Skip to main content
U.S. flag

An official website of the United States government

Dot gov

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Https

Secure .gov websites use HTTPS
A lock () or https:// means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.

Special Considerations in Children

Last Updated: August 8, 2022

Key Considerations
Key Considerations
  • SARS-CoV-2 infection is generally milder in children than in adults, and a substantial proportion of children with the infection are asymptomatic.
  • Most nonhospitalized children with COVID-19 will not require any specific therapy.
  • Observational studies describe associations between severe COVID-19 and the presence of ≥1 comorbid conditions, including cardiac disease, neurologic disorders, prematurity (in young infants), diabetes, obesity (particularly severe obesity), chronic lung disease, feeding tube dependence, and immunocompromised status. Age (<1 year and 10–14 years) and non-White race/ethnicity are also associated with severe disease.
  • Most children hospitalized for severe COVID-19 have not been fully vaccinated or are not eligible for COVID-19 vaccination.
  • Data on the pathogenesis and clinical spectrum of SARS-CoV-2 infection are more limited for children than for adults.
  • Vertical transmission of SARS-CoV-2 appears to be rare, but suspected or probable cases of vertical transmission have been described.
  • A small subset of children and young adults with SARS-CoV-2 infection may develop multisystem inflammatory syndrome in children (MIS-C). Many patients with MIS-C require intensive care management. The majority of children with MIS-C do not have underlying comorbid conditions.
  • Data on the prevalence of post-COVID conditions in children are limited but suggest that younger children may have fewer persistent symptoms than older children and adults.
Each recommendation in the Guidelines receives 2 ratings that reflect the strength of the recommendation and the quality of the evidence that supports it. See Guidelines Development for more information.

This section provides an overview of the epidemiology and clinical spectrum of disease, including COVID-19, multisystem inflammatory syndrome in children (MIS-C), and post-COVID conditions. This section also includes information on risk factors for severe COVID-19, vertical transmission, and infants born to a birth parent with SARS-CoV-2 infection. Throughout this section, COVID-19 refers to the acute, primarily respiratory illness due to infection with SARS-CoV-2. MIS-C refers to the postinfectious inflammatory condition.

For information on the prevention, treatment, and management of severe complications of COVID-19 in children, see:

Epidemiology

Data from the Centers for Disease Control and Prevention (CDC) demonstrate that SARS-CoV-2 infection and severe disease and death due to COVID-19 occur less often in children than in adults.1-4 However, the true burden of pediatric SARS-CoV-2 infection remains unclear, as children with mild symptoms are seldom systematically tested, and contact tracing and seroprevalence studies are not generally conducted. Seroprevalence data have suggested that, as of mid-2021, most children did not have evidence of prior SARS-CoV-2 infection. However, among children and adolescents, the estimated number of SARS-CoV-2 infections that occurred through May 2021 was 4.7 to 8.9 times greater than the number of COVID-19 cases.5 In a report from the CDC, by February 2022, approximately 75% of children and adolescents had serologic evidence of prior SARS-CoV-2 infection.6

Data on the pathogenesis and disease severity of SARS-CoV-2 infection in children are increasing but are still limited compared to the adult data. Although only a small percentage of children with COVID-19 will require medical attention, the percentage of intensive care unit (ICU) admissions among hospitalized children is comparable to that for hospitalized adults with COVID-19.7-18

Children from some racial and ethnic groups experience disproportionate rates of COVID-19-related hospitalization, which may be a result of barriers to accessing health care and economic and structural inequities. From 2020 to 2021, Black/African American children with COVID-19 in the United States were 2 times more likely to be hospitalized and 5 times more likely to be admitted to the ICU than White children.19

A U.S. study of children with COVID-19 who were hospitalized between April and September 2020 reported an association between race/ethnicity and disease severity.20 In a large United Kingdom study, admission to critical care was independently associated with hospitalized children who self-reported as being of Black ethnicity.14 A study in England reported that children who identified as Asian were more likely than children who identified as White to be hospitalized for COVID-19 and to be admitted to an ICU.21 The study also found that children who identified as Black or as mixed or other races/ethnicities had significantly more hospitalizations than children who identified as White.

