Coronavirus Disease 2019 (COVID-19) in Children
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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, 7.3% of all cases of COVID-19 reported to the Centers for Disease Control and Prevention (CDC) were among children (as of August 3, 2020). [1] Most cases in children are mild, and treatment consists of supportive care. No drugs or biologics have been approved by the US Food and Drug Administration (FDA) for the prevention or treatment of COVID-19, and no vaccine is currently available. [2]
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. [3, 4, 5] Other symptoms include the following:
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:
Imaging studies
Common chest radiograph findings in children with COVID-19 pneumonia include bilaterally distributed peripheral and subpleural ground-glass opacities and consolidation. [6]
Findings observed on computed tomography (CT) of the chest in children with COVID-19 include the following:
Treatment consists of supportive care, including oxygen therapy in children with hypoxia.
No drugs or biologics are approved by the FDA for the prevention or 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. [7, 8, 2] 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.
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.
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. [9]
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.
Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) is a highly infectious virus, [10] 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. 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. [11] Fecal shedding has been detected for several weeks after diagnosis, which has led to concerns about fecal-oral transmission of the virus. [12]
Based on limited data, no confirmed cases of vertical mother-to-fetus intrauterine transmission of the virus have been reported thus far. [13, 14] To date, SARS CoV-19 has not been detected in breast milk.
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. [15] Most of the children in the US data also had exposure to a patient with COVID-19 in the household or community. [3]
Cruz and Zeichner suggested that children may play a major role in community-based viral transmission. [16] 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. [17] We continue to learn more as data emerge and more cases in children are described.
Additional 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. [18]
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. [19] 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. [20]
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 July 2020 show that 7.3% of all cases of COVID-19 reported to the Centers for Disease Control and Prevention (CDC) were among children (as of August 3, 2020). The number and rate of cases in children in the US have been steadily increasing from March to July 2020. [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 that children represent 9.1% of all cases in the 49 states reporting by age. More than 406,000 children have tested positive in the United States since the onset of the pandemic as of August 13, 2020. [21]
No racial predilection has been observed in children, although US data in adults suggest that minority communities are affected disproportionately. [22] 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. [23] Slight male predominance was also seen in the US data, similar to what was observed in China. [3]
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). [24] 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. [23]
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. [23]
The data from China showed that most children with COVID-19 recovered within 1-2 weeks after the onset of symptoms. [24]
Data on hospitalizations in the United States (US) are available for 749 cases in children (29% of COVID-19 cases in patients < 18 years of age). Of these cases, 147 (estimated range, 5.7-20%) were reported to be hospitalized, with 15 (0.58-2%) admitted to the intensive care unit. Children younger than 1 year of age accounted for the highest percentage of hospitalizations (15-62%). [3]
Two US case reports describe young infants who were hospitalized with COVID-19. In the first case, late-onset sepsis developed in a 3-week-old boy with confirmed SARS-CoV-2 infection. He was successfully treated with mechanical ventilation in a pediatric intensive care unit and was discharged. [25] In the second case, a 5-week-old girl who had been admitted for fever without a source later tested positive for SARS-CoV-2. She had no respiratory distress, and her fever resolved within 30 hours. [26]
Media reports and a health alert from the New York State Department of Health have drawn attention to a newly recognized pediatric multisystem inflammatory syndrome that may be related to COVID-19. Cases have been reported in children of a wide range of ages. [27, 28]
Symptoms are reminiscent of Kawasaki disease, atypical Kawasaki disease, or toxic shock syndrome. All patients had persistent fevers, and more than half had rashes and abdominal complaints. Interestingly, respiratory symptoms were rarely described. Many patients did not have polymerase chain reaction (PCR) results that were positive for COVID-19, but many had strong epidemiologic links with close contacts who tested positive. Furthermore, many had antibody testing that was positive for SARS-CoV-2. These findings suggest recent past infection, and this syndrome may be a post-infectious inflammatory syndrome.
Riphagen et al described 8 children (aged 4-14 years) in the United Kingdom who had severe inflammation and shock. The authors noted significant cardiac involvement. The patients also developed effusions that were consistent with an inflammatory process. [29]
Whittaker et al described a case series of 58 hospitalized children with severe multisystem inflammatory syndrome; 7 of the children met the criteria for Kawasaki disease. [30] In another case series, Cheung et al reported similar clinical characteristics for 17 patients with multisystem inflammatory syndrome in children (MIS-C), 8 of whom also met criteria for typical Kawasaki disease. [31] Although MIS-C shares clinical features with Kawasaki disease, differences seen in these case series include older age at presentation and greater elevation of inflammatory markers such as C-reactive protein (CRP) associated with MIS-C.
