Bauer Christian, Mack Elisabeth, Hefter Véronique, Fischer Alexandra, Volland Kirsten, Skevaki Chrysanthi, Neubauer Andreas, Gress Thomas, Becker Stephan, Keller Christian
Department of Gastroenterology, Endocrinology, Metabolism and Infectiology, University Hospital Marburg, Philipps University, Marburg, Germany.
Department of Internal Medicine, Hematology and Oncology, University Hospital Marburg, Philipps University, Marburg, Germany.
J Med Virol. 2023 Aug;95(8):e29032. doi: 10.1002/jmv.29032.
The circulating nucleocapsid (NCP) antigen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is detectable in coronavirus disease-2019 (COVID-19) patients. To better understand the biology of disease severity, we investigated NCP clearance kinetics in hospitalized COVID-19 patients. Serum NCP was quantified using a commercial NCP-specific enzyme-linked immunoassay in hospitalized COVID-19 patients (n = 63) during their hospital stay. Results were correlated to COVID-19 disease severity, inflammation parameters, antibody response, and results of SARS-CoV-2 PCR from nasopharyngeal swabs. We demonstrate that NCP antigen levels in serum remained elevated in 21/45 (46.7%) samples from patients in intensive care units (ICU) after >8 days postdiagnosis. The proportion of ICU patients with detectable antigenemia declined only gradually from 84.6% to 25.0% over several weeks. This was in contrast to complete NCP clearance in all non-ICU patients after 8 days, and also in contrast to mucosal clearance of the virus as measured by PCR. Antigen clearance was associated with higher IgG against S1 but not NCP. Clearance of NCP antigenemia is delayed in >40% of severely ill COVID-19 patients. Thus, NCP antigenemia detected after 8 days post COVID-19 diagnosis is a characteristic of patients requiring intensive care. Prospective trials should further investigate NCP antigen clearance kinetics as a mechanistic biomarker.
在新型冠状病毒肺炎（COVID-19）患者中可检测到严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的循环核衣壳（NCP）抗原。为了更好地了解疾病严重程度的生物学机制，我们研究了住院COVID-19患者中NCP清除动力学。在住院COVID-19患者（n = 63）住院期间，使用商业化的NCP特异性酶联免疫吸附测定法对血清NCP进行定量。结果与COVID-19疾病严重程度、炎症参数、抗体反应以及鼻咽拭子SARS-CoV-2 PCR结果相关。我们证明，在诊断后>8天，来自重症监护病房（ICU）患者的45份样本中有21份（46.7%）血清中的NCP抗原水平仍保持升高。在数周内，可检测到抗原血症的ICU患者比例仅从84.6%逐渐下降至25.0%。这与所有非ICU患者在8天后NCP完全清除形成对比，也与通过PCR检测的病毒黏膜清除情况形成对比。抗原清除与针对S1而非NCP的更高IgG相关。超过40%的重症COVID-19患者NCP抗原血症清除延迟。因此，COVID-19诊断后8天检测到的NCP抗原血症是需要重症监护患者的一个特征。前瞻性试验应进一步研究NCP抗原清除动力学作为一种机制性生物标志物。
