Increased ACE2, sRAGE, and Immune Activation, but Lowered Calcium and Magnesium in COVID-19

  1. Hussein Kadhem Al-Hakeim
  2. Hawraa Kadhem Al-Jassas
  3. Gerwyn Morris
  4. Michael Maes

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Abstract

The characterization of new biomarkers that could help externally validate the diagnosis of COVID-19 and optimize treatments is extremely important. Many studies have es-tablished changes in immune-inflammatory and antibody levels, but few studies measured the soluble receptor for the advanced glycation end product (sRAGE), angiotensin-converting enzyme 2 (ACE2), calcium, and magnesium in COVID-19.

Objective:

To evaluate serum advanced glycation end-product receptor (sRAGE) and angiotensin converting enzyme (ACE)2 and peripheral oxygen saturation (SpO2) and chest CT scan abnormalities (CCTA) in COVID-19.

Methods:

sRAGE, ACE2, interleukin (IL)-6, IL-10, C-reactive protein (CRP), calcium, magnesium, and albumin were measured in 60 COVID-19 patients and 30 healthy controls.

Results:

COVID-19 is characterized by significantly increased IL-6, CRP, IL-10, sRAGE, ACE2, and lowered SpO2, albumin, magnesium, and calcium. COVID-19 with CCTAs showed lower SpO2 and albumin. SpO2 was significantly inversely correlated with IL-6, IL-10, CRP, sRAGE, and ACE2, and positively with albumin, magnesium, and calcium. Neural networks showed that a combination of calcium, IL-6, CRP, and sRAGE yielded an accuracy of 100% in detecting COVID-19 patients, with calcium being the most important predictor followed by IL-6 and CRP. Patients with positive IgG results showed a significant elevation in the serum level of IL-6, sRAGE, and ACE2 compared to the negatively IgG patient subgroup.

Conclusion:

The results show that immune-inflammatory and RAGE pathways biomarkers may be used as an external validating criterion for the diagnosis of COVID-19. Those pathways coupled with lowered SpO2, calcium, and magnesium are drug targets that may help reduce the consequences of COVID-19.

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  1. Version published to 10.2174/2772270816666220318103929
  2. ScreenIT

    SciScore for 10.1101/2021.03.26.21254383: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: However, to enhance their immunity against COVID-19 infection, some healthy controls were taken zinc and vitamins C and D. The “institutional ethics board of the University of Kufa” approved the study (617/2020).
    Consent: All participants gave written informed consent before participation in this study.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableSubjects: Sixty COVID-19 male patients aged 25-59 years were recruited at the Al-Sadr Teaching Hospital and Al-Amal Specialized Hospital for Communicable Diseases in Najaf governorate-Iraq between September and November 2020.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    All statistical analyses were performed using IBM SPSS windows version 25, 2017.
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    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.

    About SciScore

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  3. Version published to 10.1101/2021.03.26.21254383v1 on medRxiv