The Potential Role of an Aberrant Mucosal Immune Response to SARS-CoV-2 in the Pathogenesis of IgA Nephropathy

  1. Zhao Zhang
  2. Guorong Zhang
  3. Meng Guo
  4. Wanyin Tao
  5. Xingzi Liu
  6. Haiming Wei
  7. Tengchuan Jin
  8. Yuemiao Zhang
  9. Shu Zhu

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Abstract

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global concern. Immunoglobin A (IgA) contributes to virus neutralization at the early stage of infection. Longitudinal studies are needed to assess whether SARS-CoV-2-specific IgA production persists for a longer time in patients recovered from severe COVID-19 and its lasting symptoms that can have disabling consequences should also be alerted to susceptible hosts. Here, we tracked the anti-SARS-CoV-2 spike protein receptor-binding domain (RBD) antibody levels in a cohort of 88 COVID-19 patients. We found that 52.3% of the patients produced more anti-SARS-CoV-2 RBD IgA than IgG or IgM, and the levels of IgA remained stable during 4–41 days of infection. One of these IgA-dominant COVID-19 patients, concurrently with IgA nephropathy (IgAN), presented with elevated serum creatinine and worse proteinuria during the infection, which continued until seven months post-infection. The serum levels of anti-SARS-CoV-2 RBD and total IgA were higher in this patient than in healthy controls. Changes in the composition of the intestinal microbiota, increased IgA highly coated bacteria, and elevated concentration of the proinflammatory cytokine IL-18 were indicative of potential involvement of intestinal dysbiosis and inflammation to the systemic IgA level and, consequently, the disease progression. Collectively, our work highlighted the potential adverse effect of the mucosal immune response to SARS-CoV-2 infection, and that additional care should be taken with COVID-19 patients presenting with chronic diseases such as IgAN.

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  1. Version published to 10.3390/pathogens10070881
  2. ScreenIT

    SciScore for 10.1101/2020.12.11.20247668: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: This study was reviewed and approved by the Medical Ethical Committee of the First Affiliated Hospital of USTC (approval number: 2020-XG(H)-014) and the First Affiliated Hospital of Anhui Medical University (approval number: Quick-PJ 2020-04-16)
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    A standard two-tailed unpaired Student’s t-test was performed using GraphPad Prism 7.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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:
    We acknowledge that the limitation of the study is the shortness of patient and a lack of evidence from kidney biopsy in the only COVID-19 IgAN case. Nonetheless, the long-term regular follow-up, strict supervision of the patient’s kidney condition, and our laboratory evidence suggest that the high level of mucosal IgA response to SARS-CoV-2 is closely associated with the declined renal function. In conclusion, our study indicates that SARS-CoV-2 infection stimulates aberrant mucosal humoral IgA in the lung and intestine against SARS-CoV-2 and may have contributed to kidney damage and potentially promoted IgAN progression. Thus, our work highlights the potential adverse effects of the humoral immune response towards SARS-CoV-2, and additional care should be taken for COVID-19 patients with chronic diseases like IgAN.

    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 10.1101/2020.12.11.20247668v1 on medRxiv