Clinical Manifestations of COVID-19

The signs and symptoms of SARS-CoV-2 infection in symptomatic children may be similar to those in adults; however, a greater proportion of children may be asymptomatic or have only mild illness when compared with adults. Although the true incidence of asymptomatic SARS-CoV-2 infection is unknown, a small study reported that 45% of children who underwent surveillance testing at the time of hospitalization for a non-COVID-19 indication had asymptomatic infection.22 The most common signs and symptoms of COVID-19 in hospitalized children are fever, nausea/vomiting, cough, shortness of breath, and upper respiratory symptoms.14,23 The signs and symptoms of COVID-19 may overlap significantly with those of influenza and other respiratory and enteric viral infections. Critical disease, including respiratory failure, acute respiratory distress syndrome, and, less commonly, shock, may occur in children with COVID-19.24,25 The overall incidence of SARS-CoV-2 infection and, by extension, COVID-19-related hospitalizations among children has increased substantially with the emergence of recent variants of concern (VOCs), particularly Omicron.18,26

Risk Factors for Severe COVID-19

Risk factors for severe COVID-19 identified by observational studies and meta-analyses include having ≥1 comorbidities, such as cardiac disease, neurologic disorders, prematurity (in young infants), diabetes, obesity (particularly severe obesity), chronic lung disease, feeding tube dependence, and immunocompromised status. Demographic factors, such as age (<1 year and 10–14 years) and non-White race/ethnicity, have also been associated with severe disease. However, many studies did not assess the relative severity of underlying medical conditions.

Many published studies reported an increased relative risk of severe disease in children with comorbidities, but the absolute risk of severe COVID-19 among children remains low. However, protocolized admissions for certain populations (e.g., febrile young infants) may confound the association between comorbid conditions and severe COVID-19. Most children who have been hospitalized for severe COVID-19 have not been fully vaccinated—many were not eligible for COVID-19 vaccination because of their age. The CDC has additional information on the underlying conditions that are risk factors for severe COVID-19.

The children most likely to benefit from treatment are nonhospitalized patients with mild to moderate COVID-19 who are at the highest risk for severe COVID-19 (e.g., those with severe comorbidities). For a description of children considered at high risk for severe COVID-19 and the COVID-19 Treatment Guidelines Panel’s (the Panel) recommendations for their treatment, see Therapeutic Management of Hospitalized Children With COVID-19.

Age

Among all children, infants and adolescents have the highest risk of COVID-19-related ICU admission or death. From March 2020 to mid-August 2021, U.S. children aged <5 years had the highest cumulative COVID-19-related hospitalization rates, followed closely by adolescents.27 Children aged 5 to 11 years had the lowest hospitalization rates. From July to August 2021, when the Delta variant was the dominant VOC, 25% of 713 children admitted to 6 U.S. hospitals were aged <1 year, 17% were aged 1 to 4 years, 20% were aged 5 to 11 years, and 38% were aged 12 to 17 years.28 From March 2020 to mid-June 2021, 26.5% of 3,116 U.S. children hospitalized for COVID-19 were admitted to an ICU.27

An individual patient data meta-analysis reported that patients aged <1 year and those aged 10 to 14 years had the highest risks of ICU admission and death among hospitalized children with COVID-19.29 Another meta-analysis reported that neonates, but not infants aged 1 to 3 months, had an increased risk of severe COVID-19 compared with other pediatric age groups.30 When Omicron was the dominant circulating VOC, hospitalization rates among children and adolescents were higher than when the Delta VOC was dominant, and they were highest for children aged <5 years.26,31 However, the proportion of hospitalized children requiring ICU admission was significantly lower when the Omicron VOC was dominant.

Comorbidities

Several chronic conditions are prevalent in hospitalized children with COVID-19. When the Delta variant was the dominant VOC in the United States, 68% of hospitalized children had ≥1 underlying medical condition, such as obesity (32%), asthma or reactive airway disease (16%), or feeding tube dependence (8%). Obesity was present in approximately a third of hospitalized children aged 5 to 11 years, 60% of whom had a body mass index (BMI) ≥120% of the 95th percentile. For adolescents, 61% had obesity; of those patients, 61% had a BMI ≥120% of the 95th percentile.28

Meta-analyses and observational studies identified risk factors for ICU admission, mechanical ventilation, or death among hospitalized children with COVID-19.30,32,33 These risk factors included prematurity in young infants, obesity, diabetes, chronic lung disease, cardiac disease, neurologic disease, and immunocompromising conditions. Another study found that having a complex chronic condition that affected ≥2 body systems or having a progressive chronic condition or continuous dependence on technology for ≥6 months (e.g., dialysis, tracheostomy with ventilator assistance) was significantly associated with an increased risk of moderate or severe COVID-19.34 The study also found that having more severe chronic disease (e.g., active cancer treated within the previous 3 months or asthma with hospitalization within the previous 12 months), when compared with less severe conditions, increased the risk of critical COVID-19 or death. The CDC has additional information on the underlying conditions that are risk factors for severe COVID-19.

