Limited intestinal inflammation despite diarrhea, fecal viral RNA and SARS-CoV-2-specific IgA in patients with acute COVID-19

Abstract Gastrointestinal symptoms are common in COVID-19 patients but the nature of the gut immune response to SARS-CoV-2 remains poorly characterized, partly due to the difficulty of obtaining biopsy specimens from infected individuals. In lieu of tissue samples, we measured cytokines, inflammator...

Full description

Bibliographic Details
Main Authors: Graham J. Britton, Alice Chen-Liaw, Francesca Cossarini, Alexandra E. Livanos, Matthew P. Spindler, Tamar Plitt, Joseph Eggers, Ilaria Mogno, Ana S. Gonzalez-Reiche, Sophia Siu, Michael Tankelevich, Lauren Tal Grinspan, Rebekah E. Dixon, Divya Jha, Adriana van de Guchte, Zenab Khan, Gustavo Martinez-Delgado, Fatima Amanat, Daisy A. Hoagland, Benjamin R. tenOever, Marla C. Dubinsky, Miriam Merad, Harm van Bakel, Florian Krammer, Gerold Bongers, Saurabh Mehandru, Jeremiah J. Faith
Format: Article
Language:English
Published: Nature Publishing Group 2021-06-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-92740-9
id doaj-d6c31edc6052419cbb41e75506d8cb06
record_format Article
spelling doaj-d6c31edc6052419cbb41e75506d8cb062021-06-27T11:33:59ZengNature Publishing GroupScientific Reports2045-23222021-06-0111111310.1038/s41598-021-92740-9Limited intestinal inflammation despite diarrhea, fecal viral RNA and SARS-CoV-2-specific IgA in patients with acute COVID-19Graham J. Britton0Alice Chen-Liaw1Francesca Cossarini2Alexandra E. Livanos3Matthew P. Spindler4Tamar Plitt5Joseph Eggers6Ilaria Mogno7Ana S. Gonzalez-Reiche8Sophia Siu9Michael Tankelevich10Lauren Tal Grinspan11Rebekah E. Dixon12Divya Jha13Adriana van de Guchte14Zenab Khan15Gustavo Martinez-Delgado16Fatima Amanat17Daisy A. Hoagland18Benjamin R. tenOever19Marla C. Dubinsky20Miriam Merad21Harm van Bakel22Florian Krammer23Gerold Bongers24Saurabh Mehandru25Jeremiah J. Faith26Precision Immunology Institute, Icahn School of Medicine at Mount SinaiPrecision Immunology Institute, Icahn School of Medicine at Mount SinaiPrecision Immunology Institute, Icahn School of Medicine at Mount SinaiPrecision Immunology Institute, Icahn School of Medicine at Mount SinaiPrecision Immunology Institute, Icahn School of Medicine at Mount SinaiPrecision Immunology Institute, Icahn School of Medicine at Mount SinaiDepartment of Oncological Sciences, Icahn School of Medicine at Mount SinaiPrecision Immunology Institute, Icahn School of Medicine at Mount SinaiIcahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount SinaiPrecision Immunology Institute, Icahn School of Medicine at Mount SinaiPrecision Immunology Institute, Icahn School of Medicine at Mount SinaiThe Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount SinaiThe Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount SinaiPrecision Immunology Institute, Icahn School of Medicine at Mount SinaiIcahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount SinaiIcahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount SinaiPrecision Immunology Institute, Icahn School of Medicine at Mount SinaiDepartment of Microbiology, Icahn School of Medicine at Mount SinaiDepartment of Microbiology, Icahn School of Medicine at Mount SinaiDepartment of Microbiology, Icahn School of Medicine at Mount SinaiThe Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount SinaiPrecision Immunology Institute, Icahn School of Medicine at Mount SinaiIcahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount SinaiDepartment of Microbiology, Icahn School of Medicine at Mount SinaiDepartment of Oncological Sciences, Icahn School of Medicine at Mount SinaiPrecision Immunology Institute, Icahn School of Medicine at Mount SinaiPrecision Immunology Institute, Icahn School of Medicine at Mount SinaiAbstract Gastrointestinal symptoms are common in COVID-19 patients but the nature of the gut immune response to SARS-CoV-2 remains poorly characterized, partly due to the difficulty of obtaining biopsy specimens from infected individuals. In lieu of tissue samples, we measured cytokines, inflammatory markers, viral RNA, microbiome composition, and antibody responses in stool samples from a cohort of 44 hospitalized COVID-19 patients. SARS-CoV-2 RNA was detected in stool of 41% of patients and more frequently in patients with diarrhea. Patients who survived had lower fecal viral RNA than those who died. Strains isolated from stool and nasopharynx of an individual were the same. Compared to uninfected controls, COVID-19 patients had higher fecal levels of IL-8 and lower levels of fecal IL-10. Stool IL-23 was higher in patients with more severe COVID-19 disease, and we found evidence of intestinal virus-specific IgA responses associated with more severe disease. We provide evidence for an ongoing humeral immune response to SARS-CoV-2 in the gastrointestinal tract, but little evidence of overt inflammation.https://doi.org/10.1038/s41598-021-92740-9
