Coronavirus Disease 2019 (COVID-19) in Children 

Updated: Nov 16, 2020
  • Author: Ayesha Mirza, MD; Chief Editor: David J Cennimo, MD, FAAP, FACP, AAHIVS  more...
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Practice Essentials

Coronavirus disease 2019 (COVID-19) is an illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the United States and throughout the world, fewer cases of COVID-19 have been reported in children than in adults. Whereas children comprise 22% of the US population, 8.7% of all cases of COVID-19 reported to the Centers for Disease Control and Prevention (CDC) were among children (as of October 7, 2020). [1]  Most cases in children are mild, and treatment consists of supportive care. 

As of October 22, 2020, remdesivir, an antiviral agent, is the only drug approved for treatment of COVID-19. It is indicated for treatment of COVID-19 disease in hospitalized adults and children aged 12 years and older who weigh at least 40 kg. [2, 3]  An emergency use authorization (EUA) remains in place to treat pediatric patients weighing 3.5 kg to less than 40 kg or children younger than 12 years who weigh at least 3.5 kg. [4]  Several vaccines are in late stage phase 3 trials.

The American Academy of Pediatrics reports children represent more than 11% of all cases in the 49 states reporting by age. Over 927,000 children have tested positive in the United States since the onset of the pandemic as of November 5, 2020. [5]

Signs and symptoms of COVID-19 in children

Common symptoms of COVID-19 in children are cough and fever. It is important to note, however, that these symptoms may not always be present; thus, a high index of suspicion for SARS-CoV-2 infection is required in children. [6, 7, 8]  Other symptoms include the following:

  • Shortness of breath
  • Pharyngeal erythema/sore throat
  • Diarrhea
  • Myalgia
  • Fatigue
  • Rhinorrhea
  • Vomiting
  • Nasal congestion
  • Abdominal pain
  • Conjunctivitis
  • Rash
  • Loss of sense of taste (ageusia) and/or smell (anosmia)

Diagnosis

Laboratory studies

Although a consistent pattern of characteristic laboratory findings has not yet been identified in children with confirmed COVID-19, the following abnormalities have been observed:

  • Lymphopenia
  • Increased levels of liver and muscle enzymes and lactate dehydrogenase
  • Increased myoglobin and creatine kinase isoenzyme levels
  • Elevated C-reactive protein (CRP) level
  • Elevated erythrocyte sedimentation rate
  • Increased procalcitonin level
  • Elevated D-dimer

Imaging studies

Common chest radiograph findings in children with COVID-19 pneumonia include bilaterally distributed peripheral and subpleural ground-glass opacities and consolidation. [9]

Findings observed on computed tomography (CT) of the chest in children with COVID-19 include the following:

  • Ground-glass opacities/nodules
  • Consolidation with a surrounding halo sign
  • Bilateral or local patchy shadowing
  • Interstitial abnormalities

Management

Treatment consists mainly of supportive care, including oxygen therapy in children with hypoxia. 

Remdesivir, an antiviral agent, is the only drug approved by the US Food and Drug Administration (FDA) for treatment of COVID-19. Remdesivir gained emergency use authorization (EUA) from the FDA on May 1, 2020, based on preliminary data showing a faster time to recovery of hospitalized patients with severe disease. [4, 2]  The FDA expanded the EUA to include use in all hospitalized patients with confirmed or suspected COVID-19 disease, regardless of oxygen status. [10]  Convalescent plasma was granted EUA on August 23; however, safety and effectiveness in patients aged 18 years or younger have not been evaluated. The decision to treat patients < 18 years of age with COVID-19 convalescent plasma should be based on an individualized assessment of risk and benefit. For further information regarding administration, see the EUA COVID-19 Convalescent Fact Sheet for Health Care Providers. Numerous other antiviral agents, immunotherapies, and vaccines continue to be investigated and developed as potential therapies.

Please see Coronavirus Disease 2019 (COVID-19) for continually updated clinical guidance concerning COVID-19 and Treatment of Coronavirus Disease 2019 (COVID-19): Investigational Drugs and Other Therapies for updated drug information. Health care personnel are also referred to Medscape’s Novel Coronavirus Resource Center for the latest news, perspective, and resources.

