Specifying uniform eligibility criteria to strengthen causal inference studies of long-term outcomes of COVID-19

  1. Sebhat Erqou
  2. Andrew R Zullo
  3. Lan Jiang
  4. Vishal Khetpal
  5. Julia Berkowitz
  6. Nishant R. Shah
  7. Justin B. Echouffo-Tcheugui
  8. James L. Rudolph
  9. Gaurav Choudhary
  10. Wen-Chih Wu

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Abstract

Background

Causal interpretation of findings from existing epidemiological studies on long-term clinical outcomes of coronavirus disease 2019 (COVID-19) may be limited by the choice of comparator (control) group.

Objective

We compare two approaches to control group selection (based on requirement for negative SARS-CoV-2 test for eligibility) in long-term clinical outcomes after COVID-19 in patients with history of heart failure (HF).

Design

Retrospective cohort study using data from February 1, 2020 to July 31, 2021. Setting: Veteran Health Administration (VHA).

Participants

We studied two cohorts of Veterans with COVID-19 and history of HF which selected comparison group using two different approaches. In Cohort I, Veterans with HF who tested for positive for SARS-CoV-2 were age, sex, and race matched to Veterans with no evidence of COVID-19 in 1:5 ratio. In Cohort II Veterans with HF who tested positive for SARS-CoV-2 were age, sex, and race matched with Veterans with HF who tested negative for SARS-CoV-2 within +/-15 days of the positive test date within the same VHA facility.

Exposure

COVID-19 as determined by a positive SARS-CoV-2 test.

Main Outcomes and Measures

1-year all-cause mortality and hospital admissions beyond the first 30 days after COVID-19 diagnosis. Adjusted hazard ratios (HRs) accounting for comorbidity and 95% confidence intervals were calculated.

Results

Cohort I comprised 13,722 Veterans with HF with COVID-19 (mean [SD] age 72.0 [10.2] years, 2.4% female, 71.1% White) and 60,956 matched controls not known to have COVID-19. Cohort II comprised 6,725 Veterans with HF with COVID-19 (mean [SD] age 72.5 [7.5] years, 0.1% female, 80.8% White) and 6,726 matched controls with negative SARS-CoV-2 test. The adjusted HRs for 1-year mortality and hospital admission beyond the first 30 days after diagnosis of COVID-19 were 1.40 (1.32-1.49) and 1.34 (1.28-1.41), respectively, in analysis of Cohort-I (where the comparator group was not required to test negative for SARS-CoV-2). However, in Cohort-II (using the second comparator group specifying negative SARS-CoV-2 test for eligibility), the associations were markedly attenuated; adjusted HRs 1.05 (0.95-1.17) and 1.07 (0.96-1.19), respectively.

Conclusions

We found significant attenuation of associations between COVID-19 and long-term risk of mortality and hospital admissions beyond the first 30 days among patient with existing HF, when comparing with a control group selected based on a negative SARS-CoV-2 test versus control group not known to have COVID-19. The findings have implications for the design of studies of long-term CVD (and non-CVD) outcome of COVID-19.

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    SciScore for 10.1101/2022.05.30.22275733: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    No key resources detected.

    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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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 10.1101/2022.05.30.22275733v1 on medRxiv