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COVID-19 and Gastrointestinal Symptoms

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A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Coronaviruses".

Deadline for manuscript submissions: closed (25 February 2024) | Viewed by 16579

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Dr. Christian Albert Devaux

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1. Unité de Recherche Microbe Phylogeny and Evoluition (MEPHI), Institut de Recherche pour le Développement (IRD), Assistance Publique—Hôpitaux de Marseille (AP-HM), Aix-Marseille Université, 27 Boulevard Jean Moulin, 13005 Marseille, France
2. Department of Biological Sciences, Centre National de la Recherche Scientifique (CNRS)-SNC5039, Marseille, France
Interests: infectious diseases; SARS-CoV-2; ACE2; COVID-19 physiopathology; enterocytes; intercellular junctions; long COVID-19

Special Issue Information

Dear Colleagues,

Common symptoms associated with the SARS-CoV-2 infection are fever, cough, and shortness of breath. Due to the huge mobilization of the clinical teams to prevent and treat cases of patients with silent or severe hypoxia after SARS-CoV-2 infection, the study of intestinal disorders has often been considered secondary and has attracted too few research teams. However, gastrointestinal symptoms such as abdominal pain, nausea, vomiting, and diarrhea, are among the most commonly reported extrapulmonary clinical features of SARS-CoV-2 infections. The viral receptor ACE2 was found in the small intestine with the highest expression observed in the brush border of intestinal enterocytes where it functions as a chaperone for the expression of the neutral amino acid transporter B0AT1 and forms a complex with the aminopeptidase N. SARS-CoV-2 has been found able to replicate in the intestine and to impair the gastrointestinal barrier integrity. The virus was also identified in the stool.

In this Special Issue, we will focus on important questions to be answered about the route of infection of intestinal cells (e.g., animal models, full genome sequencing of intestinal strains of SARS-CoV-2 versus pulmonary isolates, viral tropism, structure and function of intestinal ACE2, clinical aspects), and the physio-pathological consequences of the infection of these cells (e.g., the virulence of SARS-CoV-2 intestinal isolates, micro-damage to the epithelium barrier, modulation in the diversity of bacterial species present in the GIT, deregulation of the immune response, pro-inflammation, invasion of distant host organs/tissues). The association of SARS-CoV-2 at the intestinal level with post-acute COVID-19 (also called long COVID-19), suggesting that the intestine could serve as a post-COVID-19 reservoir of SARS-CoV-2, is also a major scope of this Special Issue.

Priority will be given to original research papers but reviews will also be considered for publication.

Dr. Christian Albert Devaux
Guest Editor

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Keywords

COVID-19
route of infection
enterocytes infection
long COVID-19
physiopathology

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Published Papers (7 papers)

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Research

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14 pages, 16165 KiB

Open AccessArticle

Gut Microbiome and Cytokine Profiles in Post-COVID Syndrome

by Karakoz Mussabay, Samat Kozhakhmetov, Marat Dusmagambetov, Aitolkyn Mynzhanova, Madiyar Nurgaziyev, Zharkyn Jarmukhanov, Elizaveta Vinogradova, Aigul Dusmagambetova, Aiganym Daulbaeva, Laura Chulenbayeva, Ainur Tauekelova, Makhabbat Bekbossynova and Almagul Kushugulova

Viruses 2024, 16(5), 722; https://doi.org/10.3390/v16050722 - 2 May 2024

Cited by 2 | Viewed by 1958

Abstract

Recent studies highlight the crucial role of the gut microbiome in post-infectious complications, especially in patients recovering from severe COVID-19. Our research aimed to explore the connection between gut microbiome changes and the cytokine profile of patients with post-COVID syndrome. Using 16S rRNA amplicon sequencing, we analyzed the composition of the gut microbiome in 60 COVID-19 patients over the course of one year. We also measured the levels of serum cytokines and chemokines using the Milliplex system. Our results showed that severe SARS-CoV-2 infection cases, especially those complicated by pneumonia, induce a pro-inflammatory microbial milieu with heightened presence of Bacteroides, Faecalibacterium, and Prevotella_9. Furthermore, we found that post-COVID syndrome is characterized by a cross-correlation of various cytokines and chemokines MDC, IL-1b, Fractalkine, TNFa, FGF-2, EGF, IL-1RA, IFN-a2, IL-10, sCD40L, IL-8, Eotaxin, IL-12p40, and MIP-1b as well as a shift in the gut microbiome towards a pro-inflammatory profile. At the functional level, our analysis revealed associations with post-COVID-19 in homolactic fermentation, pentose phosphate, NAD salvage, and flavin biosynthesis. These findings highlight the intricate interplay between the gut microbiota, their metabolites, and systemic cytokines in shaping post-COVID symptoms. Unraveling the gut microbiome’s role in post-infectious complications opens avenues for new treatments for those patients with prolonged symptoms. Full article