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Background

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease was first reported in December 2019 from Wuhan, Hubei province, China and has since spread throughout the world. The World Health Organization declared a global pandemic on March 11, 2020. As of October 28, 2020 there were over 44 million confirmed cases of COVID-19 and over 1.1 million deaths reported globally. In the United States, confirmed cases as of October 28, 2020 is nearly 9 million with over 227,000 deaths. [10] As these numbers are constantly changing, the readers are referred to the Johns Hopkins Coronavirus Resource Center, CDC, and WHO websites for the most recent official numbers.

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Pathophysiology

Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infection is characterized by an initial cytokine storm that can result in acute respiratory distress syndrome and macrophage activation syndrome. This initial phase is then followed by a period of immune dysregulation, which is the major cause of sepsis-related fatalities. [11]

While we are learning more about SARS-CoV-2 infection almost daily, differences between adult and pediatric disease are likely the result of changes within both immune function and the angiotensin-converting enzyme (ACE) 2 receptor, used by the virus to enter type II pneumocytes in the lung. Decreases in ACE2 seen in animal models of aging result in changes in neutrophil influx and resultant lung injury. Thus, immunosenescence and changes in inflammatory responses with age likely account for the different spectrum and severity of disease in children versus adults and, furthermore, in neonates versus older children. The profound lymphopenia seen in patients with COVID-19 is likely the result of T lymphocyte infection and death that occurs as SARS CoV-2 infects these cells. [12]  

As the infection progresses, with acceleration in viral replication and epithelial-endothelial injury, the inflammatory response is accentuated. Interstitial mononuclear inflammatory infiltrates and edema followed by hyaline membrane formation occurs leading to acute respiratory distress syndrome (ARDS). These changes may be visible as ground glass opacities on a CT scan. Further injury to the endothelial tissues results in microthrombi formation and can lead to thrombotic complications such as pulmonary embolism, venous thrombosis, and thrombotic arterial complications as seen in severely ill patients. These complications have been seen more in adult than in pediatric patients, although they have been reported in the latter as well. Secondary sepsis in these individuals further contributes to the severity of the illness. [13, 14, 15]

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Etiology

Transmission

Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) is a highly infectious virus, [16]  and the main routes of transmission are respiratory droplets and contact with respiratory secretions and saliva. Aerosol particles may be another possible mode of transmission. [17] SARS CoV-2 can remain viable on various surfaces for hours to days, although transmission is much more common through respiratory droplets than through fomites. [18]  Fecal shedding has been detected for several weeks after diagnosis, which has led to concerns about fecal-oral transmission of the virus. [19]

Mother-to-child transmission

Based on limited data, no confirmed cases of vertical mother-to-fetus intrauterine transmission of the virus have been reported thus far. [20, 21]  A multicenter study involving 16 Spanish hospitals reported outcomes of 242 pregnant women diagnosed with COVID-19 during their third trimester from March 13 to May 31, 2020. The women and their 248 newborns were monitored until the infant was 1 month old. COVID-19–positive mothers who were hospitalized had a higher risk of ending their pregnancy via cesarean section (P = .027). Newborns whose mothers had been admitted owing to their COVID-19 infection had a higher risk of premature delivery (P = .006). No infants died, and no vertical or horizontal transmission was detected. The percentage of infants exclusively breastfed at discharge was 41.7% and was 40.4% at 1 month. [22]

To date, SARS CoV-2 has not been detected in breast milk. A study by Chambers et al found human milk is unlikely to transmit SARS CoV-2 from infected mothers to infants. [23] The study included 64 milk samples provided by 18 mothers infected with COVID-19. Samples were collected before and after COVID-19 diagnosis. No replication-competent virus was detectable in any of their milk samples compared with samples of human milk that were experimentally infected with SARS CoV-2.

Family clustering

Family clustering appears to play a major role in disease transmission. In one study, just over half of children with coronavirus disease 2019 (COVID-19) in China had evidence of transmission through family clustering. [24]  Most of the children in the US data also had exposure to a patient with COVID-19 in the household or community. [6]

Conversely, transmission of SARS-CoV-2 from 12 young children who acquired COVID-19 at childcare facilities to family members has been reported. Findings showed 25% of their close contacts became infected — most often mothers or siblings. Three of the children were asymptomatic, 2 of whom likely infected their contacts, including a mother who required hospitalization. One mildly symptomatic child too young for face masks (age 8 months) likely infected both parents. [25]

Posfay-Barbe et al reported on the transmission of SARS-CoV-2 within the families of 39 children (aged < 16 years) with confirmed infection in Geneva, Switzerland. [26]  In 31 of 39 households (79%), at least one adult family member had a suspected or confirmed SARS-CoV-2 infection before symptoms occurred in the child. In only 3 of 39 households (8%), the child was the first family member to develop symptoms. These findings suggest that children most often acquire COVID-19 from adult family members rather than transmitting the virus to them.