Having multiple comorbidities increases the risk of severe COVID-19 in children. A meta-analysis of data from children hospitalized with COVID-19 found that the risk of ICU admission was greater for children with 1 chronic condition than for those with no comorbid conditions, and the risk increased substantially as the number of comorbidities increased.29

COVID-19 Vaccination Status

Vaccination remains the most effective way to prevent SARS-CoV-2 infection and should be considered the first line of prevention. Most children hospitalized for COVID-19 were not fully vaccinated or were not eligible to receive COVID-19 vaccination because of their age.16,18,28,35 With the wider availability of COVID-19 vaccines for younger children, the number of COVID-19 cases among children may decrease over time.

Mortality

Death from COVID-19 is uncommon in children. Risk factors for death include having chronic conditions, such as neurologic or cardiac disease, and having multiple comorbidities. Among children aged <21 years in the United States, deaths associated with COVID-19 have been higher for children aged 10 to 20 years, especially for young adults aged 18 to 20 years, and for those who identify as Hispanic, Black, or American Indian/Alaskan Native.36,37

A systematic review and meta-analysis reported that neurologic or cardiac comorbidities were associated with the greatest increase in risk of death among hospitalized children with COVID-19.29 In the same study, an individual patient data meta-analysis reported that the risk of COVID-19-related death was greater for children with 1 chronic condition than for those with no comorbid conditions, and the risk increased substantially as the number of comorbidities increased.

Vertical Transmission and Infants Born to People With SARS-CoV-2 Infection

A systematic review and meta-analysis reported that confirmed vertical transmission of SARS-CoV-2 appears to be rare, and severe maternal COVID-19 has been associated with SARS-CoV-2 infection in babies.38 In 2 large, combined cohorts of pregnant individuals from the United States and United Kingdom, SARS-CoV-2 infection was reported in 1.8% and 2% of the babies born to people with SARS-CoV-2 infection.39

Case reports have described intrauterine fetal demise during the third trimester of pregnancy in individuals with mild COVID-19 due to infection with the Delta VOC.40,41 These individuals had evidence of placental SARS-CoV-2 infection, placental malperfusion, and placental inflammation. One case report described a person with asymptomatic SARS-CoV-2 infection and severe preeclampsia who gave birth at 25 weeks of gestation by emergency cesarean delivery. The neonate died on Day 4, and evidence of SARS-CoV-2 infection was found in placental tissues and in the infant’s lungs and vascular endothelium at autopsy.42 Evidence of placental SARS-CoV-2 infection was reported in 5 stillbirths and for 1 live-born neonate in Sweden.43

A systematic review of neonatal SARS-CoV-2 infections reported that 70% were due to postpartum transmission, and 30% were due to vertical transmission from an infected birth parent.44 Another systematic review reported that newborn infants rooming-in with the birth parent did not have an increased risk of SARS-CoV-2 transmission when compared with newborns who were isolated from the birth parent.45

Detection of SARS-CoV-2 RNA in the breast milk of individuals with confirmed cases of COVID-19 is very uncommon.46 Currently, there is no evidence of SARS-CoV-2 transmission through breast milk.47 Breast milk from people with SARS-CoV-2 infection can contain antibodies to SARS-CoV-2.48,49

Multisystem Inflammatory Syndrome in Children

A small subset of children and young adults with SARS-CoV-2 infection, including those with asymptomatic infection, may develop MIS-C. This syndrome is also called pediatric multisystem inflammatory syndrome—temporally associated with SARS-CoV-2 (PMIS-TS). Although the case definitions for these syndromes differ slightly, they are likely the same disease. The syndrome was first described in Europe, where previously healthy children with severe inflammation and Kawasaki disease-like features were identified as having current or recent infection with SARS-CoV-2.

The clinical spectrum of MIS-C has been described in the United States and is similar to that described for PMIS-TS. MIS-C is consistent with a postinfectious inflammatory syndrome related to SARS-CoV-2.50,51 Most patients with MIS-C have serologic evidence of previous SARS-CoV-2 infection, but only a minority have had a positive reverse transcription polymerase chain reaction (RT-PCR) result for SARS-CoV-2 at presentation.52,53

The peak population-based incidence of MIS-C lags about 4 weeks behind the peak of acute pediatric COVID-19-related hospitalizations. Emerging data suggests that adults may develop a similar syndrome, multisystem inflammatory syndrome in adults (MIS-A), although it is not clear if this postinfectious complication is similar to MIS-C.52-54 Published data that characterize the condition are limited.

