Department of Laboratory Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China.
Central Laboratory, Huashan Hospital, Fudan University, Shanghai 200040, China.
Clin Chim Acta. 2023 Feb 1;540:117227. doi: 10.1016/j.cca.2023.117227. Epub 2023 Jan 11.
Early stratification of disease progression remains one of the major challenges towards the post-coronavirus disease 2019 (COVID-19) era. The clinical relevance of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid load is debated due to the heterogeneity in patients' underlying health conditions. We determined the prognostic value of nasopharyngeal viral load dynamic conversion for COVID-19.
The cycling threshold (Ct) values of 28,937 nasopharyngeal SARS-CoV-2 RT-PCRs were retrospectively collected from 3,364 COVID-19 patients during hospitalization and coordinated to the onset of disease progression. The ROC curve was utilized to determine the predictive performance of the rate of Ct value alteration between two consecutive RT-PCR runs within 48 h (ΔCt%) for disease transformation across patients with different COVID-19 severity and immune backgrounds, and further validated with 1,860 SARS-CoV-2 RT-PCR results from an independent validation cohort of 262 patients. For the 67 patients with severe COVID-19, Kaplan-Meier analysis was performed to evaluate the difference in survival between patients stratified by the magnitude of Ct value alteration between the late and early stages of hospitalization.
The kinetics of viral nucleic acid conversion diversified across COVID-19 patients with different clinical characteristics and disease severities. The ΔCt% is a clinical characteristic- and host immune status-independent indicator for COVID-19 progression prediction (AUC = 0.79, 95 % CI = 0.76 to 0.81), which outperformed the canonical blood test markers, including c-reactive protein (AUC = 0.57, 95 % CI = 0.53 to 0.61), serum amyloid A (AUC = 0.61, 95 % CI = 0.54 to 0.68), lactate dehydrogenase (AUC = 0.61, 95 % CI = 0.56 to 0.67), d-dimer (AUC = 0.56, 95 % CI = 0.46 to 0.66), and lymphocyte count (AUC = 0.62, 95 % CI = 0.58 to 0.66). Patients with persistent high SARS-CoV-2 viral load (an increase of mean Ct value < 50 %) during the first 3 days of hospitalization demonstrated a significantly unfavorable survival (HR = 0.16, 95 % CI = 0.04 to 0.65, P = 2.41 × 10).
Viral nucleic acid dynamics of SARS-CoV-2 eliminates the inter-patient variance of basic health conditions and therefore, can serve as a prognostic marker for COVID-19.
疾病进展的早期分层仍然是后新冠时代的主要挑战之一。由于患者基础健康状况的异质性，严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）核酸载量的临床相关性存在争议。我们确定了鼻咽病毒载量动态转换对 COVID-19 的预后价值。
回顾性收集了 3364 例住院 COVID-19 患者 28937 次鼻咽 SARS-CoV-2 RT-PCR 的循环阈值（Ct）值，并与疾病进展的发病时间相协调。ROC 曲线用于确定在 48 小时内两次连续 RT-PCR 运行之间 Ct 值变化率（ΔCt%）对不同 COVID-19 严重程度和免疫背景患者疾病转化的预测性能，并进一步使用来自 262 例患者的独立验证队列的 1860 次 SARS-CoV-2 RT-PCR 结果进行验证。对于 67 例重症 COVID-19 患者，进行 Kaplan-Meier 分析，以评估根据住院后期和早期 Ct 值变化幅度分层的患者之间的生存差异。
具有不同临床特征和疾病严重程度的 COVID-19 患者的病毒核酸转换动力学各不相同。ΔCt%是 COVID-19 进展预测的与临床特征和宿主免疫状态无关的指标（AUC=0.79，95%CI=0.76 至 0.81），优于经典的血液检测标志物，包括 C 反应蛋白（AUC=0.57，95%CI=0.53 至 0.61）、血清淀粉样蛋白 A（AUC=0.61，95%CI=0.54 至 0.68）、乳酸脱氢酶（AUC=0.61，95%CI=0.56 至 0.67）、D-二聚体（AUC=0.56，95%CI=0.46 至 0.66）和淋巴细胞计数（AUC=0.62，95%CI=0.58 至 0.66）。在住院的前 3 天内 SARS-CoV-2 病毒载量持续升高（平均 Ct 值增加<50%）的患者生存情况明显不利（HR=0.16，95%CI=0.04 至 0.65，P=2.41×10）。
SARS-CoV-2 的病毒核酸动态消除了患者基本健康状况的个体间差异，因此可作为 COVID-19 的预后标志物。