A study from South Korea found that older children and adolescents are more likely to transmit SARS CoV-19 to family members than are younger children. The researchers reported that the highest infection rate (18.6%) was in household contacts of patients with COVID-19 aged 10-19 years and the lowest rate (5.3%) was in household contacts of those aged 0-9 years. [27]

Community transmission

Cruz and Zeichner suggested that children have a role in community-based viral transmission. [28]  They noted that children are more likely than adults to have upper respiratory tract involvement, including nasopharyngeal carriage. They may also have prolonged respiratory and fecal shedding. [29]  We continue to learn more as data emerge and more cases in children are described.

More data are emerging on the role of children in the spread of the disease. Simulation results from mathematical models of the effect of delayed school opening in South Korea showed that the number of cases could be reduced by at least 200 over a 3-week period. The models were based on different school opening dates and assumed a 10-fold increase in the transmission rate after schools opened. [30]

In addition to schools, child care facilities can play a role in the transmission of SARS CoV-19. A CDC study found that 12 children who acquired COVID-19 at facilities in Utah spread the virus to at least 12 (26%) of 46 household contacts (confirmed or probable cases). [25]

The results of a South Korean study lend more data to unapparent infections in children that may be associated with silent COVID-19 community transmission. A case series of 91 children who tested positive for COVID-19 in South Korea showed 22% were asymptomatic during the entire observation period. Among 71 symptomatic cases, 47 children (66%) had unrecognized symptoms before diagnosis, 18 (25%) developed symptoms after diagnosis, and 6 (9%) were diagnosed at the time of symptom onset. Twenty-two children (24%) had lower respiratory tract infections. The mean (SD) duration of the presence of SARS-CoV-2 RNA in upper respiratory samples was 17.6 (6.7) days. [31]

However, researchers in Milan, Italy, suggest that the role of asymptomatic children in the transmission of SARS-CoV-2 infection may need to be reconsidered, based on the results of their case-control study. Among patients hospitalized for noninfectious conditions, who had no signs or symptoms of COVID-19, only 1 in 83 children (1.2%) tested positive for SARS-CoV-2, compared with 12 in 131 adults (9.2%). [32]

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Epidemiology

Fewer cases of coronavirus disease 2019 (COVID-19) have been diagnosed in children than in adults, and the majority of the pediatric cases have been mild. Whereas children comprise 22% of the US population, data from late October 2020 show that 9% of all cases of COVID-19 reported to the Centers for Disease Control and Prevention (CDC) were among children (as of October 29, 2020). The number and rate of cases in children in the US have been steadily increasing. [1]

The true incidence of SARS-CoV-2 infection in children is not known, owing to the lack of widespread testing and the prioritization of testing for adults and those with severe illness. Hospitalization rates in children are significantly lower than hospitalization rates in adults with COVID-19, which suggests that children may have less severe illness from COVID-19 compared with adults. [1]

The American Academy of Pediatrics reports children represent 11.3% of all cases in the 49 states reporting by age. More than 927,000 children have tested positive in the US since the onset of the pandemic as of November 10, 2020. This was a 17% increase over 2 weeks (October 22 - November 5). This represents an overall rate of 1,232 cases per 100,000 children. Children were 1-3.4% of total reported hospitalizations (25 states and NYC reported), and between 0.6-6.4% of all child COVID-19 cases resulted in hospitalization. [5]

Race-, sex-, and age-related demographics

No racial predilection has been observed in children, although US data in adults suggest that minority communities are affected disproportionately. [33]  A CDC study found that a disproportionate percentage of the deaths related to COVID-19 among persons aged < 21 years occurred in Black and Hispanic youths. Of the 121 deaths reported to CDC by July 31, 2020, 94 (78%) were among Hispanic, non-Hispanic Black, and non-Hispanic American Indian/Alaskan Native persons. [34]

