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

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Abstract

We sought to characterize the role of the gastrointestinal immune system in the pathogenesis of the inflammatory response associated with COVID-19. We measured cytokines, inflammatory markers, viral RNA, microbiome composition and antibody responses in stool 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.

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Trimmomatic: a flexible trimmer for Illumina sequence data

Anthony M. Bolger, Marc Lohse, Bjoern Usadel (2014)

Motivation: Although many next-generation sequencing (NGS) read preprocessing tools already existed, we could not find any tool or combination of tools that met our requirements in terms of flexibility, correct handling of paired-end data and high performance. We have developed Trimmomatic as a more flexible and efficient preprocessing tool, which could correctly handle paired-end data. Results: The value of NGS read preprocessing is demonstrated for both reference-based and reference-free tasks. Trimmomatic is shown to produce output that is at least competitive with, and in many cases superior to, that produced by other tools, in all scenarios tested. Availability and implementation: Trimmomatic is licensed under GPL V3. It is cross-platform (Java 1.5+ required) and available at http://www.usadellab.org/cms/index.php?page=trimmomatic Contact: usadel@bio1.rwth-aachen.de Supplementary information: Supplementary data are available at Bioinformatics online.

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A pneumonia outbreak associated with a new coronavirus of probable bat origin

Peng Zhou, Xing-Lou Yang, Xian-Guang Wang … (2020)

Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.

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DADA2: High resolution sample inference from Illumina amplicon data

Benjamin J. Callahan, Paul McMurdie, Michael Rosen … (2016)

We present DADA2, a software package that models and corrects Illumina-sequenced amplicon errors. DADA2 infers sample sequences exactly, without coarse-graining into OTUs, and resolves differences of as little as one nucleotide. In several mock communities DADA2 identified more real variants and output fewer spurious sequences than other methods. We applied DADA2 to vaginal samples from a cohort of pregnant women, revealing a diversity of previously undetected Lactobacillus crispatus variants.

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Author and article information

Journal

Journal ID (nlm-ta): medRxiv

Journal ID (publisher-id): MEDRXIV

Title: medRxiv

Publisher: Cold Spring Harbor Laboratory

Publication date (Electronic): 09 December 2020

Electronic Location Identifier: 2020.09.03.20183947

Affiliations

[1 ]Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029

[2 ]Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029

[3 ]Division of Infectious Disease, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029

[4 ]The Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029

[5 ]Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029

[6 ]Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029

[7 ]Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, 10029

[8 ]Virus Engineering Center for Therapeutics and Research, Icahn School of Medicine at Mount Sinai, New York, NY 10029

[9 ]Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

Author notes

Author contributions: G.J.B.; study concept and design; acquisition of data; analysis and interpretation of data; statistical analysis; drafting of the manuscript, A.C-L.; study concept and design; acquisition of data; analysis and interpretation of data; statistical analysis; drafting of the manuscript, F.C.; study concept and design; acquisition of data; analysis and interpretation of data; statistical analysis; drafting of the manuscript, A.E.L.; study concept and design; acquisition of data; analysis and interpretation of data; statistical analysis; drafting of the manuscript, M.P.S.; study concept and design; acquisition of data; analysis and interpretation of data; statistical analysis; drafting of the manuscript, T.P.; acquisition of data, J.E.; acquisition of data, I.M.; acquisition of data, A.S.G-R.; acquisition of data; analysis and interpretation of data;, S.S.; acquisition of data, M.T.; acquisition of data, L.T.G.; acquisition of data, R.E.D; acquisition of data, D.J.; acquisition of data, A.v.d.G.; acquisition of data, Z.K.; acquisition of data, G.M-D.; acquisition of data, F.A.; technical, or material support;, D.A.H.; technical, or material support;, B.R.T.; technical, or material support, M.C.D.; technical, or material support;, M.M.; technical, or material support, H.v.B.; study supervision; technical, or material support;, F.K. study supervision; technical, or material support;, G.B.; acquisition of data; analysis and interpretation of data; statistical analysis; study concept and design, S.M.; study supervision; study concept and design; analysis and interpretation of data;, J.J.F.; study supervision; study concept and design; analysis and interpretation of data.

[†]

Equal contribution as first author (listed alphabetically)

[‡]

Equal contribution as senior author

[* ]To whom correspondence should be addressed: Jeremiah J. Faith, jeremiah.faith@ 123456mssm.edu or Saurabh Mehandru, saurabh.mehandru@ 123456mssm.edu

Article

DOI: 10.1101/2020.09.03.20183947

PMC ID: 7480054

PubMed ID: 32909002

SO-VID: de60c3a6-30b2-418d-8e19-b4e9f07cda8d

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This work is licensed under a Creative Commons Attribution 4.0 International License, which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.

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

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Abstract

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Novel Coronavirus Disease COVID-19

Most cited references 61

Trimmomatic: a flexible trimmer for Illumina sequence data

A pneumonia outbreak associated with a new coronavirus of probable bat origin

DADA2: High resolution sample inference from Illumina amplicon data

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