ABSTRACT
Infection with SARS-CoV-2 coronavirus, and the disease this agent may induce, are a cause of notable concern for the general population and, of course, among our professionals and patients. Gastrointestinal (GI) endoscopy is a high-risk diagnostic-therapeutic procedure in the case of upper GI examinations, and a moderate to low-risk intervention when involving lower GI explorations. The presence of SARS-CoV-2 RNA in the feces of patients infected with the virus, and occasionally in colonic biopsy samples, has been consistently documented. In fact, viral elimination in the feces may be more prolonged than viral identification in respiratory tract secretions. Furthermore, viral transmission may occur in asymptomatic individuals. However, as of this moment no information has been reported on the possibility of viral transmission, even to professionals, via this route.
Subject(s)
Betacoronavirus , Coronavirus Infections , Endoscopy, Gastrointestinal/methods , Pandemics , Pneumonia, Viral , Betacoronavirus/isolation & purification , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/epidemiology , Feces/virology , Gastroenterology/trends , Humans , Pneumonia, Viral/complications , Pneumonia, Viral/epidemiology , SARS-CoV-2 , Virus SheddingABSTRACT
BACKGROUND: SARS-CoV-2 has been detected not only in respiratory secretions, but also in stool collections. Here were sought to identify SARS-CoV-2 by enrichment next-generation sequencing (NGS) from fecal samples, and to utilize whole genome analysis to characterize SARS-CoV-2 mutational variations in COVID-19 patients. RESULTS: Study participants underwent testing for SARS-CoV-2 from fecal samples by whole genome enrichment NGS (n = 14), and RT-PCR nasopharyngeal swab analysis (n = 12). The concordance of SARS-CoV-2 detection by enrichment NGS from stools with RT-PCR nasopharyngeal analysis was 100%. Unique variants were identified in four patients, with a total of 33 different mutations among those in which SARS-CoV-2 was detected by whole genome enrichment NGS. CONCLUSION: These results highlight the potential viability of SARS-CoV-2 in feces, its ongoing mutational accumulation, and its possible role in fecal-oral transmission. This study also elucidates the advantages of SARS-CoV-2 enrichment NGS, which may be a key methodology to document complete viral eradication. Trial registration ClinicalTrials.gov, NCT04359836, Registered 24 April 2020, https://clinicaltrials.gov/ct2/show/NCT04359836?term=NCT04359836&draw=2&rank=1 ).
ABSTRACT
BACKGROUND: Since its declaration in december 2019, a novel coronavirus, the SARS-CoV-2 was rapidly responsible for a major pandemic. COVID-19 is mainly manifested by respiratory symptoms,however, digestive manifestations have been reported, raising the hypothesis of the viral digestive tropism. AIMS: Specify the digestive manifestations due to the SARS-CoV-2, and their impact on the disease prognosis and describe the COVID-19 effect in patients with underlying digestive disease. METHODS: Ageneral review of the medical literature was conducted via Medline® database, through various combinations of the following keywords :SARS-CoV-2, COVID-19, gastrointestinal tract, digestive system, inflammatory bowel diseases, liver, liver injury, chronic liver disease, neoplasms. The most relevant articles were selected. RESULTS: The SARS-CoV-2 tropism for the digestive tract has been confirmed by the identification of the enterocyte as a target cell of the virus. Viral particles and RNA detection in stool of infected patients has raised the potential for feco-oral transmission of the virus. Gastrointestinal manifestations were frequent and may even be revealing or isolated. Diarrhea was the most characteristic symptom. Frequent liver involvement is associated with a more severe form of the disease. Patients with digestive cancer and chronic liver disease are at risk for a severe form of SARS-CoV-2 infection. CONCLUSION: The clinician is required to know this type of manifestations in order to limit the delay in diagnosis and to better assess the prognosis.
