tetano
Editor, Senior Moderator
Infection
. 2023 Dec 22.
doi: 10.1007/s15010-023-02142-4. Online ahead of print. SARS-CoV-2 nucleocapsid protein, rather than spike protein, triggers a cytokine storm originating from lung epithelial cells in patients with COVID-19
Ying-Chuan Wang[SUP] #[/SUP][SUP] 1 [/SUP], Chih-Hsuan Tsai[SUP] #[/SUP][SUP] 2 [/SUP], Yung-Chih Wang[SUP] #[/SUP][SUP] 3 [/SUP], Li-Chen Yen[SUP] 4 [/SUP], Yao-Wen Chang[SUP] 5 [/SUP], Jun-Ren Sun[SUP] 6 [/SUP], Te-Yu Lin[SUP] 3 [/SUP], Chun-Hsiang Chiu[SUP] 7 [/SUP], Yu-Chan Chao[SUP] 8 [/SUP], Feng-Yee Chang[SUP] 3 [/SUP]
Affiliations
Purpose: The aim of this study was to elucidate the factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that may initiate cytokine cascades and correlate the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) with their serum cytokine profiles.
Methods: Recombinant baculoviruses displaying SARS-CoV-2 spike or nucleocapsid protein were constructed and transfected into A549 cells and THP-1-derived macrophages, to determine which protein initiate cytokine release. SARS-CoV-2-specific antibody titers and cytokine profiles of patients with COVID-19 were determined, and the results were associated with their clinical characteristics, such as development of pneumonia or length of hospital stay.
Results: The SARS-CoV-2 nucleocapsid protein, rather than the spike protein, triggers lung epithelial A549 cells to express IP-10, RANTES, IL-16, MIP-1α, basic FGF, eotaxin, IL-15, PDGF-BB, TRAIL, VEGF-A, and IL-5. Additionally, serum CTACK, basic FGF, GRO-α, IL-1α, IL-1RA, IL-2Rα, IL-9, IL-15, IL-16, IL-18, IP-10, M-CSF, MIF, MIG, RANTES, SCGF-β, SDF-1α, TNF-α, TNF-β, VEGF, PDGF-BB, TRAIL, β-NGF, eotaxin, GM-CSF, IFN-α2, INF-γ, and MCP-1 levels were considerably increased in patients with COVID-19. Among them, patients with pneumonia had higher serum IP-10 and M-CSF levels than patients without. Patients requiring less than 3 weeks to show negative COVID-19 tests after contracting COVID-19 had higher serum IP-10 levels than the remaining patients.
Conclusion: Our study revealed that nucleocapsid protein, lung epithelial cells, and IP-10 may be potential targets for the development of new strategies to prevent, or control, severe COVID-19.
Keywords: COVID-19; Cytokine storm; IP-10; Nucleocapsid protein; SARS-CoV-2.
. 2023 Dec 22.
doi: 10.1007/s15010-023-02142-4. Online ahead of print. SARS-CoV-2 nucleocapsid protein, rather than spike protein, triggers a cytokine storm originating from lung epithelial cells in patients with COVID-19
Ying-Chuan Wang[SUP] #[/SUP][SUP] 1 [/SUP], Chih-Hsuan Tsai[SUP] #[/SUP][SUP] 2 [/SUP], Yung-Chih Wang[SUP] #[/SUP][SUP] 3 [/SUP], Li-Chen Yen[SUP] 4 [/SUP], Yao-Wen Chang[SUP] 5 [/SUP], Jun-Ren Sun[SUP] 6 [/SUP], Te-Yu Lin[SUP] 3 [/SUP], Chun-Hsiang Chiu[SUP] 7 [/SUP], Yu-Chan Chao[SUP] 8 [/SUP], Feng-Yee Chang[SUP] 3 [/SUP]
Affiliations
- PMID: 38133713
- DOI: 10.1007/s15010-023-02142-4
Purpose: The aim of this study was to elucidate the factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that may initiate cytokine cascades and correlate the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) with their serum cytokine profiles.
Methods: Recombinant baculoviruses displaying SARS-CoV-2 spike or nucleocapsid protein were constructed and transfected into A549 cells and THP-1-derived macrophages, to determine which protein initiate cytokine release. SARS-CoV-2-specific antibody titers and cytokine profiles of patients with COVID-19 were determined, and the results were associated with their clinical characteristics, such as development of pneumonia or length of hospital stay.
Results: The SARS-CoV-2 nucleocapsid protein, rather than the spike protein, triggers lung epithelial A549 cells to express IP-10, RANTES, IL-16, MIP-1α, basic FGF, eotaxin, IL-15, PDGF-BB, TRAIL, VEGF-A, and IL-5. Additionally, serum CTACK, basic FGF, GRO-α, IL-1α, IL-1RA, IL-2Rα, IL-9, IL-15, IL-16, IL-18, IP-10, M-CSF, MIF, MIG, RANTES, SCGF-β, SDF-1α, TNF-α, TNF-β, VEGF, PDGF-BB, TRAIL, β-NGF, eotaxin, GM-CSF, IFN-α2, INF-γ, and MCP-1 levels were considerably increased in patients with COVID-19. Among them, patients with pneumonia had higher serum IP-10 and M-CSF levels than patients without. Patients requiring less than 3 weeks to show negative COVID-19 tests after contracting COVID-19 had higher serum IP-10 levels than the remaining patients.
Conclusion: Our study revealed that nucleocapsid protein, lung epithelial cells, and IP-10 may be potential targets for the development of new strategies to prevent, or control, severe COVID-19.
Keywords: COVID-19; Cytokine storm; IP-10; Nucleocapsid protein; SARS-CoV-2.