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1.
Viruses ; 13(12)2021 11 30.
Article in English | MEDLINE | ID: covidwho-1542802

ABSTRACT

Human Norovirus is currently the main viral cause of acute gastroenteritis (AGEs) in most countries worldwide. Nearly 50 years after the discovery of the "Norwalk virus" by Kapikian and colleagues, the scientific and medical community continue to generate new knowledge on the full biological and disease spectrum of Norovirus infection. Nevertheless, several areas remain incompletely understood due to the serious constraints to effectively replicate and propagate the virus. Here, we present a narrated historic perspective and summarize our current knowledge, including insights and reflections on current points of interest for a broad medical community, including clinical and molecular epidemiology, viral-host-microbiota interactions, antivirals, and vaccine prototypes. We also include a reflection on the present and future impacts of the COVID-19 pandemic on Norovirus infection and disease.


Subject(s)
Caliciviridae Infections/epidemiology , Caliciviridae Infections/prevention & control , Gastroenteritis/epidemiology , Gastroenteritis/prevention & control , Norovirus/physiology , Antiviral Agents , COVID-19/epidemiology , COVID-19/prevention & control , Caliciviridae Infections/microbiology , Caliciviridae Infections/virology , Gastroenteritis/microbiology , Gastroenteritis/virology , Gastrointestinal Microbiome , Host-Pathogen Interactions , Humans , Norovirus/genetics , Norovirus/immunology , SARS-CoV-2 , Viral Vaccines/immunology
2.
Viruses ; 12(8)2020 08 18.
Article in English | MEDLINE | ID: covidwho-1453290

ABSTRACT

Enteric viral co-infections, infections involving more than one virus, have been reported for a diverse group of etiological agents, including rotavirus, norovirus, astrovirus, adenovirus, and enteroviruses. These pathogens are causative agents for acute gastroenteritis and diarrheal disease in immunocompetent and immunocompromised individuals of all ages globally. Despite virus-virus co-infection events in the intestine being increasingly detected, little is known about their impact on disease outcomes or human health. Here, we review what is currently known about the clinical prevalence of virus-virus co-infections and how co-infections may influence vaccine responses. While experimental investigations into enteric virus co-infections have been limited, we highlight in vivo and in vitro models with exciting potential to investigate viral co-infections. Many features of virus-virus co-infection mechanisms in the intestine remain unclear, and further research will be critical.


Subject(s)
Coinfection/virology , Gastroenteritis/virology , Virus Diseases/physiopathology , Viruses/classification , Viruses/pathogenicity , Animals , Asymptomatic Infections , Disease Models, Animal , Feces/virology , Humans , Intestines/virology , Mice , Primates
3.
Viruses ; 13(10)2021 10 13.
Article in English | MEDLINE | ID: covidwho-1481011

ABSTRACT

Human noroviruses are a common pathogen causing acute gastroenteritis worldwide. Among all norovirus genotypes, GII.3 is particularly prevalent in the pediatric population. Here we report the identification of two distinct blockade antibody epitopes on the GII.3 capsid. We generated a panel of monoclonal antibodies (mAbs) from mice immunized with virus-like particle (VLP) of a GII.3 cluster 3 strain. Two of these mAbs, namely 8C7 and 8D1, specifically bound the parental GII.3 VLP but not VLPs of GII.4, GII.17, or GI.1. In addition, 8C7 and 8D1 efficiently blocked GII.3 VLP binding with its ligand, histo-blood group antigens (HBGA). These data demonstrate that 8C7 and 8D1 are GII.3-specific blockade antibodies. By using a series of chimeric VLPs, we mapped the epitopes of 8C7 and 8D1 to residues 385-400 and 401-420 of the VP1 capsid protein, respectively. These two blockade antibody epitopes are highly conserved among GII.3 cluster 3 strains. Structural modeling shows that the 8C7 epitope partially overlaps with the HBGA binding site (HBS) while the 8D1 epitope is spatially adjacent to HBS. These findings may enhance our understanding of the immunology and evolution of GII.3 noroviruses.


