Dynamics of disease characteristics and clinical management of critically ill COVID-19 patients over the time course of the pandemic: an analysis of the prospective, international, multicentre RISC-19-ICU registry
Authors: Wendel-Garcia Pedro David , Moser André , Jeitziner Marie-Madlen , Aguirre-Bermeo Hernán , Arias-Sanchez Pedro , Apolo Janina , Roche-Campo Ferran , Franch-Llasat Diego , Kleger Gian-Reto , Schrag Claudia , Pietsch Urs , Filipovic Miodrag , David Sascha , Stahl Klaus , Bouaoud Souad , Ouyahia Amel , Fodor Patricia , Locher Pascal , Siegemund Martin , Zellweger Nuria , Cereghetti Sara , Schott Peter , Gangitano Gianfilippo , Wu Maddalena Alessandra , Alfaro-Farias Mario , Vizmanos-Lamotte Gerardo , Ksouri Hatem , Gehring Nadine , Rezoagli Emanuele , Turrini Fabrizio , Lozano-Gómez Herminia , Carsetti Andrea , Rodríguez-García Raquel , Yuen Bernd , Weber Anja Baltussen , Castro Pedro , Escos-Orta Jesus Oscar , Dullenkopf Alexander , Martín-Delgado Maria C. , Aslanidis Theodoros , Perez Marie-Helene , Hillgaertner Frank , Ceruti Samuele , Franchitti Laurent Marilene , Marrel Julien , Colombo Riccardo , Laube Marcus , Fogagnolo Alberto , Studhalter Michael , Wengenmayer Tobias , Gamberini Emiliano , Buerkle Christian , Buehler Philipp K. , Keiser Stefanie , Elhadi Muhammed , Montomoli Jonathan , Guerci Philippe , Fumeaux Thierry , Schuepbach Reto A. , Jakob Stephan M. , Que Yok-Ai , Hilty Matthias Peter ,   the RISC-19-ICU Investigators, Hilty Matthias P. , Wendel-Garcia Pedro , Schuepbach Reto A. , Montomoli Jonathan , Guerci Philippe , Fumeaux Thierry , Bouaoud Souad , Ouyahia Amel , Abdoun Meriem , Rais Mounira , Alfaro-Farias Mario , Vizmanos-Lamotte Gerardo , Caballero Angel , Tschoellitsch Thomas , Meier Jens , Aguirre-Bermeo Hernán , Arias-Sanchez Pedro , Apolo Janina , Martinez Luis A. , Tirapé-Castro Hugo , Galal Islam , Tharwat Samar , Abdehaleem Ibrahim , Jurkolow Geoffrey , Guerci Philippe , Novy Emmanuel , Losser Marie-Reine , Wengenmayer Tobias , Zotzmann Viviane , David Sascha , Stahl Klaus , Seeliger Benjamin , Welte Tobias , Aslanidis Theodoros , Korsos Anita , Ahmed Luqman Abdulkhudhur , Hashim Hashim Talib , Nikandish Reza , Carsetti Andrea , Casarotta Erika , Giaccaglia Paolo , Rezoagli Emanuele , Giacomini Matteo , Magliocca Aurora , Bolondi Giuliano , Potalivo Antonella , Fogagnolo Alberto , Salvi Luca , Wu Maddalena A. , Cogliati Chiara , Colombo Riccardo , Catena Emanuele , Turrini Fabrizio , Simonini Maria S. , Fabbri Silvia , Montomoli Jonathan , Gamberini Emiliano , Gangitano Gianfilippo , Bitondo Maria M. , Maciopinto Francesca , de Camillis Enrico , Venturi Marta , Bocci Maria Grazia , Antonelli Massimo , Alansari Arowa , Abusalama Abdurraouf , Omar Osama , Binnawara Muhannud , Alameen Hind , Elhadi Muhammed , Alhadi Abdulmueti , Arhaym Ahmed , Gommers Diederik , Ince Can , Jayyab Mustafa , Alsharif Mohammed , Rodríguez-García Raquel , Gámez-Zapata Jorge , Taboada-Fraga Xiana , Castro Pedro , Fernandez Javier , Reverter Enric , Lander-Azcona Arantxa , Escós-Orta Jesús , Martín-Delgado Maria C. , Algaba-Calderon Angela , Roche-Campo Ferran , Franch-Llasat Diego , Concha Pablo , Sauras-Colón Esther , Lozano-Gómez Herminia , Zalba-Etayo Begoña , Montes Maria P. , Michot Marc P. , Klarer Alexander , Ensner Rolf , Schott Peter , Urech Severin , Siegemund Martin , Zellweger Nuria , Gebhard Caroline E. , Hollinger Alexa , Merki Lukas , Lambert Adriana , Laube Marcus , Jeitziner Marie M. , Moser Andre , Que Yok-Ai , Jakob Stephan M. , Wiegand Jan , Yuen Bernd , Lienhardt-Nobbe Barbara , Westphalen Andrea , Salomon Petra , Hillgaertner Frank , Sieber Marianne , Dullenkopf Alexander , Barana Giulio , Ksouri Hatem , Sridharan Govind O. , Cereghetti Sara , Boroli Filippo , Pugin Jerome , Grazioli Serge , Bürkle Christian , Marrel Julien , Brenni Mirko , Fleisch Isabelle , Perez Marie-Helene , Ramelet Anne-Sylvie , Weber Anja Baltussen , Gerecke Peter , Christ Andreas , Ceruti Samuele , Glotta Andrea , Biggiogero Maira , Marquardt Katharina , Hübner Tobias , Neff Thomas , Redecker Hermann , Fumeaux Thierry , Moret-Bochatay Mallory , Betello Marco , zu Bentrup Friederike Meyer , Studhalter Michael , Stephan Michael , Gehring Nadine , Selz Daniela , Kleger Gian-Reto , Schrag Claudia , Pietsch Urs , Filipovic Miodrag , Ristic Anette , Heise Antje , Franchitti Laurent Marilene , Laurent Jean-Christophe , Gaspert Tomislav , Haberthuer Christoph , Fodor Patricia , Locher Pascal , Garcia Pedro D. Wendel , Hilty Matthias P. , Schuepbach Reto , Keiser Stefanie , Heuberger Dorothea , Bartussek Jan , Bühler Philipp , Brugger Silvio , Kleinert Eva-Maria , Fehlbier Kim-Jana , Danial Aghyad , Almousa Maher , Abdulbaki Yazan , Sannah Kamil , Colak Elif , Marczin Nandor , Al-Ameri Saba 
Published: July 2022

AbstractBackgroundIt remains elusive how the characteristics, the course of disease, the clinical management and the outcomes of critically ill COVID-19 patients admitted to intensive care units (ICU) worldwide have changed over the course of the pandemic.MethodsProspective, observational registry constituted by 90 ICUs across 22 countries worldwide including patients with a laboratory-confirmed, critical presentation of COVID-19 requiring advanced organ support. Hierarchical, generalized linear mixed-effect models accounting for hospital and country variability were employed to analyse the continuous evolution of the studied variables over the pandemic.ResultsFour thousand forty-one patients were included from March 2020 to September 2021. Over this period, the age of the admitted patients (62 [95% CI 60–63] years vs 64 [62–66] years,p < 0.001) and the severity of organ dysfunction at ICU admission decreased (Sequential Organ Failure Assessment 8.2 [7.6–9.0] vs 5.8 [5.3–6.4],p < 0.001) and increased, while more female patients (26 [23–29]% vs 41 [35–48]%,p < 0.001) were admitted. The time span between symptom onset and hospitalization as well as ICU admission became longer later in the pandemic (6.7 [6.2–7.2| days vs 9.7 [8.9–10.5] days,p < 0.001). The PaO2/FiO2at admission was lower (132 [123–141] mmHg vs 101 [91–113] mmHg,p < 0.001) but showed faster improvements over the initial 5 days of ICU stay in late 2021 compared to early 2020 (34 [20–48] mmHg vs 70 [41–100] mmHg,p = 0.05). The number of patients treated with steroids and tocilizumab increased, while the use of therapeutic anticoagulation presented an inverse U-shaped behaviour over the course of the pandemic. The proportion of patients treated with high-flow oxygen (5 [4–7]% vs 20 [14–29],p < 0.001) and non-invasive mechanical ventilation (14 [11–18]% vs 24 [17–33]%,p < 0.001) throughout the pandemic increased concomitant to a decrease in invasive mechanical ventilation (82 [76–86]% vs 74 [64–82]%,p < 0.001). The ICU mortality (23 [19–26]% vs 17 [12–25]%,p < 0.001) and length of stay (14 [13–16] days vs 11 [10–13] days,p < 0.001) decreased over 19 months of the pandemic.ConclusionCharacteristics and disease course of critically ill COVID-19 patients have continuously evolved, concomitant to the clinical management, throughout the pandemic leading to a younger, less severely ill ICU population with distinctly different clinical, pulmonary and inflammatory presentations than at the onset of the pandemic.