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©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
Virological and histological evaluation of intestinal samples in COVID-19 patients
Gilberto Poggioli, Tiziana Lazzarotto, Pierluigi Viale, Antonietta D’Errico, Giada Rossini, Maria Lucia Tardio, Liliana Gabrielli, Dajana Cuicchi
Dajana Cuicchi, Gilberto Poggioli, Department of Medical and Surgical Sciences, Surgery of the Alimentary Tract, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
Liliana Gabrielli, Giada Rossini, Tiziana Lazzarotto, Department of Experimental, Diagnostic and Specialty Medicine, Microbiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
Maria Lucia Tardio, Antonietta D’Errico, Department of Experimental, Diagnostic and Specialty Medicine, Pathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
Pierluigi Viale, Department for Integrated Infectious Risk Management, Infectious Diseases Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
Pierluigi Viale, Infectious Diseases Unit, Department for Integrated Infectious Risk Management, University of Bologna, Bologna 40138, Italy
Tiziana Lazzarotto, Section of Microbiology, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna 40138, Italy
Gilberto Poggioli, Department of Medical and Surgical Sciences, University of Bologna, Bologna 40138, Italy
Author contributions: Lazzarotto T and Poggioli G contributed equally to this work. Cuicchi D, Lazzarotto T, D’Errico A and Poggioli G participated in the conceptualization and design of the study; Cuicchi D collected data and carried out the initial analyses; Cuicchi D, Gabrielli L and Tardio ML drafted the initial manuscript; Gabrielli L and Rossini G carried out the virological evaluation; Tardio ML, D’Errico A and Poggioli G carried out the histological evaluation; D’Errico A, Poggioli G and Lazzarotto T made substantial contributions to all aspects of the writing of the manuscript, which included contribution to conception, design, analysis and interpretation of the article; Lazzarotto T contributed to the review and revision of the manuscript; Poggioli G interpreted data, reviewed and revised the manuscript, and supervised and provided mentorship throughout all stages of the project and writing of the manuscript; and all authors approved the final version to be submitted.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of the Azienda Ospedaliero-Universitaria di Bologna, Italy (Approval No. 2257/2020).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All the authors report having no relevant conflicts of interest for this article.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at
dajana.cuicchi@aosp.bo.it. Participants gave informed consent for data sharing in anonymized form.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Dajana Cuicchi, MD, PhD, Surgeon, Department of Medical and Surgical Sciences, Surgery of the Alimentary Tract, IRCCS Azienda Ospedaliero-Universitaria di Bologna,
Via Massarenti 9, Bologna 40138, Italy.
dajana.cuicchi@aosp.bo.it
Received: September 2, 2022
Peer-review started: September 2, 2022
First decision: September 30, 2022
Revised: September 30, 2022
Accepted: November 17, 2022
Article in press: November 17, 2022
Published online: November 28, 2022
Processing time: 83 Days and 20.2 Hours
BACKGROUND
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the pathogen responsible for pandemic coronavirus disease 2019 (COVID-19). It is a highly contagious virus which primarily affects the respiratory tract, nevertheless, the lungs are not the only target organs of the virus. The intestinal tract could represent an additional tropism site for SARS-CoV-2. Several observations have collectively suggested that enteric infections can occur in COVID-19 patients. However, the detection of viral RNA in gastrointestinal (GI) tissue samples has not been adequately investigated and results are conflicting.
AIM
To detect the presence of SARS-CoV-2 RNA in intestinal mucosa samples and to evaluate histological features.
METHODS
The COVID-19 patients hospitalized at an Italian tertiary hospital from April 2020 to March 2021 were evaluated for enrollment in an observational, monocentric trial. The study population was composed of two groups of adult patients. In the first group (biopsy group, 30 patients), patients were eligible for inclusion if they had mild to moderate disease and if they agreed to have a rectal biopsy; in the second group (surgical specimen group, 6 patients), patients were eligible for inclusion if they underwent intestinal resection during index hospitalization. Fifty-nine intestinal mucosal samples were analyzed.
RESULTS
Viral RNA was not detectable in any of the rectal biopsies performed (0/53). Histological examination showed no enterocyte damage, but slight edema of the lamina propria with mild inflammatory lymphoplasmacytic infiltration. There was no difference in inflammatory infiltrates in patients with and without GI symptoms. SARS-CoV-2 RNA was detected in fecal samples in 6 cases out of 14 cases examined (42.9%). In the surgical specimen group, all patients underwent emergency intestinal resection. Viral RNA was detected in 2 surgical specimens of the 6 examined, both of which were from patients with active neoplastic disease. Histological examination also pointed out abundant macrophages, granulocytes and plasma cells infiltrating the muscular layer and adipose tissue, and focal vasculitis.
CONCLUSION
Mild-moderate COVID-19 may not be associated with rectal infection by the virus. More comprehensive autopsies or surgical specimens are needed to provide histological evidence of intestinal infection.
Core Tip: The detection of viral RNA in gastrointestinal tissue samples has not been adequately investigated. In this trial, 53 rectal biopsies and 6 surgical specimens from coronavirus disease 2019 patients were analyzed, with the primary objective of detecting severe acute respiratory syndrome coronavirus-2 RNA, using real time reverse transcriptase-polymerase chain reaction, and evaluating the histological features. Viral RNA was not detectable in any of the rectal biopsies performed (0/53). Histological examination of rectal biopsies showed no enterocyte damage, but mild inflammatory infiltration. Viral RNA was detected in 2 surgical specimens of the 6 examined, both of which were from patients with active neoplastic disease. Histological examination also pointed out mild inflammatory infiltration and focal vasculitis.
