A stratification strategy to predict secondary infection in critical illness-induced immune dysfunction: the REALIST score
Authors: Tremblay Jan-Alexis , Peron Florian , Kreitmann Louis , Textoris Julien , Brengel-Pesce Karen , Lukaszewicz Anne-Claire , Quemeneur Laurence , Vedrine Christophe , Tan Lionel K. , Venet Fabienne , Rimmele Thomas , Monneret Guillaume ,   the REALISM study group, Arnal Sophie , Augris-Mathieu Caroline , Bayle Frédérique , Caruso Liana , Ber Charles-Eric , Ben-amor Asma , Bellocq Anne-Sophie , Benatir Farida , Bertin-Maghit Anne , Bertin-Maghit Marc , Boibieux André , Bouffard Yves , Cejka Jean-Christophe , Cerro Valérie , Crozon-Clauzel Jullien , Davidson Julien , Debord-Peguet Sophie , Delwarde Benjamin , Deleat-Besson Robert , Delsuc Claire , Devigne Bertrand , Fayolle-Pivot Laure , Faure Alexandre , Floccard Bernard , Gatel Julie , Genin Charline , Girardot Thibaut , Gregoire Arnaud , Hengy Baptiste , Huriaux Laetitia , Jadaud Catherine , Lepape Alain , Leray Véronique , Lukaszewicz Anne-Claire , Marcotte Guillaume , Martin Olivier , Matray Marie , Maucort-Boulch Delphine , Meuret Pascal , Monard Céline , Moriceau Florent , Monneret Guillaume , Panel Nathalie , Rahali Najia , Rimmele Thomas , Truc Cyrille , Uberti Thomas , Vallin Hélène , Venet Fabienne , Tissot Sylvie , Zadam Abbès , Blein Sophie , Brengel-Pesce Karen , Cerrato Elisabeth , Cheynet Valerie , Gallet-Gorius Emmanuelle , Guichard Audrey , Jourdan Camille , Koenig Natacha , Mallet François , Meunier Boris , Moucadel Virginie , Mommert Marine , Oriol Guy , Pachot Alexandre , Peronnet Estelle , Schrevel Claire , Tabone Olivier , Textoris Julien , Marcos Javier Yugueros , Becker Jeremie , Bequet Frederic , Bounab Yacine , Brajon Florian , Canard Bertrand , Collus Muriel , Garcon Nathalie , Gorse Irene , Guyard Cyril , Lavocat Fabien , Leissner Philippe , Louis Karen , Mistretta Maxime , Moriniere Jeanne , Mouscaz Yoann , Noailles Laura , Perret Magali , Reynier Frederic , Riffaud Cindy , Rol Mary-Luz , Sapay Nicolas , Tran Trang , Vedrine Christophe , Carre Christophe , Cortez Pierre , Monfort Aymeric , Florin Karine , Fraisse Laurent , Fugier Isabelle , Payrard Sandrine , Peleraux Annick , Quemeneur Laurence , Griffiths Andrew , Toetsch Stephanie , Ashton Teri , Gough Peter J , Berger Scott B , Gardiner David , Gillespie Iain , Macnamara Aidan , Raychaudhuri Aparna , Smylie Rob , Tan Lionel , Tipple Craig 
Published: August 2022

Background

Although multiple individual immune parameters have been demonstrated to predict the occurrence of secondary infection after critical illness, significant questions remain with regards to the selection, timing and clinical utility of such immune monitoring tests.

Research question

As a sub-study of theREALISMstudy, theREALISTscore was developed as a pragmatic approach to help clinicians better identify and stratify patients at high risk for secondary infection, using a simple set of relatively available and technically robust biomarkers.

Study design and methods

This is a sub-study of a single-centre prospective cohort study of immune profiling in critically ill adults admitted after severe trauma, major surgery or sepsis/septic shock. For the REALIST score, five immune parameters were pre-emptively selected based on their clinical applicability and technical robustness. Predictive power of different parameters and combinations of parameters was assessed. The main outcome of interest was the occurrence of secondary infection within 30 days.

Results

After excluding statistically redundant and poorly predictive parameters, three parameters remained in theREALISTscore: mHLA-DR, percentage of immature (CD10−CD16−) neutrophils and serum IL-10 level. In the cohort of interest (n = 189), incidence of secondary infection at day 30 increased from 8% for patients withREALISTscore of 0 to 46% in patients with a score of 3 abnormal parameters, measured ad D5–7. When adjusted for a priori identified clinical risk factors for secondary infection (SOFA score and invasive mechanical ventilation at D5–7), a higherREALISTscore was independently associated with increased risk of secondary infection (42 events (22.2%), adjusted HR 3.22 (1.09–9.50),p = 0.034) and mortality (10 events (5.3%),p = 0.001).

Interpretation

We derived and presented theREALISTscore, a simple and pragmatic stratification strategy which provides clinicians with a clear assessment of the immune status of their patients. This new tool could help optimize care of these individuals and could contribute in designing future trials of immune stimulation strategies.

Graphical Abstract