Association of COVID-19 with risks of hospitalization and mortality from other disorders post-infection: A study of the UK Biobank

  1. Yong Xiang
  2. Ruoyu Zhang
  3. Jinghong Qiu
  4. Hon-Cheong So

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Abstract

Objective

To study whether COVID-19 infection may be associated with increased hospitalization and mortality from other diseases.

Design

Cohort study.

Setting

The UK Biobank.

Participants

All subjects in the UK Biobank with available hospitalization records and alive as of 31-Jan-2020 ( N = 412,096; age 50-87).

Main outcome measures

We investigated associations of COVID-19 with hospitalization and mortality due to different diseases post-infection. We conducted a comprehensive survey on disorders from all systems (up to 135 disease categories). Multivariable Cox and Poisson regression was conducted controlling for main confounders. For sensitivity analysis, we also conducted separate analysis for new-onset and recurrent cases, and other analysis such as the prior event rate adjustment(PERR) approach to minimize effects of unmeasured confounders. We also performed association analyses stratified by vaccination status. Time-dependent effects on subsequent hospitalization and mortality were also tested.

Results

Compared to individuals with no known history of COVID-19, those with severe COVID-19 (requiring hospitalization) exhibited higher hazards of hospitalization and/or mortality due to multiple disorders (median follow-up=608 days), including disorders of respiratory, cardiovascular, neurological, gastrointestinal, genitourinary and musculoskeletal systems. Increased hazards of hospitalizations and/or mortality were also observed for injuries due to fractures, various infections and other non-specific symptoms. These results remained largely consistent after sensitivity analyses. Severe COVID-19 was also associated with increased all-cause mortality (HR=14.700, 95% CI: 13.835-15.619).

Mild (non-hospitalized) COVID-19 was associated with modestly increased risk of all-cause mortality (HR=1.237, 95% CI 1.037-1.476) and mortality from neurocognitive disorders, as well as hospital admission from a few disorders such as aspiration pneumonitis, musculoskeletal pain and other general signs/symptoms.

All-cause mortalities and hospitalizations from other disorders post-infection were generally higher in the pre-vaccination era. The deleterious effect of COVID-19 was observed to wane over time, with maximum HR in the initial phase.

Conclusions

In conclusion, this study revealed increased risk of hospitalization and mortality from a wide variety of pulmonary and extra-pulmonary diseases after COVID-19, especially for severe infections. Mild disease was also associated with increased all-cause mortality. Causality however cannot be established due to observational nature of the study. Further studies are required to replicate our findings.

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  1. ScreenIT

    SciScore for 10.1101/2022.03.23.22272811: (What is this?)

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

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    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: We detected the following sentences addressing limitations in the study:
    Strength and limitation: The major strength of this study included large sample size of the UK Biobank with detailed health records and sufficient period of follow-up. This study is very comprehensive and covers most clinically relevant categories of diagnosis. In addition to any hospitalization/mortality, we also performed additional analysis on hospitalization with/without relevant history of disease (i.e. new-onset and recurrent diseases). Apart from these, we also made use of advanced statistical methods to evaluate whether our findings are consistent to different modeling strategies. For example, the PERR adjustment was employed to minimize unmeasured confounding. There are several limitations of this study. Firstly, this is an observational study. Although we have included many known confounders in the model and used other methods (e.g. PERR) to minimize residual confounding, confounding effects cannot be excluded completely. However, many results remained significant after PERR adjustment which provides further support to our findings. Secondly, subclinical disorders may be underestimated and some disorders may be too rare to be included for further analysis. In addition, due to the relatively small number of events for some disorders, absence of significant associations can also be due to inadequate statistical power. We also note that mild or asymptomatic infections may not be detected and considered as having no history of COVID-19; however this is likely to result ...

    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.
    • Thank you for including a protocol registration statement.

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

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  2. Version published to 10.1101/2022.03.23.22272811 on medRxiv