Subject(s)
COVID-19/complications , Gastrointestinal Diseases/epidemiology , Gastrointestinal Diseases/etiology , Humans , Prevalence , PrognosisABSTRACT
The infection with SARS-CoV-2 is reported to be accompanied by the shedding of the virus in fecal samples of infected patients. Earlier reports have suggested that COVID-19 agents can be present in the sewage samples and thus it can be a good indication of the pandemic extent in a community. However, no such studies have been reported in the Indian context. Hence, it becomes absolutely necessary to detect the presence of the SARS-CoV-2 in the wastewater samples from wastewater treatment plants (WWTPs) serving different localities of Jaipur city. Samples from different WWTPs and hospital wastewater samples were collected and wastewater based epidemiology (WBE) studies were carried out using the RT-PCR to confirm the presence of different COVID-19 target genes namely S gene, E gene, ORF1ab gene, RdRp gene and N gene. The results revealed that the untreated wastewater samples showed the presence of SARS-CoV-2 viral genome, which was correlated with the increased number of COVID-19 positive patients from the concerned areas, as reported in the publically available health data. This is the first study that investigated the presence of SARS-CoV-2 viral genome in wastewater, at higher ambient temperature (45 °C), further validating WBE as potential tool in predicting and mitigating outbreaks.
Subject(s)
COVID-19 , SARS-CoV-2 , Cities , Humans , India/epidemiology , Sewage , Wastewater-Based Epidemiological MonitoringABSTRACT
BACKGROUND: With the effective prevention and control of COVID-19 in China, the number of cured cases has increased significantly. Further monitoring of the disease prognosis and effective control of the "relapse" of the epidemic has become the next focus of work. This study analysed the clinical prognosis of discharged COVID-19 patients by monitoring their SAR-CoV-2 nucleic acid status, which provided a theoretical basis for medical institutions to formulate discharge standards and follow-up management for COVID-19 patients. METHODS: We included 13 discharged COVID-19 patients who were quarantined for 4 weeks at home. The patient's daily clinical signs were recorded and sputum and faecal specimens were regularly sent for detection of SARS-CoV-2 nucleic acid. RESULTS: The time between initial symptoms and meeting discharge criteria was 18 to 44 days with an average of 25 ± 6 days. The faecal samples of two patients still tested positive after meeting the discharge criteria and the sputum samples of four patients returned positive 5 to 14 days after discharge. The rate of the recurring positive test result in samples from the respiratory system was 31% (4/13). CONCLUSION: Under the present discharge criteria, the high presence of SARS-CoV-2 nucleic acid in faecal and respiratory samples of discharged COVID-19 patients indicates potential infectivity. Therefore, we suggest that faecal virus nucleic acid should be tested as a routine monitoring index for COVID-19 and a negative result be added to the criteria. Simultaneously, we should strengthen the regular follow-up of discharged patients with continuous monitoring of the recurrence of viral nucleic acid.
Subject(s)
COVID-19/diagnosis , Feces/virology , Patient Discharge , SARS-CoV-2/isolation & purification , Sputum/virology , Adult , Aged , China , Female , Humans , Infant , Male , Middle Aged , RNA, Viral/isolation & purification , Young AdultABSTRACT
Coronavirus disease 2019 (COVID-19) has become a pandemic with increasing numbers of cases worldwide. SARS-CoV-2, the causative virus of COVID-19, is mainly transmitted through respiratory droplets or through direct and indirect contact with an infected person. The possibility of potential faecal-oral transmission was investigated in this study. We collected 258 faecal specimens from nine provinces in China and detected the nucleic acid of SARS-CoV-2 using real-time RT-PCR. Vero cells were used to isolate the virus from SARS-CoV-2 nucleic acid positive samples, after which sequencing of Spike gene in eight samples was performed. In all, 93 of 258 (36%) stool samples were positive for SARS-CoV-2 RNA. The positive rates of critical, severe, moderate, and mild patients were 54.4%, 56.1%, 30.8%, and 33.3%, respectively. The content of nucleic acid increased within 2 weeks after the onset of the disease. From the perspective of clinical typing, the nucleic acid can be detected in the faeces of critical patients within two weeks and until four to five weeks in the faeces of severe and mild patients. SARS-CoV-2 was isolated from stool specimens of two severe patients. Four non-synonymous mutations in Spike gene were newly detected in three stool samples. A small number of patients had strong faecal detoxification ability. The live virus in faeces could be an important source of contamination, which may lead to infection and further spread in areas with poor sanitary conditions. The findings of this study have public health significance and they should be considered when formulating disease control strategies.