Although risk factors for the development of MIS-C have not been established, an analysis of MIS-C cases in the United States found that ICU admission was more likely for patients aged 6 to 12 years than for younger children, and it was more likely for children who identified as non-Hispanic Black than for those who identified as non-Hispanic White.55 Unlike most children who present with severe COVID-19, the majority of children who present with MIS-C do not seem to have common underlying comorbid conditions other than obesity.55 In addition, children whose deaths were related to MIS-C were less likely to have underlying medical conditions than children who died of COVID-19.37

Emerging evidence suggests that COVID-19 vaccination protects against the development of MIS-C.56,57 The development of MIS-C after COVID-19 vaccination is very rare.56,58

Clinical Manifestations of Multisystem Inflammatory Syndrome in Children

The current CDC case definition for MIS-C is an individual aged <21 years who:

  • Presents with fever,a laboratory evidence of inflammation,b and evidence of clinically severe illness requiring hospitalization, with multisystem (i.e., >2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic, or neurological); and
  • Has no alternative plausible diagnoses; and
  • Is positive for current or recent SARS-CoV-2 infection by RT-PCR, antigen test, or serology results; or COVID-19 exposure within the 4 weeks prior to the onset of symptoms.59

a Fever >38.0°C for ≥24 hours or report of subjective fever lasting ≥24 hours

b Including, but not limited to, ≥1 of the following: elevated levels of C-reactive protein, fibrinogen, procalcitonin, D-dimer, ferritin, lactic acid dehydrogenase, or interleukin (IL)-6; an elevated erythrocyte sedimentation rate or neutrophil count; or a reduced lymphocyte count or albumin level

Distinguishing MIS-C from other febrile illnesses in the community setting remains challenging, but the presence of persistent fever, multisystem manifestations, and laboratory abnormalities could help early recognition.60 The clinical spectrum of hospitalized cases has included younger children with mucocutaneous manifestations that overlap with Kawasaki disease, older children with more multiorgan involvement and shock, and patients with respiratory manifestations that overlap with COVID-19.

Patients with MIS-C are often critically ill, and up to 80% of children require ICU admission.61 Most patients with MIS-C have markers of cardiac injury or dysfunction, including elevated levels of troponin and brain natriuretic protein; higher levels of these markers are associated with ICU admission, myocardial dysfunction, and shock.55 In these cases, echocardiographic findings may include impaired left ventricular function, coronary artery dilations, and, rarely, coronary artery aneurysms. The reported mortality in the United States for hospitalized children with MIS-C is 1% to 2%. Longitudinal studies to examine the long-term sequelae of MIS-C are currently ongoing.

The pathogenesis of MIS-C is still being elucidated and may include distinct humoral immune responses, innate immune activation, or a superantigen effect. Differences between MIS-C and typical Kawasaki disease have been demonstrated in terms of epidemiology, cytopenias, cytokine expression, and elevation of inflammatory markers. Immunologic profiling has also shown differences in cytokine expression (tumor necrosis factor alpha and IL-10) between MIS-C and COVID-19 in children.62-64

For the Panel’s recommendations on the treatment of MIS-C, see Therapeutic Management of Hospitalized Pediatric Patients With Multisystem Inflammatory Syndrome in Children (MIS-C) (With Discussion on Multisystem Inflammatory Syndrome in Adults [MIS-A]).

Post-COVID Conditions

Persistent symptoms after COVID-19 have been described in adults and are an active area of research in children, although data on the incidence of post-COVID sequelae in children are limited and somewhat conflicting (see Clinical Spectrum of SARS-CoV-2 Infection).65-67 Cardiac imaging studies have described myocardial injury in young athletes who had only mild disease;68 additional studies are needed to identify long-term cardiac sequelae.

The reported clinical manifestations and duration of post-COVID conditions in children are highly variable.69 Not all studies included controls without SARS-CoV-2 infection, which makes determining the true incidence a challenge. The incidence of post-COVID symptoms appears to increase with age. The most common symptoms reported include persistent fatigue, headache, shortness of breath, sleep disturbances, and altered sense of smell.

Among children, health care utilization increases following COVID-19. A Norwegian study of 10,279 children with and 275,859 without SARS-CoV-2 infection reported that primary care visits for children aged 6 to 15 years increased for up to 3 months after a positive SARS-CoV-2 test result when compared with controls.66,70 For preschool-age children, visits increased for up to 6 months.

