Jean-Rémi Lavillegrand1,2, Marc Garnier2,3, Agathe Spaeth4, Nathalie Mario4, Geoffroy Hariri1,2, Antoine Pilon4, Enora Berti2,5, Fabienne Fieux3, Sara Thietart1, Tomas Urbina1,2, Matthieu Turpin2,5, Lucie Darrivere3, Muriel Fartoukh2,5, Franck Verdonk3, Guillaume Dumas1, Alain Tedgui6, Bertrand Guidet1,2, Eric Maury1,2, Yannick Chantran7, Guillaume Voiriot2,5, Hafid Ait-Oufella8,9,10. 1. Service de Médecine Intensive-Réanimation, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, 184 rue du faubourg Saint-Antoine, 75571, Paris cedex 12, France. 2. Sorbonne Université, Paris, France. 3. Service D'Anesthésie-Réanimation, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France. 4. Département de Biochimie, Hormonologie et Suivi Thérapeutique, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France. 5. Service de Médecine Intensive-Réanimation, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, Paris, France. 6. Inserm U970, Cardiovascular Research Center, Université de Paris, Paris, France. 7. Département D'Immunologie Biologique, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France. 8. Service de Médecine Intensive-Réanimation, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, 184 rue du faubourg Saint-Antoine, 75571, Paris cedex 12, France. hafid.aitoufella@aphp.fr. 9. Sorbonne Université, Paris, France. hafid.aitoufella@aphp.fr. 10. Inserm U970, Cardiovascular Research Center, Université de Paris, Paris, France. hafid.aitoufella@aphp.fr.
Abstract
BACKGROUND: SARS coronavirus 2 (SARS-CoV-2) is responsible for high morbidity and mortality worldwide, mostly due to the exacerbated inflammatory response observed in critically ill patients. However, little is known about the kinetics of the systemic immune response and its association with survival in SARS-CoV-2+ patients admitted in ICU. We aimed to compare the immuno-inflammatory features according to organ failure severity and in-ICU mortality. METHODS: Six-week multicentre study (N = 3) including SARS-CoV-2+ patients admitted in ICU. Analysis of plasma biomarkers at days 0 and 3-4 according to organ failure worsening (increase in SOFA score) and 60-day mortality. RESULTS: 101 patients were included. Patients had severe respiratory diseases with PaO2/FiO2 of 155 [111-251] mmHg), SAPS II of 37 [31-45] and SOFA score of 4 [3-7]. Eighty-three patients (83%) required endotracheal intubation/mechanical ventilation and among them, 64% were treated with prone position. IL-1β was barely detectable. Baseline IL-6 levels positively correlated with organ failure severity. Baseline IL-6 and CRP levels were significantly higher in patients in the worsening group than in the non-worsening group (278 [70-622] vs. 71 [29-153] pg/mL, P < 0.01; and 178 [100-295] vs. 100 [37-213] mg/L, P < 0.05, respectively). Baseline IL-6 and CRP levels were significantly higher in non-survivors compared to survivors but fibrinogen levels and lymphocyte counts were not different between groups. After adjustment on SOFA score and time from symptom onset to first dosage, IL-6 and CRP remained significantly associated with mortality. IL-6 changes between Day 0 and Day 3-4 were not different according to the outcome. A contrario, kinetics of CRP and lymphocyte count were different between survivors and non-survivors. CONCLUSIONS: In SARS-CoV-2+ patients admitted in ICU, a systemic pro-inflammatory signature was associated with clinical worsening and 60-day mortality.
BACKGROUND:SARS coronavirus 2 (SARS-CoV-2) is responsible for high morbidity and mortality worldwide, mostly due to the exacerbated inflammatory response observed in critically illpatients. However, little is known about the kinetics of the systemic immune response and its association with survival in SARS-CoV-2+ patients admitted in ICU. We aimed to compare the immuno-inflammatory features according to organ failure severity and in-ICU mortality. METHODS: Six-week multicentre study (N = 3) including SARS-CoV-2+ patients admitted in ICU. Analysis of plasma biomarkers at days 0 and 3-4 according to organ failure worsening (increase in SOFA score) and 60-day mortality. RESULTS: 101 patients were included. Patients had severe respiratory diseases with PaO2/FiO2 of 155 [111-251] mmHg), SAPS II of 37 [31-45] and SOFA score of 4 [3-7]. Eighty-three patients (83%) required endotracheal intubation/mechanical ventilation and among them, 64% were treated with prone position. IL-1β was barely detectable. Baseline IL-6 levels positively correlated with organ failure severity. Baseline IL-6 and CRP levels were significantly higher in patients in the worsening group than in the non-worsening group (278 [70-622] vs. 71 [29-153] pg/mL, P < 0.01; and 178 [100-295] vs. 100 [37-213] mg/L, P < 0.05, respectively). Baseline IL-6 and CRP levels were significantly higher in non-survivors compared to survivors but fibrinogen levels and lymphocyte counts were not different between groups. After adjustment on SOFA score and time from symptom onset to first dosage, IL-6 and CRP remained significantly associated with mortality. IL-6 changes between Day 0 and Day 3-4 were not different according to the outcome. A contrario, kinetics of CRP and lymphocyte count were different between survivors and non-survivors. CONCLUSIONS: In SARS-CoV-2+ patients admitted in ICU, a systemic pro-inflammatory signature was associated with clinical worsening and 60-day mortality.
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