Understanding Post-Acute Sequelae of SARS-CoV-2 Infection through Data-Driven Analysis with Longitudinal Electronic Health Records: Findings from the RECOVER Initiative

  1. Chengxi Zang
  2. Yongkang Zhang
  3. Jie Xu
  4. Jiang Bian
  5. Dmitry Morozyuk
  6. Edward J. Schenck
  7. Dhruv Khullar
  8. Anna S. Nordvig
  9. Elizabeth A. Shenkman
  10. Russel L. Rothman
  11. Jason P. Block
  12. Kristin Lyman
  13. Mark Weiner
  14. Thomas W. Carton
  15. Fei Wang
  16. Rainu Kaushal

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Abstract

Recent studies have investigated post-acute sequelae of SARS-CoV-2 infection (PASC) using real-world patient data such as electronic health records (EHR). Prior studies have typically been conducted on patient cohorts with small sample sizes 1 or specific patient populations 2,3 limiting generalizability. This study aims to characterize PASC using the EHR data warehouses from two large national patient-centered clinical research networks (PCORnet), INSIGHT and OneFlorida+, which include 11 million patients in New York City (NYC) and 16.8 million patients in Florida respectively. With a high-throughput causal inference pipeline using high-dimensional inverse propensity score adjustment, we identified a broad list of diagnoses and medications with significantly higher incidence 30-180 days after the laboratory-confirmed SARS-CoV-2 infection compared to non-infected patients. We found more PASC diagnoses and a higher risk of PASC in NYC than in Florida, which highlights the heterogeneity of PASC in different populations.

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    SciScore for 10.1101/2022.05.21.22275420: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The use of the INSIGHT data was approved by the Institutional Review Board (IRB) of Weill Cornell Medicine following NIH protocol 21-10-95-380 with protocol title: Adult PCORnet-PASC Response to the Proposed Revised Milestones for the PASC EHR/ORWD Teams (RECOVER).
    Sex as a biological variableThe collected baseline covariates included age (categorized into 20-39 years, 40-54 years, 55-4 years, 65-74 years, 75-84 years, 85 years and older), gender (female, male, other/missing), race (Asian, Black or African American, White, other, missing), ethnicity (Hispanic, not Hispanic, other/missing).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: Thank you for sharing your code.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    There are also several limitations. First, our study was based on observational data analysis, assignment to a particular exposure group was not randomized. However, we balanced high-dimensional hypothetical confounders and got consistent results from several negative outcome control analyses across two datasets, suggesting little confounding. Second, our study included the patient population from the NYC and Florida areas, which may not be representative of other geographical regions of the US or other countries. Third, the PASC is currently defined in the RECOVER protocols as “ongoing, relapsing, or new symptoms, or other health effects occurring after the acute phase of SARS-CoV-2 infection”. 27 Our study only studied incident events, and the worsening and relapsing conditions were left for future investigations. Fourth, the way these CCSR categories were defined may not reflect the actual co-occurring risk of the individual conditions contained in each in the context of PASC. In addition, our study period was from March 2020 to November 2021, which did not include patients infected during the phase dominated by the Omicron variants of SARS-CoV-2. Lastly, our analyses did not include information on vaccination status. In conclusion, this study demonstrated that adult patients surviving beyond 30 days of their SARS-CoV-2 infection exhibited high incident risks and burdens across a broad range of conditions and signs. Our findings verified that PASC is a complex condition in...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    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.
    • No protocol registration statement was detected.

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

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  2. Version published to 10.1101/2022.05.21.22275420v2 on medRxiv
  3. Version published to 10.1101/2022.05.21.22275420v1 on medRxiv