Organisms causing secondary pneumonias in COVID-19 patients at 5 UK ICUs as detected with the FilmArray test
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Abstract
Introduction
Several viral respiratory infections - notably influenza - are associated with secondary bacterial infection and additional pathology. The extent to which this applies for COVID-19 is unknown. Accordingly, we aimed to define the bacteria causing secondary pneumonias in COVID-19 ICU patients using the FilmArray Pneumonia Panel, and to determine this test’s potential in COVID-19 management.
Methods
COVID-19 ICU patients with clinically-suspected secondary infection at 5 UK hospitals were tested with the FilmArray at point of care. We collected patient demographic data and compared FilmArray results with routine culture.
Results
We report results of 110 FilmArray tests on 94 patients (16 had 2 tests): 69 patients (73%) were male, the median age was 59 yrs; 92 were ventilated. Median hospital stay before testing was 14 days (range 1-38). Fifty-nine (54%) tests were positive, with 141 bacteria detected. Most were Enterobacterales (n=55, including Klebsiella spp. [n= 35]) or Staphylococcus aureus (n=13), as is typical of hospital and ventilator pneumonia. Community pathogens, including Haemophilus influenzae (n=8) and Streptococcus pneumoniae (n=1), were rarer. FilmArray detected one additional virus (Rhinovirus/Enterovirus) and no atypical bacteria. Fewer samples (28 % vs. 54%) were positive by routine culture, and fewer species were reported per sample; Klebsiella species remained the most prevalent pathogens.
Conclusion
FilmArray had a higher diagnostic yield than culture for ICU COVID-19 patients with suspected secondary pneumonias. The bacteria found mostly were Enterobacterales, S. aureus and P. aeruginosa , as in typical HAP/VAP, but with Klebsiella spp. more prominent. We found almost no viral co-infection. Turnaround from sample to results is around 1h 15 min compared with the usual 72h for culture, giving prescribers earlier data to inform antimicrobial decisions.
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SciScore for 10.1101/2020.06.22.20131573: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Both the main trial and the sub-study have ethical approval from the London, Brighton and Sussex Research Ethics Committee (19/LO/0400) and the Health Research Authority. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources A bespoke REDCap database was used for data collection and storage (13); this provides a number of features to maintain data quality, including an audit trail, ability to query spurious data, search facilities, and validation of predefined parameters/missing data. REDCapsuggested: (REDCap, RRID:SCR_003445)Results from O…
SciScore for 10.1101/2020.06.22.20131573: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Both the main trial and the sub-study have ethical approval from the London, Brighton and Sussex Research Ethics Committee (19/LO/0400) and the Health Research Authority. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources A bespoke REDCap database was used for data collection and storage (13); this provides a number of features to maintain data quality, including an audit trail, ability to query spurious data, search facilities, and validation of predefined parameters/missing data. REDCapsuggested: (REDCap, RRID:SCR_003445)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:To redress this limitation, the present study examined these infections in severely-ill COVID-19 patients, all in ICU and almost all intubated. Patients were included based on suspicion of bacterial infection, consequently the results do not estimate the proportion of COVID-19 patients who develop secondary infection; rather, they illustrate the types of bacteria that are important in severe cases and the utility of the FilmArray PCR for detecting these. The age, sex and co-morbidity profiles of these patients are in keeping with those reported by others in severe COVID-19 disease (14). Although the inclusion criteria permitted testing of patients at any point during their hospital and ICU admission, the majority (95%) of tests were performed at least 5 days after hospital admission. In context it should be noted that hospitalised COVID-19 patients in the UK are typically admitted to a general ward then, after several days, if necessary, are transferred to ICU, where our testing was conducted (14). Although sites had the option of using the test earlier during the hospitalisation, they reported anecdotally that most recently-hospitalised COVID-19 patients were unproductive for sputum and thus not eligible (data not shown). This observation may, of itself, suggest that early-onset bacterial secondary infections are uncommon in COVID-19 illness, as they would be expected to provoke sputum production. Nonetheless, it would be pertinent to examine the microbiology earlier in the ...
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title ISRCTN16483855 NA NA 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.
- Thank you for including a protocol registration statement.
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SciScore for 10.1101/2020.06.22.20131573: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Both the main trial and the sub-study have ethical approval from the London , Brighton and Sussex Research Ethics Committee ( 19/LO/0400 ) and the Health Research Authority . Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable We report results of 110 FilmArray tests on 94 patients ( 16 had 2 tests): 69 patients ( 73 % ) were male , the median age was 59 yrs; 92 were ventilated. Cell Line Authentication A curious discrepancy was that routine serology , only obtained from one hospital , reported 6 cases positive for mycoplasma among the cohort ( Table 3) . Table 2: Resources
Antibodies Sentences Resourc… SciScore for 10.1101/2020.06.22.20131573: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Both the main trial and the sub-study have ethical approval from the London , Brighton and Sussex Research Ethics Committee ( 19/LO/0400 ) and the Health Research Authority . Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable We report results of 110 FilmArray tests on 94 patients ( 16 had 2 tests): 69 patients ( 73 % ) were male , the median age was 59 yrs; 92 were ventilated. Cell Line Authentication A curious discrepancy was that routine serology , only obtained from one hospital , reported 6 cases positive for mycoplasma among the cohort ( Table 3) . Table 2: Resources
Antibodies Sentences Resources One site found 6 patients were positive for either IgM or both IgM and IgG antibodies to M. pneumoniae: none of these were confirmed by the PCR test on the FilmArray; serological testing results have not yet been sought from other sites . IgGsuggested: NoneSoftware and Algorithms Sentences Resources A bespoke REDCap database was used for data collection and storage ( 13); this provides a number of features to maintain data quality , including an audit trail , ability to query spurious data , search facilities , and validation of predefined parameters/missing data . REDCapsuggested: (REDCap, SCR_003445)Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
- To redress this limitation, the present study examined these infections in severely-ill COVID-19 patients, all in ICU and almost all intubated.
- Patients were included based on suspicion of bacterial infection, consequently the results do not estimate the proportion of COVID-19 patients who develop secondary infection; rather, they illustrate the types of bacteria that are important in severe cases and the utility of the FilmArray PCR for detecting these.
Results from OddPub: We did not find a statement about open data. We also did not find a statement about open code. Researchers are encouraged to share open data when possible (see Nature blog).
About SciScore
SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.
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