collection DOAJ
language English
format Article
sources DOAJ
author Graham J. Britton
Alice Chen-Liaw
Francesca Cossarini
Alexandra E. Livanos
Matthew P. Spindler
Tamar Plitt
Joseph Eggers
Ilaria Mogno
Ana S. Gonzalez-Reiche
Sophia Siu
Michael Tankelevich
Lauren Tal Grinspan
Rebekah E. Dixon
Divya Jha
Adriana van de Guchte
Zenab Khan
Gustavo Martinez-Delgado
Fatima Amanat
Daisy A. Hoagland
Benjamin R. tenOever
Marla C. Dubinsky
Miriam Merad
Harm van Bakel
Florian Krammer
Gerold Bongers
Saurabh Mehandru
Jeremiah J. Faith
spellingShingle Graham J. Britton
Alice Chen-Liaw
Francesca Cossarini
Alexandra E. Livanos
Matthew P. Spindler
Tamar Plitt
Joseph Eggers
Ilaria Mogno
Ana S. Gonzalez-Reiche
Sophia Siu
Michael Tankelevich
Lauren Tal Grinspan
Rebekah E. Dixon
Divya Jha
Adriana van de Guchte
Zenab Khan
Gustavo Martinez-Delgado
Fatima Amanat
Daisy A. Hoagland
Benjamin R. tenOever
Marla C. Dubinsky
Miriam Merad
Harm van Bakel
Florian Krammer
Gerold Bongers
Saurabh Mehandru
Jeremiah J. Faith
Limited intestinal inflammation despite diarrhea, fecal viral RNA and SARS-CoV-2-specific IgA in patients with acute COVID-19
Scientific Reports
author_facet Graham J. Britton
Alice Chen-Liaw
Francesca Cossarini
Alexandra E. Livanos
Matthew P. Spindler
Tamar Plitt
Joseph Eggers
Ilaria Mogno
Ana S. Gonzalez-Reiche
Sophia Siu
Michael Tankelevich
Lauren Tal Grinspan
Rebekah E. Dixon
Divya Jha
Adriana van de Guchte
Zenab Khan
Gustavo Martinez-Delgado
Fatima Amanat
Daisy A. Hoagland
Benjamin R. tenOever
Marla C. Dubinsky
Miriam Merad
Harm van Bakel
Florian Krammer
Gerold Bongers
Saurabh Mehandru
Jeremiah J. Faith
author_sort Graham J. Britton
title Limited intestinal inflammation despite diarrhea, fecal viral RNA and SARS-CoV-2-specific IgA in patients with acute COVID-19
title_short Limited intestinal inflammation despite diarrhea, fecal viral RNA and SARS-CoV-2-specific IgA in patients with acute COVID-19
title_full Limited intestinal inflammation despite diarrhea, fecal viral RNA and SARS-CoV-2-specific IgA in patients with acute COVID-19
title_fullStr Limited intestinal inflammation despite diarrhea, fecal viral RNA and SARS-CoV-2-specific IgA in patients with acute COVID-19
title_full_unstemmed Limited intestinal inflammation despite diarrhea, fecal viral RNA and SARS-CoV-2-specific IgA in patients with acute COVID-19
title_sort limited intestinal inflammation despite diarrhea, fecal viral rna and sars-cov-2-specific iga in patients with acute covid-19
publisher Nature Publishing Group
series Scientific Reports
issn 2045-2322
publishDate 2021-06-01
description Abstract Gastrointestinal symptoms are common in COVID-19 patients but the nature of the gut immune response to SARS-CoV-2 remains poorly characterized, partly due to the difficulty of obtaining biopsy specimens from infected individuals. In lieu of tissue samples, we measured cytokines, inflammatory markers, viral RNA, microbiome composition, and antibody responses in stool samples from a cohort of 44 hospitalized COVID-19 patients. SARS-CoV-2 RNA was detected in stool of 41% of patients and more frequently in patients with diarrhea. Patients who survived had lower fecal viral RNA than those who died. Strains isolated from stool and nasopharynx of an individual were the same. Compared to uninfected controls, COVID-19 patients had higher fecal levels of IL-8 and lower levels of fecal IL-10. Stool IL-23 was higher in patients with more severe COVID-19 disease, and we found evidence of intestinal virus-specific IgA responses associated with more severe disease. We provide evidence for an ongoing humeral immune response to SARS-CoV-2 in the gastrointestinal tract, but little evidence of overt inflammation.
