Brunet-Ratnasingham Elsa, Anand Sai Priya, Gantner Pierre, Dyachenko Alina, Moquin-Beaudry Gaël, Brassard Nathalie, Beaudoin-Bussières Guillaume, Pagliuzza Amélie, Gasser Romain, Benlarbi Mehdi, Point Floriane, Prévost Jérémie, Laumaea Annemarie, Niessl Julia, Nayrac Manon, Sannier Gérémy, Orban Catherine, Messier-Peet Marc, Butler-Laporte Guillaume, Morrison David R, Zhou Sirui, Nakanishi Tomoko, Boutin Marianne, Descôteaux-Dinelle Jade, Gendron-Lepage Gabrielle, Goyette Guillaume, Bourassa Catherine, Medjahed Halima, Laurent Laetitia, Rébillard Rose-Marie, Richard Jonathan, Dubé Mathieu, Fromentin Rémi, Arbour Nathalie, Prat Alexandre, Larochelle Catherine, Durand Madeleine, Richards J Brent, Chassé Michaël, Tétreault Martine, Chomont Nicolas, Finzi Andrés, Kaufmann Daniel E
Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada.
Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC, Canada.
Sci Adv. 2021 Nov 26;7(48):eabj5629. doi: 10.1126/sciadv.abj5629.
Despite advances in COVID-19 management, identifying patients evolving toward death remains challenging. To identify early predictors of mortality within 60 days of symptom onset (DSO), we performed immunovirological assessments on plasma from 279 individuals. On samples collected at DSO11 in a discovery cohort, high severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA (vRNA), low receptor binding domain–specific immunoglobulin G and antibody-dependent cellular cytotoxicity, and elevated cytokines and tissue injury markers were strongly associated with mortality, including in patients on mechanical ventilation. A three-variable model of vRNA, with predefined adjustment by age and sex, robustly identified patients with fatal outcome (adjusted hazard ratio for log-transformed vRNA = 3.5). This model remained robust in independent validation and confirmation cohorts. Since plasma vRNA’s predictive accuracy was maintained at earlier time points, its quantitation can help us understand disease heterogeneity and identify patients who may benefit from new therapies.
尽管在新冠病毒病(COVID-19)治疗方面取得了进展,但识别病情逐渐发展至死亡的患者仍然具有挑战性。为了确定症状出现后60天内(DSO)的早期死亡预测指标,我们对279名个体的血浆进行了免疫病毒学评估。在一个发现队列中于症状出现第11天采集的样本上,严重急性呼吸综合征冠状病毒2(SARS-CoV-2)病毒RNA(vRNA)水平高、受体结合域特异性免疫球蛋白G和抗体依赖性细胞毒性低,以及细胞因子和组织损伤标志物升高与死亡率密切相关,包括接受机械通气的患者。一个由vRNA组成的三变量模型,经过年龄和性别的预定义调整,能够可靠地识别出有致命结局的患者(对数转换后的vRNA调整风险比 = 3.5)。该模型在独立验证队列和确认队列中仍然可靠。由于血浆vRNA的预测准确性在更早的时间点就能保持,对其进行定量有助于我们了解疾病异质性,并识别可能从新疗法中获益的患者。