Increased risk of psychiatric sequelae of COVID-19 is highest early in the clinical course

  1. Ben Coleman
  2. Elena Casiraghi
  3. Hannah Blau
  4. Lauren Chan
  5. Melissa Haendel
  6. Bryan Laraway
  7. Tiffany J Callahan
  8. Rachel R Deer
  9. Ken Wilkins
  10. Justin Reese
  11. Peter N Robinson

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Abstract

Background

COVID-19 has been shown to increase the risk of adverse mental health consequences. A recent electronic health record (EHR)-based observational study showed an almost two-fold increased risk of new-onset mental illness in the first 90 days following a diagnosis of acute COVID-19.

Methods

We used the National COVID Cohort Collaborative, a harmonized EHR repository with 2,965,506 COVID-19 positive patients, and compared cohorts of COVID-19 patients with comparable controls. Patients were propensity score-matched to control for confounding factors. We estimated the hazard ratio (COVID-19:control) for new-onset of mental illness for the first year following diagnosis. We additionally estimated the change in risk for new-onset mental illness between the periods of 21-120 and 121-365 days following infection.

Findings

We find a significant increase in incidence of new-onset mental disorders in the period of 21-120 days following COVID-19 (3.8%, 3.6-4.0) compared to patients with respiratory tract infections (3%, 2.8-3.2). We further show that the risk for new-onset mental illness decreases over the first year following COVID-19 diagnosis compared to other respiratory tract infections and demonstrate a reduced (non-significant) hazard ratio over the period of 121-365 days following diagnosis. Similar findings are seen for new-onset anxiety disorders but not for mood disorders.

Interpretation

Patients who have recovered from COVID-19 are at an increased risk for developing new-onset mental illness, especially anxiety disorders. This risk is most prominent in the first 120 days following infection.

Funding

National Center for Advancing Translational Sciences (NCATS).

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  1. ScreenIT

    SciScore for 10.1101/2021.11.30.21267071: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The study was exempted by the Institutional Review Board (IRB) at the Jackson Laboratory under 45 CFR 46.101(b) (Common Rule).
    Sex as a biological variablenot detected.
    RandomizationLittle’s test21 was used to characterize patterns of missingness, and results brought no evidence of data being missing completely at random.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Code availability: The analysis was implemented using SQL, Python, and R and is documented in the Supplemental material.
    Python
    suggested: (IPython, RRID:SCR_001658)

    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:
    Limitations of our study include the limited amount of information available prior to the acute COVID-19 event (median of 978 days), meaning that some portion of the events we classified as new-onset could be recurrences of a prior mental illness recorded before the period for which data were available in N3C. Samples with missing data were removed, which reduced the size of the cohort used for analysis. In addition to missingness, N3C data may be influenced by the heterogeneity of coding practices at the participating institutions related to the use of four different federated common data models and local coding practices. N3C employs a comprehensive suite of data quality checks to mitigate this issue,29 but residual problems cannot be ruled out. Our decision to perform Cox regression analysis separately on the early and late periods was made post hoc, after we determined that the assumption of proportional hazard did not hold for the entire time period. That said, anyone subsequently comparing our resulting estimates to those reported by other studies ought to bear in mind the apples-and-oranges issue inherent to Cox regression as conventionally used across studies: the non-collapsibility of the hazard ratio as a measure of exposure-outcome association, namely that estimates target distinctly different quantities when Cox models include distinct sets of covariates.30

    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.

    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.

  2. Version published to 10.1101/2021.11.30.21267071 on medRxiv