Pérez , Galiana María , Margarit Antoni , del Rio Válerie Mourre , Muxella Eva Heras , Vidal Anna 
Published: January 2021

Abstract
Background
Critically ill patients with coronavirus disease 19 (COVID-19) have a high fatality rate likely due to a dysregulated immune response. Corticosteroids could attenuate this inappropriate response, although there are still some concerns regarding its use, timing, and dose.

Methods
This is a nationwide, prospective, multicenter, observational, cohort study in critically ill adult patients with COVID-19 admitted into Intensive Care Units (ICU) in Spain from 12th March to 29th June 2020. Using a multivariable Cox model with inverse probability weighting, we compared relevant outcomes between patients treated with early corticosteroids (before or within the first 48 h of ICU admission) with those who did not receive early corticosteroids (delayed group) or any corticosteroids at all (never group). Primary endpoint was ICU mortality. Secondary endpoints included 7-day mortality, ventilator-free days, and complications.

Results
A total of 691 patients out of 882 (78.3%) received corticosteroid during their hospital stay. Patients treated with early-corticosteroids (n = 485) had lower ICU mortality (30.3% vs. never 36.6% and delayed 44.2%) and lower 7-day mortality (7.2% vs. never 15.2%) compared to non-early treated patients. They also had higher number of ventilator-free days, less length of ICU stay, and less secondary infections than delayed treated patients. There were no differences in medical complications between groups. Of note, early use of moderate-to-high doses was associated with better outcomes than low dose regimens.

Conclusion
Early use of corticosteroids in critically ill patients with COVID-19 is associated with lower mortality than no or delayed use, and fewer complications than delayed use.