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

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/FiO₂ at 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.