Epidemiology, risk factors and prognosis of ventilator-associated pneumonia during severe COVID-19: Multicenter observational study across 149 European Intensive Care Units

Abstract

Background: COVID-19 patients requiring mechanical ventilation are particularly at risk of developing ventilator-associated pneumonia (VAP). Risk factors and the prognostic impact of developing VAP during critical COVID-19 have not been fully documented.

Methods: Patients invasively ventilated for at least 48 h from the prospective multicentre COVID-ICU database were included in the analyses. Cause-specific Cox regression models were used to determine factors associated with the occurrence of VAP. Cox-regression multivariable models were used to determine VAP prognosis. Risk factors and the prognostic impact of early vs. late VAP, and Pseudomonas-related vs. non-Pseudomonas-related VAP were also determined.

Main findings: 3388 patients were analysed (63 [55-70] years, 75.8% males). VAP occurred in 1523/3388 (45.5%) patients after 7 [5-9] days of ventilation. Identified bacteria were mainly Enterobacteriaceae followed by Staphylococcus aureus and Pseudomonas aeruginosa. VAP risk factors were male gender (Hazard Ratio (HR) 1.26, 95% Confidence Interval [1.09-1.46]), concomitant bacterial pneumonia at ICU admission (HR 1.36 [1.10-1.67]), PaO₂/FiO₂ ratio at intubation (HR 0.99 [0.98-0.99] per 10 mmHg increase), neuromuscular-blocking agents (HR 0.89 [0.76-0.998]), and corticosteroids (HR 1.27 [1.09-1.47]). VAP was associated with 90-mortality (HR 1.34 [1.16-1.55]), predominantly due to late VAP (HR 1.51 [1.26-1.81]). The impact of Pseudomonas-related and non-Pseudomonas-related VAP on mortality was similar.

Conclusion: VAP affected almost half of mechanically ventilated COVID-19 patients. Several risk factors have been identified, among which modifiable risk factors deserve further investigation. VAP had a specific negative impact on 90-day mortality, particularly when it occurred between the end of the first week and the third week of ventilation.

Keywords: COVID-19; Intensive Care Unit; Invasive mechanical ventilation; Mortality; Risk factors; Ventilator-associated pneumonia.

Fig. 1

Flow chart of the selection of patients included into the COVID-ICU database for analyses.

Fig. 2

Landmark analyses of the cumulative probability of death for patients still alive and mechanically ventilated at day 5, day 10, day 15 and day 20, depending on the earlier occurrence of VAP.