(This article belongs to the Special Issue COVID-19 and Gastrointestinal Symptoms)

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12 pages, 3660 KiB

Open AccessArticle

Infectious SARS-CoV-2 Particles from Rectal Swab Samples from COVID-19 Patients in Brazil

by Ieda Pereira Ribeiro, Lilian Gonçalves do Nascimento, Luis Fernando Lopez Tort, Elisa Cavalcante Pereira, Lidiane Souza Raphael Menezes, Fabio Correia Malta, Barbara Cristina Euzebio Pereira Dias de Oliveira, João Paulo Rodrigues, Pedro Paulo de Abreu Manso, Marcelo Pelajo, Myrna Cristina Bonaldo, Paola Cristina Resende Silva, Marilda Mendonça Siqueira, Patricia Brasil and Tulio Machado Fumian

Viruses 2023, 15(5), 1152; https://doi.org/10.3390/v15051152 - 11 May 2023

Cited by 3 | Viewed by 2069

Abstract

The main objective of this study was to investigate the dynamic of SARS-CoV-2 viral excretion in rectal swab (RS), saliva, and nasopharyngeal swab (NS) samples from symptomatic patients and asymptomatic contacts. In addition, in order to evaluate the replication potential of SARS-CoV-2 in the gastrointestinal (GI) tract and the excretion of infectious SARS-CoV-2 from feces, we investigated the presence of subgenomic nucleoprotein gene (N) mRNA (sgN) in RS samples and cytopathic effects in Vero cell culture. A prospective cohort study was performed to collect samples from symptomatic patients and contacts in Rio de Janeiro, Brazil, from May to October 2020. One hundred and seventy-six patients had samples collected at home visits and/or during the follow up, resulting in a total of 1633 RS, saliva, or NS samples. SARS-CoV-2 RNA was detected in 130 (73.9%) patients who had at least one sample that tested positive for SARS-CoV-2. The presence of replicating SARS-CoV-2 in RS samples, measured by the detection of sgN mRNA, was successfully achieved in 19.4% (6/31) of samples, whilst infectious SARS-CoV-2, measured by the generation of cytopathic effects in cell culture, was identified in only one RS sample. Although rare, our results demonstrated the replication capacity of SARS-CoV-2 in the GI tract, and infectious viruses in one RS sample. There is still a gap in the knowledge regarding SARS-CoV-2 fecal–oral transmission. Additional studies are warranted to investigate fecal or wastewater exposure as a risk factor for transmission in human populations. Full article

(This article belongs to the Special Issue COVID-19 and Gastrointestinal Symptoms)

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13 pages, 1232 KiB

Open AccessArticle

Trajectory of Gastrointestinal Symptoms in Previously Hospitalized COVID-19 Survivors: The Long COVID Experience Multicenter Study

by César Fernández-de-las-Peñas, Juan Torres-Macho, Carlos Guijarro, José D. Martín-Guerrero, Oscar J. Pellicer-Valero and Gustavo Plaza-Manzano

Viruses 2023, 15(5), 1134; https://doi.org/10.3390/v15051134 - 10 May 2023

Cited by 6 | Viewed by 2841

Abstract

This multicenter cohort study used Sankey plots and exponential bar plots to visualize the fluctuating evolution and the trajectory of gastrointestinal symptoms in previously hospitalized COVID-19 survivors during the first 18 months after acute SARS-CoV-2 infection. A total of 1266 previously hospitalized COVID-19 survivors were assessed at four points: hospital admission (T0), at 8.4 months (T1), at 13.2 months (T2), and at 18.3 months (T3) after hospitalization. Participants were asked about their overall gastrointestinal symptoms and particularly diarrhea. Clinical and hospitalization data were collected from hospital medical records. The prevalence of overall gastrointestinal post-COVID symptomatology was 6.3% (n = 80) at T1, 3.99% (n = 50) at T2 and 2.39% (n = 32) at T3. The prevalence of diarrhea decreased from 10.69% (n = 135) at hospital admission (T0), to 2.55% (n = 32) at T1, to 1.04% (n = 14) at T2, and to 0.64% (n = 8) at T3. The Sankey plots revealed that just 20 (1.59%) and 4 (0.32%) patients exhibited overall gastrointestinal post-COVID symptoms or diarrhea, respectively, throughout the whole follow-up period. The recovery fitted exponential curves revealed a decreasing prevalence trend, showing that diarrhea and gastrointestinal symptoms recover during the first two or three years after COVID-19 in previously hospitalized COVID-19 survivors. The regression models did not reveal any symptoms to be associated with the presence of gastrointestinal post-COVID symptomatology or post-COVID diarrhea at hospital admission or at T1. The use of Sankey plots revealed the fluctuating evolution of gastrointestinal post-COVID symptoms during the first two years after infection. In addition, exponential bar plots revealed the decreased prevalence of gastrointestinal post-COVID symptomatology during the first three years after infection. Full article

