Inference from longitudinal laboratory tests characterizes temporal evolution of COVID-19-associated coagulopathy (CAC)

  1. Colin Pawlowski
  2. Tyler Wagner
  3. Arjun Puranik
  4. Karthik Murugadoss
  5. Liam Loscalzo
  6. AJ Venkatakrishnan
  7. Rajiv K Pruthi
  8. Damon E Houghton
  9. John C O'Horo
  10. William G Morice
  11. Amy W Williams
  12. Gregory J Gores
  13. John Halamka
  14. Andrew D Badley, MD
  15. Elliot S Barnathan
  16. Hideo Makimura
  17. Najat Khan
  18. Venky Soundararajan  Is a corresponding author
  1. nference, United States
  2. Mayo Clinic, United States
  3. Mayo Clinic Laboratories, United States
  4. Janssen pharmaceutical companies of Johnson & Johnson (J&J), United States
  5. Janssen, United States

Abstract

Temporal inference from laboratory testing results and triangulation with clinical outcomes extracted from unstructured EHR provider notes is integral to advancing precision medicine. Here, we studied 246 SARS-CoV-2 PCR-positive (COVIDpos)patients and propensity-matched 2,460 SARS-CoV-2 PCR-negative (COVIDneg) patients subjected to around 700,000 lab tests cumulatively across 194 assays. Compared to COVIDneg patients at the time of diagnostic testing, COVIDpos patients tended to have higher plasma fibrinogen levels and lower platelet counts. However, as the infection evolves, COVIDpos patients distinctively show declining fibrinogen, increasing platelet counts, and lower white blood cell counts. Augmented curation of EHRs suggests that only a minority of COVIDpos patients develop thromboembolism, and rarely, disseminated intravascular coagulopathy (DIC), with patients generally not displaying platelet reductions typical of consumptive coagulopathies. These temporal trends provide fine-grained resolution into COVID-19 associated coagulopathy (CAC) and set the stage for personalizing thromboprophylaxis.

Data availability

De-identified data will be made available upon reasonable request to the corresponding author (Venky Soundararajan, venky@nference.net).

Article and author information

Author details

  1. Colin Pawlowski

    R&D, nference, Cambridge, United States
    Competing interests
    Colin Pawlowski, This author is an employee of nference with financial interests in the company.
  2. Tyler Wagner

    R and D, nference, Cambridge, United States
    Competing interests
    Tyler Wagner, This author is an employee of nference with financial interests in the company.
  3. Arjun Puranik

    Data Science, nference, San Francisco, United States
    Competing interests
    Arjun Puranik, This author is an employee of nference with financial interests in the company.
  4. Karthik Murugadoss

    Data Sciences, nference, Cambridge, United States
    Competing interests
    Karthik Murugadoss, This author is an employee of nference with financial interests in the company.
  5. Liam Loscalzo

    Data Sciences, nference, Cambridge, United States
    Competing interests
    Liam Loscalzo, This author is an employee of nference with financial interests in the company.
  6. AJ Venkatakrishnan

    R and D, nference, Cambridge, United States
    Competing interests
    AJ Venkatakrishnan, This author is an employee of nference with financial interests in the company.
  7. Rajiv K Pruthi

    Division of Hematopathology, Department of Laboratory Medicine and Pathology, Division of Hematology, Division of Laboratory Genetics and Genomics, Department of Internal Medicine, Mayo Clinic, Rochester, United States
    Competing interests
    Rajiv K Pruthi, One or more of the investigators associated with this project and Mayo Clinic have a Financial Conflict of Interest in technology used in the research and that the investigator(s) and Mayo Clinic may stand to gain financially from the successful outcome of the research. Mayo Clinic is an investor in nference. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and is being conducted in compliance with Mayo Clinic Conflict of Interest policies..
  8. Damon E Houghton

    Thrombophilia Clinic, Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, United States
    Competing interests
    Damon E Houghton, One or more of the investigators associated with this project and Mayo Clinic have a Financial Conflict of Interest in technology used in the research and that the investigator(s) and Mayo Clinic may stand to gain financially from the successful outcome of the research. Mayo Clinic is an investor in nference. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and is being conducted in compliance with Mayo Clinic Conflict of Interest policies..
  9. John C O'Horo

    Division of Infectious Diseases, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Mayo Clinic, Rochester, United States
    Competing interests
    John C O'Horo, One or more of the investigators associated with this project and Mayo Clinic have a Financial Conflict of Interest in technology used in the research and that the investigator(s) and Mayo Clinic may stand to gain financially from the successful outcome of the research. Mayo Clinic is an investor in nference. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and is being conducted in compliance with Mayo Clinic Conflict of Interest policies..
  10. William G Morice

    Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic Laboratories, Rochester, United States
    Competing interests
    William G Morice, One or more of the investigators associated with this project and Mayo Clinic have a Financial Conflict of Interest in technology used in the research and that the investigator(s) and Mayo Clinic may stand to gain financially from the successful outcome of the research. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and is being conducted in compliance with Mayo Clinic Conflict of Interest policies. The author is also involved in the Mayo Clinic Laboratories..
  11. Amy W Williams

