The role of metabolic comorbidity in COVID-19 mortality of middle-aged adults. The case of Mexico

  1. Lenin Dominguez-Ramirez
  2. Francisco Rodriguez-Perez
  3. Francisca Sosa-Jurado
  4. Gerardo Santos-Lopez
  5. Paulina Cortes-Hernandez

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Abstract

Background

In contrast to developed countries, in Mexico more than half of COVID-19 deaths have occurred in adults <65-years-old, with at least a million years of life lost to premature mortality (YLL) in eight months. Mexico has a young population but a high prevalence of metabolic diseases like obesity and diabetes that contribute to COVID-19 adverse outcomes. COVID-19 could be particularly risky in population with specific comorbidity combinations that haven’t been analyzed.

Methods

To explore what contributes to the high COVID-19 mortality in Mexican middle-aged adults, we calculated age-stratified COVID-19 case fatality rates, YLL and relative risk (RR) of 9 comorbidities and 23 comorbidity combinations in a retrospective Mexican cohort with 905,579 PCR-confirmed COVID-19 cases/89,167 deaths, until Nov/2/2020.

Findings

Chronic kidney disease (CKD) had the highest RR for COVID-19 fatality, followed by diabetes and immunosuppression, that in turn had higher RR than obesity or hypertension as single comorbidities. The combination diabetes/hypertension with or without obesity had RR as high as CKD as a single comorbidity (>3 in <60-year-olds). Notably, the RR of comorbidities decreased with age, tending to values near 1 after age 60; suggesting that in Mexico, comorbidities increase COVID-19 fatality mostly in young and middle-aged adults. Our analysis suggests that advanced metabolic disease, marked by multimorbidity (more than one chronic disease per individual) or diabetes before age 60, contribute particularly to the younger age of COVID-19 fatalities in Mexico. Around 38% of YLL to COVID-19, were attributable to the synergy between COVID-19 and pre-existing diseases, mainly combinations between obesity, diabetes and hypertension. Yet, ¼ of deaths and 1/3 of YLL have occurred in individuals without known comorbidities.

Conclusions

The Mexican COVID-19 outbreak illustrates that middle-aged adults 45-64-yo can have high COVID-19 mortality during large outbreaks, especially if they present chronic metabolic comorbidities, but also in their absence, making them an important group of concern after elders. COVID-19 mortality in middle-aged adults is likely proportional to the gradual decline in health that accompanies ageing, which presents earlier in poorer populations that also get more exposed to SARS-CoV-2 and have less access to specialized medical attention.

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  1. ScreenIT

    SciScore for 10.1101/2020.12.15.20244160: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Relative Risk of death (RRd) and 95% CI (confidence interval) were calculated in GraphPad Prism version 7.0a, with Koopman asymptotic score, excluding cases and deaths with unknown comorbidity status, at cutoff dates Aug/6 and Sept/12, 2020, that marked >50,000 and >70,000 COVID-19 deaths in Mexico and comprise the first COVID-19 peak in the country (Fig 2A).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Years of life lost to premature mortality (YLL) were determined for each individual under the age of 70 that died of COVID-19, with the formula:

    Multivariate correspondence analyses (CA) of categorical variables and Hierarchical Clustering of Principal Components (HCPC) with the k-means method, were performed in R through Rstudio, with libraries factoextra and FactoMineR [17], as in [18].

    FactoMineR
    suggested: (FactoMineR, RRID:SCR_014602)

    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, include lack of detail about the severity and treatment of the studied comorbidities and uncertainty about underreporting of underlying diseases. Diabetes and hypertension were found in COVID-19 cases at a similar age-stratified prevalence to the general-population’s, which doesn’t suggest underreporting; but underreporting of obesity cannot be ruled out. Overweight adults were undistinguishable in the COVID-19 dataset, which lacks body-mass-index details. Being overweight may contribute to adverse COVID-19 outcomes in a subset of the adults classified as “without comorbidity”, and should be studied.

    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.

    About SciScore

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  2. Version published to 10.1101/2020.12.15.20244160v2 on medRxiv
  3. Version published to 10.1101/2020.12.15.20244160v1 on medRxiv