Evidence for gastrointestinal infection of SARS-CoV-2

Xiao, Fei; Tang, Mimi; Zheng, Xiaobin; Li, Chunna; He, Jianzhong; Hong, Zhongsi; Huang, Shenlin; Zhang, Zhenyi; Lin, Xianqi; Fang, Zhaoxiong; Lai, Renxu; Chen, Shoudeng; Liu, Jing; Huang, Jin; Xia, Jinyu; Li, Zhonghe; Jiang, Guanmin; Liu, Ye; Li, Xiaofeng; Song, Hong

doi:10.1101/2020.02.17.20023721

Cited by 712 publications

(1,110 citation statements)

References 9 publications

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“…Similar effect from COVID-19 was speculated, but a most recent study had just provided the first direct evidence that SARS-CoV-2 infection impacts male sex hormones 39 . Similarly, small intestine is the tissue with the second highest level of ACE2 expression, while SARS-CoV-2 was found in stool samples of COVID-19 patients both in China and the United States 7,42 , even after the viral RNA decreased to undetectable level in respiratory tract 43 . Additionally, we found in our normalized dataset that heart tissues also had the third highest level of ACE2 expression.…”

Section: Discussionmentioning

confidence: 98%

Atlas of ACE2 gene expression in mammals reveals novel insights in transmisson of SARS-Cov-2

Sun

et al. 2020

Preprint

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Background: COVID-19 has become a worldwide pandemic. It is caused by a novel coronavirus named SARS-CoV-2 with elusive origin. SARS-CoV-2 infects mammalian cells by binding to ACE2, a transmembrane protein. Therefore, the conservation of ACE2 and its expression pattern across mammalian species, which are yet to be comprehensively investigated, may provide valuable insights into tracing potential hosts of SARS-CoV-2. Methods:We analyzed gene conservation of ACE2 across mammals and collected more than 140 transcriptome datasets from human and common mammalian species, including presumed hosts of SARS-CoV-2 and other animals in close contact with humans. In order to enable comparisons across species and tissues, we used a unified pipeline to quantify and normalize ACE2 expression levels. Results:We first found high conservation of ACE2 genes among common mammals at both DNA and peptide levels, suggesting that a broad range of mammalian species can potentially be the hosts of SARS-CoV-2. Next, we showed that high level of ACE2 expression in certain human tissues is consistent with clinical symptoms of COVID-19 patients. Furthermore, we observed that ACE2 expressed in a species-specific manner in the mammals examined. Notably, high expression in skin and eyes in cat and dog suggested that these animals may play roles in transmitting SARS-CoV-2 to humans. Conclusions:Through building the first atlas of ACE2 expression in pets and livestock, we identified species and tissues susceptible to SARS-CoV-2 infection, yielding novel insights into the viral transmission.

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Section: Discussionmentioning

confidence: 98%

Atlas of ACE2 gene expression in mammals reveals novel insights in transmisson of SARS-Cov-2

Sun

et al. 2020

Preprint

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“…Another virological factor is that long-term virus residual in gut and other tissue, similar to SARS [26]. A recent study indicated that SARS-CoV-2 nucleic acid can persist in the digestive tract and feces for nearly 50 days [27].…”

Section: Discussionmentioning

confidence: 99%

Clinical characteristics of the recovered COVID-19 patients with re-detectable positive RNA test

Liao

Xiao

et al. 2020

Preprint

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Background It has been reported that several cases recovered from COVID-19 tested positive for SARS-CoV-2 after discharge (re-detectable positive, RP), however the clinical characteristics, significance and potential cause of RP patients remained elusive.Methods A total of 262 COVID-19 patients were discharged from January 23 to February 25, 2020, and were enrolled for analysis of their clinical parameters. The RP and non-RP (NRP) patients were grouped according to the disease severity during their hospitalization period. The clinical characterization at re-admission to the hospital was analyzed. SARS-CoV-2 RNA and plasma antibody levels were detected using high-sensitive detection methods.Findings Up to March 10, 2020, all of patients were followed up for at least 14 days, and 38/262 of RP patients (14.5%) were present. The RP patients were characterized by being less than 14-years old and having mild and moderate conditions as compared to NRP patients, while no severe patients became RP.Retrospectively, the RP patients displayed fewer symptoms, more sustained remission of CT imaging and earlier RNA negative-conversion but similar plasma antibody levels during their hospitalization period as compared to those NRP patients. When re-admitted to the hospital, these RP patients showed no obvious clinical symptoms or disease progression indicated by normal or improving CT imaging and inflammatory cytokine levels. All 21 close contacts of RP patients were tested negative for SARS-CoV-2 RNA, and no suspicious clinical symptoms were reported. However, 18/24 of RNA-negative samples detected by the commercial kit were tested to be positive for virus RNA using a hyper-sensitive method, suggesting the carrier status of virus possibly existed in patients recovered from COVID-19.Interpretation Our results showed that young and mild COVID-19 patients seem to be RP patients after discharge, who show no obviously clinical symptoms and disease progression upon re-admission. More sensitive RNA

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“…Notably, GI symptoms including abdominal pain and diarrhea were observed in 20-50% of COVID-19 patients and sometimes preceded the development of respiratory diseases ( 8–10 ). Substantial amounts of SARS-CoV-2 RNA have been consistently detected in stool specimens from COVID-19 patients ( 11–15 ). In a recent study, no infectious virus was successfully isolated from the feces of COVID-19 patients ( 16 ).…”

Section: Introductionmentioning

confidence: 99%

TMPRSS2 and TMPRSS4 mediate SARS-CoV-2 infection of human small intestinal enterocytes

Zang

Castro

McCune

et al. 2020

Preprint

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Both gastrointestinal symptoms and fecal shedding of SARS-CoV-2 RNA have been frequently observed in COVID-19 patients. However, whether SARS-CoV-2 replicate in the human intestine and its clinical relevance to potential fecal-oral transmission remain unclear. Here, we demonstrate productive infection of SARS-CoV-2 in ACE2+ mature enterocytes in human small intestinal enteroids. In addition to TMPRSS2, another mucosa-specific serine protease, TMPRSS4, also enhanced SARS-CoV-2 spike fusogenic activity and mediated viral entry into host cells. However, newly synthesized viruses released into the intestinal lumen were rapidly inactivated by human colonic fluids and no infectious virus was recovered from the stool specimens of COVID-19 patients. Our results highlight the intestine as a potential site of SARS-CoV-2 replication, which may contribute to local and systemic illness and overall disease progression.

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Evidence for gastrointestinal infection of SARS-CoV-2

Abstract: 62The new coronavirus (SARS-CoV-2) outbreak originating from Wuhan, China, poses 63 a threat to global health. While it's evident that the virus invades respiratory tract and 64 transmits from human to human through airway, other viral tropisms and transmission 65

Cited by 712 publications

References 9 publications

Atlas of ACE2 gene expression in mammals reveals novel insights in transmisson of SARS-Cov-2

Atlas of ACE2 gene expression in mammals reveals novel insights in transmisson of SARS-Cov-2

Clinical characteristics of the recovered COVID-19 patients with re-detectable positive RNA test

TMPRSS2 and TMPRSS4 mediate SARS-CoV-2 infection of human small intestinal enterocytes

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