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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.
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1 Osaka University, Research Institute for Microbial Diseases and Center for Infectious Disease Education and Research, Suita, Osaka, Japan (GRID:grid.136593.b) (ISNI:0000 0004 0373 3971)
2 Osaka University, Research Institute for Microbial Diseases and Center for Infectious Disease Education and Research, Suita, Osaka, Japan (GRID:grid.136593.b) (ISNI:0000 0004 0373 3971); TANAKA Kikinzoku Kogyo K.K, Hiratsuka, Japan (GRID:grid.480415.c)
3 Louis Pasteur Center for Medical Research, Division of Basic Research, Kyoto, Japan (GRID:grid.452539.c) (ISNI:0000 0004 0621 0957)
4 MiCAN Technologies Inc., Kyoto, Japan (GRID:grid.452539.c)
5 Institute for Advanced Co-Creation Studies, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan (GRID:grid.136593.b) (ISNI:0000 0004 0373 3971)
6 Osaka University, Trauma and Acute Critical Care Center, Suita, Osaka, Japan (GRID:grid.136593.b) (ISNI:0000 0004 0373 3971)
7 Osaka Prefectural Nakakawachi Emergency and Critical Care Center, Higashiosaka, Osaka, Japan (GRID:grid.136593.b)
8 Osaka Prefectural Hospital Organization Osaka Habikino Medical Center, Habikino, Osaka, Japan (GRID:grid.416985.7) (ISNI:0000 0004 0378 3952)
9 Yao Tokushukai General Hospital, Yao, Osaka, Japan (GRID:grid.417339.b)
10 Kobe Tokushukai Hospital, Kobe, Japan (GRID:grid.417339.b)
11 Suita Tokushukai Hospital, Suita, Osaka, Japan (GRID:grid.459995.d) (ISNI:0000 0004 4682 8284)
12 Osaka University, Institute of Scientific and Industry Research, Ibaraki, Osaka, Japan (GRID:grid.136593.b) (ISNI:0000 0004 0373 3971)