Intestinal Host Response to SARS-CoV-2 Infection and COVID-19 Outcomes in Patients With Gastrointestinal Symptoms.
Intestinal Host Response to SARS-CoV-2 Infection and COVID-19 Outcomes in Patients With Gastrointestinal Symptoms.
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DOI：
10.1053/j.gastro.2021.02.056
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发表时间：
2021-06
期刊：
影响因子：
29.4
通讯作者：
Mehandru S
中科院分区：
文献类型：
--
作者：
Livanos AE;Jha D;Cossarini F;Gonzalez-Reiche AS;Tokuyama M;Aydillo T;Parigi TL;Ladinsky MS;Ramos I;Dunleavy K;Lee B;Dixon RE;Chen ST;Martinez-Delgado G;Nagula S;Bruce EA;Ko HM;Glicksberg BS;Nadkarni G;Pujadas E;Reidy J;Naymagon S;Grinspan A;Ahmad J;Tankelevich M;Bram Y;Gordon R;Sharma K;Houldsworth J;Britton GJ;Chen-Liaw A;Spindler MP;Plitt T;Wang P;Cerutti A;Faith JJ;Colombel JF;Kenigsberg E;Argmann C;Merad M;Gnjatic S;Harpaz N;Danese S;Cordon-Cardo C;Rahman A;Schwartz RE;Kumta NA;Aghemo A;Bjorkman PJ;Petralia F;van Bakel H;Garcia-Sastre A;Mehandru S
鉴于胃肠道（GI）症状是COVID-19的主要肺外表现，我们研究了肠道感染SARS-CoV-2及其对发病机制的影响及其临床意义。从COVID-19患者（n = 19）和未感染对照（n = 10）中获得人体肠道活检组织，进行显微镜检查、飞行时间分析的细胞计数和RNA测序。此外，在美国（N = 634）和欧洲（N = 287）住院患者的2个大型独立队列中，使用多变量logistic回归检查了有和没有胃肠道症状的患者的疾病严重程度和死亡率。活检队列中的COVID-19病例患者和对照个体在年龄、性别、住院率和相关合并症方面具有可比性。在研究的17例患者中，有15例通过免疫荧光染色或电子显微镜在小肠上皮细胞中检测到SARS-CoV-2。GI组织的高维分析显示，与对照组相比，炎症水平较低，包括IFNG、CXCL8、CXCL2和IL1B等关键炎症基因下调，促炎树突状细胞的频率降低。与这些发现一致，我们发现出现胃肠道症状的患者的疾病严重程度和死亡率显著降低，这些症状与性别、年龄和合并症无关，尽管鼻咽SARS-CoV-2病毒载量相似。此外，有胃肠道症状的患者血液循环中关键炎症蛋白水平降低。这些数据强调，尽管检测到SARS-CoV-2，但胃肠道中没有促炎反应。同时，观察到出现胃肠道症状的COVID-19患者死亡率降低。胃肠道在减轻sars - cov -2相关炎症中的潜在作用需要进一步研究。
Given that gastrointestinal (GI) symptoms are a prominent extrapulmonary manifestation of COVID-19, we investigated intestinal infection with SARS-CoV-2, its effect on pathogenesis, and clinical significance. Human intestinal biopsy tissues were obtained from patients with COVID-19 (n = 19) and uninfected control individuals (n = 10) for microscopic examination, cytometry by time of flight analyses, and RNA sequencing. Additionally, disease severity and mortality were examined in patients with and without GI symptoms in 2 large, independent cohorts of hospitalized patients in the United States (N = 634) and Europe (N = 287) using multivariate logistic regressions. COVID-19 case patients and control individuals in the biopsy cohort were comparable for age, sex, rates of hospitalization, and relevant comorbid conditions. SARS-CoV-2 was detected in small intestinal epithelial cells by immunofluorescence staining or electron microscopy in 15 of 17 patients studied. High-dimensional analyses of GI tissues showed low levels of inflammation, including down-regulation of key inflammatory genes including IFNG, CXCL8, CXCL2, and IL1B and reduced frequencies of proinflammatory dendritic cells compared with control individuals. Consistent with these findings, we found a significant reduction in disease severity and mortality in patients presenting with GI symptoms that was independent of sex, age, and comorbid illnesses and despite similar nasopharyngeal SARS-CoV-2 viral loads. Furthermore, there was reduced levels of key inflammatory proteins in circulation in patients with GI symptoms. These data highlight the absence of a proinflammatory response in the GI tract despite detection of SARS-CoV-2. In parallel, reduced mortality in patients with COVID-19 presenting with GI symptoms was observed. A potential role of the GI tract in attenuating SARS-CoV-2–associated inflammation needs to be further examined.
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影响因子：
29.7
作者：
Cerutti A;Chen K;Chorny A
通讯作者：
Chorny A
影响因子：
64.8
作者：
Ke, Zunlong;Oton, Joaquin;Briggs, John A. G.
通讯作者：
Briggs, John A. G.
影响因子：
56.9
作者：
Lamers, Mart M.;Beumer, Joep;Clevers, Hans
通讯作者：
Clevers, Hans
影响因子：
82.9
作者：
Del Valle DM;Kim-Schulze S;Huang HH;Beckmann ND;Nirenberg S;Wang B;Lavin Y;Swartz TH;Madduri D;Stock A;Marron TU;Xie H;Patel M;Tuballes K;Van Oekelen O;Rahman A;Kovatch P;Aberg JA;Schadt E;Jagannath S;Mazumdar M;Charney AW;Firpo-Betancourt A;Mendu DR;Jhang J;Reich D;Sigel K;Cordon-Cardo C;Feldmann M;Parekh S;Merad M;Gnjatic S
通讯作者：
Gnjatic S
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y