Co-infection in critically ill patients with COVID-19: an observational cohort study from England

  1. Vadsala Baskaran
  2. Hannah Lawrence
  3. Louise E. Lansbury
  4. Karmel Webb
  5. Shahideh Safavi
  6. Nurul I. Zainuddin
  7. Tausif Huq
  8. Charlotte Eggleston
  9. Jayne Ellis
  10. Clare Thakker
  11. Bethan Charles
  12. Sara Boyd
  13. Tom Williams
  14. Claire Phillips
  15. Ethan Redmore
  16. Sarah Platt
  17. Eve Hamilton
  18. Andrew Barr
  19. Lucy Venyo
  20. Peter Wilson
  21. Tom Bewick
  22. Priya Daniel
  23. Paul Dark
  24. Adam R. Jeans
  25. Jamie McCanny
  26. Jonathan D. Edgeworth
  27. Martin J. Llewelyn
  28. Matthias L. Schmid
  29. Tricia M. McKeever
  30. Martin Beed
  31. Wei Shen Lim

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Abstract

Introduction. During previous viral pandemics, reported co-infection rates and implicated pathogens have varied. In the 1918 influenza pandemic, a large proportion of severe illness and death was complicated by bacterial co-infection, predominantly Streptococcus pneumoniae and Staphylococcus aureus .

Gap statement. A better understanding of the incidence of co-infection in patients with COVID-19 infection and the pathogens involved is necessary for effective antimicrobial stewardship.

Aim. To describe the incidence and nature of co-infection in critically ill adults with COVID-19 infection in England.

Methodology. A retrospective cohort study of adults with COVID-19 admitted to seven intensive care units (ICUs) in England up to 18 May 2020, was performed. Patients with completed ICU stays were included. The proportion and type of organisms were determined at <48 and >48 h following hospital admission, corresponding to community and hospital-acquired co-infections.

Results. Of 254 patients studied (median age 59 years (IQR 49–69); 64.6 % male), 139 clinically significant organisms were identified from 83 (32.7 %) patients. Bacterial co-infections/ co-colonisation were identified within 48 h of admission in 14 (5.5 %) patients; the commonest pathogens were Staphylococcus aureus (four patients) and Streptococcus pneumoniae (two patients). The proportion of pathogens detected increased with duration of ICU stay, consisting largely of Gram-negative bacteria, particularly Klebsiella pneumoniae and Escherichia coli . The co-infection/ co-colonisation rate >48 h after admission was 27/1000 person-days (95 % CI 21.3–34.1). Patients with co-infections/ co-colonisation were more likely to die in ICU (crude OR 1.78,95 % CI 1.03–3.08, P =0.04) compared to those without co-infections/ co-colonisation.

Conclusion. We found limited evidence for community-acquired bacterial co-infection in hospitalised adults with COVID-19, but a high rate of Gram-negative infection acquired during ICU stay.

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  1. Version published to 10.1099/jmm.0.001350 on Access Microbiology
  2. ScreenIT

    SciScore for 10.1101/2020.10.27.20219097: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    RandomizationWhere more than one critical care area existed at a participating site, a random selection from across areas was requested to avoid selection bias.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line AuthenticationContamination: , bronchoalveolar lavage (BAL), urine) and validated culture-independent tests such as respiratory viral PCR (see Online Resource 2), urinary antigens and serology for Mycoplasma pneumoniae (IgM/ IgG).

    Table 2: Resources

    No key resources detected.

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Strengths and limitations: This pragmatic multicentre study provides novel data on both community-acquired and nosocomial co-infection in patients with COVID-19 requiring ICU care in England. The ICU cohort represents those with severe disease who were subject to more rigorous microbiology sampling. A key limitation of the study is its retrospective observational design subject specifically to case selection, ascertainment and sampling biases. Inclusion of consecutive eligible patients was not feasible due to pandemic workload constraints. To minimise case selection bias, participating sites submitted a random sample of their eligible cohort, although random sampling methods were not standardised. The impact of ascertainment bias due to differences in the proportion of eligible cases submitted by each institution was reduced through the participation of multiple centres. The study cohort was comparable to the ICNARC cohort except for an under-representation of patients of Black, Asian and Minority Ethnicity (BAME). Our results may not be applicable to settings with larger BAME populations. Restriction of our cohort to those with completed ICU admissions excluded: i) frailer patients in whom ICU care was deemed not appropriate, and ii) patients with very long ICU stays. Co-infection, particularly nosocomial infection, may be higher in these patients. A second key limitation is that although results likely to represent contamination were excluded, some pathogens found in respir...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

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  3. Version published to 10.1101/2020.10.27.20219097v1 on medRxiv