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Observational Study
. 2021 May 25;25(1):177.
doi: 10.1186/s13054-021-03588-4.

Relationship between ventilator-associated pneumonia and mortality in COVID-19 patients: a planned ancillary analysis of the coVAPid cohort

Saad Nseir  1   2 , Ignacio Martin-Loeches  3   4 , Pedro Povoa  5   6 , Matthieu Metzelard  7 , Damien Du Cheyron  8 , Fabien Lambiotte  9 , Fabienne Tamion  10 , Marie Labruyere  11 , Demosthenes Makris  12 , Claire Boulle Geronimi  13 , Marc Pinetonde Chambrun  14 , Martine Nyunga  15 , Olivier Pouly  16 , Bruno Mégarbane  17 , Anastasia Saade  18 , Gemma Gomà  19 , Eleni Magira  20 , Jean-François Llitjos  21 , Antoni Torres  22 , Iliana Ioannidou  23 , Alexandre Pierre  24 , Luis Coelho  5 , Jean Reignier  25 , Denis Garot  26 , Louis Kreitmann  27 , Jean-Luc Baudel  28 , Guillaume Voiriot  29 , Damien Contou  30 , Alexandra Beurton  31 , Pierre Asfar  32 , Alexandre Boyer  33 , Arnaud W Thille  34 , Armand Mekontso-Dessap  35 , Vassiliki Tsolaki  12 , Christophe Vinsonneau  36 , Pierre-Edouard Floch  37 , Loïc Le Guennec  38 , Adrian Ceccato  39 , Antonio Artigas  40 , Mathilde Bouchereau  41 , Julien Labreuche  42 , Alain Duhamel  42 , Anahita Rouzé  41   43 ; coVAPid study group
Collaborators, Affiliations
Observational Study

Relationship between ventilator-associated pneumonia and mortality in COVID-19 patients: a planned ancillary analysis of the coVAPid cohort

Saad Nseir et al. Crit Care. .

Erratum in

  • Correction to: Relationship between ventilator-associated pneumonia and mortality in COVID-19 patients: a planned ancillary analysis of the coVAPid cohort.
    Nseir S, Martin-Loeches I, Povoa P, Metzelard M, Du Cheyron D, Lambiotte F, Tamion F, Labruyere M, Makris D, Boulle Geronimi C, Pinetonde Chambrun M, Nyunga M, Pouly O, Mégarbane B, Saade A, Gomà G, Magira E, Llitjos JF, Torres A, Ioannidou I, Pierre A, Coelho L, Reignier J, Garot D, Kreitmann L, Baudel JL, Voiriot G, Contou D, Beurton A, Asfar P, Boyer A, Thille AW, Mekontso-Dessap A, Tsolaki V, Vinsonneau C, Floch PE, Le Guennec L, Ceccato A, Artigas A, Bouchereau M, Labreuche J, Duhamel A, Rouzé A; coVAPid study group. Nseir S, et al. Crit Care. 2021 Aug 9;25(1):284. doi: 10.1186/s13054-021-03713-3. Crit Care. 2021. PMID: 34372897 Free PMC article. No abstract available.

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 (adjusted HR 1.70 (95% CI 1.16-2.47), p = 0.006), and influenza groups (1.75 (1.03-3.02), p = 0.045), but not in the no viral infection group (1.07 (0.64-1.78), p = 0.79). 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.

Keywords: COVID-19; Mortality; Ventilator-associated pneumonia.

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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. SN received personal fees from MSD, Bio Rad, BioMérieux, Gilead, and Pfizer. All other authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Unadjusted and Adjusted hazard ratios for 28-day mortality, extubation alive and ICU discharge alive, associated with SARS-CoV-2 pneumonia, versus influenza pneumonia and no viral infection groups. HRs were calculated using cause-specific proportional hazard models, by considering mortality as competing event for MV duration, and length of ICU stay. Adjusted HRs were calculated, including age, gender, simplified acute physiology score II, Charlson score, MacCabe classification, shock, and acute respiratory distress syndrome as pre-specified covariates in Cox’s models (after handling missing values by multiple imputation). A HR > 1 indicates a decrease in survival duration (i.e. an increased risk for mortality), MV duration (i.e. an increased risk for extubation alive) and ICU length of stay (i.e. an increased risk for discharge alive) and a HR < 1 indicates an increase in survival duration (i.e. a decreased risk for mortality), MV duration (i.e. a decreased risk for extubation alive) and ICU length of stay (i.e. a decreased risk for discharge alive). Note that the event of interest for survival is a pejorative event (death) whereas for MV duration and ICU length of stay, the event of interest is a positive event (extubation or discharge alive). Consequently, the detrimental effect of SARS-CoV-2 pneumonia (vs influenza pneumonia and no viral infection groups) was associated with a HR > 1 for overall survival but was associated with a HR < 1 for MV duration and ICU length of stay. HR, hazard ratio; ICU, intensive care unit; MV, mechanical ventilation
Fig. 2
Fig. 2
Association between ventilator-associated lower respiratory tract infections and outcomes. a 28-Day mortality. b Duration of mechanical ventilation. c Length of ICU stay. HRs were calculated using cause-specific proportional hazard models, considering the first VA-LRTI as a time dependent 3-levels categorical variable (No VA-LRTI vs. VAT vs. VAP). Adjusted HRs were calculated including age, gender, simplified acute physiology score II, Charlson score, MacCabe classification, shock, and acute respiratory distress syndrome as pre-specified covariables in Cox’s model. Since the event of interest for 28-Day mortality is a pejorative event (death), whereas for MV duration and ICU length of stay, the event of interest is a positive event (extubation or discharge alive), the detrimental effect of SARS-CoV-2 pneumonia (vs influenza pneumonia and no viral infection groups) was associated with a HR > 1 for 28-Day mortality, with a HR < 1 for MV duration and ICU length of stay. HR, hazard ratio; ICU, intensive care unit; MV, mechanical ventilation; VA-LRTI, ventilator-associated respiratory tract infection; VAP, ventilator-associated pneumonia; VAT, ventilator-associated tracheobronchitis
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