Evaluating the potential for respiratory metagenomics to improve treatment of secondary infection and detection of nosocomial transmission on expanded COVID-19 intensive care units

Genome Med. 2021 Nov 17;13(1):182. doi: 10.1186/s13073-021-00991-y.


Background: Clinical metagenomics (CMg) has the potential to be translated from a research tool into routine service to improve antimicrobial treatment and infection control decisions. The SARS-CoV-2 pandemic provides added impetus to realise these benefits, given the increased risk of secondary infection and nosocomial transmission of multi-drug-resistant (MDR) pathogens linked with the expansion of critical care capacity.

Methods: CMg using nanopore sequencing was evaluated in a proof-of-concept study on 43 respiratory samples from 34 intubated patients across seven intensive care units (ICUs) over a 9-week period during the first COVID-19 pandemic wave.

Results: An 8-h CMg workflow was 92% sensitive (95% CI, 75-99%) and 82% specific (95% CI, 57-96%) for bacterial identification based on culture-positive and culture-negative samples, respectively. CMg sequencing reported the presence or absence of β-lactam-resistant genes carried by Enterobacterales that would modify the initial guideline-recommended antibiotics in every case. CMg was also 100% concordant with quantitative PCR for detecting Aspergillus fumigatus from 4 positive and 39 negative samples. Molecular typing using 24-h sequencing data identified an MDR-K. pneumoniae ST307 outbreak involving 4 patients and an MDR-C. striatum outbreak involving 14 patients across three ICUs.

Conclusion: CMg testing provides accurate pathogen detection and antibiotic resistance prediction in a same-day laboratory workflow, with assembled genomes available the next day for genomic surveillance. The provision of this technology in a service setting could fundamentally change the multi-disciplinary team approach to managing ICU infections. The potential to improve the initial targeted treatment and rapidly detect unsuspected outbreaks of MDR-pathogens justifies further expedited clinical assessment of CMg.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / therapeutic use
  • COVID-19 / pathology*
  • COVID-19 / virology
  • Coinfection / drug therapy
  • Coinfection / microbiology
  • Corynebacterium / genetics
  • Corynebacterium / isolation & purification
  • Cross Infection / microbiology
  • Cross Infection / transmission*
  • DNA, Bacterial / chemistry
  • DNA, Bacterial / metabolism
  • Drug Resistance, Multiple, Bacterial / genetics
  • Female
  • Humans
  • Intensive Care Units
  • Klebsiella pneumoniae / genetics
  • Klebsiella pneumoniae / isolation & purification
  • Male
  • Metagenomics*
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • SARS-CoV-2 / isolation & purification
  • Sequence Analysis, DNA
  • beta-Lactamases / genetics


  • Anti-Bacterial Agents
  • DNA, Bacterial
  • beta-Lactamases

Supplementary concepts

  • Corynebacterium striatum