Enhancement of IL-6 Production Induced by SARS-CoV-2 Nucleocapsid Protein and Bangladeshi COVID-19 Patients’ Sera

• Published in: Viruses Vol. 15; no. 10; p. 2018
• Main Authors: Hasan, Abu, Rahim, Rummana, Nakayama, Emi E, Uno, Kazuko, Hasan, Nazmul, Rahman, Mizanur, Shioda, Tatsuo
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 28.09.2023; MDPI
• Subjects: anti-N antibody; Antibodies; Biomarkers; Blood; C-reactive protein; Cloning; Coronaviruses; COVID-19; Creatinine; Cytokines; Disease; Dyspnea; Ferritin; Fever; Health aspects; Hematocrit; Hematology; Hemoglobin; Hospitals; IL-6; Immune response; Infections; Information systems; Interleukin 6; Leukocytes (neutrophilic); Lymphocytes; Medical research; Mortality; Myeloid cells; N protein; nucleocapsid; Nucleocapsids; Oxygen saturation; Patients; Pneumonia; Proteins; Respiratory tract infection; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Viral proteins; Bangladesh; United States > US; China; Japan
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v15102018

Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by severe acute respiratory syndrome coronavirus 2 that can have detrimental effects on multiple organs and accelerate patient mortality. This study, which encompassed 130 confirmed COVID-19 patients who were assessed at three different time points (i.e., 3, 7, and 12 days) after the onset of symptoms, investigated interleukin-6 (IL-6) enhancement induced by a viral nucleocapsid (N) protein from a myeloid cell line. Disease severity was categorized as mild, moderate, or severe. The severe cases were characterized as having significant elevations in serum IL-6, C-reactive protein, D-dimer, ferritin, creatinine, leukocytes, and neutrophil-to-lymphocyte ratio and decreased hemoglobin, hematocrit, and albumin levels compared with mild and moderate cases. To evaluate IL-6-inducing activity, heat-inactivated sera from these patients were incubated with and without the N protein. The findings showed a progressive increase in IL-6 production in severe cases upon N protein stimulation. There was a strong correlation between anti-N antibodies and levels of IL-6 secreted by myeloid cells in the presence of N protein and sera, indicating the crucial role that the anti-N antibody plays in inducing IL-6 production. Uncontrolled IL-6 production played a pivotal role in disease pathogenesis, exacerbating both disease severity and mortality. Efficiently targeting the N protein could potentially be employed as a therapeutic strategy for regulating the immune response and alleviating inflammation in severe cases.