Research ArticleCORONAVIRUS

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

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Science Immunology  13 May 2020:
Vol. 5, Issue 47, eabc3582
DOI: 10.1126/sciimmunol.abc3582

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  • RE: SARS-CoV-2 and Gastrointestinal pH

    Dear Editors,
    Zang et al. demonstrated that SARS-CoV-2 was rapidly inactivated by simulated human colonic fluid, and a limited number of viral RNA-positive fecal samples did not contain the infectious virus (1). This report needs to be carefully discussed, as it leads to the important conclusion of denying SARS-Cov-2 fecal infections. Two important issues are pointed out.
    Firstly, they used simulated colonic fluid at pH 7.8, but in humans, the pH of the colonic lumen does not persist at 7.8 for several hours. Studies until 2001 reported that the luminal pH of the colon and rectum was 6.1–7.5 (2), whereas the Smartpill measurements reported in 2015 showed a pH of 6.04–6.77 in the colon (3). Similarly, a study in 2015 using the Intellicap® system showed that the colonic pH varied between 5 and 8 (4).
    Secondly, SARS-CoV-2 was inactivated in a short time by simulated gastric fluid at pH 1.6. This suggests that in people with sufficient gastric acid production, the virus becomes inactive in the stomach, and the infectious virus does not reach the intestine even if the virus enters orally. Thus, in order to properly assess studies of intestinal mucosal infection, the mechanism by which SARS-CoV-2 is not inactivated by the gastric acid needs to be discussed. pH stability, especially in acidic conditions, is a common property of enteric viruses and is crucial for viral infection, since the virus must survive the stomach pH to reach the target cells in the...

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    Competing Interests: None declared.
  • RE: Risk of fecal-oral transmission in COVID-19 still remains inconclusive
    • Ashutosh Kumar, Clinical Researcher and Anatomist, Department of Anatomy, All India Institute of Medical Sciences (AIIMS), Patna, India
    • Other Contributors:
      • Muneeb A. Faiq, Clinical Researcher, New York University (NYU) Langone Health Center, NYU Robert I Grossman School of Medicine, New York, New York, USA
      • Maheswari Kulandhasamy, Clinical Biochemist, Department of Biochemistry, Maulana Azad Medical College (MAMC), New Delhi, India
      • Kamla Kant, Clinical Microbiologist, Department of Microbiology, All India Institute of Medical Sciences (AIIMS), Bathinda, India
      • Chiman Kumari, Clinical Researcher and Anatomist, Department of Anatomy, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
      • Vikas Pareek, Clinical Researcher & Pharmacist, National Brain Research Center, Manesar, Haryana, India
      • Ravi Kant Narayan, Clinical Researcher and Anatomist, Department of Anatomy, All India Institute of Medical Sciences (AIIMS), Patna, India

    Dear Editor,
    We read with interest the important paper by Zang et al who reported their observations for rapid inactivation of SARS-CoV-2 in the human gastro-intestinal tract (GIT) and absence of any infectious virus in the feces of the infected patients (1). Though the study is a collection of certain coherent experiments, but their observations are highly speculative and have led them to unsubstantiated conclusions. In this communication, we wish to present our arguments against the observations and conclusions reported in this study.
    Zang et al investigated, in vitro, the stability of a recombinant SARS-CoV-2 mNeonGreen reporter virus in the fasted simulated gut fluid (Gastric Fluid/FaSSGF, pH 1.6, Intestinal Fluid/FaSSIF-V2, pH 6.5, and Colonic Fluid/FaSSCoF, pH 7.8). They used as control Rotavirus - a double-stranded RNA virus in which fecal-oral transmission is well established. They showed that SARS-CoV-2 lost infectivity in the low pH simulated gastric fluid 10 min post-incubation. However, there was residual virus in simulated human small intestinal fluid but was inactivated by certain components in the simulated human colonic fluids. As per their report, the virus titers decreased by 5-fold within 1 hour, and virus was undetectable after 24-hours of incubation. In contrast, rotavirus remained stable in all simulated gastric and enteric fluids they tested. A difference of result between intestinal and colonic simulation fluid, they concluded, might hav...

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    Competing Interests: None declared.

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