*Article* **Next-Generation Sequencing in Critically Ill COVID-19 Patients with Suspected Bloodstream Infections: A Retrospective Cohort Study**

**Christoph J. Leitl 1,\*, Sandra E. Stoll 1, Wolfgang A. Wetsch 1, Tobias Kammerer 1, Alexander Mathes 1, Bernd W. Böttiger 1, Harald Seifert <sup>2</sup> and Fabian Dusse <sup>1</sup>**


**Abstract:** Background: Rapid pathogen identification and appropriate antimicrobial therapy are crucial in critically ill COVID-19 patients with bloodstream infections (BSIs). This study aimed to evaluate the diagnostic performance and potential therapeutic benefit of additional next-generation sequencing (NGS) of microbial DNA from plasma in these patients. Methods: This monocentric descriptive retrospective study reviewed clinical data and pathogen diagnostics in COVID-19 ICU patients. NGS (DISQVER®) and blood culture (BC) samples were obtained on suspicion of BSIs. Data were reviewed regarding the adjustment of antimicrobial therapy and diagnostic procedures seven days after sampling and analyzed using the Chi2-test. Results: Twenty-five cases with simultaneous NGS and BC sampling were assessed. The NGS positivity rate was 52% (13/25) with the detection of 23 pathogens (14 bacteria, 1 fungus, 8 viruses), and the BC positivity rate was 28% (7/25, 8 bacteria; *p* = 0.083). The NGS-positive patients were older (75 vs. 59.5 years; *p* = 0.03) with a higher prevalence of cardiovascular disease (77% vs. 33%; *p* = 0.03). These NGS results led to diagnostic procedures in four cases and to the commencement of four antimicrobial therapies in three cases. Empirical treatment was considered appropriate and continued in three cases. Conclusions: In COVID-19 patients with suspected BSIs, NGS may provide a higher positivity rate than BC and enable new therapeutic approaches.

**Keywords:** blood culture; sepsis; antimicrobial therapy; bacteremia; DISQVER®
