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

Zang, Ruochen; Castro, María Florencia Gómez; McCune, Broc T.; Zeng, Qiru; Rothlauf, Paul W.; Sonnek, Naomi; Liu, Zhuoming; Brulois, Kevin; Wang, Xin; Greenberg, Harry B.; Diamond, Michael S.; Ciorba, Matthew A.; Whelan, Sean P. J.; Ding, Siyuan

doi:10.1101/2020.04.21.054015

Cited by 63 publications

(49 citation statements)

References 56 publications

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“…In addition to respiratory disease, COVID-19 patients frequently develop gastrointestinal symptoms, which is in keeping with the high expression of TMPRSS2 and ACE2 documented in enterocytes [8]. Furthermore, the SARS-CoV-2 antigen was found post mortem in the spleen and lymph nodes with pathological signs of damage.…”

Section: Introductionmentioning

confidence: 55%

Infection of human lymphomononuclear cells by SARS-CoV-2

Pontelli

Castro

Martins

et al. 2020

Preprint

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Although SARS-CoV-2 severe infection is associated with a hyperinflammatory state, lymphopenia is an immunological hallmark, and correlates with poor prognosis in COVID-19. However, it remains unknown if circulating human lymphocytes and monocytes are susceptible to SARS-CoV-2 infection. In this study, SARS-CoV-2 infection of human peripheral blood mononuclear cells (PBMCs) was investigated both in vitro and in vivo. We found that in vitro infection of whole PBMCs from healthy donors was productive of virus progeny. Results revealed that monocytes, as well as B and T lymphocytes, are susceptible to SARS-CoV-2 active infection and viral replication was indicated by detection of double-stranded RNA. Moreover, flow cytometry and immunofluorescence analysis revealed that SARS-CoV-2 was frequently detected in monocytes and B lymphocytes from COVID-19 patients, and less frequently in CD4+T lymphocytes. The rates of SARS-CoV-2-infected monocytes in PBMCs from COVID-19 patients increased over time from symptom onset. Additionally, SARS-CoV-2-positive monocytes and B and CD4+T lymphocytes were detected by immunohistochemistry in post mortem lung tissue. SARS-CoV-2 infection of blood circulating leukocytes in COVID-19 patients may have important implications for disease pathogenesis, immune dysfunction, and virus spread within the host.

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Section: Introductionmentioning

confidence: 55%

Infection of human lymphomononuclear cells by SARS-CoV-2

Pontelli

Castro

Martins

et al. 2020

Preprint

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“…45 TMPRSS2 and TMPRSS4 mediate infection of small intestinal epithelial cells. 47 These enzymes might additionally be an interesting target for therapeutic intervention, since a clinically approved protease inhibitor is available. 7 Less is known regarding the gastrointestinal distribution of CD147.…”

Section: From Oral To Rectal Mucosa: What We Know About the Involvementioning

confidence: 99%

Immunology of COVID‐19: Mechanisms, clinical outcome, diagnostics, and perspectives—A report of the European Academy of Allergy and Clinical Immunology (EAACI)

Sokołowska

Łukasik

Agache

et al. 2020

Allergy

145

158

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With the worldwide spread of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) resulting in declaration of a pandemic by the World Health Organization (WHO) on March 11, 2020, the SARS-CoV-2-induced coronavirus disease-19 (COVID-19) has become one of the main challenges of our times. The high infection rate and the severe disease course led to major safety and social restriction measures worldwide. There is an urgent need of unbiased expert knowledge guiding the development of efficient treatment and prevention strategies. This report summarizes current immunological data on mechanisms associated with the SARS-CoV-2 infection and COVID-19 development and progression to the most severe forms. We characterize the differences between adequate innate and adaptive immune response in mild disease and the deep immune dysfunction in the severe multiorgan disease. The similarities of the human immune response to SARS-CoV-2 and the SARS-CoV and MERS-CoV are underlined. We also summarize known and potential SARS-CoV-2 receptors on epithelial barriers, immune cells, endothelium and clinically involved organs such as lung, gut, kidney, cardiovascular, and neuronal system. Finally, we discuss the known and potential mechanisms underlying the involvement of comorbidities, gender, and age in development of COVID-19. Consequently, we highlight the knowledge gaps and urgent research requirements to provide a quick roadmap for ongoing and needed COVID-19 studies.

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“…2). These variations especially include inflammation and immune response regulation [10,11,[13][14][15][16][17]19,24,27,29,31,32,[46][47][48][49][50][51][52][53]. Furthermore, increased expression of ACE2 and TMPRSS2 may contribute to complications in the heart, lungs, and different organs of the nervous system [47,54].…”

Section: Genetic Alterations In Covid-19mentioning

confidence: 99%

The potential of JAK/STAT pathway inhibition by ruxolitinib in the treatment of COVID-19

Bağca

Avcı

2020

Cytokine & Growth Factor Reviews

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Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

show abstract

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

Cited by 63 publications

References 56 publications

Infection of human lymphomononuclear cells by SARS-CoV-2

Infection of human lymphomononuclear cells by SARS-CoV-2

Immunology of COVID‐19: Mechanisms, clinical outcome, diagnostics, and perspectives—A report of the European Academy of Allergy and Clinical Immunology (EAACI)

The potential of JAK/STAT pathway inhibition by ruxolitinib in the treatment of COVID-19

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