Relationship between SARS-CoV-2 infection and the incidence of ventilator-associated lower respiratory tract infections: a European multicenter cohort study

Anahita Rouzé, Ignacio Martin-Loeches, Pedro Povoa, Demosthenes Makris, Antonio Artigas, Mathilde Bouchereau, Fabien Lambiotte, Matthieu Metzelard, Pierre Cuchet, Claire Boulle Geronimi, Marie Labruyere, Fabienne Tamion, Martine Nyunga, Charles-Edouard Luyt, Julien Labreuche, Olivier Pouly, Justine Bardin, Anastasia Saade, Pierre Asfar, Jean-Luc Baudel, Alexandra Beurton, Denis Garot, Iliana Ioannidou, Louis Kreitmann, Jean-François Llitjos, Eleni Magira, Bruno Mégarbane, David Meguerditchian, Edgar Moglia, Armand Mekontso-Dessap, Jean Reignier, Matthieu Turpin, Alexandre Pierre, Gaetan Plantefeve, Christophe Vinsonneau, Pierre-Edouard Floch, Nicolas Weiss, Adrian Ceccato, Antoni Torres, Alain Duhamel, Saad Nseir, coVAPid study Group, Raphaël Favory, Sébastien Preau, Mercé Jourdain, Julien Poissy, Chaouki Bouras, Piehr Saint Leger, Hanane Fodil, François Aptel, Thierry Van Der Linden, Arnaud W Thille, Elie Azoulay, Frédéric Pène, Keyvan Razazi, François Bagate, Damien Contou, Guillaume Voiriot, Didier Thevenin, Bertrand Guidet, Loïc Le Guennec, Achille Kouatchet, Stephan Ehrmann, Guillaume Brunin, Elise Morawiec, Alexandre Boyer, Laurent Argaud, Sebastian Voicu, Ania Nieszkowska, Benjamin Kowalski, Gemma Goma, Emilio Diaz, Luis Morales, Vassiliki Tsolaki, George Gtavriilidis, Spyros D Mentzelopoulos, David Nora, Sean Boyd, Luis Coelho, Julien Maizel, Damien Du Cheyron, Mehdi Imouloudene, Jean-Pierre Quenot, Arnaud Guilbert, Catia Cilloniz, Anahita Rouzé, Ignacio Martin-Loeches, Pedro Povoa, Demosthenes Makris, Antonio Artigas, Mathilde Bouchereau, Fabien Lambiotte, Matthieu Metzelard, Pierre Cuchet, Claire Boulle Geronimi, Marie Labruyere, Fabienne Tamion, Martine Nyunga, Charles-Edouard Luyt, Julien Labreuche, Olivier Pouly, Justine Bardin, Anastasia Saade, Pierre Asfar, Jean-Luc Baudel, Alexandra Beurton, Denis Garot, Iliana Ioannidou, Louis Kreitmann, Jean-François Llitjos, Eleni Magira, Bruno Mégarbane, David Meguerditchian, Edgar Moglia, Armand Mekontso-Dessap, Jean Reignier, Matthieu Turpin, Alexandre Pierre, Gaetan Plantefeve, Christophe Vinsonneau, Pierre-Edouard Floch, Nicolas Weiss, Adrian Ceccato, Antoni Torres, Alain Duhamel, Saad Nseir, coVAPid study Group, Raphaël Favory, Sébastien Preau, Mercé Jourdain, Julien Poissy, Chaouki Bouras, Piehr Saint Leger, Hanane Fodil, François Aptel, Thierry Van Der Linden, Arnaud W Thille, Elie Azoulay, Frédéric Pène, Keyvan Razazi, François Bagate, Damien Contou, Guillaume Voiriot, Didier Thevenin, Bertrand Guidet, Loïc Le Guennec, Achille Kouatchet, Stephan Ehrmann, Guillaume Brunin, Elise Morawiec, Alexandre Boyer, Laurent Argaud, Sebastian Voicu, Ania Nieszkowska, Benjamin Kowalski, Gemma Goma, Emilio Diaz, Luis Morales, Vassiliki Tsolaki, George Gtavriilidis, Spyros D Mentzelopoulos, David Nora, Sean Boyd, Luis Coelho, Julien Maizel, Damien Du Cheyron, Mehdi Imouloudene, Jean-Pierre Quenot, Arnaud Guilbert, Catia Cilloniz

Abstract

Purpose: Although patients with SARS-CoV-2 infection have several risk factors for ventilator-associated lower respiratory tract infections (VA-LRTI), the reported incidence of hospital-acquired infections is low. We aimed to determine the relationship between SARS-CoV-2 pneumonia, as compared to influenza pneumonia or no viral infection, and the incidence of VA-LRTI.

Methods: Multicenter retrospective European cohort performed in 36 ICUs. All adult patients receiving invasive mechanical ventilation > 48 h were eligible if they had: SARS-CoV-2 pneumonia, influenza pneumonia, or no viral infection at ICU admission. VA-LRTI, including ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP), were diagnosed using clinical, radiological and quantitative microbiological criteria. All VA-LRTI were prospectively identified, and chest-X rays were analyzed by at least two physicians. Cumulative incidence of first episodes of VA-LRTI was estimated using the Kalbfleisch and Prentice method, and compared using Fine-and Gray models.

Results: 1576 patients were included (568 in SARS-CoV-2, 482 in influenza, and 526 in no viral infection groups). VA-LRTI incidence was significantly higher in SARS-CoV-2 patients (287, 50.5%), as compared to influenza patients (146, 30.3%, adjusted sub hazard ratio (sHR) 1.60 (95% confidence interval (CI) 1.26 to 2.04)) or patients with no viral infection (133, 25.3%, adjusted sHR 1.7 (95% CI 1.2 to 2.39)). Gram-negative bacilli were responsible for a large proportion (82% to 89.7%) of VA-LRTI, mainly Pseudomonas aeruginosa, Enterobacter spp., and Klebsiella spp.

Conclusions: The incidence of VA-LRTI is significantly higher in patients with SARS-CoV-2 infection, as compared to patients with influenza pneumonia, or no viral infection after statistical adjustment, but residual confounding may still play a role in the effect estimates.

Keywords: COVID-19; Critical illness; SARS-CoV-2; Ventilator-associated pneumonia; Ventilator-associated tracheobronchitis.

Conflict of interest statement

AR received personal fees from MaatPharma, IML received personal fees from MSD, and Gilead. AA received personal fees from Lilly Foundation, and grants from Grifols and Fischer & Paykel. CEL received personal fees from Bayer, Merck, Aerogen, Biomérieux, ThermoFischer Brahms, and Carmat. NW received personal fees from MedDay pharmaceuticals. SN received personal fees from MSD, Bio Rad, BioMérieux, Gilead, and Pfizer. All other authors declare no competing interests.

Figures

Fig. 1
Fig. 1
The 28-day cumulative incidence of ventilator-associated lower respiratory tract infections. Cumulative incidence estimated using Kalbfleish and Prentice method, considering extubation (dead or alive) within 28 days as competing event. VA-LRTI ventilator-associated respiratory tract infection, MV mechanical ventilation

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