Subject(s)
Norovirus/genetics , Norovirus/immunology , Amino Acid Sequence , Animals , Antibodies, Blocking/immunology , Antibodies, Monoclonal/immunology , Antibodies, Viral/immunology , Binding Sites/genetics , Blood Group Antigens/genetics , Caliciviridae Infections/genetics , Capsid/immunology , Capsid Proteins/genetics , Capsid Proteins/immunology , Epitopes/genetics , Epitopes/immunology , Gastroenteritis/virology , Genotype , Humans , Mice , Protein Binding/genetics , Protein Binding/immunology , Protein Domains/genetics
4.
J Med Virol ; 93(4): 2543-2547, 2021 04.
Article in English | MEDLINE | ID: covidwho-1217399

ABSTRACT

We described the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in stool samples from patients presenting only acute gastroenteritis (AGE) symptoms. From January to July 2020, 121 AGE stool samples were screened by quantitative reverse-transcription polymerase chain reaction. We detected SARS-CoV-2 in 27.5% of samples received during the epidemic period. No infectious viruses were observed in Vero E6 cells.


Subject(s)
COVID-19/diagnosis , COVID-19/virology , Gastroenteritis/virology , RNA, Viral/isolation & purification , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Adult , Brazil/epidemiology , COVID-19/epidemiology , COVID-19 Testing , Feces/virology , Female , Humans , Infant , Male , Reverse Transcriptase Polymerase Chain Reaction/methods , Young Adult
5.
Nat Rev Gastroenterol Hepatol ; 18(4): 269-283, 2021 04.
Article in English | MEDLINE | ID: covidwho-1085424

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to more than 200 countries and regions globally. SARS-CoV-2 is thought to spread mainly through respiratory droplets and close contact. However, reports have shown that a notable proportion of patients with coronavirus disease 2019 (COVID-19) develop gastrointestinal symptoms and nearly half of patients confirmed to have COVID-19 have shown detectable SARS-CoV-2 RNA in their faecal samples. Moreover, SARS-CoV-2 infection reportedly alters intestinal microbiota, which correlated with the expression of inflammatory factors. Furthermore, multiple in vitro and in vivo animal studies have provided direct evidence of intestinal infection by SARS-CoV-2. These lines of evidence highlight the nature of SARS-CoV-2 gastrointestinal infection and its potential faecal-oral transmission. Here, we summarize the current findings on the gastrointestinal manifestations of COVID-19 and its possible mechanisms. We also discuss how SARS-CoV-2 gastrointestinal infection might occur and the current evidence and future studies needed to establish the occurrence of faecal-oral transmission.


Subject(s)
COVID-19/physiopathology , Diarrhea/physiopathology , Dysbiosis/physiopathology , Gastroenteritis/physiopathology , Gastrointestinal Microbiome , Nausea/physiopathology , Vomiting/physiopathology , Abdominal Pain/physiopathology , Angiotensin-Converting Enzyme 2/metabolism , Animals , Anorexia/physiopathology , COVID-19/transmission , Cell Line , Colon/metabolism , Cytokines/metabolism , Disease Models, Animal , Feces/chemistry , Gastroenteritis/virology , Humans , Intestinal Mucosa/metabolism , Intestine, Small/metabolism , Leukocyte L1 Antigen Complex/metabolism , Organoids , RNA, Viral , Receptors, Coronavirus/metabolism , SARS-CoV-2/metabolism , Serine Endopeptidases/metabolism , Viral Load , Virus Shedding
6.
Commun Dis Intell (2018) ; 452021 Jan 29.
Article in English | MEDLINE | ID: covidwho-1080878

ABSTRACT

ABSTRACT: Significant reductions in the incidence of enteroviruses and noroviruses, both transmitted primarily by the faecal-oral route, were noted in 2020 compared to the previous decade, in Victoria, Australia. The enterovirus specimen positivity rate was reduced by 84.2% in 2020, while the norovirus outbreak positivity rate declined by 49.0%. The most likely explanation for these reductions is the concurrence of social restrictions, physical distancing, personal hygiene awareness and international and domestic border closures in response to the COVID-19 pandemic.


