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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
Dajana Cuicchi, Liliana Gabrielli, Maria Lucia Tardio, Giada Rossini, Antonietta D’Errico, Pierluigi Viale, Tiziana Lazzarotto, Gilberto Poggioli
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
ARTICLE HIGHLIGHTS
Research background
Although some observations provide evidence for intestinal infection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the mechanisms leading to this infection are not known.
Research motivation
The detection of viral RNA in gastrointestinal (GI) tissue samples has not been adequately investigated and results are conflicting. More GI tissue samples, comprehensive autopsy and surgical specimens are needed to provide histological evidence of intestinal infection.
Research objectives
Intestinal mucosal samples from mild-moderate coronavirus disease 2019 (COVID-19) patients were analyzed with the primary objective of detecting SARS-CoV-2 RNA and evaluating histological features.
Research methods
This is a monocentric trial in which real time reverse transcriptase-polymerase chain reaction and histological features were used to detect SARS-CoV-2 RNA in intestinal mucosal samples. The study population was composed of two groups of patients hospitalized for COVID-19. In the first group (biopsy group), the patients were eligible for inclusion if they had mild to moderate disease and if they agreed to have a rectal biopsy regardless of the presence or absence of GI symptoms; in the second group (surgical specimen group), patients were eligible for inclusion if they underwent intestinal resection during index hospitalization. The data obtained in this study are valuable because rectal biopsies were carried out on 30 patients who did not need the procedure to frame their disease status. The study therefore provides data that are not only more numerous but also qualitatively different from those available up to now.
Research results
Overall, we analyzed 53 rectal biopsies and 6 surgical specimens. 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. 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.
Research conclusions
Mild-moderate COVID-19 may not be associated with rectal infection by the virus. Although the present data are unable to support the observations suggesting that enteric infection can occur in COVID-19 patients, the detection of the viral RNA observed and the inflammatory cell infiltration to the colonic tissue of patients with active cancer could serve as hypothesis generators, leading to the analyzing more comprehensive autopsy or surgical specimens in order to assess the potential link between SARS-CoV-2 and enteric infections in this population.
Research perspectives
Does intestinal infection lead to increased expression of inflammatory cytokines in the intestine and/or serum? Since the two positive samples were both from patients with active cancer, could a weakened immune system, induced by the neoplastic disease, increase the risk of the intestinal infection of SARS-CoV-2?