In a retrospective Chinese study of 2143 children younger than 18 years with confirmed or suspected COVID-19, slightly more of the cases occurred in boys (56.6%) than in girls (43.4%), but the difference was not statistically significant. The ages of the children in the study ranged from 1 day to 18 years; the median age was 7 years. [35]  Slight male predominance was also seen in the US data, similar to what was observed in China. [6]

While the numbers are much smaller than in adults, emerging data do suggest that children of color are disproportionately affected similar to what has been reported in adults. [36]  

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Prognosis

Morbidity/mortality

Morbidity

Although most children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have either asymptomatic infection or mild illness, severe illness has been reported in 2.5% of pediatric cases in China, according to the World Health Organization (WHO). [37]  In a study of more than 2000 children in China, Dong et al found that approximately 4% of children with coronavirus disease 2019 (COVID-19) were asymptomatic, 51% had mild illness, and 39% had moderate illness. About 6% of pediatric patients had severe or critical illness, and one patient (a 14-year-old boy) died. [35]

The Chinese investigators also found that severe or critical illness was more common in infants and toddlers than in older children. More than 10% of infants had severe or critical illness compared with 7% of children aged 1-5 years, 4% of those aged 6-10 years, 4% of those aged 11-15 years, and 3% of those aged 16 years or older. [35]

The data from China showed that most children with COVID-19 recovered within 1-2 weeks after the onset of symptoms. [37]

Data on hospitalizations from 25 states and New York City showed that children were 0.7-3.6% of total reported hospitalizations, and between 0.2-7.9% of all child COVID-19 cases resulted in hospitalization. [38]  

Overall, current data continue to support the fact that while children are infected with SAR CoV-2 similar to adults, they are more likely to be asymptomatic or have less severe disease. [39]  

Mortality

The CDC reports that 121 deaths related to SARS-CoV-2 infection occurred among persons younger than 21 years of age in the United States from February to July 2020. Of the persons who died, 63% were male, 10% were aged < 1 year, 20% were aged 1-9 years, and 70% were aged 10-20 years. Ninety-one (75%) had an underlying medical condition. [34]

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Presentation

History

The typical incubation period of coronavirus disease 2019 (COVID-19) ranges from 1 to 14 days, with an average of 3-7 days [40, 41]  (mean, 6.4 days [42] ). However, longer incubation periods (up to 24 days) have been reported. [43]  In most of the early pediatric cases reported from China, the patient had a close contact with COVID-19 or was part of a family cluster of cases. [44]  

Physical examination

Lu et al evaluated 171 children with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who were treated at the Wuhan Children’s Hospital in China. [7]  They reported that the most common signs and symptoms were cough (48.5% of patients), pharyngeal erythema (46.2%), and fever (41.5%). Other signs and symptoms included the following:

  • Diarrhea (8.8% of patients)
  • Fatigue (7.6%)
  • Rhinorrhea (7.6%)
  • Vomiting (6.4%)
  • Nasal congestion (5.3%)

About 29% of patients had tachypnea on admission, and about 42% had tachycardia. Slightly more than 2% of children had an oxygen saturation of < 92% during their hospitalization. [7]

Wu et al reported on the clinical characteristics of 68 pediatric patients with COVID-19 in China. [45] They found that the most common initial symptoms among the 44 symptomatic patients were cough (32.43%) and fever (27.03%). This finding also highlights the significant number of children with SARS-CoV-2 infection who are asymptomatic.

We know now that gastrointestinal manifestations often accompany the initial presentation with fever. These commonly include abdominal pain, diarrhea, and/or vomiting. Neurologic manifestations have also been described. [46, 47, 48]

Rash has been reported in patients with COVID-19. [49]  An 8-year-old Italian girl with confirmed SARS-CoV-2 infection presented with an asymptomatic papulovesicular exanthem and mild cough. Her symptoms resolved without therapy within a week. [50]

According to Shen et al, children with SARS-CoV-2 infection who are at risk for severe disease include those with underlying conditions (eg, congenital heart disease, bronchial pulmonary hypoplasia, respiratory tract anomaly, abnormal hemoglobin level, or severe malnutrition) and those with immune deficiency or immunocompromised status (eg, as a result of long-term immunosuppressant use). [41]  The following conditions indicate a greater likelihood of severe disease:

  • Dyspnea: Respiration rate of >50 breaths/min in children aged 2-12 months; >40 breaths/min in children aged 1-5 years; >30 breaths/min in patients older than 5 years old (after excluding the effects of fever and crying).
  • Persistent high fever for 3-5 days.
  • Poor mental response, lethargy, disturbance of consciousness, and other changes of consciousness.
  • Abnormally increased levels of enzymes, such as myocardial and liver enzymes and lactate dehydrogenase.
  • Unexplained metabolic acidosis.
  • Chest imaging findings indicating bilateral or multi-lobe infiltration, pleural effusion, or rapid progression of conditions during a very brief period.
  • Age younger than 3 months.
  • Extrapulmonary complications.
  • Coinfection with other viruses or bacteria.

