Relationship between ventilator-associated pneumonia and mortality in COVID-19 patients: a planned ancillary analysis of the coVAPid cohort
Authors: Nseir Saad , Martin-Loeches Ignacio , Povoa Pedro , Metzelard Matthieu , Du Cheyron Damien , Lambiotte Fabien , Tamion Fabienne , Labruyere Marie , Makris Demosthenes , Boulle Geronimi Claire , Pinetonde Chambrun Marc , Nyunga Martine , Pouly Olivier , Mégarbane Bruno , Saade Anastasia , Gomà Gemma , Magira Eleni , Llitjos Jean-François , Torres Antoni , Ioannidou Iliana , Pierre Alexandre , Coelho Luis , Reignier Jean , Garot Denis , Kreitmann Louis , Baudel Jean-Luc , Voiriot Guillaume , Contou Damien , Beurton Alexandra , Asfar Pierre , Boyer Alexandre , Thille Arnaud W. , Mekontso-Dessap Armand , Tsolaki Vassiliki , Vinsonneau Christophe , Floch Pierre-Edouard , Le Guennec Loïc , Ceccato Adrian , Artigas Antonio , Bouchereau Mathilde , Labreuche Julien , Duhamel Alain , Rouzé Anahita ,   the coVAPid study group, Favory Raphaël , Préau Sébastien , Jourdain Mercé , Poissy Julien , Leger Piehr Saint , Van der Linden Thierry , Veinstein Anne , Azoulay Elie , Pene Frédéric , Martin Maelle , Razazi Keyvan , Plantefeve Gaëtan , Fartoukh Muriel , Thevenin Didier , Guidet Bertrand , Weiss Nicolas , Kouatchet Achille , Salmon Charlotte , Brunin Guillaume , Nemlaghi Safaa , Meguerditchian David , Argaud Laurent , Voicu Sebastian , Luyt Charles-Edouard , Kowalski Benjamin , Moglia Edgar , Morales Luis , Koutsoukou Antonia , Mentzelopoulos Spyros D. , Nora David , Boyd Sean , Maizel Julien , Cuchet Pierre , Delforge Quentin , Quenot Jean-Pierre , Boyer Déborah , Cilloniz Catia 
Published: May 2021

Abstract
Background
Patients with SARS-CoV-2 infection are at higher risk for ventilator-associated pneumonia (VAP). No study has evaluated the relationship between VAP and mortality in this population, or compared this relationship between SARS-CoV-2 patients and other populations. The main objective of our study was to determine the relationship between VAP and mortality in SARS-CoV-2 patients.

Methods
Planned ancillary analysis of a multicenter retrospective European cohort. VAP was diagnosed using clinical, radiological and quantitative microbiological criteria. Univariable and multivariable marginal Cox’s regression models, with cause-specific hazard for duration of mechanical ventilation and ICU stay, were used to compare outcomes between study groups. Extubation, and ICU discharge alive were considered as events of interest, and mortality as competing event.

Findings
Of 1576 included patients, 568 were SARS-CoV-2 pneumonia, 482 influenza pneumonia, and 526 no evidence of viral infection at ICU admission. VAP was associated with significantly higher risk for 28-day mortality in SARS-CoV-2 group (adjusted HR 1.65 (95% CI 1.11–2.46), p = 0.013), but not in influenza (1.74 (0.99–3.06), p = 0.052), or no viral infection groups (1.13 (0.68–1.86), p = 0.63). VAP was associated with significantly longer duration of mechanical ventilation in the SARS-CoV-2 group, but not in the influenza or no viral infection groups. VAP was associated with significantly longer duration of ICU stay in the 3 study groups. No significant difference was found in heterogeneity of outcomes related to VAP between the 3 groups, suggesting that the impact of VAP on mortality was not different between study groups.

Interpretation
VAP was associated with significantly increased 28-day mortality rate in SARS-CoV-2 patients. However, SARS-CoV-2 pneumonia, as compared to influenza pneumonia or no viral infection, did not significantly modify the relationship between VAP and 28-day mortality.

Clinical trial registration

The study was registered at ClinicalTrials.gov, number NCT04359693.