In a study of 6,804 adolescents in England, 30% of the 3,065 participants who tested positive for SARS-CoV-2 infection reported ≥3 symptoms at a 3-month follow-up visit.71 Common symptoms included tiredness (39%), headache (23%), and shortness of breath (23%). In the same study, only 16% of the 3,739 participants who tested negative for SARS-CoV-2 infection reported ≥3 symptoms at the 3-month follow-up visit.

A study in Denmark examined persistent symptoms among 16,836 children with and 16,620 children without SARS-CoV-2 infection. The number of children with SARS-CoV-2 infection who reported symptoms that persisted for >4 weeks increased as age increased. Among the preschool-age children, more children in the control arm than in the SARS-CoV-2 arm reported experiencing symptoms that persisted for >4 weeks.72

Additional research is needed to define the incidence, spectrum, and severity of post-COVID conditions in children and to identify optimal strategies for prevention, diagnosis, and treatment of those conditions.

References

  1. Centers for Disease Control and Prevention. COVID-19 weekly cases and deaths per 100,000 population by age, race/ethnicity, and sex. 2022. Available at: https://covid.cdc.gov/covid-data-tracker/#demographicsovertime. Accessed July 26, 2022.
  2. Centers for Disease Control and Prevention. Provisional COVID-19 deaths: focus on ages 0–18 years. 2022. Available at: https://data.cdc.gov/NCHS/Provisional-COVID-19-Deaths-Focus-on-Ages-0-18-Yea/nr4s-juj3. Accessed July 26, 2022.
  3. Centers for Disease Control and Prevention. Demographic trends of COVID-19 cases and deaths in the US reported to CDC. 2022. Available at: https://covid.cdc.gov/covid-data-tracker/#demographics. Accessed July 26, 2022.
  4. Centers for Disease Control and Prevention. COVID-NET laboratory-confirmed COVID-19 hospitalizations. 2022. Available at: https://covid.cdc.gov/covid-data-tracker/#covidnet-hospitalization-network. Accessed July 26, 2022.
  5. Couture A, Lyons BC, Mehrotra ML, et al. Severe acute respiratory syndrome coronavirus 2 seroprevalence and reported coronavirus disease 2019 Cases in US children, August 2020–May 2021. Open Forum Infect Dis. 2022;9(3):ofac044. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35198651.
  6. Clarke KEN, Jones JM, Deng Y, et al. Seroprevalence of infection-induced SARS-CoV-2 antibodies—United States, September 2021–February 2022. MMWR Morb Mortal Wkly Rep. 2022;71(17):606-608. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35482574.
  7. Dong Y, Mo X, Hu Y, et al. Epidemiology of COVID-19 among children in China. Pediatrics. 2020;145(6):e20200702. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32179660.
  8. CDC COVID-19 Response Team. Coronavirus disease 2019 in children—United States, February 12–April 2, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(14):422-426. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32271728.
  9. Cui X, Zhang T, Zheng J, et al. Children with coronavirus disease 2019: a review of demographic, clinical, laboratory, and imaging features in pediatric patients. J Med Virol. 2020;92(9):1501-1510. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32418216.
  10. Livingston E, Bucher K. Coronavirus disease 2019 (COVID-19) in Italy. JAMA. 2020;323(14):1335. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32181795.
  11. Tagarro A, Epalza C, Santos M, et al. Screening and severity of coronavirus disease 2019 (COVID-19) in children in Madrid, Spain. JAMA Pediatr. 2020;Published online ahead of print. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32267485.
  12. DeBiasi RL, Song X, Delaney M, et al. Severe coronavirus disease-2019 in children and young adults in the Washington, DC, metropolitan region. J Pediatr. 2020;223:199-203. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32405091.
  13. Chao JY, Derespina KR, Herold BC, et al. Clinical characteristics and outcomes of hospitalized and critically ill children and adolescents with coronavirus disease 2019 at a tertiary care medical center in New York City. J Pediatr. 2020;223:14-19. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32407719.
  14. Swann OV, Holden KA, Turtle L, et al. Clinical characteristics of children and young people admitted to hospital with COVID-19 in United Kingdom: prospective multicentre observational cohort study. BMJ. 2020;370:m3249. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32960186.
  15. Gotzinger F, Santiago-Garcia B, Noguera-Julian A, et al. COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study. Lancet Child Adolesc Health. 2020;4(9):653-661. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32593339.
  16. Shi DS, Whitaker M, Marks KJ, et al. Hospitalizations of children aged 5–11 years with laboratory-confirmed COVID-19—COVID-NET, 14 states, March 2020–February 2022. MMWR Morb Mortal Wkly Rep. 2022;71(16):574-581. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35446827.
