Bacterial Pulmonary Superinfections Are Associated with Unfavourable Outcomes in Critically Ill COVID-19 Patients

Background: While superinfections are associated with unfavourable disease course, their impact on clinical outcomes in critically ill COVID-19 patients remains largely unknown. We aimed to investigate the impact of superinfections in critically ill patients with COVID-19.Methods: In this prospective single centre cohort study in an intensive care unit (ICU) setting patients aged ≥ 18 years with COVID-19 Acute Respiratory Distress Syndrome (CARDS) and confirmed SARS-CoV-2 infection were assessed for concomitant microbial infections by longitudinal analysis of tracheobronchial secretions (TBS), bronchoalveolar lavages (BAL) and blood. Our primary outcome was ventilator-free survival on day 28 in patients with and without clinically relevant superinfection. Further outcomes included the association of superinfection with ICU length of stay, incidence of bacteremia, viral reactivations, and fungal colonization.Findings: In a total of 45 critically ill COVID-19 patients, we identified 19 patients with superinfections (42·2%) by longitudinal analysis of 433 TBS, 35 BAL and 455 blood samples, respectively. On average, superinfections were detected on day 10 after ICU admission despite the majority of patients already being on empiric antibiotic therapy. The most frequently isolated clinically relevant bacteria were Enterobacter/Citrobacter , Klebsiella spp., Streptococcus pneumoniae, Escherichia coli and Pseudomonas aeruginosa. Ventilator-free survival (VFS) at 28 days was substantially lower in patients with superinfection (subhazard ratio 0·37, 95%-CI 0·15-0·90, p=0·028). Patients with pulmonary superinfections more often had bacteraemia, virus reactivations, yeast colonization, and needed ICU treatment for a significantly longer time.Interpretation: The detection of superinfections was frequent and associated with reduced ventilator-free survival. A more severe disease course in critically ill COVID-19 patients with superinfections thus seems likely, also reflected by a substantially increased ICU length of stay despite empirical broad-spectrum antimicrobial therapy. Longitudinal microbiologic sampling in COVID-19 patients could allow targeted antimicrobial therapy, and therefore minimize the use of broad-spectrum and reserve antibiotics.Funding: Promedica-Foundation, unrestricted grant.Declaration of Interests: All other authors have no conflict of interest. Ethics Approval Statement: The study was approved by the local ethics committee of the Canton of Zurich, Switzerland (Kantonale Ethikkommission Zurich BASEC ID 2020 - 00646).