Subject(s)
COVID-19/epidemiology , Caliciviridae Infections/virology , Enterovirus , Gastroenteritis/epidemiology , Gastroenteritis/virology , Norovirus , Caliciviridae Infections/epidemiology , Enterovirus Infections/epidemiology , Enterovirus Infections/virology , Humans , Incidence , SARS-CoV-2 , Victoria/epidemiology
7.
Gastroenterology ; 160(5): 1647-1661, 2021 04.
Article in English | MEDLINE | ID: covidwho-1065985

ABSTRACT

BACKGROUND & AIMS: Gastrointestinal (GI) manifestations have been increasingly reported in patients with coronavirus disease 2019 (COVID-19). However, the roles of the GI tract in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are not fully understood. We investigated how the GI tract is involved in SARS-CoV-2 infection to elucidate the pathogenesis of COVID-19. METHODS: Our previously established nonhuman primate (NHP) model of COVID-19 was modified in this study to test our hypothesis. Rhesus monkeys were infected with an intragastric or intranasal challenge with SARS-CoV-2. Clinical signs were recorded after infection. Viral genomic RNA was quantified by quantitative reverse transcription polymerase chain reaction. Host responses to SARS-CoV-2 infection were evaluated by examining inflammatory cytokines, macrophages, histopathology, and mucin barrier integrity. RESULTS: Intranasal inoculation with SARS-CoV-2 led to infections and pathologic changes not only in respiratory tissues but also in digestive tissues. Expectedly, intragastric inoculation with SARS-CoV-2 resulted in the productive infection of digestive tissues and inflammation in both the lung and digestive tissues. Inflammatory cytokines were induced by both types of inoculation with SARS-CoV-2, consistent with the increased expression of CD68. Immunohistochemistry and Alcian blue/periodic acid-Schiff staining showed decreased Ki67, increased cleaved caspase 3, and decreased numbers of mucin-containing goblet cells, suggesting that the inflammation induced by these 2 types of inoculation with SARS-CoV-2 impaired the GI barrier and caused severe infections. CONCLUSIONS: Both intranasal and intragastric inoculation with SARS-CoV-2 caused pneumonia and GI dysfunction in our rhesus monkey model. Inflammatory cytokines are possible connections for the pathogenesis of SARS-CoV-2 between the respiratory and digestive systems.


Subject(s)
COVID-19/transmission , Gastroenteritis/pathology , Gastrointestinal Tract/pathology , Lung/pathology , Animals , Bronchi/metabolism , Bronchi/pathology , COVID-19/immunology , COVID-19/metabolism , COVID-19/pathology , COVID-19 Nucleic Acid Testing , Caspase 3/metabolism , Cytokines/immunology , Disease Models, Animal , Gastric Mucosa , Gastroenteritis/metabolism , Gastroenteritis/virology , Gastrointestinal Tract/immunology , Gastrointestinal Tract/metabolism , Goblet Cells/pathology , Intestine, Small/metabolism , Intestine, Small/pathology , Ki-67 Antigen/metabolism , Lung/diagnostic imaging , Lung/immunology , Lung/metabolism , Macaca mulatta , Nasal Mucosa , RNA, Viral/isolation & purification , Random Allocation , Rectum/metabolism , Rectum/pathology , SARS-CoV-2 , Trachea/metabolism , Trachea/pathology
8.
J Med Virol ; 92(11): 2582-2592, 2020 11.
Article in English | MEDLINE | ID: covidwho-942384