A New York State study and a study funded by the Centers for Disease Control and Prevention (CDC) have further clarified the clinical picture of MIS-C. [32, 33] In both studies, children and adolescents with MIS-C frequently presented with gastrointestinal symptoms (80% and 92% of study participants, respectively). Cardiac involvement (including coronary artery aneurysms in 10-20% of patients) and elevated levels of inflammatory markers, such as CRP, D-dimer, and troponin, were common. In an accompanying editorial in the New England Journal of Medicine, Levin suggests that because MIS-C usually occurs after antibodies to SARS-CoV-2 have developed, an abnormal cellular or humoral adaptive immune response may play a key role in the syndrome. [34]
MIS-C appears to be clinically distinct from Kawasaki disease, according to researchers who assessed a cohort of 25 patients with MIS-C. Neutrophilia and elevated monocyte counts, which are features of Kawasaki disease, were not observed in the cohort, and only 2 patients met the criteria for complete Kawasaki disease. [35]
The typical incubation period of coronavirus disease 2019 (COVID-19) ranges from 1 to 14 days, with an average of 3-7 days [36, 37] (mean, 6.4 days [38] ). However, longer incubation periods (up to 24 days) have been reported. [39] 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. [40]
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. [4] 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:
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. [4]
Wu et al reported on the clinical characteristics of 68 pediatric patients with COVID-19 in China. [41] 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.
Rash has been reported in patients with COVID-19. [42] 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. [43]
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). [37] The following conditions indicate a greater likelihood of severe disease:
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. [44]
The following conditions are included in the differential diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection:
A consistent pattern of laboratory abnormalities has not yet been identified in children with confirmed coronavirus disease 2019 (COVID-19). 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. [41] 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. [37]
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. [45] In a study that included 20 pediatric inpatients in Wuhan, China, 80% of the children had elevated PCT levels. [4] 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. [46]
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 [6] :
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. [4] Other CT findings include the following:
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. [44] 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. [6]
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.
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. [37]
No drugs or biologics are approved by the US Food and Drug Administration (FDA) for the prevention or treatment of COVID-19 in children. Numerous antiviral agents and immunotherapies are being investigated as potential therapies. [47, 48, 49]
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. [7, 8, 2] Safety and effectiveness have not been assessed in children. Pediatric dosing within the EUA was derived based on pharmacokinetic data from adult healthy volunteers.
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. [50]
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. [51]
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. [52]
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.
The American Academy of Pediatrics (AAP) has created a website for Critical Updates on COVID-19 to provide clinicians with resources.
The American Academy of Pediatrics Committee on Fetus and Newborn, Section on Neonatal Perinatal Medicine, and Committee on Infectious Diseases has issued guidance on the management of infants born to mothers with coronavirus disease 2019 (COVID-19). [14]
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.
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.
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
If possible, mothers with COVID-19 should be separated from their newborns upon birth. These newborns should be kept in an area that is separate from other infants. Families who opt to keep the newborn near the mother should be educated concerning the potential risks of SARS-CoV-2 transmission.
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. [53]
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.
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 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.
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 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?
How common is severe or critical pediatric coronavirus disease 2019 (COVID-19) in China?
What is the typical incubation period of coronavirus disease 2019 (COVID-19) in 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)?
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Bayan Issa, MD Resident Physician, Department of Pediatrics, University of Florida College of Medicine-Jacksonville
Bayan Issa, MD is a member of the following medical societies: American Academy of Pediatrics, Syrian American Medical Society, Syrian Arab Red Crescent, National Union of Syrian Students
Disclosure: Nothing to disclose.
Ayesha Mirza, MD Associate Professor of Pediatric Infectious Diseases, University of Florida College of Medicine-Jacksonville
Ayesha Mirza, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Tropical Medicine and Hygiene, HIV Medicine Association, Infectious Diseases Society of America, Pediatric Infectious Diseases Society
Disclosure: Nothing to disclose.
Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Nothing to disclose.
John Anello Managing Senior Editor, eMedicine from WebMD
Disclosure: Nothing to disclose.
David J Cennimo, MD, FAAP, FACP, AAHIVS Assistant Professor of Medicine and Pediatrics, Adult and Pediatric Infectious Diseases, Rutgers New Jersey Medical School
David J Cennimo, MD, FAAP, FACP, AAHIVS is a member of the following medical societies: American Academy of HIV Medicine, American Academy of Pediatrics, American College of Physicians, American Medical Association, HIV Medicine Association, Infectious Diseases Society of America, Medical Society of New Jersey, Pediatric Infectious Diseases Society
Disclosure: Nothing to disclose.
Coronavirus Disease 2019 (COVID-19) in Children
Research & References of Coronavirus Disease 2019 (COVID-19) in Children |A&C Accounting And Tax Services
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