COVID-19 in Children

Masked child sitting in hospital bed holding a stuffed toy.There is a great deal still to learn about how COVID-19 infection affects children. Children can become infected with the virus that causes COVID-19 and can get sick with COVID-19. Although most have mild or no symptoms, children with underlying medical conditions and infants younger than 1 year old may be at increased risk for severe illness from COVID-19.

Physicians around the world are also investigating multisystem inflammatory syndrome in children (MIS-C) that seems to be related to previous exposure to COVID-19. MIS-C is a spectrum of inflammatory processes with features that overlap with toxic shock syndrome and are similar to the heart condition known as Kawasaki disease. MIS-C can present with symptoms seemingly unrelated to COVID-19, such as severe abdominal pain. MIS-C usually affects school-age children, specifically those who were previously healthy and who may have initially had only mild COVID-19 symptoms or no symptoms at all.

Among NICHD’s efforts are co-leading, with the National Institute on Drug Abuse, the Trans-NIH COVID-19 Workgroup on Pregnant & Lactating Women and Children, which coordinates NIH’s Strategic Response Activities for these populations.

Some NICHD research activities, including collaborations across NIH, on COVID-19 in children and MIS-C include the following :

  • The Trans-NIH COVID-19 Workgroup on Pregnant & Lactating Women and Children supported several projects to better understand the effects of the COVID-19 pandemic on children and adolescents, including brain and cognitive development, substance use, and mental health in adolescents; and prenatal exposure to environmental tobacco smoke, COVID-19-related psychosocial stress, and neurodevelopment.
    • The COVID pandemic has not only put people at risk for adverse physical and mental health outcomes, but it has also made it more difficult to access services that might mitigate them. Promising interventions, particularly in a virtual setting, can help promote access to treatment resources to address stressors related to the COVID-19 pandemic. Several research groups are studying these issues by examining access to care and adapting interventions for populations at high risk for poor outcomes, including traumatized youth or chronically stressed youth.
  • NIH’s Collaboration to Assess Risk and Identify loNG-term outcomes for Children with COVID (CARING for Children with COVID) program aims to better understand why symptoms vary among children with COVID-19 disease, and how to identify children at risk for severe illness from SARS-CoV-2 infection, including MIS-C. NIH effort seeks to understand MIS-C, range of SARS-CoV-2 effects on children explains more about the CARING for Children with COVID program.
  • Methods to distinguish children at risk for severe COVID-19 complications, including conditions such as MIS-C, are needed for earlier interventions to improve pediatric outcomes. Multiple HHS divisions, including NICHD, are working together on the Pediatric COVID-19 Data Challenge to leverage de-identified electronic health records to study COVID-19 in children. This challenge encourages researchers to develop, train, and validate computational models that can predict severe COVID-19 complications so that healthcare providers have the information and tools they need to identify at-risk pediatric patients.
  • In addition, HHS has organized an interagency team, which includes leadership teams from NICHD and the National Heart, Lung, and Blood Institute, among other institutes, centers, and offices, to collaboratively address the Departmental response to MIS-C. This interagency team is collaborating with domestic and international partners to better understand MIS-C, including its epidemiology, establish a coordinated system for surveillance and research, and eventually provide guidance and recommendations to parents and healthcare providers. NICHD will be involved in the coordination of clinical trials, primarily through its funded networks.
    • For example, the International Maternal, Pediatric, Adolescent AIDS Clinical Trials (IMPAACT) Network, co-funded by NICHD, the National Institute of Allergy and Infectious Diseases, and the National Institute of Mental Health (NIMH), is a global collaboration that conducts clinical trials of HIV (and other infectious diseases) therapy, prevention, and potential remission/cure in maternal, pediatric, and adolescent patients. IMPAACT researchers are initiating a study to characterize immune responses in U.S. children with a history of COVID-19 infection and identify associations with the clinical course of COVID-19. The researchers will collect biosamples, medical history (including HIV exposure), and demographics at enrollment and at several follow-up visits over 2 to 12 months. This project can shed light on why most children have mild COVID-19 disease, investigate the impact of HIV co-infection, and potentially serve as controls/comparison population for studies of MIS-C.
  • An NICHD-led project—Predicting Viral-Associated Inflammatory Disease Severity in Children with Laboratory Diagnostics and Artificial Intelligence (PreVAIL kIds)—aims to encourage development of cutting-edge approaches for understanding the underlying factors that influence the spectrum of conditions that may occur in children infected with the SARS-CoV-2 virus. Part of the trans-NIH Rapid Acceleration of Diagnostics (RADxSM) initiative, PreVAIL kIds aims to understand the range of symptoms of COVID-19 and the factors leading to MIS-C. Studies funded through PreVAIL kIds will evaluate genes and other biomarkers in COVID-19 pediatric cases, as well as examine how the virus interacts with its host and how the immune system responds.
  • NICHD will manage the Safe Return to School Diagnostic Testing Initiative, a part of the RADx-Underserved Populations (RADx-UP) program, which will fund projects to build evidence on safely returning students, teachers, and support staff to in-person school in areas with vulnerable and underserved populations.
    • The ABC Science Collaborative, an initiative connecting scientists and physicians with school and community leaders across 18 states, published a suite of research on COVID-19 and the return to in-person learning in underserved K-12 schools external link. Research focuses on topics such as implementing diagnostic testing programs, supporting COVID-19 school safety for children with disabilities and medical complexity, and adhering to mask policies in K-12 schools, among other topics. The collaborative is funded in part by RADx-UP, as part of its Safe Return to School Diagnostic Testing Initiative, and PTN.
  • The institute is also working with NIMH on a range of studies related to the effects of the pandemic on school-age children. These projects, which include studies of the mental health effects of school disruptions and development of new diagnostic approaches to enable the return to in-person school, will provide an evidence base for the U.S. effort to get children back to in-person learning.
    • Safe Return to School For All external link summarizes current evidence and best practices to help administrators, educators, and families and students—including students with disabilities—return to school safely in the context of COVID-19. The information provided is based on collaborative research from the NICHD-funded Washington University Intellectual and Developmental Disabilities Research Center, the University of Missouri-Kansas City Institute of Human Development, and the Kennedy Krieger Institute (Maryland), in collaboration with the Special School District of St. Louis County, Missouri.

The NIH Director’s Blog post, What We Know About COVID-19’s Effects on Child and Maternal Health featured highlights from an interview with NICHD Director Diana W. Bianchi, M.D., and NIH Director Francis S. Collins, M.D., Ph.D., during which they discussed SARS-CoV-2 and COVID in children.

Dr. Bianchi also used her March Director’s Corner to discuss NIH-wide efforts to understand Post-Acute Sequelae of COVID (PASC), long-term effects of infection that persist after a person should feel better. NICHD will be studying children who are among these so-called “COVID long haulers.” Dr. Bianchi highlights some more recent research on PASC in children in her December blog: Understanding Long COVID in Children.

Beyond the short- and long-term effects of COVID-19 on children’s physical health, NICHD researchers are also examining the mental and emotional impact on children who experience the sudden loss of a parent due to COVID complications. A study funded by NICHD’s Population Dynamics Branch provides estimates and projections of COVID-19 and parental death in the United States (PMID: 33818598). The study found that between 37,300 and 43,000 children have lost a parent to COVID-19 (for comparison, the September 11, 2001, attacks left 3,000 children without a parent). Black children are disproportionately affected, comprising only 14% of U.S. children but 20% of those who lost a parent to COVID-19. Additional research is needed to understand the level and type of assistance these children will need as well as their grief processes.