*Article* **Incidence, Outcomes and Risk Factors of Recurrent Ventilator Associated Pneumonia in COVID-19 Patients: A Retrospective Multicenter Study**

**Ines Gragueb-Chatti 1,\*, Hervé Hyvernat 2, Marc Leone 3, Geoffray Agard 1, Noémie Peres 4, Christophe Guervilly 1,5, Mohamed Boucekine 5, Dany Hamidi 2, Laurent Papazian 1,5, Jean Dellamonica 2, Alexandre Lopez <sup>3</sup> and Sami Hraiech 1,5**


**Abstract:** Background: High incidence of ventilator associated pneumonia (VAP) has been reported in critically ill patients with COVID-19. Among these patients, we aimed to assess the incidence, outcomes and risk factors of VAP recurrences. Methods: We conducted an observational retrospective study in three French intensive care units (ICUs). Patients admitted for a documented COVID-19 from March 2020 to May 2021 and requiring mechanical ventilation (MV) for ≥48 h were included. The study main outcome was the incidence of VAP recurrences. Secondary outcomes were the duration of MV, ICU and hospital length of stay and mortality according to VAP and recurrences. We also assessed the factors associated with VAP recurrences. Results: During the study period, 398 patients met the inclusion criteria. A total of 236 (59%) of them had at least one VAP episode during their ICU stay and 109 (46%) of these patients developed at least one recurrence. The incidence of VAP recurrence considering death and extubation as competing events was 29.6% (IC = [0.250–0.343]). Seventy-eight percent of recurrences were due to the same bacteria (relapses). Patients with a VAP recurrence had a longer duration of MV as compared with one VAP and no VAP patients (41 (25–56) vs. 16 (8–30) and 10 (5–18) days; *p* < 0.001) and a longer ICU length of stay (46 (29–66) vs. 22 (12–36) and 14 (9–25) days; *p* < 0.001). The 90-day mortality was higher in the recurrence group as compared with the no VAP group only (31.2 vs. 21.0% (*p* = 0.021)). In a multivariate analysis including bacterial co-infection at admission, the use of immunosuppressive therapies and the bacteria responsible for the first VAP episode, the duration of MV was the only factor independently associated with VAP recurrence. Conclusion: In COVID-19 associated respiratory failure, recurrences affected 46% of patients with a first episode of VAP. VAP recurrences were mainly relapses and were associated with a prolonged duration of MV and ICU length of stay but not with a higher mortality. MV duration was the only factor associated with recurrences.

**Keywords:** COVID-19; ICU; ventilator-associated pneumonia; acute respiratory distress syndrome; recurrence of VAP