Subject(s)
COVID-19/epidemiology , COVID-19/transmission , Feces/virology , Pandemics , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Animals , COVID-19/diagnosis , COVID-19/virology , Child , Child, Preschool , China/epidemiology , Chlorocebus aethiops , Female , High-Throughput Nucleotide Sequencing , Humans , Infant , Male , Middle Aged , Mutation , Phylogeny , Public Health , Real-Time Polymerase Chain Reaction , SARS-CoV-2/classification , SARS-CoV-2/isolation & purification , Severity of Illness Index , Time Factors , Vero CellsABSTRACT
In order to understand the clinical manifestations and incidence of gastrointestinal symptoms of coronavirus disease (COVID-19) in children and discuss the importance of fecal nucleic acid testing.We retrospectively analyzed studies on gastrointestinal symptoms and fecal nucleic acid detection in pediatric COVID-19 patients from January 1, 2020 to August 10, 2020, including prospective clinical studies and case reports. The results of fecal nucleic acid detection were analyzed systematically. Stata12.0 software was used for meta-analysis.The results showed that the most common gastrointestinal symptoms in children with COVID-19 were vomiting and diarrhea, with a total incidence of 17.7% (95% Cl 13.9-21.5%). However, the prevalence of gastrointestinal symptoms in other countries (21.1%, 95% CI 16.5-25.7%) was higher compared to China (12.9%, 95% CI 8-17.7%). In Wuhan, the pooled prevalence was much higher (41.3%, 95% CI 3.2-79.4%) compared to areas outside Wuhan in China (7.1%, 95% CI 4.0-10.3%). The positive rate of fecal nucleic acid testing in COVID-19 children was relatively high at 85.8% (91/106). Additionally, 71.2% (52/73) were still positive for fecal nucleic acid after respiratory tract specimens turned negative. One and two weeks after the respiratory tract specimens turned nucleic acid-negative, 45.2% (33/73) and 34.2% (25/73) patients, respectively, remained fecal nucleic acid-positive. The longest interval between the respiratory tract specimens turning negative and fecal specimens turning negative exceeded 70 days. Conclusions and relevance: gastrointestinal symptoms in pediatric COVID-19 are relatively common. Attention should be paid to the detection of fecal nucleic acids in children. Fecal nucleic acid-negative status should be considered as one of the desegregation standards.
Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/diagnosis , Feces/virology , Gastrointestinal Diseases/diagnosis , Pneumonia, Viral/diagnosis , Betacoronavirus/isolation & purification , COVID-19 , Child , Coronavirus Infections/complications , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Diarrhea/complications , Diarrhea/diagnosis , Diarrhea/epidemiology , Gastrointestinal Diseases/complications , Gastrointestinal Diseases/epidemiology , Humans , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Prevalence , Prognosis , RNA, Viral/metabolism , SARS-CoV-2ABSTRACT
PURPOSE: The objective was to collect the data available regarding the presence of laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in gastrointestinal system and to evaluate whether the digestive system could contribute to viral transmission. METHODS: Bibliographic databases were searched to identify all studies documenting, in adult patients with a confirmed diagnosis of coronavirus disease 2019 (COVID-19): (1) the presence of SARS-CoV-2 ribonucleic acid in the feces; (2) the presence of SARS-CoV-2 ribonucleic acid in the intestinal cells; (3) live SARS-CoV-2 in the feces. RESULTS: Twenty seven met the inclusion criteria. In 26 studies, the presence or absence of SARS-CoV-2 ribonucleic acid in the feces of COVID-19 patients had been reported. Out of the 671 patients, 312 (46.5%) had a positive stool sample for viral nucleic acid. Of these patients, 63.9% remained positive for viral nucleic acid in the feces after pharyngeal swabs became negative; Three studies also evaluated the viral ribonucleic acid in the gastrointestinal tissues and the presence of SARS-CoV-2 nucleic acid was found in samples of 3 patients out of 8 examined (37.5%). The presence of the live virus in stool samples was confirmed in two studies but no in in a recent study from Germany. These results suggested that SARS-CoV-2 could infect gastrointestinal epithelial cells and it may be transmitted through the digestive tract. CONCLUSION: In order to control the pandemic, every effort should be made to understand all the possible routes of transmission of the infections, even the less important ones.
