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While evaluating adolescents who have endured a history of vomiting for several days diarrheaMentioned the possible causes of viruses, including SARS-CoV-2 infection. His well-informed mother replied, “He has no respiratory symptoms. Does COVID cause gastrointestinal illness?”
Indeed, the gastrointestinal (GI) tract is not only a potential portal of viral invasion, but also a site of mediation of both local and distant damage, and thus a precursor to a more serious clinical phenotype. There is a possibility.
As we learn more about the clinical spectrum of COVID, it is becoming increasingly clear that certain features of gastrointestinal involvement may establish a timeline for the clinical course and possibly predict outcomes.
Gastrointestinal involvement is not surprising
How the gastrointestinal tract functions as a target organ for SARS-CoV-2 Assumed in the literature.. In part, this is related to the presence of abundant receptors for SARS-CoV-2 cell binding and internalization. The virus uses the angiotensin converting enzyme 2 (ACE-2) receptor to invade a variety of cells. These receptors are highly expressed not only in lung cells but also in intestinal cells. Binding of SARS-CoV-2 to the ACE-2 receptor allows GI involvement, causing microscopic mucosal inflammation, increased permeability, and altered intestinal absorption.
The Clinical GI symptoms of this include AnorexiaNausea, vomiting, diarrhea, and abdominal pain. the oldest, Or the only sign of COVID-19, often present before the onset of fever or respiratory symptoms. in fact, On and colleaguesThe term “GI-COVID” is used in discussions of patients with primary GI SARS-CoV-2 infections and symptoms.
Clinical course of gastrointestinal symptoms
After exposure to SARS-CoV-2, adults most commonly show respiratory symptoms and gastrointestinal symptoms 10% to 15% of cases.. However, the overall incidence of GI involvement during SARS-CoV-2 infection varies with age and in some children. More likely than an adult Reveal intestinal symptoms.
There are also differences in the reported incidence when comparing inpatients and non-inpatients. Early reports from the onset of the COVID-19 pandemic show that 11%――――43% Among the adult patients in the hospital, they showed gastrointestinal symptoms.Notably, the presence of GI symptoms Related to more serious illness Therefore, we predict the outcome of patients admitted to the hospital.
of Multicenter joint research When evaluating pediatric inpatients with COVID-19, GI symptoms were found in 57% of patients and 14% were the first. Adjusted by confounding factors, people with gastrointestinal symptoms were at increased risk of being admitted to the pediatric intensive care unit (PICU). Patients admitted to the PICU also had higher levels of serum C-reactive protein and aspartate aminotransferase.
New data for MIS-C
Previously healthy children and adolescents may develop serious and life-threatening complications of multisystem inflammatory syndrome (MIS-C) in children. 2-6 weeks after acute infection With SARS-CoV-2. MIS-C Looks like It is an immunostimulatory syndrome and is presumed to be a delay in the immunological sequelae of mild / asymptomatic SARS-CoV-2 infection.This response Appears as Hyperinflammation with peak antibody production after a few weeks.
One report Of the 186 MIS-C children in the United States, 92% of the organ systems involved are the gastrointestinal tract, followed by 80% of the cardiovascular system, 76% of the blood system, 74% of the mucosal skin system, and the respiratory system. It states that it is 70%. Affected children were hospitalized for a median of 7 days, 80% required intensive care and 20% were hospitalized. Mechanical ventilation, And 48% have vascular support. 2% died.of Similar studies Eighty-eight percent of patients admitted to New York City had gastrointestinal symptoms (abdominal pain, vomiting, and / or diarrhea). Retrospective chart review The majority of patients with MIS-C showed GI symptoms with potentially involvement in any part of the gastrointestinal tract, but inflammation of the ileum and colon was predominant.
Whittaker and colleagues Eight hospitals in the United Kingdom described the clinical characteristics of children who met the MIS-C criteria temporarily associated with SARS-CoV-2. In the presentation, all patients showed non-specific gastrointestinal symptoms such as fever (45%), abdominal pain (53%) and diarrhea (52%). During hospitalization, 50% developed shock with evidence of myocardial dysfunction.
Belay and colleagues He described the clinical features of a large cohort of MIS-C patients reported to the US Centers for Disease Control and Prevention (CDC). Of the 1733 patients identified, GI symptoms were reported in 53% -67%. More than half developed hypotension or shock and were admitted to the intensive care unit. Younger children presented more often with abdominal pain, in contrast to adolescents who showed more frequent respiratory symptoms.
of Multicenter retrospective study 38% of Italian children with COVID-19 who had a pandemic from the onset to the beginning of 2021 had GI symptoms. These symptoms are mild and self-limited and are comparable to other viral bowel infections. However, a subset of children (9.5%) showed severe GI symptoms of MIS-C, defined as a medical and / or radiological diagnosis of acute abdomen. appendicitis, Intussusception, pancreatitis, ascites collection, or diffuse mesenteritis requiring surgical examination. Overall, 42% of this group underwent surgery. The authors stated that abdominal pain, lymphopenia, and clinical manifestations of increased C-reactive protein and ferritin levels were associated with a 9-30-fold increase in the probability of these severe sequelae.In addition, the severity of gastrointestinal symptoms was correlated with age (5-10 years: overall response). [OR], 8.33;> 10 years: or 6.37). Again, the presence of gastrointestinal symptoms was a precursor to hospitalization and PICU hospitalization.
Given that GI symptoms are a common symptom of MIS-C, the diagnosis may be delayed as the clinician first considers other GI / viral infections. Inflammatory bowel diseaseAlso Kawasaki disease.. By quickly identifying GI involvement and recognizing potential outcomes, you can guide management and improve outcomes.
These studies provide a clear picture of the different presentation functions of COVID-19 and MIS-C. Although there may be other environmental / genetic factors that govern incidence, effects, and symptoms, the status of COVID as an ongoing pandemic provides global relevance to these observations.This is obvious in Recent reports Record prominent gastrointestinal symptoms in African children with COVID-19.
However, keep in mind that the public data cited here reflects the effects of early variants of SARS-CoV-2. The GI binding, effects, and aftermath of infection by delta and omicron mutants are not yet known.
Cause and effect, or just coincidence?
Insight into the etiology of MIS-C provided by Yonker and colleagues In their analysis of biological specimens from 100 children: 19 in MIS-C, 26 in acute COVID-19, and 55 controls. They found that in MIS-C children, the long-term presence of SARS-CoV-2 in the gastrointestinal tract releases the intestinal permeability biomarker zonulin, followed by the SARS-CoV-2 antigen transport into the bloodstream. Shown to be done. Leads to hyperinflammation. Later, they were able to reduce plasma SARS-CoV-2 spike antigen levels and inflammatory markers, resulting in clinical improvement after administration of the zonulin antagonist larazotide.
These observations on the potential mechanisms and triggers of MIS-C may provide biomarkers for early detection and / or strategy for the prevention and treatment of MIS-C.
Conclusion
The gastrointestinal tract is the target of the immune inflammatory response caused by SARS-CoV-2, and MIS-C is the main symptom of the resulting high degree of inflammation. These observations can increase awareness of the non-respiratory symptoms of SARS-CoV-2 infection by clinicians working in the emergency department and primary care environment.
Clues that may enhance the ability of pediatric clinicians to recognize the potential for severe GI involvement include the development of abdominal pain, leukopenia, and elevated inflammatory markers. Their presence should raise suspicion of MIS-C and lead to early evaluation.
Notably, COVID-19 mRNA vaccination Decreased incidence of MIS-C in adolescence.. This underscores the importance of COVID vaccination for all eligible children. Still, we are clearly cutting out our work. Of the 107 MIS-C children hospitalized in France, 31% were vaccinated adolescents. but, No one was completely vaccinated.. At the end of 2021 CDC data It was noted that less than 1% of vaccinated children (12-17 years) were completely vaccinated.
The Pfizer-BioNTech vaccine is currently available for children ages 5-11 years, ie Highest risk of MIS-C.. However, despite the approval of vaccines for these young children, access is restricted in some parts of the United States during times of high incidence.
We look forward to the widespread availability of pediatric vaccination strategies. In addition, it focuses on safe and effective treatments for SARS-CoV-2 infection and quickly establishes strategies to prevent and / or treat life-threatening symptoms and long-term effects of MIS-C. I want to for example, Recently reported The central role of the gut microbiota in immunity against SARS-CoV-2 infection provides the potential for “microbiota regulation” to reduce GI damage and increase vaccine efficacy.
William F. Ballistrelli, MD, is a professor of pediatrics at Dorothy MM Karsten. He is the Honorary Director of the Pediatric Liver Care Center. He is an Honorary Medical Director, Liver Transplantation; Professor of Cincinnati University School of Medicine, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center. He has been the director of the Department of Gastroenterology, Liver and Nutrition at Cincinnati Childrens for 25 years and frequently covers topics related to Gastroenterology, Liver and Nutrition in Medscape. Dr. Ballistrelli is currently the Editor-in-Chief. Pediatrics Journal, Previously, he was the editor-in-chief of several journals and textbooks. He was also the first pediatrician to serve as president of the American Association for the Study of Hepatology. In his spare time, he teaches young lacrosse.
