Plasma SARS-CoV-2 nucleocapsid antigen levels are associated with progression to severe disease in hospitalized COVID-19,Critical Care

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Plasma SARS-CoV-2 nucleocapsid antigen levels are associated with progression to severe disease in hospitalized COVID-19
Critical Care ( IF 8.8 ) Pub Date : 2022-09-14 , DOI: 10.1186/s13054-022-04153-3
Katherine D Wick ₁ , Aleksandra Leligdowicz _{1,

2,

3} , Andrew Willmore ₄ , Sidney A Carrillo ₄ , Rajani Ghale ₄ , Alejandra Jauregui ₄ , Suzanna S Chak ₄ , Viet Nguyen _{1,

5} , Deanna Lee _{1,

5} , Chayse Jones ₄ , Robin Dewar ₆ , H Clifford Lane ₇ , Kirsten N Kangelaris ₈ , Carolyn M Hendrickson ₅ , Kathleen D Liu _{9,

10} , Pratik Sinha _{11,

12} , David J Erle _{1,

13,

14,

15} , Charles R Langelier _{16,

17} , Matthew F Krummell _{14,

18} , Prescott G Woodruff _{1,

4} , Carolyn S Calfee _{1,

4} , Michael A Matthay _{1,

19} ,

Affiliation

Cardiovascular Research Institute, University of California San Francisco, 503 Parnassus Ave, HSE 760, San Francisco, CA, 94143, USA.
Division of Critical Care, Departments of Medicine and Microbiology and Immunology, Western University, London, ON, Canada.
Robarts Research Institute, Western University, London, ON, Canada.
Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Zuckerberg San Francisco General Hospital and Trauma Center, University of California San Francisco, San Francisco, USA.
Virus Isolation and Serology Laboratory, Applied and Developmental Directorate, Frederick National Laboratory, Frederick, MD, USA.
Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Department of Hospital Medicine, University of California San Francisco, San Francisco, CA, USA.
Division of Nephrology, Department of Medicine, University of California San Francisco School of Medicine, San Francisco, CA, USA.
Division of Critical Care Medicine, Department of Anesthesia, University of California San Francisco School of Medicine, San Francisco, CA, USA.
Department of Anesthesia, Division of Critical Care, Washington University, St. Louis, MO, USA.
Division of Clinical and Translational Research, Washington University School of Medicine, St. Louis, MO, USA.
Lung Biology Center, University of California San Francisco, San Francisco, CA, USA.
ImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA.
UCSF CoLabs, University of California San Francisco, San Francisco, CA, USA.
Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA.
Chan Zuckerberg Biohub, University of California San Francisco, San Francisco, CA, USA.
Departments of Medicine and Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA.
Departments of Medicine and Anesthesia, University of California San Francisco, San Francisco, CA, USA.

Studies quantifying SARS-CoV-2 have focused on upper respiratory tract or plasma viral RNA with inconsistent association with clinical outcomes. The association between plasma viral antigen levels and clinical outcomes has not been previously studied. Our aim was to investigate the relationship between plasma SARS-CoV-2 nucleocapsid antigen (N-antigen) concentration and both markers of host response and clinical outcomes. SARS-CoV-2 N-antigen concentrations were measured in the first study plasma sample (D0), collected within 72 h of hospital admission, from 256 subjects admitted between March 2020 and August 2021 in a prospective observational cohort of hospitalized patients with COVID-19. The rank correlations between plasma N-antigen and plasma biomarkers of tissue damage, coagulation, and inflammation were assessed. Multiple ordinal regression was used to test the association between enrollment N-antigen plasma concentration and the primary outcome of clinical deterioration at one week as measured by a modified World Health Organization (WHO) ordinal scale. Multiple logistic regression was used to test the association between enrollment plasma N-antigen concentration and the secondary outcomes of ICU admission, mechanical ventilation at 28 days, and death at 28 days. The prognostic discrimination of an externally derived “high antigen” cutoff of N-antigen ≥ 1000 pg/mL was also tested. N-antigen on D0 was detectable in 84% of study participants. Plasma N-antigen levels significantly correlated with RAGE (r = 0.61), IL-10 (r = 0.59), and IP-10 (r = 0.59, adjusted p = 0.01 for all correlations). For the primary outcome of clinical status at one week, each 500 pg/mL increase in plasma N-antigen level was associated with an adjusted OR of 1.05 (95% CI 1.03–1.08) for worse WHO ordinal status. D0 plasma N-antigen ≥ 1000 pg/mL was 77% sensitive and 59% specific (AUROC 0.68) with a positive predictive value of 23% and a negative predictive value of 93% for a worse WHO ordinal scale at day 7 compared to baseline. D0 N-antigen concentration was independently associated with ICU admission and 28-day mechanical ventilation, but not with death at 28 days. Plasma N-antigen levels are readily measured and provide important insight into the pathogenesis and prognosis of COVID-19. The measurement of N-antigen levels early in-hospital course may improve risk stratification, especially for identifying patients who are unlikely to progress to severe disease.

中文翻译：

血浆 SARS-CoV-2 核衣壳抗原水平与住院 COVID-19 进展为严重疾病相关

量化 SARS-CoV-2 的研究主要集中在上呼吸道或血浆病毒 RNA，与临床结果的关联性不一致。先前尚未研究血浆病毒抗原水平与临床结果之间的关联。我们的目的是研究血浆 SARS-CoV-2 核衣壳抗原（N 抗原）浓度与宿主反应标志物和临床结果之间的关系。在入院 72 小时内收集的第一份研究血浆样本 (D0) 中测量了 SARS-CoV-2 N 抗原浓度，该样本来自 2020 年 3 月至 2021 年 8 月期间入院的 256 名受试者，这些受试者是住院新冠肺炎患者的前瞻性观察队列。 19.评估血浆 N 抗原与组织损伤、凝血和炎症的血浆生物标志物之间的等级相关性。使用多重序数回归来测试入组 N 抗原血浆浓度与一周内临床恶化的主要结果之间的关联，该结果是通过修改后的世界卫生组织 (WHO) 序数量表测量的。使用多元逻辑回归来检验入组血浆 N 抗原浓度与 ICU 入住、28 天机械通气和 28 天死亡等次要结果之间的关联。还测试了 N 抗原≥ 1000 pg/mL 的外部来源“高抗原”截止值的预后辨别。 84% 的研究参与者可检测到 D0 上的 N 抗原。血浆 N 抗原水平与 RAGE (r = 0.61)、IL-10 (r = 0.59) 和 IP-10 (r = 0.59，所有相关性调整后的 p = 0.01) 显着相关。对于一周临床状态的主要结果，血浆 N 抗原水平每增加 500 pg/mL，调整后的 OR 为 1.05（95% CI 1.03-1.05）。08) 世卫组织排名更差。 D0 血浆 N 抗原≥ 1000 pg/mL 的敏感性为 77%，特异性为 59% (AUROC 0.68)，与基线相比，第 7 天的 WHO 排序量表较差的阳性预测值为 23%，阴性预测值为 93% 。 D0 N 抗原浓度与 ICU 入住和 28 天机械通气独立相关，但与 28 天死亡无关。血浆 N 抗原水平易于测量，可为了解 COVID-19 的发病机制和预后提供重要见解。在院内早期测量 N 抗原水平可能会改善风险分层，特别是对于识别不太可能进展为严重疾病的患者。

更新日期：2022-09-14

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