Delayed intubation and 60-day mortality in severe COVID-19-associated acute respiratory failure in an emulated target trial using the OUTCOMEREA network
Abstract
The benefits of non-invasive respiratory support strategies (NIRS), such as high-flow nasal oxygen therapy, in delaying intubation remain uncertain. We used an emulated target trial approach to evaluate outcomes associated with late intubation in patients with severe acute respiratory failure due to COVID-19. We conducted a retrospective multicentre cohort study using the French prospective OUTCOMEREA database. Adult patients admitted to intensive care units (ICUs) for severe SARS-CoV-2 pneumonia with an ICU length of stay of at least seven days were included in the study. Descriptive analyses were used to compare patients who were intubated after day 6 with those who remained under NIRS. In the emulated target trial, patients who were eligible between ICU days 7 and 12 were assigned to undergo late intubation or to remain under NIRS. Weighted Cox proportional hazards models were used. The primary outcome was 60-day mortality. Of the 1206 ICU patients with SARS-CoV-2 pneumonia, 288 were still in the ICU on day 7. Of these, 65 (22.6%) subsequently underwent late intubation and had a 60-day mortality rate of 78.5%. In the emulated target trial, which included 234 patients at risk of intubation, 57 underwent late intubation. Late intubation was associated with a higher risk of death (adjusted hazard ratio: 2.89; 95% confidence interval: 1.50-3.92). The estimated absolute difference in 60-day survival was - 0.34 (95% CI - 0.62 to 0.30). The restricted mean survival time was 17.8 days shorter in the late intubation group (95% CI - 30.6 to 10.8). In this multicentre cohort, patients requiring late intubation had a very high mortality rate. In the emulated target trial analysis, late intubation was associated with poorer survival compared to continued NIRS, suggesting a subgroup of patients with progressive respiratory failure rather than a direct effect of intubation timing.
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BibTeX
@article{phillipshoulbracq2026delayed,
title = {{Delayed intubation and 60-day mortality in severe COVID-19-associated acute respiratory failure in an emulated target trial using the OUTCOMEREA network}},
author = {Mathilde Phillips-Houlbracq and Mathilde Neuville and Karl Bitar and Shidasp Siami and Shidasp Siami and Yves Cohen and Virginie Laurent and Bruno Mourvillier and Bruno Mourvillier and Bruno Mourvillier and Bruno Mourvillier and Jean Reignier and Jean Reignier and Dany Goldgran-Toledano and Carole Schwebel and Carole Schwebel and Stéphane Ruckly and Stéphane Ruckly and Etienne de Montmollin and Etienne de Montmollin and Niccolo Buetti and Niccolo Buetti and Charles Cerf and Jean-François Timsit and Jean-François Timsit and Jean-François Timsit and Claire Dupuis and Claire Dupuis and Claire Dupuis and Elie Azoulay and Maïté Garrouste-Orgeas and Jean-Ralph Zahar and Michael Darmon and Corinne Alberti and Sébastien Bailly and Aurélien Vannieuwenhuyze and Christophe Adrie and Carole Agasse and Bernard Allaouchiche and Olivier Andremont and Pascal Andreu and Laurent Argaud and Elie Azoulay and Francois Barbier and Jean-Pierre Bedos and Jérome Bedel and Asael Berger and Julien Bohé and Lila Bouadma and Jeremy Bourenne and Noel Brule and Frank Chemouni and Julien Carvelli and Martin Cour and Michael Darmon and Anais Dartevelle and Julien Dessajan and Marc Doman and Loa Dopeux and Anne-Sylvie Dumenil},
journal = {Scientific Reports},
year = {2026},
month = jun,
doi = {10.1038/s41598-026-47102-8},
url = {https://hal.science/hal-05751883v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Delayed intubation and 60-day mortality in severe COVID-19-associated acute respiratory failure in an emulated target trial using the OUTCOMEREA network
AU - Mathilde Phillips-Houlbracq
AU - Mathilde Neuville
AU - Karl Bitar
AU - Shidasp Siami
AU - Shidasp Siami
AU - Yves Cohen
AU - Virginie Laurent
AU - Bruno Mourvillier
AU - Bruno Mourvillier
AU - Bruno Mourvillier
AU - Bruno Mourvillier
AU - Jean Reignier
AU - Jean Reignier
AU - Dany Goldgran-Toledano
AU - Carole Schwebel
AU - Carole Schwebel
AU - Stéphane Ruckly
AU - Stéphane Ruckly
AU - Etienne de Montmollin
AU - Etienne de Montmollin
AU - Niccolo Buetti
AU - Niccolo Buetti
AU - Charles Cerf
AU - Jean-François Timsit
AU - Jean-François Timsit
AU - Jean-François Timsit
AU - Claire Dupuis
AU - Claire Dupuis
AU - Claire Dupuis
AU - Elie Azoulay
AU - Maïté Garrouste-Orgeas
AU - Jean-Ralph Zahar
AU - Michael Darmon
AU - Corinne Alberti
AU - Sébastien Bailly
AU - Aurélien Vannieuwenhuyze
AU - Christophe Adrie
AU - Carole Agasse
AU - Bernard Allaouchiche
AU - Olivier Andremont
AU - Pascal Andreu
AU - Laurent Argaud
AU - Elie Azoulay
AU - Francois Barbier
AU - Jean-Pierre Bedos
AU - Jérome Bedel
AU - Asael Berger
AU - Julien Bohé
AU - Lila Bouadma
AU - Jeremy Bourenne
AU - Noel Brule
AU - Frank Chemouni
AU - Julien Carvelli
AU - Martin Cour
AU - Michael Darmon
AU - Anais Dartevelle
AU - Julien Dessajan
AU - Marc Doman
AU - Loa Dopeux
AU - Anne-Sylvie Dumenil
PY - 2026
DA - 2026/06/23
JO - Scientific Reports
DO - 10.1038/s41598-026-47102-8
UR - https://hal.science/hal-05751883v1
AB - The benefits of non-invasive respiratory support strategies (NIRS), such as high-flow nasal oxygen therapy, in delaying intubation remain uncertain. We used an emulated target trial approach to evaluate outcomes associated with late intubation in patients with severe acute respiratory failure due to COVID-19. We conducted a retrospective multicentre cohort study using the French prospective OUTCOMEREA database. Adult patients admitted to intensive care units (ICUs) for severe SARS-CoV-2 pneumonia with an ICU length of stay of at least seven days were included in the study. Descriptive analyses were used to compare patients who were intubated after day 6 with those who remained under NIRS. In the emulated target trial, patients who were eligible between ICU days 7 and 12 were assigned to undergo late intubation or to remain under NIRS. Weighted Cox proportional hazards models were used. The primary outcome was 60-day mortality. Of the 1206 ICU patients with SARS-CoV-2 pneumonia, 288 were still in the ICU on day 7. Of these, 65 (22.6%) subsequently underwent late intubation and had a 60-day mortality rate of 78.5%. In the emulated target trial, which included 234 patients at risk of intubation, 57 underwent late intubation. Late intubation was associated with a higher risk of death (adjusted hazard ratio: 2.89; 95% confidence interval: 1.50-3.92). The estimated absolute difference in 60-day survival was - 0.34 (95% CI - 0.62 to 0.30). The restricted mean survival time was 17.8 days shorter in the late intubation group (95% CI - 30.6 to 10.8). In this multicentre cohort, patients requiring late intubation had a very high mortality rate. In the emulated target trial analysis, late intubation was associated with poorer survival compared to continued NIRS, suggesting a subgroup of patients with progressive respiratory failure rather than a direct effect of intubation timing.
SN - 2045-2322
ER -