Subject(s)
COVID-19/transmission , Feces/virology , Gastrointestinal Tract/virology , Humans , Mouth , RNA, Viral/analysis , SARS-CoV-2/geneticsABSTRACT
BACKGROUND: Sewage transmission of SARS-CoV-2 has never been demonstrated. During a COVID-19 outbreak in Guangzhou, China in April 2020, we investigated the mode of transmission. METHODS: We collected clinical and environmental samples from quarantined residents and their environment for RT-PCR testing and genome sequencing. A case was a resident with a positive RT-PCR test regardless of symptoms. We conducted a retrospective cohort study of all residents of cases' buildings to identify risk factors. RESULTS: We found 8 cases (onset: 5-21 April). During incubation period, cases 1 and 2 frequented market T where a COVID-19 outbreak was ongoing; cases 3-8 never visited market T, lived in separate buildings and never interacted with cases 1 and 2. Working as a janitor or wastepicker (RR = 13; 95% CIexact, 2.3-180), not changing to clean shoes (RR = 7.4; 95% CIexact, 1.8-34) and handling dirty shoes by hand (RR = 6.3; 95% CIexact, 1.4-30) after returning home were significant risk factors. RT-PCR detected SARS-CoV-2 in 19% of 63 samples from sewage puddles or pipes, and 24% of 50 environmental samples from cases' apartments. Viruses from the squat toilet and shoe-bottom dirt inside the apartment of cases 1 and 2 were homologous with those from cases 3-8 and the sewage. Sewage from the apartment of cases 1 and 2 leaked out of a cracked pipe onto streets. Rainfall after the onset of cases 1 and 2 flooded the streets. CONCLUSIONS: SARS-CoV-2 might spread by sewage, highlighting the importance of sewage management during outbreaks.
Subject(s)
COVID-19 , Sewage , China/epidemiology , Disease Outbreaks , Humans , Retrospective Studies , SARS-CoV-2ABSTRACT
BACKGROUND: There is little published evidence on the gastrointestinal features of COVID-19. AIMS: To report on the gastrointestinal manifestations and pathological findings of patients with COVID-19, and to discuss the possibility of faecal transmission. METHODS: We have reviewed gastrointestinal features of, and faecal test results in, COVID-19 from case reports and retrospective clinical studies relating to the digestive system published since the outbreak. RESULTS: With an incidence of 3% (1/41)-79% (159/201), gastrointestinal symptoms of COVID-19 included anorexia 39.9% (55/138)-50.2% (101/201), diarrhoea 2% (2/99)-49.5% (146/295), vomiting 3.6% (5/138)-66.7% (4/6), nausea 1% (1/99)-29.4% (59/201), abdominal pain 2.2% (3/138)-6.0% (12/201) and gastrointestinal bleeding 4% (2/52)-13.7% (10/73). Diarrhoea was the most common gastrointestinal symptom in children and adults, with a mean duration of 4.1 ± 2.5 days, and was observed before and after diagnosis. Vomiting was more prominent in children. About 3.6% (5/138)-15.9% (32/201) of adult and 6.5% (2/31)-66.7% (4/6) of children patients presented vomiting. Adult and children patients can present with digestive symptoms in the absence of respiratory symptoms. The incidence of digestive manifestations was higher in the later than in the early stage of the epidemic, but no differences in digestive symptoms among different regions were found. Among the group of patients with a higher proportion of severe cases, the proportion of gastrointestinal symptoms in severe patients was higher than that in nonsevere patients (anorexia 66.7% vs 30.4%; abdominal pain 8.3% vs 0%); while in the group of patients with a lower severe rate, the proportion with gastrointestinal symptoms was similar in severe and nonsevere cases (nausea and vomiting 6.9% vs 4.6%; diarrhoea 5.8% vs 3.5%). Angiotensin converting enzyme 2 and virus nucleocapsid protein were detected in gastrointestinal epithelial cells, and infectious virus particles were isolated from faeces. Faecal PCR testing was as accurate as respiratory specimen PCR detection. In 36% (5/14)-53% (39/73) faecal PCR became positive, 2-5 days later than sputum PCR positive. Faecal excretion persisted after sputum excretion in 23% (17/73)-82% (54/66) patients for 1-11 days. CONCLUSIONS: Gastrointestinal symptoms are common in patients with COVID-19, and had an increased prevalence in the later stage of the recent epidemic in China. SARS-CoV-2 enters gastrointestinal epithelial cells, and the faeces of COVID-19 patients are potentially infectious.