ABSTRACT

Rotavirus infections have become one of the most common causes of infectious gastroenteritis in children. Although rotavirus infections have been intensively studied in infants and young children, the study in adults has been limited. As such, this study assessed the prevalence of rotaviruses and performed the molecular characterization of rotaviruses circulating in Thai adults experiencing acute gastroenteritis between January 2018 and December 2018. Group A human rotaviruses were detected in 100 feces samples by rapid immunochromatography. The peak incidence of infection occurred in February and began to decline in the summer months. From January 2018 to December 2018, there were 1344 acute gastroenteritis adult cases in the Hospital for Tropical Diseases, Bangkok, Thailand. Among these, 310 cases were rotavirus-suspected cases. Only 100 samples tested positive for rotavirus via an immunochromatography test. Twentynine out of the 100 rotavirus-positive samples were further characterized by real-time polymerase chain reaction. The G3[P8] strain was identified as the most prevalent (31.0%) followed by G1P[8], G8P[8] and G9P[8], and G2P[8], which accounted for 20.8%, 17.2%, and 13.8%, respectively. Because of the detection of rare rotavirus genotypes, such as G8, the surveillance of rotavirus epidemiology is crucial in monitoring new emergences of rotavirus strains, leading to a better understanding of the effects of strain variation for further vaccine development.


Subject(s)
Rotavirus Infections/epidemiology , Rotavirus Infections/virology , Rotavirus/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Feces/virology , Female , Gastroenteritis/epidemiology , Gastroenteritis/virology , Genotype , Humans , Incidence , Male , Middle Aged , Molecular Epidemiology , Phylogeny , Prevalence , Rotavirus/classification , Rotavirus/isolation & purification , Seasons , Thailand/epidemiology , Young Adult
9.
J Med Virol ; 92(10): 1834-1844, 2020 10.
Article in English | MEDLINE | ID: covidwho-935120

ABSTRACT

Coronaviruses have long been studied in both human and veterinary fields. Whereas the initial detection of endemic human respiratory coronaviruses was problematic, detection of these and newly discovered human coronaviruses has been greatly facilitated with major advances in the laboratory. Nevertheless, technological factors can affect the accuracy and timeliness of virus detection. Many human coronaviruses can be variably found in stool samples. All human coronaviruses have been variably associated with symptoms of gastroenteritis. Coronaviruses can occasionally be cultured from enteric specimens, but most detection is accomplished with genetic amplification technologies. Excretion of viral RNA in stool can extend for a prolonged period. Culture-positive stool samples have been found to exceed a fourteen day period after onset of infection for some coronaviruses. Virus can also sometimes be cultured from patients' respiratory samples during the late incubation period. Relatively asymptomatic patients may excrete virus. Both viable and nonviable virus can be found in the immediate environment of the patient, the health care worker, and less often the public. These lessons from the past study of animal and human coronaviruses can be extended to presumptions for severe acute respiratory syndrome coronavirus 2. Already, the early reports from the coronavirus disease-2019 pandemic are confirming some concerns. These data have the cumulative potential to cause us to rethink some current and common public health and infection control strategies.


Subject(s)
COVID-19 , Coronavirus Infections/complications , Gastrointestinal Diseases/virology , Animals , Gastroenteritis/virology , Humans , SARS-CoV-2
10.
Gastroenterology ; 160(1): 39-46, 2021 01.
Article in English | MEDLINE | ID: covidwho-936157

ABSTRACT

The role of angiotensin converting enzyme 2 has expanded from regulating the renin angiotensin system to regulating intestinal amino acid homeostasis and the gut microbiome. Recently, angiotensin converting enzyme 2 was identified as a primary receptor for severe acute respiratory syndrome coronaviruses 1 and 2 being expressed in multiple tissues including the luminal surface of the gut. In this brief perspective, we examine the role of angiotensin converting enzyme 2 as the receptor for severe acute respiratory syndrome coronavirus 2 and the impact of coronavirus disease 19 infection on the gut microbiome and on the gut epithelium.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/enzymology , Gastroenteritis/enzymology , Gastrointestinal Microbiome , Intestinal Mucosa/enzymology , Receptors, Virus/metabolism , SARS-CoV-2/pathogenicity , Angiotensin-Converting Enzyme 2/therapeutic use , Animals , Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/microbiology , COVID-19/virology , Feces/microbiology , Feces/virology , Gastroenteritis/drug therapy , Gastroenteritis/microbiology , Gastroenteritis/virology , Gastrointestinal Microbiome/drug effects , Host-Pathogen Interactions , Humans , Intestinal Mucosa/drug effects , Intestinal Mucosa/microbiology , Intestinal Mucosa/virology , Renin-Angiotensin System , SARS-CoV-2/drug effects , Virus Internalization
11.
Pediatr Infect Dis J ; 39(7): 645-649, 2020 07.
Article in English | MEDLINE | ID: covidwho-336444

