Viral and immune factors associated with COVID-19 outcome in the C3PO trial of convalescent plasma

Clara Di Germanio, Erika G Marques de Menezes, Robert Clevenger, Ian Rines, Valerie L Durkalski-Mauldin, Eric Leifer, Sharon Yeatts, Xutao Deng, Brendan G Balasko, John F McDyer, Leilani Montalvo, Daniel Chafets, Nadine N Talia, Alexandra Weissman, Sumith R Panicker, Yogen Kanthi, Mars Stone, Frederick K Korley, Clifton W Callaway, Philip J Norris
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Abstract

We examined innate and antibody responses in C3PO clinical trial participants of COVID-19 convalescent plasma to identify predictors of disease progression. We found SARS-CoV-2 viremia in 64% of participants at enrollment, and we could also quantify viremia in approximately half of those samples using an RT-PCR assay. Viremia was associated with increased risk of disease progression (OR 3.0, 95% CI 1.7–5.0). Participants with viremia at baseline had lower SARS-CoV-2 binding antibody levels and higher pro-inflammatory cytokine levels, including IP-10 (CXCL10), TNF-α, calprotectin, and CRP. Disease progression correlated with extracellular vesicle levels from multiple cell types in the convalescent but not acute phase of the disease. Male sex predicted worse disease outcome and was associated with higher baseline levels of several pro-inflammatory cytokines. Viremia’s strong predictive value for disease progression argues for further study of its use to predict which patients with COVID-19 might require more intensive therapy or monitoring.
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恢复期血浆C3PO试验中与COVID-19结局相关的病毒和免疫因子
我们研究了 COVID-19 康复血浆 C3PO 临床试验参与者的先天和抗体反应,以确定疾病进展的预测因素。我们发现 64% 的参与者在入组时感染了 SARS-CoV-2 病毒,我们还使用 RT-PCR 检测法对其中约一半的样本进行了病毒定量。病毒血症与疾病进展风险的增加有关(OR 3.0,95% CI 1.7-5.0)。基线病毒血症患者的 SARS-CoV-2 结合抗体水平较低,促炎细胞因子水平较高,包括 IP-10 (CXCL10)、TNF-α、calprotectin 和 CRP。疾病进展与疾病恢复期(而非急性期)多种细胞类型的细胞外囊泡水平相关。男性预示着病情恶化,并与多种促炎细胞因子的基线水平较高有关。病毒血症对疾病进展具有很强的预测价值,因此需要进一步研究如何利用病毒血症来预测哪些 COVID-19 患者可能需要加强治疗或监测。
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