BY JANET COULTER, MSN, MS, RN, CCM, FCM, AND MARYANN OTT, RN, BSN, CCM, CPC
The COVID-19 pandemic resembles a blockbuster horror movie. Understanding the effects of COVID-19 on children is a challenge, and the findings remain controversial. Most children who contract COVID-19 experience mild symptoms or no symptoms at all. According to the National Institutes of Health, COVID-19 is milder in children than in adults, and a substantial proportion of children with COVID-19 are asymptomatic. Most children with mild or moderate COVID-19 will not progress to more severe illness and can be managed with supportive care alone. Children who are severely immunocompromised or have underlying medical conditions such as chronic lung disease, obesity, cardiopulmonary disease, congenital heart disease or neurological and developmental disorders are at a higher risk of being infected with COVID-19 (World Health Organization, 2022).
A small number of children develop a delayed immune post-viral hyper-inflammatory response called “multisystem inflammatory syndrome in children,” which is referred to as MIS-C. This syndrome can develop in children with no prior COVID-19 symptoms and can cause severe inflammation in organs and tissues including the heart, lungs, blood vessels, kidneys, brain, eyes, skin, gastrointestinal system and liver. MIS-C symptoms can range from mild to severe depending upon the areas of the body that are inflamed. Symptoms may include persistent fever, abdominal pain, vomiting, diarrhea, skin rash, hypotension, confusion or shock. Liver enzymes may be elevated. The American Association for the Study of Liver Diseases recommends evaluation of all children with elevated transaminases. It is thought that the organ damage is not caused by the virus but by the immune response after the virus disappears. Children with autoimmune hepatitis, inflammatory bowel disease or non-alcoholic fatty liver disease (NAFLD) may have a higher incidence of MIS-C (Stevens, Brownell, Freeman, and Bashaw, 2020). Additionally, there are higher risk factors in the United States among children of Black and Latino heritage. Those factors may be due to genetic risks and differences in healthcare information access (Mayo Clinic, 2021).
Many specialists consider MIS-C to be a complication of COVID-19. Acute pancreatitis can be the first symptom of MIS-C. Appendicitis, intussusception or peritonitis may occur but are rare (Stevens, Brownell, Freeman, and Bashaw, 2020). Most of the children with MIS-C do not seem to have underlying comorbid conditions other than obesity. Also, most children eventually get better with medical care. However, without early diagnosis and treatment, some children could rapidly progress to permanent damage or even death (Mayo Clinic, 2021).
MIS-C is rare and usually occurs between the ages of 3 and 12 years old, with the average age being 8 years old. Children with MIS-C are often critically ill, and up to 80% require admission to an intensive care unit. The peak incidence of MIS-C lags about four weeks behind the peak of acute pediatric COVID-19 hospitalizations. There are no results available from clinical trials that evaluated treatments for COVID-19 in children. Observational data on the safety or efficacy of drug therapy in children with COVID-19 are extremely limited. More high-quality studies, including randomized trials, are urgently needed. The reported mortality rate in the United States for hospitalized children with MIS-C is 1% to 2%. Longitudinal studies are currently ongoing to examine the long-term effects of MIS-C (Genceli, Akcan, Pekan, 2022).
The effects of MIS-C on the livers of children are getting worldwide attention. The increased number of reports of acute hepatitis of unknown origin among young children could be due to an increase in hepatitis cases or an increase in the awareness and reporting of cases. The actual cause remains unknown. Symptoms include markedly elevated liver enzymes, abdominal pain, diarrhea and vomiting. The common viruses that can cause viral hepatitis (hepatitis viruses A, B, C, D and E) have not been detected. International travel or links to other countries have not been identified as factors. As of April 2022, at least 169 cases of acute hepatitis of unknown origin have been reported. Adenovirus has been detected in 74 cases. Case have been reported in 11 countries including the United Kingdom of Great Britain, Northern Ireland, Spain, Israel, the United States, Denmark and the Republic of Ireland. These children are between one month and 16 years old. Ten percent have required a liver transplant and at least one death has been reported. The United Kingdom has experienced a significant increase in adenovirus cases. They also reported 114 cases of hepatitis (World Health Organization, 2022).