Xia et al found that 8 of 20 pediatric inpatients with COVID‐19 infection were co-infected with other pathogens, including influenza viruses A and B, mycoplasma, respiratory syncytial virus, and cytomegalovirus. [51]

Chao et al retrospectively reviewed medical charts for all children aged 1 month to 21 years between March 15 and April 13, 2020 who were seen at Children’s Hospital Emergency Department at Montefiore in New York City. Sixty-seven patients (34.5%) tested positive for SARS-CoV-2 infection. Of these, 46 patients were admitted to the hospital, with 13 requiring PICU care. The most common symptoms at admission were cough (63%) and fever (50.9%). The clinical symptom found to be significantly associated with PICU admission was shortness of breath (92.3% vs 30.3%; P< .001). [52]  

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Differential Diagnoses

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Workup

Laboratory studies

A consistent pattern of laboratory abnormalities has not yet been identified in children with confirmed coronavirus disease 2019 (COVID-19), although some patterns are emerging. [53]  Early in the course of the disease, the white blood cell count is normal or decreased, and the lymphocyte count is decreased. The majority of patients have normal neutrophil counts.

In a study by Wu et al of 68 pediatric patients with COVID-19 in China, 23 children (31.08%) had abnormal white blood cell counts, and 10 (13.51%) had an abnormal lymphocyte count. [45] Slightly more than half of the children who underwent nucleic acid testing for common respiratory pathogens showed co-infection with pathogens other than SARS-CoV-2. This finding illustrates the need to test for COVID-19 even in the setting of other confirmed viral infections. Finally, 10 (13.51%) children in the study had reverse transcription–polymerase chain reaction (RT-PCR) analysis of fecal specimens, and 8 demonstrated the prolonged existence of SARS-CoV-2 RNA. This finding may suggest the risk of further transmission.

Levels of liver and muscle enzymes and myoglobin are increased in some children. Many patients have elevated C-reactive protein (CRP) levels and erythrocyte sedimentation rates. In severe cases, patients have high D-dimer levels and progressively decreasing lymphocyte counts. [41]

In a literature review of case reports involving 66 children and adolescents with confirmed COVID-19, Henry et al found that CRP and procalcitonin (PCT) levels were elevated in 13.6% and 10.6% of cases, respectively. [54]  In a study that included 20 pediatric inpatients in Wuhan, China, 80% of the children had elevated PCT levels. [7]  Because PCT values can increase significantly in systemic bacterial infections and sepsis, higher levels are strongly suggestive of bacterial co-infection in patients with COVID-19. [55]

For more information on testing, please see Laboratory Studies in Coronavirus Disease 2019 (COVID-19).

Imaging studies

Common chest radiograph findings in children with COVID-19 pneumonia include bilaterally distributed peripheral and subpleural ground-glass opacities and consolidation. Nonspecific findings include the following [9] :

  • Unilateral ground-glass opacities and consolidation
  • Bilateral peribronchial thickening and peribronchial opacities
  • Multifocal or diffuse ground-glass opacities and consolidation without specific distribution

A common abnormality seen on computed tomography (CT) of the chest in children with COVID-19 is ground-glass opacity and nodules, which are usually bilateral. [7]  Other CT findings include the following:

  • Local patchy shadowing
  • Bilateral patchy shadowing
  • Interstitial abnormalities

Chest CT findings in children with COVID-19 are similar to those seen in adults. Xia et al reported that consolidation with a surrounding halo sign was observed in up to 50% of cases, and they suggested that this finding could be considered a typical sign in pediatric patients. [51]  Pleural effusion is rare. Radiographic changes may be seen in children without severe disease.

