A novel haemocytometric COVID-19 prognostic score developed and validated in an observational multicentre European hospital-based study

  1. Joachim Linssen
  2. Anthony Ermens
  3. Marvin Berrevoets
  4. Michela Seghezzi
  5. Giulia Previtali
  6. Simone van der Sar-van der Brugge
  7. Henk Russcher
  8. Annelies Verbon
  9. Judith MEP Gillis
  10. Jürgen Riedl
  11. Eva de Jongh
  12. Jarob Saker
  13. Marion Münster
  14. Imke CA Munnix
  15. Anthonius Dofferhof
  16. Volkher Scharnhorst
  17. Heidi Ammerlaan
  18. Kathleen Deiteren
  19. Stephan JL Bakker
  20. Lucas Joost Van Pelt
  21. Yvette Kluiters-de Hingh
  22. Mathie PG Leers
  23. Andre J van der Ven  Is a corresponding author
  1. Sysmex Europe GMBH, Germany
  2. Amphia Hospital, Netherlands
  3. Elisabeth-Tweesteden Hospital, Netherlands
  4. Hospital Papa Giovanni XXIII Bergamo, Italy
  5. Erasmus MC, University Medical Center, Netherlands
  6. Leiden University Medical Center, Netherlands
  7. Albert Schweitzer Hospital, Netherlands
  8. Canisius Wilhelmina Hospital, Netherlands
  9. Catharina Hospital, Netherlands
  10. University Hospital Antwerp, Belgium
  11. University Medical Center Groningen, University of Groningen, Netherlands
  12. Zuyderland Medical Center, Netherlands
  13. Radboud University Medical Center, Netherlands

Abstract

COVID-19 induces haemocytometric changes. Complete blood count changes, including new cell activation parameters, from 982 confirmed COVID-19 adult patients from 11 European hospitals were retrospectively analysed for distinctive patterns based on age, gender, clinical severity, symptom duration and hospital days. The observed haemocytometric patterns formed the basis to develop a multi-haemocytometric-parameter prognostic score to predict, during the first three days after presentation, which patients will recover without ventilation or deteriorate within a two-week timeframe, needing intensive care or with fatal outcome. The prognostic score, with ROC curve AUC at baseline of 0.753 (95% CI 0.723-0.781) increasing to 0.875 (95% CI 0.806-0.926) on day 3, was superior to any individual parameter at distinguishing between clinical severity. Findings were confirmed in a validation cohort. Aim is that the score and haemocytometry results are simultaneously provided by analyser software, enabling wide applicability of the score as haemocytometry is commonly requested in COVID-19 patients.

Data availability

All data analysed during this study are included in the manuscript and supportinng files . Source data files have been provided for figures 3, 4, 5, 6, 7, 8, 9, 10 and 12, and tables 2, 3, 5, 6 and 7.

Article and author information

Author details

  1. Joachim Linssen

    Medical Scientific Department, Sysmex Europe GMBH, Hamburg, Germany
    Competing interests
    Joachim Linssen, Joachim Linssen is a permanent employee of Sysmex Europe GMBH who provided free of charge study reagents to the study centres..
  2. Anthony Ermens

    Clinical Chemistry and Hematology Laboratory, Amphia Hospital, Breda, Netherlands
    Competing interests
    No competing interests declared.
  3. Marvin Berrevoets

    Infectious Diseases/Acute Medicine, Elisabeth-Tweesteden Hospital, Tilburg, Netherlands
    Competing interests
    No competing interests declared.
  4. Michela Seghezzi

    Clinical Chemistry Laboratory, Hospital Papa Giovanni XXIII Bergamo, Bergamo, Italy
    Competing interests
    No competing interests declared.
  5. Giulia Previtali

    Clinical Chemistry Laboratory, Hospital Papa Giovanni XXIII Bergamo, Bergamo, Italy
    Competing interests
    No competing interests declared.
  6. Simone van der Sar-van der Brugge

    Pulmonology, Amphia Hospital, Breda, Netherlands
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6462-075X
  7. Henk Russcher

    Clinical Chemistry, Erasmus MC, University Medical Center, Rotterdam, Netherlands
    Competing interests
    No competing interests declared.
  8. Annelies Verbon

    Medical Microbiology and Infectious Diseases, Erasmus MC, University Medical Center, Rotterdam, Netherlands
    Competing interests
    No competing interests declared.
  9. Judith MEP Gillis

    Clinical Chemistry, Leiden University Medical Center, Leiden, Netherlands
    Competing interests
    No competing interests declared.
  10. Jürgen Riedl

    Clinical Chemistry, Albert Schweitzer Hospital, Dordrecht, Netherlands
    Competing interests
    No competing interests declared.
  11. Eva de Jongh

    Clinical Hematology, Albert Schweitzer Hospital, Dordrecht, Netherlands
    Competing interests
    No competing interests declared.
  12. Jarob Saker

    Medical Scientific Department, Sysmex Europe GMBH, Hamburg, Germany
    Competing interests
    Jarob Saker, Jarob saker is a permanent employee of Sysmex Europe GMBH who provided free of charge study reagents to the study centres..
  13. Marion Münster

    Medical Scientific Department, Sysmex Europe GMBH, Hamburg, Germany
    Competing interests
    Marion Münster, Marion Münster is a permanent employee of Sysmex Europe GMBH who provided free of charge study reagents to the study centres..
  14. Imke CA Munnix

    Clinical Chemistry/Hematology Laboratory, Canisius Wilhelmina Hospital, Nijmegen, Netherlands
    Competing interests
    No competing interests declared.
  15. Anthonius Dofferhof