  17. Siegel DA, Reses HE, Cool AJ, et al. Trends in COVID-19 cases, emergency department visits, and hospital admissions among children and adolescents aged 0–17 years—United States, August 2020–August 2021. MMWR Morb Mortal Wkly Rep. 2021;70(36):1249-1254. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34499628.
  18. Marks KJ, Whitaker M, Anglin O, et al. Hospitalizations of children and adolescents with laboratory-confirmed COVID-19—COVID-NET, 14 states, July 2021–January 2022. MMWR Morb Mortal Wkly Rep. 2022;71(7):271-278. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35176003.
  19. Holmes L, Jr, Wu C, Hinson R, et al. Black-White risk differentials in pediatric COVID-19 hospitalization and intensive care unit admissions in the USA. J Racial Ethn Health Disparities. 2022;Published online ahead of print. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35604543.
  20. Antoon JW, Grijalva CG, Thurm C, et al. Factors associated with COVID-19 disease severity in US children and adolescents. J Hosp Med. 2021;16(10):603-610. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34613896.
  21. Saatci D, Ranger TA, Garriga C, et al. Association between race and COVID-19 outcomes among 2.6 million children in England. JAMA Pediatr. 2021;175(9):928-938. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34152371.
  22. Poline J, Gaschignard J, Leblanc C, et al. Systematic severe acute respiratory syndrome coronavirus 2 screening at hospital admission in children: a French prospective multicenter study. Clin Infect Dis. 2021;72(12):2215-2217. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32710743.
  23. Kim L, Whitaker M, O’Halloran A, et al. Hospitalization rates and characteristics of children aged <18 years hospitalized with laboratory-confirmed COVID-19—COVID-NET, 14 states, March 1–July 25, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(32):1081-1088. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32790664.
  24. Feldstein LR, Tenforde MW, Friedman KG, et al. Characteristics and outcomes of US children and adolescents with multisystem inflammatory syndrome in children (MIS-C) compared with severe acute COVID-19. JAMA. 2021;325(11):1074-1087. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33625505.
  25. Bhalala US, Gist KM, Tripathi S, et al. Characterization and outcomes of hospitalized children with coronavirus disease 2019: a report from a multicenter, viral infection and respiratory illness universal study (coronavirus disease 2019) registry. Crit Care Med. 2022;50(1):e40-e51. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34387240.
  26. Marks KJ, Whitaker M, Agathis NT, et al. Hospitalization of infants and children aged 0–4 years with laboratory-confirmed COVID-19—COVID-NET, 14 states, March 2020–February 2022. MMWR Morb Mortal Wkly Rep. 2022;71(11):429-436. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35298458.
  27. Delahoy MJ, Ujamaa D, Whitaker M, et al. Hospitalizations associated with COVID-19 among children and adolescents—COVID-NET, 14 states, March 1, 2020–August 14, 2021. MMWR Morb Mortal Wkly Rep. 2021;70(36):1255-1260. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34499627.
  28. Wanga V, Gerdes ME, Shi DS, et al. Characteristics and clinical outcomes of children and adolescents aged <18 years hospitalized with COVID-19—six hospitals, United States, July–August 2021. MMWR Morb Mortal Wkly Rep. 2021;70(5152):1766-1772. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34968374.
  29. Harwood R, Yan H, Talawila Da Camara N, et al. Which children and young people are at higher risk of severe disease and death after hospitalisation with SARS-CoV-2 infection in children and young people: a systematic review and individual patient meta-analysis. EClinicalMedicine. 2022;44:101287. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35169689.
  30. Choi JH, Choi SH, Yun KW. Risk factors for severe COVID-19 in children: a systematic review and meta-analysis. J Korean Med Sci. 2022;37(5):e35. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35132841.
  31. Dorabawila V, Hoefer D, Bauer UE, et al. Risk of infection and hospitalization among vaccinated and unvaccinated children and adolescents in New York after the emergence of the Omicron variant. JAMA. 2022;327(22):2242-2244. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35559959.
  32. Shi Q, Wang Z, Liu J, et al. Risk factors for poor prognosis in children and adolescents with COVID-19: a systematic review and meta-analysis. EClinicalMedicine. 2021;41:101155. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34693233.
  33. Kompaniyets L, Agathis NT, Nelson JM, et al. Underlying medical conditions associated with severe COVID-19 illness among children. JAMA Netw Open. 2021;4(6):e2111182. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34097050.
