Study protocol for the Innovative Support for Patients with SARS-COV-2 Infections Registry (INSPIRE): A longitudinal study of the medium and long-term sequelae of SARS-CoV-2 infection

  1. Kelli N. O’Laughlin
  2. Matthew Thompson
  3. Bala Hota
  4. Michael Gottlieb
  5. Ian D. Plumb
  6. Anna Marie Chang
  7. Lauren E. Wisk
  8. Aron J. Hall
  9. Ralph C. Wang
  10. Erica S. Spatz
  11. Kari A. Stephens
  12. Ryan M. Huebinger
  13. Samuel A. McDonald
  14. Arjun Venkatesh
  15. Nikki Gentile
  16. Benjamin H. Slovis
  17. Mandy Hill
  18. Sharon Saydah
  19. Ahamed H. Idris
  20. Robert Rodriguez
  21. Harlan M. Krumholz
  22. Joann G. Elmore
  23. Robert A. Weinstein
  24. Graham Nichol
  25. for the INSPIRE Investigators

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Abstract

Reports on medium and long-term sequelae of SARS-CoV-2 infections largely lack quantification of incidence and relative risk. We describe the rationale and methods of the Innovative Support for Patients with SARS-CoV-2 Registry (INSPIRE) that combines patient-reported outcomes with data from digital health records to understand predictors and impacts of SARS-CoV-2 infection.

Methods

INSPIRE is a prospective, multicenter, longitudinal study of individuals with symptoms of SARS-CoV-2 infection in eight regions across the US. Adults are eligible for enrollment if they are fluent in English or Spanish, reported symptoms suggestive of acute SARS-CoV-2 infection, and if they are within 42 days of having a SARS-CoV-2 viral test (i.e., nucleic acid amplification test or antigen test), regardless of test results. Recruitment occurs in-person, by phone or email, and through online advertisement. A secure online platform is used to facilitate the collation of consent-related materials, digital health records, and responses to self-administered surveys. Participants are followed for up to 18 months, with patient-reported outcomes collected every three months via survey and linked to concurrent digital health data; follow-up includes no in-person involvement. Our planned enrollment is 4,800 participants, including 2,400 SARS-CoV-2 positive and 2,400 SARS-CoV-2 negative participants (as a concurrent comparison group). These data will allow assessment of longitudinal outcomes from SARS-CoV-2 infection and comparison of the relative risk of outcomes in individuals with and without infection. Patient-reported outcomes include self-reported health function and status, as well as clinical outcomes including health system encounters and new diagnoses.

Results

Participating sites obtained institutional review board approval. Enrollment and follow-up are ongoing.

Conclusions

This study will characterize medium and long-term sequelae of SARS-CoV-2 infection among a diverse population, predictors of sequelae, and their relative risk compared to persons with similar symptomatology but without SARS-CoV-2 infection. These data may inform clinical interventions for individuals with sequelae of SARS-CoV-2 infection.

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  1. Version published to 10.1371/journal.pone.0264260
  2. Version published to 10.1101/2021.08.01.21261397v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.08.01.21261397: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsConsent: Individuals direct Hugo to share their health records with the research team according to the terms in the informed consent.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power AnalysisThese power calculations are agnostic to the outcome of interest but based on the aim to examine relative differences in long-term outcomes between individuals with and without SARS-CoV-2 based on and between age strata.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Additional outcomes: assessed include post-infectious sequelae (e.g., dyspnea, cough) [34–36], post-traumatic stress disorder (PC-PTSD-5) [37], and exercise (exercise vital sign; 2 question survey to assess habitual physical activity) [38–40], using previously validated questionnaires.
    PC-PTSD-5
    suggested: None
    , approved 1/21/2021), the University of Texas Southwestern Medical Center (STU 2020-1352, approved 2/3/2021), the University of Texas, Houston (HSC-MS-20-0981, approved 9/10/2020), the University of California, San Francisco (20-32222
    HSC-MS-20-0981
    suggested: None
    Software and Algorithms
    SentencesResources
    Deidentified, individual-level data are sent from Hugo to the analytic team periodically for quality assurance and analysis.
    Hugo
    suggested: (HUGO, RRID:SCR_012800)

    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:
    Strengths and limitations: Our cohort study integrates detailed self-reports of participants with automated capture of their EHR information to provide more comprehensive data than traditional approaches. This innovative method enables capturing of baseline medical conditions, accounting for intermediate events between SARS-CoV-2 infection and sequelae, and objective assessments over time. Merging self-reported and digital data in this manner paves the way for similar research into long-term sequelae in other disease entities, including non-infectious illnesses such as trauma. Using the on-line digital platform to collect patient-oriented outcomes enables us to adapt the survey content in real time as new information emerges. Additionally, there is the potential for this cohort to be engaged in future research as new questions arise relating to long-term sequalae, therapies and other related issues. Recruitment design strengths include the inclusion of participants with a range of disease severity, including participants with and without a history of hospitalization. Additionally, we seek to recruit participants who are ethnically diverse and geographically dispersed. Further, our design includes concurrent controls with negative SARS-CoV-2 diagnostic results to overcome the variable exposure to healthcare access as well as to COVID-19 mitigation strategies implemented in the community (e.g., masking mandates, shut-downs) which could otherwise bias assessment of the risk of p...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04610515RecruitingInnovative Support for Patients With SARS-COV2 Infections (C…

    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.

    Results from scite Reference Check: We found no unreliable references.

    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 checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  4. Version published to 10.1101/2021.08.01.21261397v1 on medRxiv