Imaging recommendations

Chest imaging is not generally recommended for initial screening of mildly symptomatic or asymptomatic children with suspected COVID-19 unless they are at risk for disease progression or have worsening symptoms, according to an international expert consensus statement. [9]

An initial chest radiograph may be appropriate for children with moderate to severe symptoms, and a chest CT scan may be warranted if the results could affect clinical management. A series of chest radiographs may be useful to assess therapeutic response, evaluate clinical worsening, or determine positioning of life support devices.

Post-recovery imaging may be appropriate for asymptomatic children who initially had moderate to severe illness and who may be at risk for long-term lung injury. In addition, follow-up imaging may be warranted for children with persistent or worsening symptoms regardless of the severity of the initial illness.

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Treatment

Supportive care

Recommendations for supportive care for children with coronavirus disease 2019 (COVID-19) are similar to those for adults. Among the recommendations are bed rest and ensuring sufficient calorie and water intake. Oxygen therapy is recommended for patients with hypoxia. Antibiotics should generally be reserved for children with bacterial co-infection. [41]

Investigational drugs and biologics

As of October 22, 2020, remdesivir, an antiviral agent, is the only drug approved for treatment of COVID-19. [3]  Numerous antiviral agents and immunotherapies are being investigated as potential therapies. [56, 57, 58]

Antiviral agents

Remdesivir is indicated for treatment of COVID-19 disease in hospitalized adults and children aged 12 years and older who weigh at least 40 kg. [3]  An emergency use authorization (EUA) remains in place to treat pediatric patients weighing 3.5 kg to less than 40 kg or children younger than 12 years who weigh at least 3.5 kg. [4]   

The initial EUA for remdesivir was based on preliminary data analysis of the Adaptive COVID-19 Treatment Trial (ACTT) and was announced on April 29, 2020. The final analysis included 1,062 hospitalized patients with advanced COVID-19 and lung involvement, showing that patients treated with 10 days of remdesivir recovered faster than similar patients who received placebo. Results showed that patients who received remdesivir had a 31% faster time to recovery than those who received placebo (P< 0.001). Specifically, the median time to recovery was 10 days in patients treated with remdesivir compared with 15 days in those who received placebo. Patients with severe disease (n = 957) had a median time to recovery of 11 days compared with 18 days for placebo. A statistically significant difference was not reached for mortality by day 15 (remdesivir 6.7% vs placebo 11.9%) or by day 29 (remdesivir 11.4% vs placebo 15.2%). [2]  

Remdesivir has been available through compassionate use to children with severe COVID-19 disease since February 2020. A phase 2/3 trial (CARAVAN) of remdesivir was initiated in June 2020 to assess safety, tolerability, pharmacokinetics, and efficacy in children with moderate-to-severe COVID-19. CARAVAN is an open-label, single-arm study of remdesivir in children from birth to age 18 years. [59]

Data were presented on compassionate use of remdesivir in children at the virtual COVID-19 Conference held July 10-11, 2020. Results showed most of the 77 children with severe COVID-19 improved with remdesivir. Clinical recovery was observed in 80% of children on ventilators or extracorporeal membrane oxygenation and in 87% of those not on invasive oxygen support. [60]

A study funded by the National Institutes of Health will assess the pharmacokinetics of drugs currently given to children and adolescents with COVID-19, including antiviral and anti-inflammatory agents. The goal of this study is to provide specific dosing recommendations and safety data for these drugs in pediatric patients. Data will be collected at more than 40 sites throughout the United States. [61]

Antibody-directed therapy

Bamlanivimab (LY-CoV555; Eli Lilly & Co, AbCellera) is a neutralizing IgG1 monoclonal antibody (mAb) directed against the spike protein of SARS-CoV-2. It is designed to block viral attachment and entry into human cells, thus neutralizing the virus, potentially preventing and treating COVID-19. 

The FDA issued an emergency use authorization (EUA) for bamlanivimab on November 9, 2020. The EUA permits bamlanivimab to be administered for treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in adults and pediatric patients with positive results of direct SARS-CoV-2 viral testing who are age 12 years and older weighing at least 40 kg, and at high risk for progressing to severe COVID-19 and/or hospitalization. [62]   

An interim analysis from the Blocking Viral Attachment and Cell Entry with SARS-CoV-2 Neutralizing Antibodies (BLAZE-1) study provided the basis of support for the EUA. In this ongoing phase 2 trial, bamlanivimab given to people recently diagnosed with COVID-19 in the ambulatory setting showed a reduced rate of hospitalization or emergency department visits compared with placebo. [63]

For more information on investigational drugs and biologics being evaluated for COVID-19, see Treatment of Coronavirus Disease 2019 (COVID-19): Investigational Drugs and Other Therapies.

