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重症新型冠状病毒肺炎患者的内毒素血症与循环菌组

Endotoxemia and circulating bacteriome in severe COVID-19 patients.

作者信息

Sirivongrangson Phatadon, Kulvichit Win, Payungporn Sunchai, Pisitkun Trairak, Chindamporn Ariya, Peerapornratana Sadudee, Pisitkun Prapaporn, Chitcharoen Suwalak, Sawaswong Vorthon, Worasilchai Navaporn, Kampunya Sarinya, Putcharoen Opass, Thawitsri Thammasak, Leelayuwatanakul Nophol, Kongpolprom Napplika, Phoophiboon Vorakamol, Sriprasart Thitiwat, Samransamruajkit Rujipat, Tungsanga Somkanya, Tiankanon Kanitha, Lumlertgul Nuttha, Leelahavanichkul Asada, Sriphojanart Tueboon, Tantawichien Terapong, Thisyakorn Usa, Chirathaworn Chintana, Praditpornsilpa Kearkiat, Tungsanga Kriang, Eiam-Ong Somchai, Sitprija Visith, Kellum John A, Srisawat Nattachai

机构信息

Division of Nephrology, Department of Medicine, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Bangkok, 10330, Thailand.

Excellence Center for Critical Care Nephrology, King Chulalongkorn Memorial Hospital, Bangkok, Thailand.

出版信息

Intensive Care Med Exp. 2020 Dec 7;8(1):72. doi: 10.1186/s40635-020-00362-8.

Abstract

BACKGROUND

When severe, COVID-19 shares many clinical features with bacterial sepsis. Yet, secondary bacterial infection is uncommon. However, as epithelium is injured and barrier function is lost, bacterial products entering the circulation might contribute to the pathophysiology of COVID-19.

METHODS

We studied 19 adults, severely ill patients with COVID-19 infection, who were admitted to King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between 13th March and 17th April 2020. Blood samples on days 1, 3, and 7 of enrollment were analyzed for endotoxin activity assay (EAA), (1 → 3)-β-D-glucan (BG), and 16S rRNA gene sequencing to determine the circulating bacteriome.

RESULTS

Of the 19 patients, 13 were in intensive care and 10 patients received mechanical ventilation. We found 8 patients with high EAA (≥ 0.6) and about half of the patients had high serum BG levels which tended to be higher in later in the illness. Although only 1 patient had a positive blood culture, 18 of 19 patients were positive for 16S rRNA gene amplification. Proteobacteria was the most abundant phylum. The diversity of bacterial genera was decreased overtime.

CONCLUSIONS

Bacterial DNA and toxins were discovered in virtually all severely ill COVID-19 pneumonia patients. This raises a previously unrecognized concern for significant contribution of bacterial products in the pathogenesis of this disease.

摘要

背景

重症新型冠状病毒肺炎(COVID-19)与细菌性败血症有许多共同的临床特征。然而,继发性细菌感染并不常见。然而,由于上皮细胞受损且屏障功能丧失,进入循环系统的细菌产物可能会影响COVID-19的病理生理过程。

方法

我们研究了2020年3月13日至4月17日期间入住泰国曼谷朱拉隆功国王纪念医院的19例成年重症COVID-19感染患者。在入组第1天、第3天和第7天采集血样,进行内毒素活性测定(EAA)、(1→3)-β-D-葡聚糖(BG)检测以及16S rRNA基因测序,以确定循环细菌群落。

结果

19例患者中,13例在重症监护室,10例接受机械通气。我们发现8例患者EAA水平较高(≥0.6),约一半患者血清BG水平较高,且在疾病后期往往更高。虽然只有1例患者血培养呈阳性,但19例患者中有18例16S rRNA基因扩增呈阳性。变形菌门是最丰富的菌门。随着时间的推移,细菌属的多样性降低。

结论

几乎在所有重症COVID-19肺炎患者中都发现了细菌DNA和毒素。这引发了一个此前未被认识到的问题,即细菌产物在这种疾病的发病机制中可能起重大作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f62/7721922/19da8be64da2/40635_2020_362_Fig1_HTML.jpg

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