    Internal Medicine, Canisius Wilhelmina Hospital, Nijmegen, Netherlands
    Competing interests
    No competing interests declared.
  16. Volkher Scharnhorst

    Clinical Chemistry, Catharina Hospital, Eindhoven, Netherlands
    Competing interests
    No competing interests declared.
  17. Heidi Ammerlaan

    Internal Medicine, Catharina Hospital, Eindhoven, Netherlands
    Competing interests
    No competing interests declared.
  18. Kathleen Deiteren

    Clinical Chemistry, University Hospital Antwerp, Antwerp, Belgium
    Competing interests
    No competing interests declared.
  19. Stephan JL Bakker

    Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
    Competing interests
    No competing interests declared.
  20. Lucas Joost Van Pelt

    Clinical Chemistry, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5538-1806
  21. Yvette Kluiters-de Hingh

    Clinical Chemistry, Elisabeth-Tweesteden Hospital, Tilburg, Netherlands
    Competing interests
    No competing interests declared.
  22. Mathie PG Leers

    Clinical Chemistry, Zuyderland Medical Center, Sittard-Geleen, Netherlands
    Competing interests
    No competing interests declared.
  23. Andre J van der Ven

    Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands
    For correspondence
    andre.vanderven@radboudumc.nl
    Competing interests
    Andre J van der Ven, Andre van der Ven has an ad hoc consultancy agreement with Sysmex Europe GMBH who provided free of charge study reagents to the study centres,.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1833-3391

Funding

Sysmex Europe GMBH provided free of charge reagents for the study. No monetary payments were made to any of the investigators. Joachim Linssen, Jarob Saker and Marion Münster are full-time employees of Sysmex Europe GMBH and Andre van der Ven has an ad hoc consultancy agreement with Sysmex Europe GMBH.

Ethics

Human subjects: The study was reviewed by all participating centre ethics committees with approval granted in Italy (Registration Number 54/20) and Belgium (Registration Number 3002020000105) and exemption in the Netherlands, with need for informed consent waived by all.

Copyright

© 2020, Linssen et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 34,866
    views
  • 1,905
    downloads
  • 42
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Joachim Linssen
  2. Anthony Ermens
  3. Marvin Berrevoets
  4. Michela Seghezzi
  5. Giulia Previtali
  6. Simone van der Sar-van der Brugge
  7. Henk Russcher
  8. Annelies Verbon
  9. Judith MEP Gillis
  10. Jürgen Riedl
  11. Eva de Jongh
  12. Jarob Saker
  13. Marion Münster
  14. Imke CA Munnix
  15. Anthonius Dofferhof
  16. Volkher Scharnhorst
  17. Heidi Ammerlaan
  18. Kathleen Deiteren
  19. Stephan JL Bakker
  20. Lucas Joost Van Pelt
  21. Yvette Kluiters-de Hingh
  22. Mathie PG Leers
  23. Andre J van der Ven
(2020)
A novel haemocytometric COVID-19 prognostic score developed and validated in an observational multicentre European hospital-based study
eLife 9:e63195.
https://doi.org/10.7554/eLife.63195

Share this article

https://doi.org/10.7554/eLife.63195

Further reading

    1. Medicine
    2. Microbiology and Infectious Disease
    3. Epidemiology and Global Health
    4. Immunology and Inflammation
    Edited by Jos WM van der Meer et al.
    Collection

    eLife has published articles on a wide range of infectious diseases, including COVID-19, influenza, tuberculosis, HIV/AIDS, malaria and typhoid fever.

    1. Medicine
    Mitsuru Sugimoto, Tadayuki Takagi ... Hiromasa Ohira
    Research Article

    Background:

    Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is a severe and deadly adverse event following ERCP. The ideal method for predicting PEP risk before ERCP has yet to be identified. We aimed to establish a simple PEP risk score model (SuPER model: Support for PEP Reduction) that can be applied before ERCP.

    Methods:

    This multicenter study enrolled 2074 patients who underwent ERCP. Among them, 1037 patients each were randomly assigned to the development and validation cohorts. In the development cohort, the risk score model for predicting PEP was established via logistic regression analysis. In the validation cohort, the performance of the model was assessed.

    Results:

    In the development cohort, five PEP risk factors that could be identified before ERCP were extracted and assigned weights according to their respective regression coefficients: –2 points for pancreatic calcification, 1 point for female sex, and 2 points for intraductal papillary mucinous neoplasm, a native papilla of Vater, or the pancreatic duct procedures (treated as ‘planned pancreatic duct procedures’ for calculating the score before ERCP). The PEP occurrence rate was 0% among low-risk patients (≤0 points), 5.5% among moderate-risk patients (1–3 points), and 20.2% among high-risk patients (4–7 points). In the validation cohort, the C statistic of the risk score model was 0.71 (95% CI 0.64–0.78), which was considered acceptable. The PEP risk classification (low, moderate, and high) was a significant predictive factor for PEP that was independent of intraprocedural PEP risk factors (precut sphincterotomy and inadvertent pancreatic duct cannulation) (OR 4.2, 95% CI 2.8–6.3; p<0.01).

    Conclusions:

    The PEP risk score allows an estimation of the risk of PEP prior to ERCP, regardless of whether the patient has undergone pancreatic duct procedures. This simple risk model, consisting of only five items, may aid in predicting and explaining the risk of PEP before ERCP and in preventing PEP by allowing selection of the appropriate expert endoscopist and useful PEP prophylaxes.

    Funding:

    No external funding was received for this work.