(This article belongs to the Special Issue COVID-19 and Gastrointestinal Symptoms)

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Review

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16 pages, 1680 KiB

Open AccessReview

Exploring the Interplay between COVID-19 and Gut Health: The Potential Role of Prebiotics and Probiotics in Immune Support

by Marta Giovanetti, Gianfranco Pannella, Annamaria Altomare, Giulia Rocchi, Michele Guarino, Massimo Ciccozzi, Elisabetta Riva and Giovanni Gherardi

Viruses 2024, 16(3), 370; https://doi.org/10.3390/v16030370 - 27 Feb 2024

Cited by 4 | Viewed by 2184

Abstract

The COVID-19 pandemic has profoundly impacted global health, leading to extensive research focused on developing strategies to enhance outbreak response and mitigate the disease’s severity. In the aftermath of the pandemic, attention has shifted towards understanding and addressing long-term health implications, particularly in individuals experiencing persistent symptoms, known as long COVID. Research into potential interventions to alleviate long COVID symptoms has intensified, with a focus on strategies to support immune function and mitigate inflammation. One area of interest is the gut microbiota, which plays a crucial role in regulating immune responses and maintaining overall health. Prebiotics and probiotics, known for their ability to modulate the gut microbiota, have emerged as potential therapeutic agents in bolstering immune function and reducing inflammation. This review delves into the intricate relationship between long COVID, the gut microbiota, and immune function, with a specific focus on the role of prebiotics and probiotics. We examine the immune response to long COVID, emphasizing the importance of inflammation and immune regulation in the persistence of symptoms. The potential of probiotics in modulating immune responses, including their mechanisms in combating viral infections such as COVID-19, is discussed in detail. Clinical evidence supporting the use of probiotics in managing long COVID symptoms is summarized, highlighting their role as adjunctive therapy in addressing various aspects of SARS-CoV-2 infection and its aftermath. Full article

(This article belongs to the Special Issue COVID-19 and Gastrointestinal Symptoms)

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24 pages, 1449 KiB

Open AccessReview

Gastrointestinal Manifestations of SARS-CoV-2: Transmission, Pathogenesis, Immunomodulation, Microflora Dysbiosis, and Clinical Implications

by Siva Sundara Kumar Durairajan, Abhay Kumar Singh, Udhaya Bharathy Saravanan, Mayurikaa Namachivayam, Moorthi Radhakrishnan, Jian-Dong Huang, Rahul Dhodapkar and Hongjie Zhang

Viruses 2023, 15(6), 1231; https://doi.org/10.3390/v15061231 - 24 May 2023

Cited by 14 | Viewed by 2962

Abstract

The clinical manifestation of COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in the respiratory system of humans is widely recognized. There is increasing evidence suggesting that SARS-CoV-2 possesses the capability to invade the gastrointestinal (GI) system, leading to the manifestation of symptoms such as vomiting, diarrhea, abdominal pain, and GI lesions. These symptoms subsequently contribute to the development of gastroenteritis and inflammatory bowel disease (IBD). Nevertheless, the pathophysiological mechanisms linking these GI symptoms to SARS-CoV-2 infection remain unelucidated. During infection, SARS-CoV-2 binds to angiotensin-converting enzyme 2 and other host proteases in the GI tract during the infection, possibly causing GI symptoms by damaging the intestinal barrier and stimulating inflammatory factor production, respectively. The symptoms of COVID-19-induced GI infection and IBD include intestinal inflammation, mucosal hyperpermeability, bacterial overgrowth, dysbiosis, and changes in blood and fecal metabolomics. Deciphering the pathogenesis of COVID-19 and understanding its exacerbation may provide insights into disease prognosis and pave the way for the discovery of potential novel targets for disease prevention or treatment. Besides the usual transmission routes, SARS-CoV-2 can also be transmitted via the feces of an infected person. Hence, it is crucial to implement preventive and control measures in order to mitigate the fecal-to-oral transmission of SARS-CoV-2. Within this context, the identification and diagnosis of GI tract symptoms during these infections assume significance as they facilitate early detection of the disease and the development of targeted therapeutics. The present review discusses the receptors, pathogenesis, and transmission of SARS-CoV-2, with a particular focus on the induction of gut immune responses, the influence of gut microbes, and potential therapeutic targets against COVID-19-induced GI infection and IBD. Full article