  34. Forrest CB, Burrows EK, Mejias A, et al. Severity of acute COVID-19 in children <18 years old March 2020 to December 2021. Pediatrics. 2022;149(4):e2021055765. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35322270.
  35. Olson SM, Newhams MM, Halasa NB, et al. Effectiveness of BNT162b2 vaccine against critical COVID-19 in adolescents. N Engl J Med. 2022;386(8):713-723. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35021004.
  36. Bixler D, Miller AD, Mattison CP, et al. SARS-CoV-2-associated deaths among persons aged <21 years—United States, February 12–July 31, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(37):1324-1329. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32941417.
  37. McCormick DW, Richardson LC, Young PR, et al. Deaths in children and adolescents associated with COVID-19 and MIS-C in the United States. Pediatrics. 2021;148(5):e2021052273. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34385349.
  38. Allotey J, Chatterjee S, Kew T, et al. SARS-CoV-2 positivity in offspring and timing of mother-to-child transmission: living systematic review and meta-analysis. BMJ. 2022;376:e067696. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35296519.
  39. Mullins E, Hudak ML, Banerjee J, et al. Pregnancy and neonatal outcomes of COVID-19: coreporting of common outcomes from PAN-COVID and AAP-SONPM registries. Ultrasound Obstet Gynecol. 2021;57(4):573-581. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33620113.
  40. Shook LL, Brigida S, Regan J, et al. SARS-CoV-2 placentitis associated with B.1.617.2 (Delta) variant and fetal distress or demise. J Infect Dis. 2022;225(5):754-758. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35024844.
  41. Guan M, Johannesen E, Tang CY, et al. Intrauterine fetal demise in the third trimester of pregnancy associated with mild infection with the SARS-CoV-2 Delta variant without protection from vaccination. J Infect Dis. 2022;225(5):748-753. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35024853.
  42. Reagan-Steiner S, Bhatnagar J, Martines RB, et al. Detection of SARS-CoV-2 in neonatal autopsy tissues and placenta. Emerg Infect Dis. 2022;28(3):510-517. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35138244.
  43. Zaigham M, Gisselsson D, Sand A, et al. Clinical-pathological features in placentas of pregnancies with SARS-CoV-2 infection and adverse outcome: case series with and without congenital transmission. BJOG. 2022;129(8):1361-1374. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35243759.
  44. Raschetti R, Vivanti AJ, Vauloup-Fellous C, et al. Synthesis and systematic review of reported neonatal SARS-CoV-2 infections. Nat Commun. 2020;11(1):5164. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33060565.
  45. Walker KF, O’Donoghue K, Grace N, et al. Maternal transmission of SARS-CoV-2 to the neonate, and possible routes for such transmission: a systematic review and critical analysis. BJOG. 2020;127(11):1324-1336. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32531146.
  46. Kumar J, Meena J, Yadav A, Kumar P. SARS-CoV-2 detection in human milk: a systematic review. J Matern Fetal Neonatal Med. 2021;35(25):5456-5463. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33550866.
  47. Centeno-Tablante E, Medina-Rivera M, Finkelstein JL, et al. Transmission of SARS-CoV-2 through breast milk and breastfeeding: a living systematic review. Ann N Y Acad Sci. 2021;1484(1):32-54. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32860259.
  48. Bauerl C, Randazzo W, Sanchez G, et al. SARS-CoV-2 RNA and antibody detection in breast milk from a prospective multicentre study in Spain. Arch Dis Child Fetal Neonatal Ed. 2022;107(2):216-221. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34417223.
  49. Duncombe CJ, McCulloch DJ, Shuey KD, et al. Dynamics of breast milk antibody titer in the six months following SARS-CoV-2 infection. J Clin Virol. 2021;142:104916. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34315010.
  50. Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet. 2020;395(10237):1607-1608. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32386565.
  51. Whittaker E, Bamford A, Kenny J, et al. Clinical characteristics of 58 children with a pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2. JAMA. 2020;324(3):259-269. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32511692.
  52. Dufort EM, Koumans EH, Chow EJ, et al. Multisystem inflammatory syndrome in children in New York State. N Engl J Med. 2020;383(4):347-358. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32598830.
  53. Feldstein LR, Rose EB, Horwitz SM, et al. Multisystem inflammatory syndrome in U.S. children and adolescents. N Engl J Med. 2020;383(4):334-346. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32598831.
