key: cord-0315576-ol6faq1y
authors: Houghton, R.; Moore, N.; Williams, R.; El-Bakri, F.; Peters, J.; Mori, M.; Vernet, G.; Lynch, J.; Lewis, H.; Tavener, M.; Durham, T.; Bowyer, J.; Saeed, K.; Pollara, G.
title: C-reactive protein guided use of procalcitonin in COVID-19
date: 2021-02-15
journal: nan
DOI: 10.1101/2021.02.10.21251350
sha: da7a8bbf72e2b7cf8eec5657f5312a6dfca4632c
doc_id: 315576
cord_uid: ol6faq1y

Low procalcitonin (PCT) concentrations (<0.5ng/mL) can facilitate exclusion of bacterial co-infection in viral infections, including COVID-19. However, costs associated with PCT measurement preclude universal adoption, indicating a need to identify settings where PCT provides clinical information beyond that offered by other inflammatory markers, such as C-reactive protein (CRP) and white cell count (WCC). In an unselected cohort of 299 COVID-19 patients, we tested the hypothesis that PCT<0.5ng/mL was associated with lower levels of CRP and WCC. We demonstrated that CRP values below the geometric mean of the entire patient population had a negative predictive value for PCT<0.5ng/mL of 97.6% and 100% at baseline and 48 hours into admission respectively, and that this relationship was not confounded by intensive care admission or microbiological findings. CRP-guided PCT testing algorithms can reduce costs and support antimicrobial stewardship strategies in COVID-19.

adoption, indicating a need to identify settings where PCT provides clinical information beyond that offered 23 by other inflammatory markers, such as C-reactive protein (CRP) and white cell count (WCC). In an unselected 24 cohort of 299 COVID-19 patients, we tested the hypothesis that PCT<0.5ng/mL was associated with lower 25 levels of CRP and WCC. We demonstrated that CRP values below the geometric mean of the entire patient 26 population had a negative predictive value for PCT0.5ng/mL of 97.6% and 100% at baseline and 48 hours 27 into admission respectively, and that this relationship was not confounded by intensive care admission or 28 microbiological findings. CRP-guided PCT testing algorithms can reduce costs and support antimicrobial 29 stewardship strategies in COVID-19. 30

. CC-BY-NC-ND 4.0 International license It is made available under a perpetuity.

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The copyright holder for this this version posted February 12, 2021. ; https://doi.org/10.1101/2021.02.10.21251350 doi: medRxiv preprint Main text 31 Unnecessary antibiotic prescriptions during the COVID-19 pandemic will increase selection for antibiotic 32 resistance (1). Optimising antimicrobial stewardship approaches in COVID-19 is a global priority, and a recent 33 study has indicated that procalcitonin (PCT) <0.5ng/mL offered a high negative predictive value (>95%) for 34 the presence of bacterial co-infections (2). Elevated PCT is associated more frequently with bacterial than 35 viral infections (3), and thus low PCT can support cessation of antibiotic prescriptions in both COVID-19 and 36 non-COVID-19 settings (4-8). Unlike the inflammatory markers C-reactive protein (CRP) and white cell count 37 (WCC), PCT is not routinely measured (9), partly due to the costs associated with its testing (10,11). Elevations 38 in PCT, CRP and WCC can be concordant (12), and therefore a key research question is to identify scenarios 39

in which PCT provides clinical information beyond that offered by other inflammatory markers, in turn 40 informing algorithms that avoid the expense of redundant PCT measurements. 41

We identified 299 adult patients with compatible clinical syndromes for COVID-19 and SARS-CoV-2 confirmed 42 on molecular testing, admitted to Hampshire Hospitals NHS Trust between 5 th March and 26 th April 2020. The 43 measurement of PCT, CRP and WCC at baseline and daily during hospital admission was standard of care. We 44 tested the hypothesis that PCT concentration was closely related to CRP or WCC levels, choosing 45 PCT≥0.5ng/mL as threshold for the presence of bacterial pulmonary infection (4,7,8,13,14). PCT≥0.5ng/mL 46 was associated with greater levels of CRP on admission and 48 hours into admission, independent of the 47 need for intensive care unit (ICU) admission during the hospital stay (figs 1A+C). In contrast, PCT≥0.5ng/mL 48 was associated with only a modestly greater WCC in non-ICU attending patients ( fig 1B+D) . Next, we used 49 pairwise comparison to test the hypothesis that low levels of CRP/WCC could exclude PCT≥0.5 ng/ml. We 50 used the geometric mean of CRP or WCC for the entire patient population at each timepoint as cut-offs for 51 low and high levels of these markers. Strikingly, low CRP was strongly associated with PCT<0.5ng/mL (NPV 52 97.6% and 100% at baseline and 48 hours into admission respectively) ( fig 1C) . A similar relationship was 53 observed for WCC, although with lower NPV (91.0% and 84.9% respectively) ( fig 1D) . Notably, patients with 54 significant microbiological results, as previously defined (2), were not associated with elevated levels of any 55 inflammatory marker ( fig 1C+D) (9) . 56 . CC-BY-NC-ND 4.0 International license It is made available under a perpetuity.

is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted February 12, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted February 12, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted February 12, 2021. ; https://doi.org/10.1101/2021.02.10.21251350 doi: medRxiv preprint

Antimicrobial Resistance: Parallel and Interacting Health Emergencies

Limited Utility of Procalcitonin in 82

Identifying Community-Associated Bacterial Infections in Patients Presenting with Coronavirus Disease 83 2019

Procalcitonin as a Marker of 85

Etiology in Adults Hospitalized With Community-Acquired Pneumonia

Efficacy and safety of 88 procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a 89 randomised, controlled, open-label trial

Evaluation of procalcitonin as a 91 contribution to antimicrobial stewardship in SARS-CoV-2 infection: a retrospective cohort study

Use of procalcitonin for antibiotic 94 stewardship in patients with COVID-19: A quality improvement project in a district general hospital

Procalcitonin as 97 an antibiotic stewardship tool in COVID-19 patients in the intensive care unit

The Use of Procalcitonin as an Antimicrobial 100

Stewardship Tool and a Predictor of Disease Severity in COVID-19

. CC-BY-NC-ND 4.0 International license It is made available under a perpetuity.is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprintThe copyright holder for this this version posted February 12, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint