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1.
Mucosal Immunol ; 14(6): 1381-1392, 2021 11.
Article in English | MEDLINE | ID: covidwho-1366810

ABSTRACT

The SARS-CoV-2 pandemic has so far claimed over three and a half million lives worldwide. Though the SARS-CoV-2 mediated disease COVID-19 has first been characterized by an infection of the upper airways and the lung, recent evidence suggests a complex disease including gastrointestinal symptoms. Even if a direct viral tropism of intestinal cells has recently been demonstrated, it remains unclear, whether gastrointestinal symptoms are caused by direct infection of the gastrointestinal tract by SARS-CoV-2 or whether they are a consequence of a systemic immune activation and subsequent modulation of the mucosal immune system. To better understand the cause of intestinal symptoms we analyzed biopsies of the small intestine from SARS-CoV-2 infected individuals. Applying qRT-PCR and immunohistochemistry, we detected SARS-CoV-2 RNA and nucleocapsid protein in duodenal mucosa. In addition, applying imaging mass cytometry and immunohistochemistry, we identified histomorphological changes of the epithelium, which were characterized by an accumulation of activated intraepithelial CD8+ T cells as well as epithelial apoptosis and subsequent regenerative proliferation in the small intestine of COVID-19 patients. In summary, our findings indicate that intraepithelial CD8+ T cells are activated upon infection of intestinal epithelial cells with SARS-CoV-2, providing one possible explanation for gastrointestinal symptoms associated with COVID-19.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Duodenum/immunology , Immunity, Mucosal , Intestinal Diseases/immunology , Intestinal Mucosa/immunology , Intraepithelial Lymphocytes/immunology , Lymphocyte Activation , SARS-CoV-2/immunology , Adult , Aged , Animals , Apoptosis , CD8-Positive T-Lymphocytes/virology , COVID-19/pathology , COVID-19/virology , Case-Control Studies , Cell Proliferation , Chlorocebus aethiops , Duodenum/pathology , Duodenum/virology , Female , Host-Pathogen Interactions , Humans , Intestinal Diseases/pathology , Intestinal Diseases/virology , Intestinal Mucosa/pathology , Intestinal Mucosa/virology , Intraepithelial Lymphocytes/virology , Male , Re-Epithelialization , SARS-CoV-2/pathogenicity , Vero Cells , Viral Load
2.
Am J Surg Pathol ; 46(1): 89-96, 2022 01 01.
Article in English | MEDLINE | ID: covidwho-1254925

ABSTRACT

Approximately 20% of patients with symptomatic syndrome-associated coronavirus-2 (SARS-CoV-2) infection have gastrointestinal bleeding and/or diarrhea. Most are managed without endoscopic evaluation because the risk of practitioner infection outweighs the value of biopsy analysis unless symptoms are life-threatening. As a result, much of what is known about the gastrointestinal manifestations of coronavirus disease-2019 (COVID-19) has been gleaned from surgical and autopsy cases that suffer from extensive ischemic injury and/or poor preservation. There are no detailed reports describing any other gastrointestinal effects of SARS-CoV-2 even though >3,000,000 people have died from COVID-19 worldwide. The purpose of this study is to report the intestinal findings related to SARS-CoV-2 infection by way of a small case series including one with evidence of direct viral cytopathic effect and 2 with secondary injury attributed to viral infection. Infection can be confirmed by immunohistochemical stains directed against SARS-CoV-2 spike protein, in situ hybridization for spike protein-encoding RNA, and ultrastructural visualization of viruses within the epithelium. It induces cytoplasmic blebs and tufted epithelial cells without inflammation and may not cause symptoms. In contrast, SARS-CoV-2 infection can cause gastrointestinal symptoms after the virus is no longer detected, reflecting systemic activation of cytokine and complement cascades rather than direct viral injury. Reversible mucosal ischemia features microvascular injury with hemorrhage, small vessel thrombosis, and platelet-rich thrombi. Systemic cytokine elaboration and dysbiosis likely explain epithelial cell injury that accompanies diarrheal symptoms. These observations are consistent with clinical and in vitro data and contribute to our understanding of the protean manifestations of COVID-19.


Subject(s)
COVID-19/pathology , Intestinal Diseases/pathology , Intestinal Diseases/virology , Intestines/pathology , Intestines/virology , Adult , Aged , Aged, 80 and over , Biomarkers/metabolism , Biopsy , COVID-19/diagnosis , COVID-19/immunology , Cytokines/metabolism , Gastrointestinal Hemorrhage/diagnosis , Gastrointestinal Hemorrhage/immunology , Gastrointestinal Hemorrhage/pathology , Gastrointestinal Hemorrhage/virology , Humans , Intestinal Diseases/diagnosis , Intestinal Diseases/immunology , Intestines/immunology , Ischemia/diagnosis , Ischemia/immunology , Ischemia/pathology , Ischemia/virology , Male , Thrombosis/diagnosis , Thrombosis/immunology , Thrombosis/pathology , Thrombosis/virology
3.
BMC Surg ; 21(1): 97, 2021 Feb 22.
Article in English | MEDLINE | ID: covidwho-1094031

ABSTRACT

BACKGROUND: In patients who are critically ill with COVID-19, multiple extrapulmonary manifestations of the disease have been observed, including gastrointestinal manifestations. CASE PRESENTATION: We present a case of a 65 year old man with severe COVID-19 pneumonia that developed hypercoagulation and peritonitis. Emergent laparotomy was performed and we found bowel necrosis in two sites. CONCLUSIONS: Although rare, the presentation of COVID-19 with bowel necrosis requires emergency treatments, and it has high mortality rate.


Subject(s)
COVID-19 , Intestinal Diseases , Aged , COVID-19/complications , COVID-19/therapy , Humans , Intestinal Diseases/pathology , Intestinal Diseases/virology , Male , Necrosis , Severity of Illness Index
4.
J Pediatr Gastroenterol Nutr ; 72(3): 384-387, 2021 03 01.
Article in English | MEDLINE | ID: covidwho-1072474

ABSTRACT

ABSTRACT: Multisystem inflammatory syndrome in children (MIS-C) is a recently identified syndrome that appears to be temporally associated with novel coronavirus 2019 infection. MIS-C presents with fever and evidence of systemic inflammation, which can manifest as cardiovascular, pulmonary, neurologic, and gastrointestinal (GI) system dysfunction. Presenting GI symptoms are seen in the majority, including abdominal pain, diarrhea, and vomiting. Any segment of the GI tract may be affected; however, inflammation in the ileum and colon predominates. Progressive bowel wall thickening can lead to luminal narrowing and obstruction. Most will have resolution of intestinal inflammation with medical therapies; however, in rare instances, surgical resection may be required.


Subject(s)
COVID-19/complications , Intestinal Diseases/virology , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/complications , Abdominal Pain/virology , Child , Diarrhea/virology , Female , Gastrointestinal Tract/virology , Humans , Male , Vomiting/virology
5.
Appl Microbiol Biotechnol ; 104(14): 6091-6100, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-306184

ABSTRACT

Porcine enteric coronaviruses (CoVs) cause highly contagious enteric diarrhea in suckling piglets. These COV infections are characterized by clinical signs of vomiting, watery diarrhea, dehydration, and high morbidity and mortality, resulting in significant economic losses and tremendous threats to the pig farming industry worldwide. Because the clinical manifestations of pigs infected by different CoVs are similar, it is difficult to differentiate between the specific pathogens. Effective high-throughput detection methods are powerful tools used in the prevention and control of diseases. The immune system of piglets is not well developed, so serological methods to detect antibodies against these viruses are not suitable for rapid and early detection. This paper reviews various PCR-based methods used for the rapid and efficient detection of these pathogenic CoVs in swine intestines. KEY POINTS: 1. Swine enteric coronaviruses (CoVs) emerged and reemerged in past years. 2. Enteric CoVs infect pigs at all ages with high mortality rate in suckling pigs. 3. Rapid and efficient detection methods are needed and critical for diagnosis.


Subject(s)
Coronavirus Infections/veterinary , Coronavirus/isolation & purification , Intestinal Diseases/veterinary , Polymerase Chain Reaction/methods , Swine Diseases/virology , Animals , Coronavirus/classification , Coronavirus/genetics , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Feces/virology , Intestinal Diseases/virology , Phylogeny , Swine , Swine Diseases/diagnosis
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