Subject(s)
Coronavirus Infections/complications , Coronavirus Infections/transmission , Feces/virology , Gastrointestinal Diseases/virology , Pneumonia, Viral/complications , Pneumonia, Viral/transmission , Adult , Betacoronavirus , COVID-19 , Child , China/epidemiology , Coronavirus Infections/epidemiology , Diarrhea/epidemiology , Diarrhea/virology , Disease Outbreaks , Gastrointestinal Diseases/epidemiology , Humans , Incidence , Pandemics , Pneumonia, Viral/epidemiology , SARS-CoV-2 , Vomiting/epidemiology , Vomiting/virologyABSTRACT
BACKGROUND AND AIMS: The presence of gastrointestinal symptoms and high levels of viral RNA in the stool suggest active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication within enterocytes. METHODS: Here, in multiple, large cohorts of patients with inflammatory bowel disease (IBD), we have studied the intersections between Coronavirus Disease 2019 (COVID-19), intestinal inflammation, and IBD treatment. RESULTS: A striking expression of ACE2 on the small bowel enterocyte brush border supports intestinal infectivity by SARS-CoV-2. Commonly used IBD medications, both biologic and nonbiologic, do not significantly impact ACE2 and TMPRSS2 receptor expression in the uninflamed intestines. In addition, we have defined molecular responses to COVID-19 infection that are also enriched in IBD, pointing to shared molecular networks between COVID-19 and IBD. CONCLUSIONS: These data generate a novel appreciation of the confluence of COVID-19- and IBD-associated inflammation and provide mechanistic insights supporting further investigation of specific IBD drugs in the treatment of COVID-19. Preprint doi: https://doi.org/10.1101/2020.05.21.109124.
Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/enzymology , Inflammatory Bowel Diseases/enzymology , Intestinal Mucosa/enzymology , SARS-CoV-2/pathogenicity , Serine Endopeptidases/metabolism , Angiotensin-Converting Enzyme 2/genetics , Animals , Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/genetics , COVID-19/virology , Case-Control Studies , Clinical Trials as Topic , Cross-Sectional Studies , Disease Models, Animal , Female , Gene Regulatory Networks , Host-Pathogen Interactions , Humans , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/genetics , Intestinal Mucosa/drug effects , Intestinal Mucosa/virology , Longitudinal Studies , Male , Mice , SARS-CoV-2/drug effects , Serine Endopeptidases/genetics , Signal Transduction , COVID-19 Drug TreatmentABSTRACT
INTRODUCTION: The new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the etiologic agent of coronavirus disease 2019. Some authors reported pieces of evidence that patients with SARS-CoV-2 infection could have direct involvement of the gastrointestinal tract, and in symptomatic cases, gastrointestinal symptoms (diarrhea, nausea/vomiting, abdominal pain) could be very common. AREA COVERED: In this article, we reviewed current-published data of the gastrointestinal aspects involved in SARS-CoV-2 infection, including prevalence and incidence of specific symptoms, the presumptive biological mechanism of GI infection, prognosis, clinical management, and public health-related concerns on the possible risk of oral-fecal transmission. EXPERT OPINION: Different clues point to direct virus infection and replication in mucosal cells of the gastrointestinal tract. In vitro studies showed that SARS-CoV-2 could enter into the gastrointestinal epithelial cells by the Angiotensin-Converting enzyme two membrane receptor. These findings, coupled with the identification of viral RNA found in stools of patients, clearly suggest that direct involvement of the gastrointestinal tract is very likely. This can justify most of the gastrointestinal symptoms but also suggest a risk for an oral-fecal route for transmission, additionally or alternatively to the main respiratory route.
Subject(s)
COVID-19/complications , Gastrointestinal Diseases/epidemiology , Gastrointestinal Diseases/virology , RNA, Viral/analysis , SARS-CoV-2/physiology , Abdominal Pain/epidemiology , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/transmission , Diarrhea/epidemiology , Epithelial Cells/metabolism , Feces/chemistry , Gastrointestinal Tract/cytology , Humans , Incidence , Nausea/epidemiology , Prevalence , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/metabolism , Virus Attachment , Vomiting/epidemiologyABSTRACT
The presence of SARS-CoV-2 in the feces of infected patients and wastewater has drawn attention, not only to the possibility of fecal-oral transmission but also to the use of wastewater as an epidemiological tool. The COVID-19 pandemic has highlighted problems in evaluating the epidemiological scope of the disease using classical surveillance approaches, due to a lack of diagnostic capacity, and their application to only a small proportion of the population. As in previous pandemics, statistics, particularly the proportion of the population infected, are believed to be widely underestimated. Furthermore, analysis of only clinical samples cannot predict outbreaks in a timely manner or easily capture asymptomatic carriers. Threfore, community-scale surveillance, including wastewater-based epidemiology, can bridge the broader community and the clinic, becoming a valuable indirect epidemiological prediction tool for SARS-CoV-2 and other pandemic viruses. This article summarizes current knowledge and discusses the critical factors for implementing wastewater-based epidemiology of COVID-19.
