Cytokine and chemokine profile in patients hospitalized with COVID-19: A comparative study

  1. Abdisa Tufa
  2. Tewodros Haile Gebremariam
  3. Tsegahun Manyazewal
  4. Tewodros Getinet
  5. Dominic-Luc Webb
  6. Per M. Hellström
  7. Solomon Genet

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Abstract

Abnormal cytokine and chemokine concentrations during SARS-CoV-2 infection may represent disease severity. We aimed to assess plasma cytokine and chemokine concentrations in patients with SARS-CoV-2 in Addis Ababa, Ethiopia. In this study, 260 adults: 126 hospitalized patients with confirmed COVID-19 sorted into severity groups: severe (n=68) and mild or moderate (n=58), and 134 healthy controls were enrolled. We quantified 39 plasma cytokines and chemokines using multiplex ELISA. Spearman rank correlation and Mann-Whitney U test were used to identify mechanistically coupled cytokines/chemokines and compare disease severity. Compared to healthy controls, patients with COVID-19 had significantly higher levels of interleukins 1α, 2, 6, 7, 8, 10 and 15, C-reactive protein (CRP), serum amyloid A (SAA), intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion protein 1 (VCAM-1), IFN-γ-inducible protein-10 (IP-10), macrophage inflammatory protein-1 alpha (MIP-1α), eotaxin-3, interferon-gamma (IFN-ϒ), tumor necrosis factor-α (TNF-α), basic fibroblast growth factor (bFGF), placental growth factor (PlGF), and fms-like tyrosine kinase 1 (Flt-1). Patients with severe COVID-19 had higher IL-10 and lower macrophage-derived chemokine (MDC) compared to the mild or moderate group ( P<0.05 ). In the receiver operating characteristic curve, SAA, IL-6 and CRP showed strong sensitivity and specificity predicting the severity and prognosis of COVID-19. Greater age and higher CRP had a significant association with disease severity ( P<0.05 ). Our findings reveal that CRP, SAA, VCAM-1, IP-10, MDC and IL-10 levels are promising biomarkers for COVID-19 disease severity, suggesting that plasma cytokines/chemokines could be used as warning indicators of COVID-19 severity, aid in COVID-19 prognosis and treatment.

IMPORTANCE

SARS-CoV-2 triggers inflammatory reaction resulting in respiratory discomfort and in critical case may result in death. Cytokines and chemokines are inflammatory biomarkers that regulate and determine the nature of immune responses. Measuring cytokine and chemokine levels is useful in stratification, management and treatment of COVID-19 patients as well as guide resource allocations and therapeutic options. Here, we examined ctytokine and chemokine profiles in COVID-19 patients. Understanding how distinct cytokines and chemokines change over time as COVID-19 disease progresses might aid clinicians in detecting severe illness earlier and thereby improve patient prognosis.

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    SciScore for 10.1101/2022.03.17.484837: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Ethical considerations: The study was approved by departmental research ethics and review committee of the Department of Biochemistry, CHS, AAU (Ref.No.SoM/BCHM/068/2013) and by the institutional review board of College of Health Sciences, Addis Ababa University (Meeting 01/2021, Protocol 004/21/Biochem).
    Field Sample Permit: Permission to conduct the study was also obtained from TASH.
    Consent: All participants in the study (both COVID-19 patients and healthy controls) signed a written informed consent form.
    Sex as a biological variableParticipants who were anemic, pregnant or had taken a corticosteroid or immunosuppressant within 14 days of admission were all excluded from the study.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Statistical analysis: IBM SPSS version 25.0 (Chicago, IL) and Prism version 8 were used.
    SPSS
    suggested: (SPSS, RRID:SCR_002865)
    Prism
    suggested: (PRISM, RRID:SCR_005375)

    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 discrepancy could be due to the data limitations that were revealed during the meta analysis. Similarly, TGF-β levels were found to be decreased in severe patients compared to mild or moderate patients and healthy controls (Table 3 and 4). This is consistent with the concept that serum TGF-β levels peak during the first two weeks of acute COVID-19 infection and limit NK cell function in a TGF-dependent way (43). As a result, premature TGF-β production is thought to be a characteristic of severe COVID-19. TGF-β is released from a variety of sources in response to SARS-CoV-2 infection, including dysregulated coagulation and fibrinolytic pathways; neutrophils infiltrating the lungs in large numbers and macrophages migrating to the lungs to phagocytize apoptotic bronchial epithelial cells, pneumocytes, T-lymphocytes and neutrophils (44). The potential of this cytokine to recruit more neutrophils and remodel the airways through modulating processes used by the virus to generate pulmonary fibrosis explains its influence in SARS-CoV-2 infection. The severe group had significantly greater levels of VEGF-D than the mild or moderate group. There was a data shortage for this biomarker, but it was consistent with the prior research, which compared critical and severe group (45). We hypothesized that a high level of VEGF-D is linked to a storm of blood clots in COVID-19 patients, which eventually leads to disease severity. The ROC curve data further revealed that CRP, SAA and IL-6 lev...

    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.

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

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  2. Version published to 10.1101/2022.03.17.484837v1 on bioRxiv