Anti-nucleocapsid antibodies enhance the production of IL-6 induced by SARS-CoV-2 N protein

Sci Rep. 2022 May 16;12(1):8108. doi: 10.1038/s41598-022-12252-y.


A cytokine storm induces acute respiratory distress syndrome, the main cause of death in coronavirus disease 2019 (COVID-19) patients. However, the detailed mechanisms of cytokine induction due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain unclear. To examine the cytokine production in COVID-19, we mimicked the disease in SARS-CoV-2-infected alveoli by adding the lysate of SARS-CoV-2-infected cells to cultured macrophages or induced pluripotent stem cell-derived myeloid cells. The cells secreted interleukin (IL)-6 after the addition of SARS-CoV-2-infected cell lysate. Screening of 25 SARS-CoV-2 protein-expressing plasmids revealed that the N protein-coding plasmid alone induced IL-6 production. The addition of anti-N antibody further enhanced IL-6 production, but the F(ab')2 fragment did not. Sera from COVID-19 patients also enhanced IL-6 production, and sera from patients with severer disease induced higher levels of IL-6. These results suggest that anti-N antibody promotes IL-6 production in SARS-CoV-2-infected alveoli, leading to the cytokine storm of COVID-19.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Viral* / metabolism
  • COVID-19*
  • Coronavirus Nucleocapsid Proteins* / immunology
  • Cytokine Release Syndrome / etiology
  • Cytokine Release Syndrome / metabolism
  • Cytokines
  • Humans
  • Interleukin-6* / metabolism
  • Phosphoproteins / immunology
  • SARS-CoV-2* / immunology
  • SARS-CoV-2* / metabolism


  • Antibodies, Viral
  • Coronavirus Nucleocapsid Proteins
  • Cytokines
  • Interleukin-6
  • Phosphoproteins
  • nucleocapsid phosphoprotein, SARS-CoV-2