    Division of Nephrology & Internal Medicine, Department of Internal Medicine, Mayo Clinic, Rochester, United States
    Competing interests
    Amy W Williams, One or more of the investigators associated with this project and Mayo Clinic have a Financial Conflict of Interest in technology used in the research and that the investigator(s) and Mayo Clinic may stand to gain financially from the successful outcome of the research. Mayo Clinic is an investor in nference. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and is being conducted in compliance with Mayo Clinic Conflict of Interest policies..
  12. Gregory J Gores

    Division of Nephrology & Internal Medicine, Department of Internal Medicine, Mayo Clinic, Rochester, United States
    Competing interests
    Gregory J Gores, One or more of the investigators associated with this project and Mayo Clinic have a Financial Conflict of Interest in technology used in the research and that the investigator(s) and Mayo Clinic may stand to gain financially from the successful outcome of the research. Mayo Clinic is an investor in nference. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and is being conducted in compliance with Mayo Clinic Conflict of Interest policies..
  13. John Halamka

    Mayo Clinic Platform, Mayo Clinic, Rochester, United States
    Competing interests
    John Halamka, One or more of the investigators associated with this project and Mayo Clinic have a Financial Conflict of Interest in technology used in the research and that the investigator(s) and Mayo Clinic may stand to gain financially from the successful outcome of the research. Mayo Clinic is an investor in nference. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and is being conducted in compliance with Mayo Clinic Conflict of Interest policies..
  14. Andrew D Badley, MD

    Mayo Clinic Platform, Mayo Clinic, Rochester, United States
    Competing interests
    Andrew D Badley, MD, One or more of the investigators associated with this project and Mayo Clinic have a Financial Conflict of Interest in technology used in the research and that the investigator(s) and Mayo Clinic may stand to gain financially from the successful outcome of the research. Mayo Clinic is an investor in nference. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and is being conducted in compliance with Mayo Clinic Conflict of Interest policies..
  15. Elliot S Barnathan

    Cardiovascular & Metabolism Therapeutic Area, Janssen pharmaceutical companies of Johnson & Johnson (J&J), Spring House, United States
    Competing interests
    Elliot S Barnathan, This author is an employee of the Janssen pharmaceutical companies of J&J with financial interests in the company.
  16. Hideo Makimura

    Cardiovascular & Metabolism Therapeutic Area, Janssen pharmaceutical companies of Johnson & Johnson (J&J), Spring House, United States
    Competing interests
    Hideo Makimura, This author is an employee of the Janssen pharmaceutical companies of J&J with financial interests in the company.
  17. Najat Khan

    R&D Data Sciences, R&D Strategy & Operations, Janssen, Spring House, United States
    Competing interests
    Najat Khan, This author is an employee of the Janssen pharmaceutical companies of J&J with financial interests in the company.
  18. Venky Soundararajan

    R&D, nference, Cambridge, United States
    For correspondence
    venky@nference.net
    Competing interests
    Venky Soundararajan, The author is an employee of nference and has financial interests in the company. Outside the submitted work, Venky Soundararajan is listed as inventor of the following patent: Systems.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7434-9211

Funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: This research was conducted under IRB 20-003278, "Study of COVID-19 patient characteristics with augmented curation of Electronic Health Records (EHR) to inform strategic and operational decisions". All analysis of EHRs was performed in the privacy-preserving environment secured and controlled by the Mayo Clinic.nference, the Mayo Clinic, and the Janssen pharmaceutical companies of Johnson & Johnson (J&J) subscribe to the basic ethical principles underlying the conduct of research involving human subjects as set forth in the Belmont Report and strictly ensure compliance with the Common Rule in the Code of Federal Regulations (45 CFR 46) on the Protection of Human Subjects.

Reviewing Editor

  1. Frank L van de Veerdonk, Radboud University Medical Center, Netherlands

Version history

  1. Received: May 22, 2020
  2. Accepted: August 14, 2020
  3. Accepted Manuscript published: August 17, 2020 (version 1)
  4. Version of Record published: September 4, 2020 (version 2)
  5. Version of Record updated: November 10, 2020 (version 3)

Copyright

© 2020, Pawlowski 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.

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  1. Colin Pawlowski
  2. Tyler Wagner
  3. Arjun Puranik
  4. Karthik Murugadoss
  5. Liam Loscalzo
  6. AJ Venkatakrishnan
  7. Rajiv K Pruthi
  8. Damon E Houghton
  9. John C O'Horo
  10. William G Morice
  11. Amy W Williams
  12. Gregory J Gores
  13. John Halamka
  14. Andrew D Badley, MD
  15. Elliot S Barnathan
  16. Hideo Makimura
  17. Najat Khan
  18. Venky Soundararajan
(2020)
Inference from longitudinal laboratory tests characterizes temporal evolution of COVID-19-associated coagulopathy (CAC)
eLife 9:e59209.
https://doi.org/10.7554/eLife.59209

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https://doi.org/10.7554/eLife.59209

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