Farnsworth Christopher W, Roemmich Brittany, Prostko John, Davis Gerard, Murtagh Gillian, Jackson Laurel, Jacobson Christopher, Jeanblanc Nicolette, Griffiths Timothy, Frias Edwin, Daghfal David J
Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA.
Abbott Diagnostics, Abbott Park, Illinois, USA.
Microbiol Spectr. 2025 Apr;13(4):e0245924. doi: 10.1128/spectrum.02459-24. Epub 2025 Feb 19.
Systemic inflammation is associated with COVID-19 mortality rates, but the impact of inflammation on neutralizing antibodies to severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and on outcomes is poorly understood. This study aimed to determine the association between neutralizing antibody responses, inflammation, and clinical outcomes in hospitalized patients with COVID-19. Two hundred and eight patients presenting to the ED with symptomatic SARS-CoV-2 were included. Neutralization was assessed using the architect angiotensin-converting enzyme-2 (ACE2) binding inhibition assay, and inflammation was assessed using C reactive protein (CRP) and interleukin 6 (IL-6). Medical records were examined for 30-day mortality and 10-day intubation. Correlation between biomarkers was assessed and Kaplan-Meier curves and Cox proportional hazards models were constructed for outcomes. Thirty-seven (18%) patients died and 59 (28%) required intubation. There was a correlation between IL-6 and CRP ( = 0.34) but not ACE-2 ( < 0.06). Patients that died had higher CRP (14 mg/dl, 8-21) than those that survived (5 mg/dl, 2-11) and IL-6 (died = 344 pg/ml, 138-870 vs. survived = 65 pg/ml, 28-140). ACE-2 inhibition trended higher in those who survived (18%, 0%-65%) than those who died (3%, 0%-48%). Patients with elevated IL-6, elevated CRP, or low ACE2 inhibition had higher mortality. Only IL-6 (hazard ratio: 1.28, 95% CI 1.08-1.52) and age (1.04, 1.01-1.08) were associated with mortality in multivariate models. Elevated IL-6 was associated with 30-day mortality from SARS-CoV-2 infection. Lower ACE-2 inhibition was not independently associated with mortality or correlated with inflammatory markers, implying the importance of other aspects of the immune response for reducing SARS-CoV-2 mortality risk.IMPORTANCEWhile systemic inflammation associated with worse outcomes from SARS-CoV-2 infection, it is not associated with neutralizing antibody concentrations, implying the importance of other aspects of the immune response for reducing SARS-CoV-2 mortality risk.
全身炎症与新型冠状病毒肺炎（COVID-19）死亡率相关，但炎症对严重急性呼吸综合征相关冠状病毒2（SARS-CoV-2）中和抗体及预后的影响尚不清楚。本研究旨在确定COVID-19住院患者中和抗体反应、炎症与临床预后之间的关联。纳入了208例因有症状的SARS-CoV-2感染就诊于急诊科的患者。使用全自动血管紧张素转换酶2（ACE2）结合抑制试验评估中和作用，使用C反应蛋白（CRP）和白细胞介素6（IL-6）评估炎症。检查病历以了解30天死亡率和10天插管情况。评估生物标志物之间的相关性，并构建Kaplan-Meier曲线和Cox比例风险模型以分析预后。37例（18%）患者死亡，59例（28%）需要插管。IL-6与CRP之间存在相关性（r = 0.34），但与ACE2无相关性（r < 0.06）。死亡患者的CRP水平（14 mg/dl，8 - 21）高于存活患者（5 mg/dl，2 - 11），IL-6水平（死亡患者 = 344 pg/ml，138 - 870 vs. 存活患者 = 65 pg/ml，28 - 140）也更高。存活患者的ACE2抑制率呈上升趋势（18%，0% - 65%），高于死亡患者（3%，0% - 48%）。IL-6升高、CRP升高或ACE2抑制率低的患者死亡率更高。在多变量模型中，只有IL-6（风险比：1.28，95%置信区间1.08 - 1.52）和年龄（1.04，1.01 - 1.08）与死亡率相关。IL-6升高与SARS-CoV-2感染30天死亡率相关。较低的ACE2抑制率与死亡率无独立相关性，也与炎症标志物无相关性，这意味着免疫反应的其他方面对于降低SARS-CoV-2死亡风险很重要。
重要性
虽然全身炎症与SARS-CoV-2感染的不良预后相关，但它与中和抗体浓度无关，这意味着免疫反应的其他方面对于降低SARS-CoV-2死亡风险很重要。