In a study titled, “Long COVID-19 Liver Manifestation in Children,” researchers in Israel published findings from a small, retrospective study that suggests that prior infection with COVID-19, and its impact on the immune system, could play a role in the hepatitis outbreak. The study describes five children, between three months and 13 years old, who recovered from a mild or asymptomatic COVID-19 infection and later showed signs of liver damage. All the subjects were previously healthy and tested negative for the usual culprits of liver injury. The researchers hypothesized that the liver damage was not caused by the virus itself, but rather the immune response after the virus disappears. This is similar to the symptoms of long COVID phenomena. The children in the study didn’t meet the diagnostic criteria for MIS-C. This study has several limitations. The sample size was very small; the study was observational and the mechanisms of liver injury were not investigated (Cooper, Tobar, Konen, Orenstein, 2022).
The occurrence of acute liver injury has been reported in liver transplant recipients; however, the findings on children remain controversial. Another study found that COVID-19 cases among pediatric liver transplant recipients had a high complication rate. This is the first extensive, worldwide report on the impact of COVID-19 on pediatric liver transplant recipients. No mortality was reported. Pediatric liver transplant recipients who had undergone transplantation less than six months before contracting COVID-19 had a greater number of hospital admissions than those who had undergone transplantation more than six months prior. The researchers proposed that pediatric liver transplant recipients should be followed closely (Sin, Díaz, Martínez, 2021).
An article published in Pediatric Gastroenterology and Nutrition reported that early in the pandemic, COVID-19 disease was mostly mild in pediatric solid organ transplant recipients with no rejection, patient death or graft loss observed (Sin, Díaz, Martínez, Mercedes 2021) (Paul, Royal, Lee, 2022).
Continued monitoring, testing and research is imperative to better understand how the COVID-19 virus works and the short- and long-term effects on children. MIS-C and post COVID-19 liver injury in children is not fully understood. The United States Centers for Disease Control and Prevention and the National Institutes of Health are working to learn more about risk factors, improving diagnosis and treatment of MIS-C. Although research is a step in the right direction, right now we are left with more questions than answers.
Stevens, J., Brownell, J., Freeman, J., and Bashaw, H. (2020). Long COVID-19 Liver Manifestations in Children. Journal of Pediatric Gastroenterology and Nutrition, 71, 669-671.
Sin, P., Díaz, L., Martínez, M., More (2021). Acute Liver Injury Among Pediatric Liver Transplantation Recipients with Coronavirus Disease 2019: An International Collaborative Study. Journal of Pediatric Gastroenterology and Nutrition, 73, 391-394.
Cooper S., Tobar A., Konen O., Orenstein N., More. (2022). Long COVID-19 Liver Manifestations in Children. Journal of Pediatric Gastroenterology and Nutrition, 74, 3521.
Mayo Clinic. (2021) Multisystem inflammatory syndrome in children (MIS-C) and COVID-19. Retrieved From the Mayo Clinic website: https://www.mayoclinic.org.
World Health Organization (2022, April 23). Multi-Country – Acute, Severe Hepatitis of Unknown Origin in Children. Retrieved From the World Health Organization website https://www.WHO.int.
Gençeli, M., Akcan, O., Pekcan, S., More (2022). Outcomes of COVID-19 Infections in Children: A Single-Center Retrospective Study. Pediatric Pulmonology, 10,1002.
Paul, S., Royal, S., Lee, M., More (2022) SARS-CoV-2 Infection in Pediatric Solid Organ Transplant Recipients – A Single Center Observation. Journal of Pediatric Gastroenterology and Nutrition, 74, 3548.
Janet Coulter, MSN, MS, RN, CCM, FCM, is a transplant case manager with a wide variety of experiences including educator, administrator, team leader and director of case management. Janet holds a master of science in nursing degree from West Virginia University and a master of science in adult education degree from Marshall University. She has published many articles in CMSA Today and the Professional Case Management Journal and served as a reviewer for the Core Curriculum for Case Management Third Edition. She currently serves as Chair of the CMSA Today Editorial Board and Secretary of the CMSA Foundation board. Janet was the recipient of the CMSA National Award of Service Excellence and Southern Ohio Valley CMSA Case Management Leadership award and was recently inducted as a Case Management Fellow from CMSA.
Maryann Ott, RN, BSN, CCM, CPC, is retired from the State of Ohio, Bureau of Workers’ Compensation. In addition to being a Certified Case Manager, she is also a Certified Professional Coder. Maryann has a diversified background in many aspects of nursing and case management. She has co-presented at CMSA annual and chapter conferences and is a co-editor for articles in CMSA Today. She is the Co-founder and three-term past president of the Cleveland Chapter of CMSA. Currently, she is serving as the chapter treasurer.
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