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Multisystem Inflammatory Syndrome in Children

In mid-April 2020, over a period of 10 days, an unprecedented cluster of cases was reported from the South Thames Retrieval Service in London. They noted eight children who presented with signs of hyperinflammation and shock with features similar to Kawasaki disease (KD) or toxic shock syndrome. Four of these children had known family exposure to COVID-19. All tested negative for SARS-CoV-2 on bronchoalveolar lavage or nasopharyngeal aspirates. Seven of these children were noted to have abnormalities in cardiac function on echocardiograms, including coronary dilatations with giant coronary aneurysm noted in one child a week after discharge from the intensive care unit. [64]  This was the first case cluster highlighting what has since been termed multisystem inflammatory syndrome in children (MIS-C) by the CDC. Since the initial reporting, multiple case clusters have been reported from different countries and, as of October 1, 2020, there were 1,027 cases reported in the United States with a total of 20 deaths. [65]  The CDC case definition for MIS-C is as follows:

  • An individual aged < 21 years presenting with fever, laboratory evidence of inflammation, and evidence of clinically severe illness requiring hospitalization, with multisystem (>2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic or neurological); AND
  • No alternative plausible diagnoses; AND
  • Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or exposure to a suspected or confirmed COVID-19 case within the 4 weeks prior to the onset of symptoms.

Since initial reporting, the American Academy of Pediatrics has also published interim guidelines on MIS-C. [66]   

Children reported seem to be predominantly Hispanic and Black (non-Hispanic). This is different from KD, which seems to affect children of Asian descent more often. Also unlike KD, affected children have been predominantly in the 5-9 and 9-14 age groups. The pathophysiology of MIS-C in children has been described in its initial stages, with COVID-19 infection triggering macrophage activation followed by helper T-cell activation. This in turn leads to massive cytokine release with B-cell and plasma cell activation and the production of antibodies, which leads to immune dysregulation and a hyperimmune response. [67]   

Children with severe MIS-C present with a cytokine storm believed to be related to delayed interferon gamma responses and slow viral clearance, further leading to more pronounced inflammation. [68]  They present with systemic signs of inflammation, often with significant cardiac, neurologic, and/or hematologic abnormalities. They require a multidisciplinary team of individuals who should be involved in their management, including intensivists and pediatric infectious disease, rheumatology, cardiology, and hematology specialists. Guidelines for management have been proposed by several of these specialty groups. [69, 70, 71, 72]  

For more information on testing for patients with MIS-C, please see Laboratory Studies in Coronavirus Disease 2019 (COVID-19).

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SARS CoV-2 Infection in Neonates

The American Academy of Pediatrics Committee on Fetus and Newborn, Section on Neonatal Perinatal Medicine, and Committee on Infectious Diseases initially issued guidance on the management of infants born to mothers with coronavirus disease 2019 (COVID-19) on April 2, 2020. [21]  These guidelines have since been revised as more data have emerged. [73]  

Early evidence has shown low rates of peripartum severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and uncertainty concerning in utero viral transmission. To date there does not seem to be any conclusive evidence indicating vertical transmission of COVID-19 from infected pregnant mothers to their neonates. [20]  

Neonates can be infected by SARS-CoV-2 after birth. Because of their immature immune systems, they are vulnerable to serious respiratory viral infections. SARS-CoV-2 may be able to cause severe disease in neonates. A recent review of neonates born to mothers with perinatal confirmed COVID-19 infection showed that severe maternal disease can lead to fetal distress, premature delivery, and other adverse outcomes. These small case series are predominantly out of China. [74]

Another case series of 33 infants born to mothers with COVID-19 from China also described a varying course of the disease with an overall favorable outcome, including a 31-weeks' gestation infant who developed Enterobacter sepsis; however, the baby recovered. [75]   

Infection-control measures for birth attendants 

Staff attending deliveries involving women with COVID-19 should observe airborne, droplet, and contact precautions owing to the increased risk of aerosolized virus and the potential requirement for administering resuscitation to newborns with SARS-CoV-2 infection.

