Using the kinetics of C-reactive protein response to improve the differential diagnosis between acute bacterial and viral infections



Differential diagnosis between acute viral and bacterial infection is an emerging common challenge for a physician in the emergency department. Serum C-reactive protein (CRP) is used to support diagnosis of bacterial infection, but in patients admitted with low CRP, its ability to discriminate between viral and bacterial infections is limited. We aimed to use two consecutive CRP measurements in order to improve differential diagnosis between bacterial and viral infection.


A single-center retrospective cohort (n = 1629) study of adult patients admitted to the emergency department with a subsequent microbiological confirmation of either viral or bacterial infection. Trend of CRP was defined as the absolute difference between the first two measurements of CRP divided by the time between them, and we investigated the ability of this parameter to differentiate between viral and bacterial infection.


In patients with relatively low initial CRP concentration (< 60 mg/L, n = 634 patients), where the uncertainty regarding the type of infection is the highest, the trend improved diagnosis accuracy (AUC 0.83 compared to 0.57 for the first CRP measurement). Trend values above 3.47 mg/L/h discriminated bacterial from viral infection with 93.8% specificity and 50% sensitivity.


The proposed approach for using the kinetics of CRP in patients whose first CRP measurement is low can assist in differential diagnosis between acute bacterial and viral infection.

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R.S. was supported in part by the Israel Science Foundation (Grant 1339/18), by Grant 2016694 from the United States–Israel Binational Science Foundation (BSF), Jerusalem, Israel, and the United States National Science Foundation (NSF), and by the Naomi Prawer Kadar Foundation. S.S.T. was supported by the ELROV grant. D.C. was supported, in part, by fellowships from the Edmond J. Safra Center for Bioinformatics at Tel Aviv University and from Google.


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DC—planned and conducted the study, collected and interpreted data, drafted the manuscript and approved the final submission. AW—collected and interpreted data, drafted the manuscript and approved the final submission. EF—collected and interpreted data, drafted the manuscript and approved the final submission. OR—planned and conducted the study, drafted the manuscript and approved the final submission. DZ—collected data and approved the final submission. IS—collected data and approved the final submission. DB—collected and interpreted data, drafted the manuscript and approved the final submission. AM—collected data and approved the final submission. ER—collected data and approved the final submission. PH—collected data and approved the final submission. SB—planned the study, interpreted data and approved the final submission. SS-T—planned the study, interpreted data, drafted the manuscript and approved the final submission. RS—planned and supervised the study, interpreted data, drafted the manuscript and approved the final submission.

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Correspondence to Shani Shenhar-Tsarfaty.

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The study was reviewed and approved by Sourasky Tel Aviv Medical Center Institutional Review Board (number 0491-17).

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The work described has not been published before and it is not under consideration for publication anywhere else. This publication has been approved by all co-authors.

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Coster, D., Wasserman, A., Fisher, E. et al. Using the kinetics of C-reactive protein response to improve the differential diagnosis between acute bacterial and viral infections. Infection 48, 241–248 (2020).

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  • Bacterial
  • Viral
  • C-reactive protein
  • Differential diagnosis
  • Infection