Department of Medicine, Duke University School of Medicine, Durham, NC, 27710, USA.
Duke Medical Scientist Training Program, Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, 27710, USA.
BMC Pulm Med. 2024 Jul 29;24(1):366. doi: 10.1186/s12890-024-03183-7.
Severe COVID-19 carries a high morbidity and mortality. Previous studies have shown an association between COVID-19 severity and SARS-CoV-2 viral load (VL). We sought to measure VL in multiple compartments (urine, plasma, lower respiratory tract) in patients admitted to the intensive care unit (ICU) with severe COVID-19 pneumonia and correlate with clinical outcomes.
Plasma, urine, and endotracheal aspirate (ETA) samples were obtained on days 1, 3, 7, 14, and 21 from subjects admitted to the ICU with severe COVID-19. VL was measured via reverse transcriptase polymerase chain reaction. Clinical data was collected from the electronic health record. Grouped comparisons were performed using Student's t-test or 1-way ANOVA. Linear regression was used to correlate VL from different compartments collected at the same time. Logistic regression was performed to model ventilator-freedom at 28 days as a function of peak plasma VL.
We enrolled 57 subjects with severe COVID-19 and measured VL in plasma (n = 57), urine (n = 25), and ETA (n = 34). Ventilator-associated pneumonia developed in 63% of subjects. 49% of subjects were viremic on study day 1. VL in plasma and ETA both significantly decreased by day 14 (P < 0.05), and the two were weakly correlated on study day 1 (P = 0.0037, r = 0.2343) and on all study days (P < 0.001, r = 0.2211). VL were not detected in urine. While no associations were observed with peak ETA VL, subjects with higher peak plasma VL experienced a greater number of respiratory complications, including ventilator-associated pneumonia and fewer ventilator-free and hospital-free days. There was no association between VL in either plasma or ETA and mortality. In viremic patients, plasma VL was significantly lower in subjects that were ICU-free and ventilator-free (P < 0.05), with trends noted for hospital-freedom, ventilator-associated pneumonia, and survival to discharge (P < 0.1). By logistic regression, plasma VL was inversely associated with ventilator-freedom at 28 days (odds ratio 0.14, 95% confidence interval 0.02-0.50).
Elevated SARS-CoV-2 VL in the plasma but not in the lower respiratory tract is a novel biomarker in severe COVID-19 for respiratory complications.
严重的 COVID-19 具有很高的发病率和死亡率。先前的研究表明，COVID-19 的严重程度与 SARS-CoV-2 病毒载量（VL）之间存在关联。我们试图测量入住重症监护病房（ICU）的严重 COVID-19 肺炎患者的多个部位（尿液、血浆、下呼吸道）的 VL，并与临床结果相关联。
从入住 ICU 的严重 COVID-19 患者中，在第 1、3、7、14 和 21 天分别采集血浆、尿液和气管内吸出物（ETA）样本。通过逆转录聚合酶链反应测量 VL。从电子病历中收集临床数据。使用学生 t 检验或单因素方差分析进行组间比较。使用线性回归分析同一时间采集的不同部位的 VL 相关性。使用逻辑回归分析作为函数建模 28 天内的呼吸机自由情况。
我们共招募了 57 名患有严重 COVID-19 的患者，并测量了血浆中的 VL（n=57）、尿液中的 VL（n=25）和 ETA 中的 VL（n=34）。63%的患者发生呼吸机相关性肺炎。49%的患者在研究第 1 天存在病毒血症。第 14 天血浆和 ETA 中的 VL 均明显下降（P<0.05），第 1 天两者呈弱相关（P=0.0037，r=0.2343），且在所有研究日均呈弱相关（P<0.001，r=0.2211）。尿液中未检测到 VL。虽然与 ETA 峰值 VL 无相关性，但具有更高的血浆峰值 VL 的患者出现更多的呼吸并发症，包括呼吸机相关性肺炎，并且呼吸机自由和住院自由天数较少。VL 在血浆或 ETA 中均与死亡率无关。在病毒血症患者中，无 ICU 入住和无呼吸机使用的患者血浆 VL 明显降低（P<0.05），ICU 自由、呼吸机相关性肺炎和存活至出院的趋势（P<0.1）。通过逻辑回归，血浆 VL 与 28 天的呼吸机自由呈反比关系（优势比 0.14，95%置信区间 0.02-0.50）。
血浆中升高的 SARS-CoV-2 VL 而不是下呼吸道中的升高是严重 COVID-19 中与呼吸并发症相关的新型生物标志物。
