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

tetano

Editor, Senior Moderator
Sci Rep


. 2022 May 16;12(1):8108.
doi: 10.1038/s41598-022-12252-y.
Anti-nucleocapsid antibodies enhance the production of IL-6 induced by SARS-CoV-2 N protein


Emi E Nakayama[SUP] 1 [/SUP], Ritsuko Kubota-Koketsu[SUP] 2 [/SUP], Tadahiro Sasaki[SUP] 2 [/SUP], Keita Suzuki[SUP] 2 3 [/SUP], Kazuko Uno[SUP] 4 [/SUP], Jun Shimizu[SUP] 5 [/SUP], Toru Okamoto[SUP] 6 [/SUP], Hisatake Matsumoto[SUP] 7 [/SUP], Hiroshi Matsuura[SUP] 8 [/SUP], Shoji Hashimoto[SUP] 9 [/SUP], Toshio Tanaka[SUP] 9 [/SUP], Hiromasa Harada[SUP] 10 [/SUP], Masafumi Tomita[SUP] 11 [/SUP], Mitsunori Kaneko[SUP] 12 [/SUP], Kazuyuki Yoshizaki[SUP] 13 [/SUP], Tatsuo Shioda[SUP] 2 [/SUP]



Affiliations

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')[SUP]2[/SUP] 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.
 
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