ABSTRACT

Since human coronavirus (HCoV)-like particles were detected in the stool specimens of acute gastroenteritis and necrotizing enterocolitis children with electron microscopy, the relationship between HCoV and the pediatric gastrointestinal illness had been recognized. In recent years, the overall detection rates have been low and have varied by region. HCoVs have not been considered as the major pathogens in pediatric acute gastroenteritis. HCoVs detected in children with acute gastroenteritis have included 229E, OC43, HKU1, NL63, and severe acute respiratory syndrome coronavirus, Middle East Respiratory Syndrome Coronavirus and severe acute respiratory syndrome coronavirus-2 have also been associated with gastrointestinal symptoms in children. Although digestive tract has been recognized as an infection route, it has not been possible to fully investigate the association between HCoVs infection and the gastrointestinal symptoms because of the limited number of pediatric cases. Furthermore, pathologic features have not been clear. Till now, our knowledge of severe acute respiratory syndrome coronavirus-2 is limited. However, diarrhea and vomiting have been seen in pediatric cases, particularly in newborns and infants. It has been necessary to pay more attention on gastrointestinal transmission to identify the infected children early and avoid the children without apparent or mild symptoms becoming the sources of infection.


Subject(s)
Coronavirus Infections/physiopathology , Gastroenteritis/virology , Age Factors , Betacoronavirus/isolation & purification , COVID-19 , Child , Coronavirus Infections/virology , Diarrhea/virology , Enterocolitis, Necrotizing/virology , Gastroenteritis/physiopathology , Humans , Middle East Respiratory Syndrome Coronavirus/isolation & purification , Pandemics , Pneumonia, Viral/virology , Respiratory Tract Infections/virology , SARS-CoV-2 , Vomiting/virology
12.
Am J Nephrol ; 51(5): 337-342, 2020.
Article in English | MEDLINE | ID: covidwho-19673

ABSTRACT

Novel coronavirus disease 2019 (COVID-19) is a highly infectious, rapidly spreading viral disease with an alarming case fatality rate up to 5%. The risk factors for severe presentations are concentrated in patients with chronic kidney disease, particularly patients with end-stage renal disease (ESRD) who are dialysis dependent. We report the first US case of a 56-year-old nondiabetic male with ESRD secondary to IgA nephropathy undergoing thrice-weekly maintenance hemodialysis for 3 years, who developed COVID-19 infection. He has hypertension controlled with angiotensin receptor blocker losartan 100 mg/day and coronary artery disease status-post stent placement. During the first 5 days of his febrile disease, he presented to an urgent care, 3 emergency rooms, 1 cardiology clinic, and 2 dialysis centers in California and Utah. During this interval, he reported nausea, vomiting, diarrhea, and low-grade fevers but was not suspected of COVID-19 infection until he developed respiratory symptoms and was admitted to the hospital. Imaging studies upon admission were consistent with bilateral interstitial pneumonia. He was placed in droplet-eye precautions while awaiting COVID-19 test results. Within the first 24 h, he deteriorated quickly and developed acute respiratory distress syndrome (ARDS), requiring intubation and increasing respiratory support. Losartan was withheld due to hypotension and septic shock. COVID-19 was reported positive on hospital day 3. He remained in critical condition being treated with hydroxychloroquine and tocilizumab in addition to the standard medical management for septic shock and ARDS. Our case is unique in its atypical initial presentation and highlights the importance of early testing.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Gastroenteritis/virology , Kidney Failure, Chronic/complications , Pneumonia, Viral/complications , COVID-19 , Coronavirus Infections/diagnostic imaging , Humans , Kidney Failure, Chronic/therapy , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnostic imaging , Renal Dialysis , SARS-CoV-2 , Tomography, X-Ray Computed , Travel-Related Illness
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