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住院 COVID-19 患者队列中疾病严重程度的表型:IMPACC 研究结果。

Phenotypes of disease severity in a cohort of hospitalized COVID-19 patients: Results from the IMPACC study.

机构信息

Clinical & Data Coordinating Center (CDCC); Precision Vaccines Program, Boston Children's Hospital, Boston, MA, United States.

David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, United States.

出版信息

EBioMedicine. 2022 Sep;83:104208. doi: 10.1016/j.ebiom.2022.104208. Epub 2022 Aug 8.

Abstract

BACKGROUND

Better understanding of the association between characteristics of patients hospitalized with coronavirus disease 2019 (COVID-19) and outcome is needed to further improve upon patient management.

METHODS

Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) is a prospective, observational study of 1164 patients from 20 hospitals across the United States. Disease severity was assessed using a 7-point ordinal scale based on degree of respiratory illness. Patients were prospectively surveyed for 1 year after discharge for post-acute sequalae of COVID-19 (PASC) through quarterly surveys. Demographics, comorbidities, radiographic findings, clinical laboratory values, SARS-CoV-2 PCR and serology were captured over a 28-day period. Multivariable logistic regression was performed.

FINDINGS

The median age was 59 years (interquartile range [IQR] 20); 711 (61%) were men; overall mortality was 14%, and 228 (20%) required invasive mechanical ventilation. Unsupervised clustering of ordinal score over time revealed distinct disease course trajectories. Risk factors associated with prolonged hospitalization or death by day 28 included age ≥ 65 years (odds ratio [OR], 2.01; 95% CI 1.28-3.17), Hispanic ethnicity (OR, 1.71; 95% CI 1.13-2.57), elevated baseline creatinine (OR 2.80; 95% CI 1.63- 4.80) or troponin (OR 1.89; 95% 1.03-3.47), baseline lymphopenia (OR 2.19; 95% CI 1.61-2.97), presence of infiltrate by chest imaging (OR 3.16; 95% CI 1.96-5.10), and high SARS-CoV2 viral load (OR 1.53; 95% CI 1.17-2.00). Fatal cases had the lowest ratio of SARS-CoV-2 antibody to viral load levels compared to other trajectories over time (p=0.001). 589 survivors (51%) completed at least one survey at follow-up with 305 (52%) having at least one symptom consistent with PASC, most commonly dyspnea (56% among symptomatic patients). Female sex was the only associated risk factor for PASC.

INTERPRETATION

Integration of PCR cycle threshold, and antibody values with demographics, comorbidities, and laboratory/radiographic findings identified risk factors for 28-day outcome severity, though only female sex was associated with PASC. Longitudinal clinical phenotyping offers important insights, and provides a framework for immunophenotyping for acute and long COVID-19.

FUNDING

NIH.

摘要

背景

为了进一步改善患者管理,需要更好地了解因感染 2019 年冠状病毒病(COVID-19)而住院的患者的特征与预后之间的关系。

方法

冠状病毒病 19 免疫表型评估队列研究(IMPACC)是一项在美国 20 家医院进行的前瞻性观察性研究,共纳入 1164 例患者。使用基于呼吸疾病严重程度的 7 分序数量表评估疾病严重程度。出院后 1 年,通过每季度进行一次调查,前瞻性地调查 COVID-19 的急性后遗症(PASC)。在 28 天内采集患者的人口统计学、合并症、影像学表现、临床实验室值、SARS-CoV-2 PCR 和血清学数据。采用多变量逻辑回归进行分析。

结果

中位年龄为 59 岁(四分位距[IQR] 20);711 例(61%)为男性;总体死亡率为 14%,228 例(20%)需要有创机械通气。对时间上的序数量表进行无监督聚类,发现了不同的疾病进展轨迹。与第 28 天住院时间延长或死亡相关的危险因素包括年龄≥65 岁(比值比[OR],2.01;95%置信区间[CI],1.28-3.17)、西班牙裔(OR,1.71;95%CI,1.13-2.57)、基线肌酐(OR,2.80;95%CI,1.63-4.80)或肌钙蛋白(OR,1.89;95%CI,1.03-3.47)升高、基线淋巴细胞减少(OR,2.19;95%CI,1.61-2.97)、胸部影像学存在浸润影(OR,3.16;95%CI,1.96-5.10)和高 SARS-CoV-2 病毒载量(OR,1.53;95%CI,1.17-2.00)。死亡病例的 SARS-CoV-2 抗体与病毒载量比值与其他轨迹相比在整个时间内最低(p=0.001)。589 例存活者(51%)完成了至少一次随访调查,其中 305 例(52%)至少有 1 种符合 PASC 的症状,最常见的是呼吸困难(56%的有症状患者)。女性是 PASC 的唯一相关危险因素。

结论

PCR 循环阈值和抗体值与人口统计学、合并症和实验室/影像学表现相结合,确定了 28 天预后严重程度的危险因素,但只有女性与 PASC 相关。纵向临床表型分析提供了重要的见解,并为急性和长期 COVID-19 的免疫表型分析提供了框架。

资金来源

美国国立卫生研究院。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e14/9385554/e90d739d0fde/gr1.jpg

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