  54. Morris SB, Schwartz NG, Patel P, et al. Case series of multisystem inflammatory syndrome in adults associated with SARS-CoV-2 infection—United Kingdom and United States, March–August 2020. MMWR Morb Mortal Wkly Rep. 2020;69(40):1450-1456. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33031361.
  55. Abrams JY, Oster ME, Godfred-Cato SE, et al. Factors linked to severe outcomes in multisystem inflammatory syndrome in children (MIS-C) in the USA: a retrospective surveillance study. Lancet Child Adolesc Health. 2021;5(5):323-331. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33711293.
  56. Zambrano LD, Newhams MM, Olson SM, et al. Effectiveness of BNT162b2 (Pfizer-BioNTech) mRNA vaccination against multisystem inflammatory syndrome in children among persons aged 12–18 years—United States, July–December 2021. MMWR Morb Mortal Wkly Rep. 2022;71(2):52-58. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35025852.
  57. Levy M, Recher M, Hubert H, et al. Multisystem inflammatory syndrome in children by COVID-19 vaccination status of adolescents in France. JAMA. 2022;327(3):281-283. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34928295.
  58. Yousaf AR, Cortese MM, Taylor AW, et al. Reported cases of multisystem inflammatory syndrome in children aged 12–20 years in the USA who received a COVID-19 vaccine, December, 2020, through August, 2021: a surveillance investigation. Lancet Child Adolesc Health. 2022;6(5):303-312. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35216660.
  59. Centers for Disease Control and Prevention. Information for healthcare providers about multisystem inflammatory syndrome in children (MIS-C). 2021. Available at: https://www.cdc.gov/mis/mis-c/hcp/index.html. Accessed July 26, 2022.
  60. Carlin RF, Fischer AM, Pitkowsky Z, et al. Discriminating multisystem inflammatory syndrome in children requiring treatment from common febrile conditions in outpatient settings. J Pediatr. 2021;229:26-32. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33065115.
  61. Godfred-Cato S, Bryant B, Leung J, et al. COVID-19-associated multisystem inflammatory syndrome in children—United States, March–July 2020. MMWR Morb Mortal Wkly Rep. 2020;69(32):1074-1080. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32790663.
  62. Lee PY, Day-Lewis M, Henderson LA, et al. Distinct clinical and immunological features of SARS-CoV-2-induced multisystem inflammatory syndrome in children. J Clin Invest. 2020;130(11):5942-5950. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32701511.
  63. Rowley AH, Shulman ST, Arditi M. Immune pathogenesis of COVID-19-related multisystem inflammatory syndrome in children. J Clin Invest. 2020;130(11):5619-5621. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32870815.
  64. Diorio C, Henrickson SE, Vella LA, et al. Multisystem inflammatory syndrome in children and COVID-19 are distinct presentations of SARS-CoV-2. J Clin Invest. 2020;130(11):5967-5975. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32730233.
  65. Zimmermann P, Pittet LF, Curtis N. How common is long COVID in children and adolescents? Pediatr Infect Dis J. 2021;40(12):e482-e487. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34870392.
  66. Zimmermann P, Pittet LF, Curtis N. Long COVID in children and adolescents. BMJ. 2022;376:o143. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35058281.
  67. Molteni E, Sudre CH, Canas LS, et al. Illness duration and symptom profile in symptomatic UK school-aged children tested for SARS-CoV-2. Lancet Child Adolesc Health. 2021;5(10):708-718. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34358472.
  68. Rajpal S, Tong MS, Borchers J, et al. Cardiovascular magnetic resonance findings in competitive athletes recovering from COVID-19 infection. JAMA Cardiol. 2021;6(1):116-118. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32915194.
  69. Fainardi V, Meoli A, Chiopris G, et al. Long COVID in children and adolescents. Life (Basel). 2022;12(2):285. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35207572.
  70. Magnusson K, Skyrud KD, Suren P, et al. Healthcare use in 700,000 children and adolescents for six months after COVID-19: before and after register based cohort study. BMJ. 2022;376:e066809. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35039315.
  71. Stephenson T, Pinto Pereira SM, Shafran R, et al. Physical and mental health 3 months after SARS-CoV-2 infection (long COVID) among adolescents in England (CLoCk): a national matched cohort study. Lancet Child Adolesc Health. 2022;6(4):230-239. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35143770.
  72. Borch L, Holm M, Knudsen M, Ellermann-Eriksen S, Hagstroem S. Long COVID symptoms and duration in SARS-CoV-2 positive children—a nationwide cohort study. Eur J Pediatr. 2022;181(4):1597-1607. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35000003.