June 15, 2020
Responses by: Beth Thielen, MD, PhD- Medical Fellow, Infectious Disease and International Medicine and Pediatric Infectious Diseases and Immunology
How likely are children to be infected with SARS-CoV2-?
In a study from China examining the spread of SARS-CoV-2 within households, children were just as likely as adults to become infected. However, children were less likely to develop severe symptoms or have typical symptoms like fever. This likely led to underdiagnosis of SARS-CoV-2 infection in children because early on in the COVID-19 pandemic, there were shortages of testing supplies and testing was prioritized for hospitalized patients. Even now with wider availability of testing, the numbers of children being tested remains low so we do not yet know how many children have been infected with SARS-CoV-2. The use of population-based surveillance and antibody testing may help us better understand how many children have been infected.
Does SARS-CoV2 affect children differently than adults?
SARS-CoV-2 infection can cause a febrile respiratory illness in children similar to adults, but there is increasing evidence for a unique syndrome in children that seems to be linked to SARS-CoV-2 infection. Beginning in February and March 2020, pediatricians caring for children in Europe began to see children with a hyperinflammatory syndrome termed Paediatric Multisystem Inflammatory Syndrome temporally associated with COVID-19 or PIMS-TS. Shortly afterwards, a similar syndrome was observed among children in parts of the United States hit earliest by COVID-19. As a result of these observations by clinicians, the Centers for Disease Control and Prevention issued a health advisory that established a case definition for this new syndrome termed Multisystem Inflammatory Syndrome in Children or MIS-C. Since then, cases of this syndrome have been diagnosed around the United States, including in Minnesota.
The characteristics of this syndrome include fever and signs of inflammation in multiple body tissues, including the heart, gastrointestinal tract, kidneys, brain and skin. Gastrointestinal symptoms including abdominal pain, vomiting and diarrhea are common but difficulty breathing and cough are much less common than in adults. The majority of these children test positive by at least one SARS-CoV-2 laboratory test. These include both PCR tests that detect the viral RNA genome and serologies, which detect antibodies made by the infected person’s immune system to fight the virus. Epidemiological studies have shown regional peaks of MIS-C/PIMS-TS occur several weeks after the peaks of SARS-CoV-2 infections occurring in these same regions.
Because of the delays observed between SARS-CoV-2 exposure and onset of MIS-C, physicians speculate that this may be a post-inflammatory complication of infection rather than direct effect of the virus. This has important implications for treatment as the disease may be more responsive to immunomodulatory medications rather than direct antiviral medication.
There are also some similarities between MIS-C and a childhood illness called Kawasaki disease. Kawasaki disease was initially described in the 1960s and is a rare inflammatory disorder of children. It is characterized by inflammation of the blood vessels, including those in the heart and skin. Some features of this disorder suggest it may be triggered by an infectious disease, including clusters of cases that occur during the winter and spring months. However, there has never been one single infection consistently linked to this disorder.
Although there are some similarities between MIS-C and Kawasaki disease, there are important differences as well. While most children diagnosed with Kawasaki disease are preschool age, a larger percentage of MIS-C cases have been older children, including in teenagers. Both Kawasaki disease and MIS-C can affect the heart, but the way in which the heart is affected has been different. In severe cases, Kawasaki disease causes inflammation and enlargement of the coronary arteries, the blood vessels that deliver blood to the heart muscle itself. In severe cases of MIS-C, the disease affects the heart muscle directly and can cause dangerously low blood pressures. While this can occur in typical Kawasaki disease, it is much less common than in patients with MIS-C. Lastly, most patients with Kawasaki disease improve when given treatment with intravenous immunoglobulin, high levels of pooled antibodies from human donors that help to dampen the immune response. Patients with MIS-C more commonly require additional anti-inflammatory treatments. Thus, MIS-C seems to be a new and unique clinical entity.
What treatments are available for children with COVID-19 or MIS-C?
Several types of treatment have been employed for children with COVID-19.
- The majority of children most likely will not need any specific treatment beyond supportive care as most infections are probably mild.
- Remdesivir is an antiviral medication that has been shown to shorten time to recovery from SARS-CoV-2 infection in adult patients, specifically those admitted to the hospital with respiratory failure. This drug is currently available for adult patients via an Emergency Use Authorization from the Food and Drug Administration. There is limited data on the use of remdesivir in children, but the drug can be obtained for use in pediatric patients on a compassionate use basis.
- In children with MIS-C, the disease affects many organ systems so it is recommended that affected children be cared for in centers, such as the University of Minnesota Masonic Children’s Hospital, that have access to interdisciplinary care, including specialists in pediatric critical care, infectious diseases, cardiology, hematology, and rheumatology. Though not all children with MIS-C will become critically ill, access to appropriate supportive care in intensive care units is critical for these children, specifically those who develop heart involvement.
- Because MIS-C shares many common features with Kawasaki disease, treatment approaches have been adopted from what we know works for Kawasaki disease. Intravenous immunoglobulin and aspirin are the mainstay of treatment for Kawasaki disease but many children with MIS-C do not improve with these therapies alone. Many other types of immune modulating therapies are being explored, including corticosteroids and monoclonal antibody therapies that block a variety of pro-inflammatory signaling molecules called cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha). Many children also received anticoagulant medications to prevent clots, similar to adult patients. At this point we do not know which of these therapies will work best to treat MIS-C. Because the number of children affected nationwide is small, collaboration between these specialized pediatric centers to study and share best practices is key.
The good news is that, with appropriate care, most children recover from SARS-CoV-2 infection.