Phagocytosis of SARS-CoV-2 nucleocapsid- and RNA-containing immune complexes drives inflammatory cytokine production and endothelial dysfunction.

RNA-containing immune complexes made of SARS-CoV-2 RNA, nucleocapsid protein, and anti-N IgG1 are internalized by primary human monocytes and trigger cytokine and chemokine production.

• Why it matters: Severe COVID-19 inflammation is not fully explained, and persistent viral RNA and nucleocapsid with anti-N antibodies suggest immune complexes could drive harmful innate responses.
• What they did: Monocytes were exposed to RNA–N–anti-N IgG1 immune complexes; cytokines/chemokines were measured, with dependence tested via Fcγ receptors and partial toll-like receptor-8 involvement. Nasopharyngeal samples showed RNA and N captured by anti-N monoclonal antibody without lysing reagents.
• The result: Monocyte inflammation from RNA-containing immune complexes caused endothelial dysfunction in vascularized micro-organs, and in an early COVID-19 wave higher anti-N IgG:IgM ratios were associated with more severe outcomes.

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