Subject(s)
Betacoronavirus , Coronavirus Infections , Pandemics , Pneumonia, Viral , COVID-19 , Humans , SARS-CoV-2 , Wastewater-Based Epidemiological MonitoringABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has a direct impact on the gastrointestinal system, as up to 50% of fecal samples from coronavirus disease 2019 (COVID-19) patients contain detectable viral RNA despite a negative rhino-pharyngeal swab. This finding, together with an intestinal expression of angiotensin conversion enzyme 2 protein, suggests a possible fecal-oral transmission for SARS-CoV-2. Furthermore, gastrointestinal (GI) symptoms are common in COVID-19 patients including watery diarrhea, vomiting-particularly in children-nausea, and abdominal pain. Pathogenesis of SARS-CoV-2 infection presents significant similarities to those of some immune-mediated diseases, such as inflammatory bowel diseases or rheumatoid arthritis, leading to the hypothesis that targeted therapies used for the treatment of immune-mediated disease could be effective to treat (and possibly prevent) the main complications of COVID-19. In this review, we synthesize the present and future impact of SARS-CoV-2 infection on the gastrointestinal system and on gastroenterology practice, hypothesizing a potential role of the "gut-lung axis" and perhaps of the gut and lung microbiota into the interindividual differential susceptibility to COVID-19 19 disease. Finally, we speculate on the reorganization of outpatient gastroenterology services, which need to consider, among other factors, the major psychological impact of strict lockdown measures on the whole population.
Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Gastrointestinal Diseases/virology , Pneumonia, Viral/complications , COVID-19 , Coronavirus Infections/virology , Feces/virology , Gastrointestinal Tract/virology , Humans , Pandemics , Pneumonia, Viral/virology , RNA, Viral/analysis , SARS-CoV-2ABSTRACT
The pandemic of coronavirus disease 2019 (COVID-19), caused by a newly identified ß-coronavirus (SARS-CoV-2) has emerged as a dire health problem, causing a massive crisis for global health. Primary method of transmission was firstly thought to be animal to human transmission. However, it has been observed that the virus is transmitted from human to human via respiratory droplets. Interestingly, SARS-CoV-2 ribonucleic acid (RNA) has been isolated from patient stools, suggesting a possible gastrointestinal (GI) involvement. Most commonly reported clinical manifestations are fever, fatigue and dry cough. Interestingly, a small percentage of patients experience GI symptoms with the most common being anorexia, diarrhea, nausea and vomiting. The presence of viral RNA in stools is also common and fecal tests can be positive even after negative respiratory samples. The exact incidence of digestive symptoms is a matter of debate. The distribution of Angiotensin converting enzyme type 2 receptors in multiple organs in the body provides a possible explanation for the digestive symptoms' mechanism. Cases with solely GI symptoms have been reported in both adults and children. Viral RNA has also been detected in stool and blood samples, indicating the possibility of liver damage, which has been reported in COVID-19 patients. The presence of chronic liver disease appears to be a risk factor for severe complications and a poorer prognosis, however data from these cases is lacking. The aim of this review is firstly, to briefly update what is known about the origin and the transmission of SARS-CoV-2, but mainly to focus on the manifestations of the GI tract and their pathophysiological background, so that physicians on the one hand, not to underestimate or disregard digestive symptoms due to the small number of patients exhibiting exclusively this symptomatology and on the other, to have SARS-CoV-2 on their mind when the "gastroenteritis" type symptoms predominate.