url https://doi.org/10.1038/s41598-021-92740-9
work_keys_str_mv AT grahamjbritton limitedintestinalinflammationdespitediarrheafecalviralrnaandsarscov2specificigainpatientswithacutecovid19
AT alicechenliaw limitedintestinalinflammationdespitediarrheafecalviralrnaandsarscov2specificigainpatientswithacutecovid19
AT francescacossarini limitedintestinalinflammationdespitediarrheafecalviralrnaandsarscov2specificigainpatientswithacutecovid19
AT alexandraelivanos limitedintestinalinflammationdespitediarrheafecalviralrnaandsarscov2specificigainpatientswithacutecovid19
AT matthewpspindler limitedintestinalinflammationdespitediarrheafecalviralrnaandsarscov2specificigainpatientswithacutecovid19
AT tamarplitt limitedintestinalinflammationdespitediarrheafecalviralrnaandsarscov2specificigainpatientswithacutecovid19
AT josepheggers limitedintestinalinflammationdespitediarrheafecalviralrnaandsarscov2specificigainpatientswithacutecovid19
AT ilariamogno limitedintestinalinflammationdespitediarrheafecalviralrnaandsarscov2specificigainpatientswithacutecovid19
AT anasgonzalezreiche limitedintestinalinflammationdespitediarrheafecalviralrnaandsarscov2specificigainpatientswithacutecovid19
AT sophiasiu limitedintestinalinflammationdespitediarrheafecalviralrnaandsarscov2specificigainpatientswithacutecovid19
AT michaeltankelevich limitedintestinalinflammationdespitediarrheafecalviralrnaandsarscov2specificigainpatientswithacutecovid19
AT laurentalgrinspan limitedintestinalinflammationdespitediarrheafecalviralrnaandsarscov2specificigainpatientswithacutecovid19
AT rebekahedixon limitedintestinalinflammationdespitediarrheafecalviralrnaandsarscov2specificigainpatientswithacutecovid19
AT divyajha limitedintestinalinflammationdespitediarrheafecalviralrnaandsarscov2specificigainpatientswithacutecovid19
AT adrianavandeguchte limitedintestinalinflammationdespitediarrheafecalviralrnaandsarscov2specificigainpatientswithacutecovid19
AT zenabkhan limitedintestinalinflammationdespitediarrheafecalviralrnaandsarscov2specificigainpatientswithacutecovid19
AT gustavomartinezdelgado limitedintestinalinflammationdespitediarrheafecalviralrnaandsarscov2specificigainpatientswithacutecovid19
AT fatimaamanat limitedintestinalinflammationdespitediarrheafecalviralrnaandsarscov2specificigainpatientswithacutecovid19
AT daisyahoagland limitedintestinalinflammationdespitediarrheafecalviralrnaandsarscov2specificigainpatientswithacutecovid19
AT benjaminrtenoever limitedintestinalinflammationdespitediarrheafecalviralrnaandsarscov2specificigainpatientswithacutecovid19
AT marlacdubinsky limitedintestinalinflammationdespitediarrheafecalviralrnaandsarscov2specificigainpatientswithacutecovid19
AT miriammerad limitedintestinalinflammationdespitediarrheafecalviralrnaandsarscov2specificigainpatientswithacutecovid19
AT harmvanbakel limitedintestinalinflammationdespitediarrheafecalviralrnaandsarscov2specificigainpatientswithacutecovid19
AT floriankrammer limitedintestinalinflammationdespitediarrheafecalviralrnaandsarscov2specificigainpatientswithacutecovid19
AT geroldbongers limitedintestinalinflammationdespitediarrheafecalviralrnaandsarscov2specificigainpatientswithacutecovid19
AT saurabhmehandru limitedintestinalinflammationdespitediarrheafecalviralrnaandsarscov2specificigainpatientswithacutecovid19
AT jeremiahjfaith limitedintestinalinflammationdespitediarrheafecalviralrnaandsarscov2specificigainpatientswithacutecovid19
_version_ 1721357697896415232