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严重 2019 冠状病毒病患者的腹泻与炎症细胞因子谱改变:对疾病进程和住院死亡率的影响。

Diarrhea and altered inflammatory cytokine pattern in severe coronavirus disease 2019: Impact on disease course and in-hospital mortality.

机构信息

Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

J Gastroenterol Hepatol. 2021 Feb;36(2):421-429. doi: 10.1111/jgh.15166. Epub 2020 Jul 13.

DOI:10.1111/jgh.15166
PMID:32602128
Abstract

BACKGROUND AND AIM

Dynamic changes of immunocyte subsets and inflammatory profiles in coronavirus disease 2019 (COVID-19) patients with gastrointestinal symptoms were undetermined.

METHODS

A single-center retrospective analysis of 409 severe, hospitalized COVID-19 patients from 20 January to 29 February 2020 was performed. The longitudinal characteristics of immune inflammatory cytokines in patients with/without diarrhea were analyzed. The relations of diarrhea and immuno-inflammatory factors with illness course and clinical outcomes were further explored.

RESULTS

Diarrhea was more common and more serious with longer duration (4.9 ± 1.5 vs 4.2 ± 1.5 days, P = 0.039) and higher frequency (5.5 ± 2.1 vs 4.0 ± 2.0 times/day, P = 0.001) in deceased patients than in the survivors. Also, diarrhea patients were more inclined to develop multi-organ damage: survivors have longer illness course (media 41.0 vs 36.0 days, P = 0.052) and hospital stays (media 27.0 vs 23.0 days, P = 0.041), and the deceased patients had higher mortality (33.0% vs 22.6%, P = 0.045) and earlier death (media 20.0 vs 25.0 days, P = 0.038). Progressively, neutrophilia and lymphopenia, especially the declined CD8 T cells, were demonstrated in diarrhea patients relative to the non-diarrhea cases. The inflammatory cytokines including IL-6, IL-10, and TNF-α were intensively increased in patients with diarrhea. The multivariable logistic analysis showed longer duration of diarrhea (P = 0.036), higher neutrophil counts (P = 0.011), and lower lymphocyte counts (P < 0.001) were independent risk factors of in-hospital death. The proportional hazards model indicated that longer duration of diarrhea (P = 0.002), higher frequency of diarrhea (P = 0.058), higher neutrophil counts (P = 0.001), lower lymphocyte counts (P = 0.035), and decreased proportion of CD8 T cells (P < 0.001) were independently associated with longer illness course of the survivors.

CONCLUSIONS

Diarrhea patients were more likely to present with neutrophilia, lymphopenia, and cytokine storm and to develop multi-organ damage. The inflammatory patterns were independent factors associated with illness course of the survivors and in-hospital death of severe COVID-19.

摘要

背景与目的

患有胃肠道症状的 2019 年冠状病毒病(COVID-19)患者的免疫细胞亚群和炎症特征的动态变化尚不确定。

方法

对 2020 年 1 月 20 日至 2 月 29 日期间的 409 例严重住院 COVID-19 患者进行了单中心回顾性分析。分析了有/无腹泻的患者免疫炎性细胞因子的纵向特征。进一步探讨了腹泻与免疫炎症因子与病程和临床结局的关系。

结果

死亡患者的腹泻更常见、更严重,持续时间更长(4.9±1.5 天 vs 4.2±1.5 天,P=0.039),频率更高(5.5±2.1 次/天 vs 4.0±2.0 次/天,P=0.001)。此外,腹泻患者更易发生多器官损伤:幸存者的病程更长(中位数 41.0 天 vs 36.0 天,P=0.052),住院时间更长(中位数 27.0 天 vs 23.0 天,P=0.041),死亡患者的死亡率更高(33.0% vs 22.6%,P=0.045),死亡时间更早(中位数 20.0 天 vs 25.0 天,P=0.038)。与非腹泻患者相比,腹泻患者表现为中性粒细胞增多和淋巴细胞减少,特别是 CD8 T 细胞减少。腹泻患者的炎症细胞因子包括 IL-6、IL-10 和 TNF-α 明显增加。多变量逻辑分析表明,腹泻时间较长(P=0.036)、中性粒细胞计数较高(P=0.011)和淋巴细胞计数较低(P<0.001)是住院死亡的独立危险因素。比例风险模型表明,腹泻持续时间较长(P=0.002)、腹泻频率较高(P=0.058)、中性粒细胞计数较高(P=0.001)、淋巴细胞计数较低(P=0.035)和 CD8 T 细胞比例降低(P<0.001)与幸存者病程较长有关。

结论

腹泻患者更易出现中性粒细胞增多、淋巴细胞减少和细胞因子风暴,并发生多器官损伤。炎症模式是与幸存者病程和严重 COVID-19 住院死亡相关的独立因素。

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