Subject(s)
Betacoronavirus , Coronavirus Infections/physiopathology , Gastrointestinal Diseases/virology , Liver Diseases/virology , Pneumonia, Viral/physiopathology , Adult , COVID-19 , COVID-19 Testing , Child , Clinical Laboratory Techniques , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Coronavirus Infections/transmission , Gastrointestinal Diseases/diagnosis , Gastrointestinal Diseases/physiopathology , Global Health , Humans , Liver Diseases/diagnosis , Liver Diseases/physiopathology , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Pneumonia, Viral/transmission , Risk Factors , SARS-CoV-2ABSTRACT
BACKGROUND: Since the start of the COVID-19 pandemic, there have been many scientific reports regarding gastrointestinal manifestations. Several reports indicate the possibility of viral shedding via faeces and the possibility of faecal-oral transmission. AIMS: To critically assess the clinical relevance of testing stool samples and anal swabs and provide an overview of the potential faecal-oral transmission of SARS-CoV-2. METHODS: A systematic literature search with MeSH terms was performed, scrutinising the Embase database, Google scholar, MEDLINE database through PubMed and The Cochrane Library, including articles from December 2019 until July 7 2020. Data were subsequently analysed with descriptive statistics. RESULTS: Ninety-five studies were included in the qualitative analysis. 934/2149 (43%) patients tested positive for SARS-CoV-2 in stool samples or anal swabs, with positive test results up to 70 days after symptom onset. A meta-analysis executed with studies of at least 10 patients revealed a pooled positive proportion of 51.8% (95% CI 43.8 - 59.7%). Positive faecal samples of 282/443 patients (64%) remained positive for SARS-CoV-2 for a mean of 12.5 days, up to 33 days maximum, after respiratory samples became negative for SARS-CoV-2. Viable SARS-CoV-2 was found in 6/17 (35%) patients in whom this was specifically investigated. CONCLUSIONS: Viral shedding of SARS-CoV-2 in stool samples occurs in a substantial proportion of patients, making faecal-oral transmission plausible. Furthermore, detection in stool samples or anal swabs can persist long after negative respiratory testing. Therefore, stool sample or anal swab testing should be (re)considered in relation to decisions for isolating or discharging a patient.
Subject(s)
Coronavirus Infections/pathology , Feces/virology , Pneumonia, Viral/pathology , Virus Shedding/physiology , Adult , Betacoronavirus , COVID-19 , Gastrointestinal Tract/virology , Humans , Pandemics , SARS-CoV-2ABSTRACT
The virus SARS-CoV-2, which has caused the recent COVID-19 pandemic, may be present in the stools of COVID-19 patients. Therefore, we aimed to detect SARS-CoV-2 in wastewater for surveillance of SARS-CoV-2 in the population. Samples of untreated wastewater were collected from 33 wastewater treatment plants (WWTPs) of different sizes within the Czech Republic. SARS-CoV-2 RNA was concentrated from wastewater and viral RNA was determined using real-time reverse transcription polymerase chain reaction (RT-qPCR). SARS-CoV-2 RNA was detected in 11.6% of samples and more than 27.3% of WWTPs; in some of them, SARS-CoV-2 was detected repeatedly. Our preliminary results indicate that an epidemiology approach that focuses on the determination of SARS-CoV-2 in wastewater could be suitable for SARS-CoV-2 surveillance in the population.
Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/virology , Pneumonia, Viral/virology , Wastewater/virology , COVID-19 , Coronavirus Infections/epidemiology , Czech Republic/epidemiology , Feces/virology , Humans , Pandemics , Pneumonia, Viral/epidemiology , RNA, Viral , Real-Time Polymerase Chain Reaction , SARS-CoV-2ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into a major pandemic called coronavirus disease 2019 (COVID-19) that has created unprecedented global health emergencies, and emerged as a serious threat due to its strong ability for human-to-human transmission. The reports indicate the ability of SARS-CoV-2 to affect almost any organ due to the presence of a receptor known as angiotensin converting enzyme 2 (ACE2) across the body. ACE2 receptor is majorly expressed in the brush border of gut enterocytes along with the ciliated cells and alveolar epithelial type II cells in the lungs. The amino acid transport function of ACE2 has been linked to gut microbial ecology in gastrointestinal (GI) tract, thereby suggesting that COVID-19 may, to some level, be linked to the enteric microbiota. The significant number of COVID-19 patients shows extra-pulmonary symptoms in the GI tract. Many subsequent studies revealed viral RNA of SARS-CoV-2 in fecal samples of COVID-19 patients. This presents a new challenge in the diagnosis and control of COVID-19 infection with a caution for proper sanitation and hygiene. Here, we aim to discuss the immunological co-ordination between gut and lungs that facilitates SARS-CoV-2 to infect and multiply in the inflammatory bowel disease (IBD) and non-IBD patients.
Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/immunology , Cytokine Release Syndrome/immunology , Dysbiosis/immunology , Gastrointestinal Tract/immunology , Inflammatory Bowel Diseases/immunology , Lung/immunology , Pneumonia, Viral/immunology , Angiotensin-Converting Enzyme 2 , Antibodies, Monoclonal/therapeutic use , Antiviral Agents/therapeutic use , Betacoronavirus/immunology , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/microbiology , Coronavirus Infections/virology , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/microbiology , Cytokine Release Syndrome/virology , Cytokines/antagonists & inhibitors , Cytokines/genetics , Cytokines/immunology , Dysbiosis/drug therapy , Dysbiosis/microbiology , Dysbiosis/virology , Gastrointestinal Microbiome/immunology , Gastrointestinal Tract/drug effects , Gastrointestinal Tract/microbiology , Gastrointestinal Tract/virology , Gene Expression , Host-Pathogen Interactions/immunology , Humans , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/microbiology , Inflammatory Bowel Diseases/virology , Lung/drug effects , Lung/microbiology , Lung/virology , Pandemics , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/immunology , Pneumonia, Viral/drug therapy , Pneumonia, Viral/microbiology , Pneumonia, Viral/virology , Receptors, Virus/genetics , Receptors, Virus/immunology , SARS-CoV-2ABSTRACT
OBJECTIVE: Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was detected in faeces of patients with COVID-19, the activity and infectivity of the virus in the GI tract during disease course is largely unknown. We investigated temporal transcriptional activity of SARS-CoV-2 and its association with longitudinal faecal microbiome alterations in patients with COVID-19. DESIGN: We performed RNA shotgun metagenomics sequencing on serial faecal viral extractions from 15 hospitalised patients with COVID-19. Sequencing coverage of the SARS-CoV-2 genome was quantified. We assessed faecal microbiome composition and microbiome functionality in association with signatures of faecal SARS-CoV-2 infectivity. RESULTS: Seven (46.7%) of 15 patients with COVID-19 had stool positivity for SARS-CoV-2 by viral RNA metagenomic sequencing. Even in the absence of GI manifestations, all seven patients showed strikingly higher coverage (p=0.0261) and density (p=0.0094) of the 3' vs 5' end of SARS-CoV-2 genome in their faecal viral metagenome profile. Faecal viral metagenome of three patients continued to display active viral infection signature (higher 3' vs 5' end coverage) up to 6 days after clearance of SARS-CoV-2 from respiratory samples. Faecal samples with signature of high SARS-CoV-2 infectivity had higher abundances of bacterial species Collinsella aerofaciens, Collinsella tanakaei, Streptococcus infantis, Morganella morganii, and higher functional capacity for nucleotide de novo biosynthesis, amino acid biosynthesis and glycolysis, whereas faecal samples with signature of low-to-none SARS-CoV-2 infectivity had higher abundances of short-chain fatty acid producing bacteria, Parabacteroides merdae, Bacteroides stercoris, Alistipes onderdonkii and Lachnospiraceae bacterium 1_1_57FAA. CONCLUSION: This pilot study provides evidence for active and prolonged 'quiescent' GI infection even in the absence of GI manifestations and after recovery from respiratory infection of SARS-CoV-2. Gut microbiota of patients with active SARS-CoV-2 GI infection was characterised by enrichment of opportunistic pathogens, loss of salutary bacteria and increased functional capacity for nucleotide and amino acid biosynthesis and carbohydrate metabolism.
Subject(s)
COVID-19/complications , COVID-19/microbiology , Feces/microbiology , Feces/virology , SARS-CoV-2/isolation & purification , Adult , Aged , COVID-19/diagnosis , Female , Gastrointestinal Microbiome , Hospitalization , Humans , Longitudinal Studies , Male , Middle Aged , Pilot Projects , Prospective Studies , Young AdultABSTRACT
In addition to the typical respiratory response, new coronavirus disease 2019 (COVID-19) is also associated with very common gastrointestinal symptoms. Cases with gastrointestinal symptoms are more likely to be complicated by liver injury and acute respiratory distress syndrome (ARDS). If not treated in time, coma and circulatory failure may ensue. As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects the human body through the combination of angiotensin-converting enzyme 2 (ACE2) in the gastrointestinal tract, the mechanism underlying the gastrointestinal symptoms may involve damage to the intestinal mucosal barrier and promotion of the production of inflammatory factors. Indeed, after cells in the lungs become infected by SARS-CoV-2, effector CD4+ T cells reach the small intestine through the gut-lung axis, causing intestinal immune damage and diarrhea; early extensive use of antibacterial and antiviral drugs can also lead to diarrhea in patients. Thus, treatment options for COVID-19 patients should be promptly adjusted when they have gastrointestinal symptoms. As SARS-CoV-2 has been detected in the feces of COVID-19 patients, future prevention and control efforts must consider the possibility of fecal-oral transmission of the virus.