Effect modification of the association between comorbidities and severe course of COVID-19 disease by age of study participants: a systematic review and meta-analysis

  1. Nathalie Verónica Fernández Villalobos
  2. Jördis Jennifer Ott
  3. Carolina Judith Klett-Tammen
  4. Annabelle Bockey
  5. Patrizio Vanella
  6. Gérard Krause
  7. Berit Lange

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Abstract

Background

Comprehensive evidence synthesis on the associations between comorbidities and behavioural factors with hospitalisation, intensive care unit (ICU) admission, and death due to COVID-19 is required for deriving national and international recommendations on primary targets for non-pharmacological interventions (NPI) and vaccination strategies.

Methods

We performed a rapid systematic review and meta-analysis on studies and publicly accessible data to quantify associations between predisposing health conditions, demographics, behavioural factors on the one hand and hospitalisation, ICU admission, and death from COVID-19 on the other hand. We provide ranges of reported and calculated effect estimates and pooled relative risks derived from a meta-analysis and meta-regression.

Results

Seventy-five studies were included in qualitative and 74 in quantitative synthesis, with study populations ranging from 19 to 44,672 COVID-19 cases. The risk of dying from COVID-19 was significantly associated with cerebrovascular [pooled relative risk (RR) 2.7 (95% CI 1.7–4.1)] and cardiovascular [RR 3.2 (CI 2.3–4.5)] diseases, hypertension [RR 2.6 (CI 2.0–3.4)], and renal disease [RR 2.5 (CI 1.8–3.4)], with high heterogeneity in pooled estimates, partly but not solely explained by age of study participants. For some comorbidities, our meta-regression showed a decrease in effect on the severity of disease with a higher median age of the study population. Compared to death, associations between several comorbidities and hospitalisation and ICU admission were less pronounced.

Conclusions

We obtained robust estimates on the magnitude of risk for COVID-19 hospitalisation, ICU admission, and death associated with comorbidities, demographic, and behavioural risk factors and show that these estimates are modified by age of study participants. This interaction is an important finding to be kept in mind for current vaccination strategies and for the protection of individuals with high risk for a severe COVID-19 course.

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  1. Version published to 10.1186/s13643-021-01732-3
  2. ScreenIT

    SciScore for 10.1101/2020.07.30.20165050: (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
    Search strategy: We performed a systematic review (registration number in PROSPERO CRD42020190548), following PRISMA guidelines (27), in MEDLINE, bioRXiv, and MedRXiv, searching for publications on COVID-19 and risk groups for severe or lethal disease outcomes (search terms “novel coronavirus”, “COVID-19”, “SARS-CoV-2”).
    MEDLINE
    suggested: (MEDLINE, RRID:SCR_002185)
    bioRXiv
    suggested: (bioRxiv, RRID:SCR_003933)

    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:
    The limitations of our work derive from the restricted search, which was a rapid approach in one main data base of medical literature. With this review type, we sought for contextualised evidence to inform decision makers in terms of vulnerable population groups. Moreover, we did not include articles in Chinese language into our search due to lack of interpreters, and that could have affected our included studies and findings. The nature of the included data were often based on hospital recording implying bias in a sense that more severely symptomatic patients are more likely included. Although our assessment revealed high to moderate study quality, studies based on hospital records are highly selective regarding the population included. Regarding our analyses, we did not consider age groups separately due to wide ranges and inconsistencies in reporting from the studies, which would have implied major assumptions for our meta-analyses. However, we approached this by assessing effect modification of age on different comorbidities and found effect modification for several comorbidities. The meta-analyses we conducted is univariate, and we did not adjust for co-morbidities that appear in parallel. Generalisability and country-comparisons of results from publicly available data are limited by different data sources used. Also, our effect estimates for some countries only investigate subgroup of hospitalised cases (e.g. France), which may lead to a systematic underestimation of th...

    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

    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.

  3. Version published to 10.1101/2020.07.30.20165050v1 on medRxiv