Anti-nucleocapsid antibodies enhance the production of IL-6 induced by SARS-CoV-2 N protein
Emi E. Nakayama, Ritsuko Kubota‐Koketsu, Tadahiro Sasaki, Keita Suzuki, Kazuko Uno, Jun Shimizu, Toru Okamoto, Hisatake Matsumoto, Hiroshi Matsuura, S. Hashimoto, Toshio Tanaka, Hiromasa Harada, M. Tomita, Mitsunori Kaneko, Kazuyuki Yoshizaki, Tatsuo Shioda
Abstract
Abstract 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.