Anemia and iron metabolism in COVID-19: a systematic review and meta-analysis

  1. Petek Eylul Taneri
  2. Sergio Alejandro Gómez-Ochoa
  3. Erand Llanaj
  4. Peter Francis Raguindin
  5. Lyda Z. Rojas
  6. Zayne Milena Roa-Díaz
  7. Dante Salvador
  8. Dion Groothof
  9. Beatrice Minder
  10. Doris Kopp-Heim
  11. Wolf E. Hautz
  12. Michele F. Eisenga
  13. Oscar H. Franco
  14. Marija Glisic
  15. Taulant Muka

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Abstract

Iron metabolism and anemia may play an important role in multiple organ dysfunction syndrome in Coronavirus disease 2019 (COVID-19). We conducted a systematic review and meta-analysis to evaluate biomarkers of anemia and iron metabolism (hemoglobin, ferritin, transferrin, soluble transferrin receptor, hepcidin, haptoglobin, unsaturated iron-binding capacity, erythropoietin, free erythrocyte protoporphyrine, and erythrocyte indices) in patients diagnosed with COVID-19, and explored their prognostic value. Six bibliographic databases were searched up to August 3rd 2020. We included 189 unique studies, with data from 57,563 COVID-19 patients. Pooled mean hemoglobin and ferritin levels in COVID-19 patients across all ages were 129.7 g/L (95% Confidence Interval (CI), 128.51; 130.88) and 777.33 ng/mL (95% CI, 701.33; 852.77), respectively. Hemoglobin levels were lower with older age, higher percentage of subjects with diabetes, hypertension and overall comorbidities, and admitted to intensive care. Ferritin level increased with older age, increasing proportion of hypertensive study participants, and increasing proportion of mortality. Compared to moderate cases, severe COVID-19 cases had lower hemoglobin [weighted mean difference (WMD), − 4.08 g/L (95% CI − 5.12; − 3.05)] and red blood cell count [WMD, − 0.16 × 10 12 /L (95% CI − 0.31; − 0.014)], and higher ferritin [WMD, − 473.25 ng/mL (95% CI 382.52; 563.98)] and red cell distribution width [WMD, 1.82% (95% CI 0.10; 3.55)]. A significant difference in mean ferritin levels of 606.37 ng/mL (95% CI 461.86; 750.88) was found between survivors and non-survivors, but not in hemoglobin levels. Future studies should explore the impact of iron metabolism and anemia in the pathophysiology, prognosis, and treatment of COVID-19.

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  1. Version published to 10.1007/s10654-020-00678-5
  2. ScreenIT

    SciScore for 10.1101/2020.06.04.20122267: (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 variableFor the adult population, anemia was defined according to World Health Organization (WHO) guidelines (hemoglobin levels for males < 130 g/L and for females < 120 g/L).

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Data source and strategy: We searched MEDLINE (National Library of Medicine, US), EMBASE (Elsevier, Netherlands), Web of Science (Clarivate Analytics, US), Cochrane (Cochrane Collaboration, UK), the WHO COVID-19 database and Google Scholar (Google, Inc., US) to identify relevant articles.
    MEDLINE
    suggested: (MEDLINE, RRID:SCR_002185)
    EMBASE
    suggested: (EMBASE, RRID:SCR_001650)
    Cochrane (Cochrane Collaboration
    suggested: None
    Google Scholar
    suggested: (Google Scholar, RRID:SCR_008878)
    We used STATA 15.1 (Statacorp, Texas, US, 2017) for all the analyses.
    STATA
    suggested: (Stata, RRID:SCR_012763)
    Statacorp
    suggested: None

    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:
    This study has several limitations. First, considering we restricted our review to articles in English, we cannot rule out publication bias, which could limit our overall findings. Second, the interpretation of the findings should be based on the quality of the included studies. Despite most studies being of high quality, the data provided are mainly of cross-sectional nature. Third, there was heterogeneity in the definition of moderate and severe cases of COVID-19 patients and in the definition of comorbid patients, which could have contributed to the observed heterogeneity in our meta-analysis. This meta-analysis suggests that hemoglobin and ferritin levels vary according to the severity of COVID-19 as well as age, gender and presence of comorbidity among COVID-19 patients. Whether hemoglobin and ferritin can be used for prognostic purposes, or have further implications for identifying novel treatment targets, needs further investigation

    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 10.1101/2020.06.04.20122267v1 on medRxiv