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

Background

It 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.

Methods

Prospective, 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.

Results

Four 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.

Conclusion

Characteristics 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.