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

Graham J Britton ,Saurabh Mehandru,Lauren Tal Grinspan,Matthew P Spindler,Adriana Van De Guchte,Alice Chen-Liaw,Sophia Siu,Gerold Bongers,Francesca Cossarini,Zenab Khan,Daisy A Hoagland,Rebekah E Dixon,Gustavo Martínez-Delgado ,Miriam Mérad ,Marla Dubinsky ,Fatima Amanat,Joseph Eggers,Ana S González-Reiche ,Michael Tankelevich,Ilaria Mogno,Alexandra E Livanos,Benjamin R Tenoever,Florian Krammer,Divya Jha,Tamar Plitt,Harm Van Bakel,Jeremiah J Faith

doi:10.1038/s41598-021-92740-9

Graham J Britton , Saurabh Mehandru + Show 25 more

Open Access

https://doi.org/10.1038/s41598-021-92740-9

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Journal: Scientific Reports	Publication Date: Jun 25, 2021
Citations: 54	License type: open-access

Affiliation: Icahn School of Medicine at Mount Sinai

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.

Highlights

SARS-CoV-2 (Severe Acute Respiratory Syndrome CoronaVirus 2) a novel Betacoronavirus that causes COVID19 (Coronavirus Disease 2019)) emerged in Wuhan, China December 20191 and rapidly spread, leading to a worldwide pandemic
We collected stool samples from 44 symptomatic COVID-19 patients hospitalized in New York City between April 15 and May 21 2020 (Table S1 and Date file S1)
During hospitalization 10 of the 22 (45.5%) patients who presented with moderate disease developed severe COVID-19 disease, while none of the patients who presented with mild symptoms had clinical worsening during hospitalization (Table 1 and Date file S1)

Summary

Introduction

SARS-CoV-2 (Severe Acute Respiratory Syndrome CoronaVirus 2) a novel Betacoronavirus that causes COVID19 (Coronavirus Disease 2019)) emerged in Wuhan, China December 20191 and rapidly spread, leading to a worldwide pandemic. 2 (ACE2), the putative receptor for SARS-CoV-2, is highly expressed on the small intestinal e pithelium[9,10] and viral RNA has been detected in the stools of patients with COVID-19 for prolonged periods of time[11,12]. Systemic immune dysregulation is associated with severe COVID-19 infection, as high serum interleukin (IL)-6 IL-8, IL-10 and tumor necrosis factor (TNFα) correlate with increased disease severity and poor prognoses[21,22,23,24,25,26]

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