*Article* **Invasiveness of Ventilation Therapy Is Associated to Prevalence of Secondary Bacterial and Fungal Infections in Critically Ill COVID-19 Patients**

**Marie Louise de Hesselle 1, Stefan Borgmann 2, Siegbert Rieg 3, Jörg Janne Vehreshild 4,5,6, Christoph D. Spinner 7,8, Carolin E. M. Koll 5,6, Martin Hower 9, Melanie Stecher 5,6, Daniel Ebert 1, Frank Hanses 10,†, Julia Schumann 1,\*,† and on behalf of the LEOSS Study Group ‡**


**Abstract:** Superinfections are a fundamental critical care problem, and their significance in severe COVID-19 cases needs to be determined. This study analyzed data from the Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS) cohort focusing on intensive care patients. A retrospective analysis of patient data from 840 cases of COVID-19 with critical courses demonstrated that co-infections were frequently present and were primarily of nosocomial origin. Furthermore, our analysis showed that invasive therapy procedures accompanied an increased risk for healthcareassociated infections. Non-ventilated ICU patients were rarely affected by secondary infections. The risk of infection, however, increased even when non-invasive ventilation was used. A further, significant increase in infection rates was seen with the use of invasive ventilation and even more so with extracorporeal membrane oxygenation (ECMO) therapy. The marked differences among ICU techniques used for the treatment of COVID-19-induced respiratory failure in terms of secondary infection risk profile should be taken into account for the optimal management of critically ill COVID-19 patients, as well as for adequate antimicrobial therapy.

**Keywords:** COVID-19; SARS-CoV-2; multidrug-resistant pathogens; bacterial infections; fungal infections; secondary infections; intensive care medicine; ventilation; ECMO