(This article belongs to the Special Issue COVID-19 and Gastrointestinal Symptoms)

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Other

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11 pages, 459 KiB

Open AccessOpinion

Scoping Review of Clinical Presentations and Outcomes in Patients with Concomitant COVID-19 Infection and Acute Mesenteric Ischaemia

by Wenyi Cai, Yi Zhao and Sreelakshmi Mallappa

Viruses 2024, 16(4), 506; https://doi.org/10.3390/v16040506 - 26 Mar 2024

Viewed by 1015

Abstract

Objectives: COVID-19 infection confers an increased risk of coagulation dysfunction (1) predisposing to thromboembolism in many anatomical sites including the gastrointestinal tract (GIT) (2). This study investigates the clinical presentation and outcome in patients presenting with concurrent COVID-19 infection and gastrointestinal tract ischaemia. Furthermore, differentiation and comparisons are drawn between those with arterial and venous aetiology for mesenteric ischaemia. Methods: A systematic search was undertaken on EMBASE, PubMed, and MEDLINE. Two independent reviewers screened titles, abstracts, and full-text articles according to the inclusion criteria and extracted relevant data. Data analyses were conducted using Excel^®. Results: Forty-one studies were included in the data analyses, yielding 44 patients. Twenty-six patients had mesenteric arterial occlusion, sixteen patients had mesenteric venous occlusion, and two patients had both arterial and venous mesenteric occlusion. All patients had concurrent COVID-19 infection. The survival rate in patients with arterial aetiology was 38.5% in contrast to 68.8% in patients with venous aetiology. Twelve patients (29.3%) experienced respiratory symptoms in the community before the onset of gastrointestinal symptoms, and five (12.2%) developed gastrointestinal symptoms during their inpatient stay for COVID-19 pneumonitis. Conclusions: Acute mesenteric ischaemia presents a clinical challenge to diagnose due to its non-specific symptoms. Concurrent COVID-19 infection with its predominant respiratory symptoms adds a further challenge in recognising the non-specific symptoms of mesenteric ischaemia. Our study draws attention to the increased thromboembolic risk posed by COVID-19 infection and the need for a high index of suspicion to aid prompt diagnosis and management of acute mesenteric ischaemia, even in the post-pandemic era. Full article

(This article belongs to the Special Issue COVID-19 and Gastrointestinal Symptoms)

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33 pages, 1104 KiB

Open AccessSystematic Review

A Systematic Review of the Prevalence of Persistent Gastrointestinal Symptoms and Incidence of New Gastrointestinal Illness after Acute SARS-CoV-2 Infection

by Michael J. Hawkings, Natasha Marcella Vaselli, Dimitrios Charalampopoulos, Liam Brierley, Alex J. Elliot, Iain Buchan and Daniel Hungerford

Viruses 2023, 15(8), 1625; https://doi.org/10.3390/v15081625 - 26 Jul 2023

Cited by 4 | Viewed by 2799

Abstract

It is known that SARS-CoV-2 infection can result in gastrointestinal symptoms. For some, these symptoms may persist beyond acute infection, in what is known as ‘post-COVID syndrome’. We conducted a systematic review to examine the prevalence of persistent gastrointestinal symptoms and the incidence of new gastrointestinal illnesses following acute SARS-CoV-2 infection. We searched the scientific literature using MedLine, SCOPUS, Europe PubMed Central and medRxiv from December 2019 to July 2023. Two reviewers independently identified 45 eligible articles, which followed participants for various gastrointestinal outcomes after acute SARS-CoV-2 infection. The study quality was assessed using the Joanna Briggs Institute Critical Appraisal Tools. The weighted pooled prevalence for persistent gastrointestinal symptoms of any nature and duration was 10.8% compared with 4.9% in healthy controls. For seven studies at low risk of methodological bias, the symptom prevalence ranged from 0.2% to 24.1%, with a median follow-up time of 18 weeks. We also identified a higher risk for future illnesses such as irritable bowel syndrome, dyspepsia, hepatic and biliary disease, liver disease and autoimmune-mediated illnesses such as inflammatory bowel disease and coeliac disease in historically SARS-CoV-2-exposed individuals. Our review has shown that, from a limited pool of mostly low-quality studies, previous SARS-CoV-2 exposure may be associated with ongoing gastrointestinal symptoms and the development of functional gastrointestinal illness. Furthermore, we show the need for high-quality research to better understand the SARS-CoV-2 association with gastrointestinal illness, particularly as population exposure to enteric infections returns to pre-COVID-19-restriction levels. Full article

(This article belongs to the Special Issue COVID-19 and Gastrointestinal Symptoms)

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