Co-Infections, Secondary Infections, and Antimicrobial Usage in Hospitalised Patients with COVID-19 from the ISARIC WHO CCP-UK Study: A Prospective, Multicentre Cohort Study

Abstract

Background: Microbiological characterisation of co-infections and secondary infections in COVID-19 is lacking, while antimicrobial usage is high. We aimed to describe microbiologically-confirmed co-/secondary infections, and antimicrobial usage, in hospitalised patients with COVID-19.

Methods: Hospitalised patients in England, Scotland, and Wales with confirmed/high likelihood SARS-CoV-2 infection were recruited to the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK) prospective cohort study. Patients admitted between 6^th February–8^th June 2020 with a recorded outcome 28 days after admission were included. Organisms considered clinically insignificant were excluded.

Findings: Microbiological investigations were recorded for 8649/48 902 patients, with significant respiratory or bloodstream bacterial/fungal infections recorded for 1107 patients. These were mostly secondary infections diagnosed >2 days after admission (70·6%, 762/1080 with known sample timing). Staphylococcus aureus then Haemophilus influenzae were the most common pathogens causing respiratory co-infections (diagnosed ≤2 days after admission), with Enterobacteriaceae and S. aureus most common in secondary respiratory infections. Bloodstream infections were most frequently caused by Escherichia coli then S. aureus. Among patients with available data, 37·0% (13 390/36 145) received antimicrobials prior to admission and 85·2% (39 258/46 061) in hospital, highest in critical care. We identified frequent use of broad-spectrum agents and use of carbapenems over carbapenem-sparing alternatives.

Interpretation: In hospitalised patients with COVID-19, microbiologically-confirmed bacterial/fungal infections are rare, and more likely to be secondary infections. Gram-negative organisms and S. aureus are the predominant pathogens. The frequency and nature of antimicrobial usage is concerning, but tractable targets for stewardship interventions exist.

Funding: This work is supported by grants from: the National Institute for Health Research (NIHR) [award CO-CIN-01], the Medical Research Council [grant MC_PC_19059] and by the NIHR Health Protection Research Unit (HPRU)in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford [award 200907], NIHR HPRU in Respiratory Infections at Imperial College London with PHE [award 200927], Wellcome Trust and Department for International Development [215091/Z/18/Z], and the Bill and Melinda Gates Foundation[OPP1209135], and Liverpool Experimental Cancer Medicine Centre (Grant Reference: C18616/A25153), NIHR Biomedical Research Centre at Imperial College London [IS-BRC-1215-20013], EU Platform foR European Preparedness Against (Re-) emerging Epidemics (PREPARE) [FP7 project 602525] and NIHR Clinical Research Network for providing infrastructure support for this research. LT is supported by a Wellcome Trust fellowship [205228/Z/16/Z]. PJMO is supported by a NIHR Senior Investigator Award [award 201385]. This research was funded in whole, or in part, by the Wellcome Trust. For the purpose of Open Access, the authors have applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. The views expressed are those of the authors and not necessarily those of the DHSC, DID, NIHR, MRC, Wellcome Trust or PHE.

Conflict of Interest: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support from the National Institute for Health Research (NIHR), the Medical Research Council (MRC), the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool, NIHR HPRU in Respiratory Infections at Imperial College London, NIHR Biomedical Research Centre at ImperialCollege London, and NIHR Clinical Research Network for the submitted work; ABD reports grants fromDepartment of Health and Social Care (DHSC), during the conduct of the study, grants from Wellcome Trust, outside the submitted work; PJMO reports personal fees from consultancies and from European RespiratorySociety, grants from MRC, MRC Global Challenge Research Fund, EU, NIHR BRC, MRC/GSK, WellcomeTrust, NIHR (Health Protection Research Unit (HPRU) in Respiratory Infection), and is NIHR senior investigator outside the submitted work; his role as President of the British Society for Immunology was unpaid but travel and accommodation at some meetings was provided by the Society; JKB reports grants from MRC UK;MGS reportsgrants from DHSC NIHR UK, grants from MRC UK, grants from HPRU in Emerging and Zoonotic Infections,University of Liverpool, during the conduct of the study, other from Integrum Scientific LLC, Greensboro, NC, USA, outside the submitted work.

Ethical Approval: Ethical approval was given by the South Central-Oxford C Research Ethics Committee in England (13/SC/0149), the Scotland A Research Ethics Committee (20/SS/0028), and the WHO Ethics Review Committee (RPC571 and RPC572, April 2013).

Keywords: co-infection; secondary infection; bacteria; antimicrobial; SARS-CoV-2; COVID-19