Separation of mother and newborn

A pilot study suggests that rooming in for term or near term neonates may be considered for mothers with asymptomatic COVID-19 infection. Infection control measures still need to be followed strictly. [76]

A more recent study looking at 49 infants (36 weeks' gestational age) who were allowed to room in with their mothers with asymptomatic COVID-19 infection did not demonstrate any symptoms up to two weeks after discharge. One infant did have a positive reverse transcriptase polymerase chain reaction (RT_PCR), but repeat RT-PCR at 48 hours was negative. [77]  

Breastfeeding

As of April 2, 2020, SARS-CoV-2 has not been detected in breast milk. Mothers with COVID-19 may express breast milk after appropriate hand and breast hygiene to be fed to the newborn by caregivers without COVID-19.

Breastfeeding guidelines from AAP are available for post hospital discharge for mothers or infants with suspected or confirmed SARS-CoV-2 infection. [78]  

Neonatal testing for COVID-19

Following birth, newborns born to mothers with COVID-19 should be bathed to remove virus from the skin. Newborns should undergo testing for SARS-CoV-2 at 24 hours and 48 hours (if still at the birth facility) after birth. Centers with limited testing resources can make testing decisions on a case-by-case basis. [73]

Follow-up

Newborns who have documented SARS-CoV-2 infection or who are at risk for postnatal transmission because of testing inability require frequent outpatient follow-up (via telephone or telemedicine) or in-person assessments for 14 days after discharge.

Precautions following discharge

After discharge from the hospital, mothers with symptomatic COVID-19 should stay at least 6 feet away from their newborns. If a closer proximity is required, the mother should wear a mask and observe hand hygiene for newborn care until (1) her temperature has normalized for 72 hours without antipyretic therapy and (2) at least 1 week (7 days) has passed since the onset of symptoms.

Ongoing in-hospital neonatal care

Mothers with COVID-19 whose newborns require ongoing hospital care should maintain separation until (1) her temperature has normalized for 72 hours without antipyretic therapy, (2) her respiratory symptoms have improved, and (3) a minimum of 2 consecutive nasopharyngeal swab tests collected at least 24 hours apart are negative for SARS-CoV-2.

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Guidelines

The American Academy of Pediatrics (AAP) has created a website for Critical Updates on COVID-19 to provide clinicians with resources. 

In addition to guidance on the management of infants born to mothers with coronavirus disease 2019 (COVID-19), which is summarized below, the AAP has provided guidance on the following topics:

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Questions & Answers

Overview

How is coronavirus disease 2019 (COVID-19) characterized in children?

What are common symptoms of pediatric coronavirus disease 2019 (COVID-19)?

What are lab findings of pediatric coronavirus disease 2019 (COVID-19)?

What are the CT findings of pediatric coronavirus disease 2019 (COVID-19)?

How is pediatric coronavirus disease 2019 (COVID-19) treated?

What is the pathophysiology of pediatric coronavirus disease 2019 (COVID-19)?

How does pediatric coronavirus disease 2019 (COVID-19) spread?

Can coronavirus disease 2019 (COVID-19) be passed from mother to fetus or through breast milk?

What is the role of family clustering in the spread of pediatric coronavirus disease 2019 (COVID-19)?

What role do children play in the spread of coronavirus disease 2019 (COVID-19)?

Are school closings effective in preventing spread of coronavirus disease 2019 (COVID-19)?

How common is coronavirus disease 2019 (COVID-19) in children?

What are the race-, age-, and sex-based differences in the epidemiology of pediatric coronavirus disease 2019 (COVID-19)?

How common is severe or critical pediatric coronavirus disease 2019 (COVID-19) in China?

How common is hospitalization for pediatric coronavirus disease 2019 (COVID-19) in the United States?

What is the typical incubation period of coronavirus disease 2019 (COVID-19) in children?

What are common signs and symptoms of coronavirus disease 2019 (COVID-19) among hospitalized children?

What are the risk factors for severe coronavirus disease 2019 (COVID-19) in children?

How common are coinfections in children with coronavirus disease 2019 (COVID-19)?

Which lab findings are commonly found in pediatric coronavirus disease 2019 (COVID-19)?

What is the role of CT scanning in the workup of pediatric coronavirus disease 2019 (COVID-19)?

What are the components of supportive care in children with coronavirus disease 2019 (COVID-19)?

Which drugs are effective for pediatric coronavirus disease 2019 (COVID-19)?

What are the AAP guidelines for the management of infants born to mothers with coronavirus disease 2019 (COVID-19)?

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