Covid-19 in Children

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the novel coronavirus that is the causative agent of Covid-19 and the global pandemic that started at the end of 2019. Information regarding Covid-19 is changing rapidly as our understanding of the virus and its transmission and effects evolves. Staying up to date with changes in the virus, the pandemic itself, the response to vaccination, national guidelines, and local practices is critical.

Because of lack of access to testing early on in the pandemic, pediatric cases of Covid-19 were likely higher than reported. As of May 2023, the American Academy of Pediatrics (AAP) reported about 15 million children (representing 18% of all cases) have tested positive for Covid-19 in the United States since the onset of the pandemic. Although children typically have milder disease than adults, multisystem inflammatory syndrome in children (MIS-C), which has many similarities to Kawasaki disease, is a rare sequela of SARS-CoV-2 infection in children.

SARS-CoV-2 in the Neonate

Infection with SARS-CoV-2 during pregnancy is associated with complications in addition to preterm birth and perinatal morbidity. Vertical transmission of SARS-CoV-2 via the intrauterine, intrapartum, or peripartum route has been reported but is rare. Transmission from mother to neonate primarily occurs through droplet spread after birth. The risk for neonatal infection is higher if the mother has onset of Covid-19 symptoms close to the time of delivery. Most infants who have had documented infection have been asymptomatic or mildly symptomatic. More-severe illness has been reported but appears to be rare, and infants with underlying conditions, including prematurity, may be at greater risk.

Guidelines for the care of the neonate born to a mother with Covid-19 are center-specific and rapidly changing. The AAP has developed recommendations to guide the care of infants born to mothers with Covid-19.

Covid-19 Presentation in Children

Symptoms: Although a large proportion of children with SARS-CoV-2 do not have symptoms, 6% of children have been reported to have moderate-to-severe illness. Vaccination significantly reduces the severity of illness. The presentation of Covid-19 in children is similar to the presentation in adults. The most common symptoms described in children with Covid-19 include fever, chills, and cough — symptoms frequently indistinguishable from other respiratory viral infections. In general, children have milder symptoms and more-frequent reports of gastrointestinal symptoms (diarrhea, nausea, and abdominal pain) than adults. These gastrointestinal symptoms may occur in the absence of respiratory symptoms. The unique occurrence of reddish discoloration of the toes has been described in patients of all ages but more often in older children and adults.

Multisystem inflammatory syndrome in children (MIS-C): MIS-C is a disease process that has features similar to Kawasaki disease and occurs in a minority of children following infection with SARS-CoV-2. As of May 2023, the CDC has reported 9472 cases of MIS-C and 79 deaths. In an early case series of 186 children in the United States with MIS-C, the average age was 8.3 years, 31% were Hispanic or Latino, 25% were Black non-Hispanic, and 19% were white. The majority of children (80%) required intensive care, 20% received mechanical ventilation, and 48% required vasoactive support. Four children (2%) died.

A 2021 report of 539 pediatric patients with MIS-C and 577 pediatric patients with Covid-19 indicated that patients with MIS-C were more likely than children with Covid-19 alone to be 6−12 years of age, non-Hispanic Black, and have cardiovascular or mucocutaneous involvement. In this study, 74% of children with MIS-C and 44% of children with Covid-19 were admitted to the intensive care unit. Ten children (1.9%) with MIS-C and eight (1.4%) with Covid-19 died during the follow-up period.

Reports of MIS-C cases during the 2022 Delta and Omicron waves suggest that variant type may affect the development and severity of MIS-C. Data also demonstrate that vaccination is protective against MIS-C.

The following is the CDC case definition for MIS-C associated with Covid-19:

• An individual aged <21 years presenting with fever as defined below*, laboratory evidence of inflammation**, and evidence of clinically severe illness requiring hospitalization, with multisystem (>2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic, or neurologic); AND

• No alternative plausible diagnoses; AND

• Positive for current or recent SARS-CoV-2 infection by reverse transcription-polymerase chain-reaction (RT-PCR), serology, or antigen test; or Covid-19 exposure within the 4 weeks prior to the onset of symptoms

*Fever ≥38.0°C for ≥24 hours, or report of subjective fever lasting ≥24 hours

**Including, but not limited to, one or more of the following: an elevated C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen, procalcitonin, D-dimer, ferritin, lactic dehydrogenase (LDH), or interleukin-6 (IL-6), elevated neutrophils, reduced lymphocyte count, and low albumin

Cardiac manifestations of MIS-C: Although the symptoms of MIS-C are similar to those of Kawasaki disease, MIS-C appears to be a unique entity, with the following distinctive cardiac or laboratory manifestations:

• elevated B-type natriuretic peptide (BNP) levels

• elevated troponins

• ventricular dysfunction

• hypotension requiring vasoactive support

• coronary artery aneurysms

Some children who fulfill full or partial criteria for Kawasaki disease should be reported if they meet the case definition for MIS-C. Consider MIS-C in fatal pediatric cases that are associated with a history of prior SARS-CoV-2 infection.

Covid-19 and ARDS: Most morbidity and mortality in children with Covid-19 is related to acute hypoxemia secondary to acute respiratory distress syndrome (ARDS). Children are at risk for the development of pediatric ARDS, especially if underlying risk factors exist. Guidelines on the management of pediatric ARDS can be found on the NIH website.

Complications of Covid-19: Data suggest that children who have been infected with Covid-19 can experience long-term symptoms known as “long Covid” or “post-Covid” syndrome. Although a pediatric case definition for long Covid has not been established, children may experience fatigue, shortness of breath, and cognitive dysfunction significant enough to interfere with school attendance or participation in extracurricular activities. Some studies indicate that symptoms may wane over time.

Treatment

Treatment of children diagnosed with Covid-19 should involve pediatric infectious disease consultation, as management guidelines are continuously being updated. Treatment guidelines have been published by the National Institute of Health as well as the Infectious Diseases Society of America.

The behavioral, educational, and emotional toll on children during the pandemic has been substantial and may have long-lasting effects. The American Academy of Pediatrics has published “Interim Guidance on Supporting the Emotional and Behavioral Health Needs of Children, Adolescents, and Families During the Covid-19 Pandemic” to address the impact of these often unrecognized challenges. Further, given the interruption in delivery of routine preventive care, immunization rates declined during the pandemic resulting in health care inequality. Assessment of immunization status and updating of vaccines when indicated is critical during all pediatric encounters.

Treatment of MIS-C requires a multidisciplinary team typically comprised of rheumatologists, infectious disease specialists, cardiologists, and intensivists. The American College of Rheumatology has created treatment guidelines for pediatric patients with MIS-C that continue to be updated.

Prevention

Prevention of Covid-19 is a critical part of keeping children and the community in which they live healthy. Although children are less severely affected, some children do become significantly ill and may transmit viruses to people in other age groups who have higher rates of morbidity and mortality. Spread can be limited when children older than 2 years wear masks when interacting with others outside their household and, like adults, practice hand hygiene and physical distancing, avoiding crowds and unnecessary travel until community rates drop significantly.

Covid-19 vaccines: Messenger RNA (mRNA) vaccines and adenovirus vector vaccines were rapidly developed early on in the pandemic to protect against SARS-CoV-2 infection. However, vaccine distribution and administration have varied widely. In the United States, both mRNA vaccines (Pfizer-BioNTech and Moderna) are available for children as young as 6 months of age. Recently, the Novavax polysaccharide vaccine was approved for individuals age 12 years and older. The vaccines have been very effective at reducing the risk of severe illness. Waning immunity and the emergence of new variants have necessitated the development of variant-specific boosters.