COVID-19 associated pediatric complications

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Harmeet Kharoud M.D.[2]; Abdelrahman Ibrahim Abushouk, MD[3]

Overview

• Pediatric cases of COVID-19 have been reported in children. It ranges from asymptomatic mild cases to Multisystem Inflammatory Syndrome in Children (MIS-C). There are less cases of SARS CoV 2 in children compared to adults.

Epidemiology and Demographics

• Among the 1,761,503 aggregate cases reported to CDC during January 22–May 30, the incidence of confirmed cases was 403.6 cases per 100,000 population.

Data of children age 1-9 years with the total number of cases 20,458 reported by CDC for a period of January 22 to May 30

• Lowest cumulative incidence being in the group of children less than 9 years. (51.1)

Data of children with the total number of cases 20,458 reported by CDC for a period of January 22 to May 30

	Age
Different comorbidities	<9	10-19
Underlying medical condition	2896(14.2%)	7123(14.5%)
Cardiovascular disorders	78(2.7%)	164(2.3%)
Chronic lung disease	363(12.5%)	1285(18%)
Renal disease	21(0.7%)	34(0.5%)
Diabetes	12(0.4%)	34(0.5%)
Liver disease	5(0.2%)	19(0.3%)
Immunicompromised	61(2.1%)	146(2.0%)
Neurological disease	41(1.4%)	113(1.6%)
Total cases in the population 1,320,488	20458	49245

In China, 2.2% of confirmed cases of COVID-19 were among persons aged <19 years old.1 In Italy, 1.2% of COVID-19 cases were among children aged <18 years.2 In Spain, 0.8% of confirmed cases of COVID-19 were among persons aged < 18 years.5

Presentations

• Presentation of COVID-19 is less severe in children as compared to adults.
• According to CDC, as of April 2, 2020, 1.7% confirmed cases of COVID-19 were reported in children aged <18 years age among the total number of confirmed cases of COVID-19.
• Illness severity of COVID-19 in children ranges from asymptomatic to critical.

Symptoms

• Fever and Cough are one of the most common symptoms reported in children. One study showed fever is prevalent in 47.5% of children and cough in 41.5% among the 1124 children with COVID-19.According to the CDC, fever, and cough was reported in 56% and 54% of children with COVID 19
• Dyspnea, nasal congestion, pharyngeal erythema, and sore throat are also common presentations in children.
• Gastrointestinal symptoms-The gastrointestinal manifestation in COVID-19 positive children are diarrhea, vomiting, abdominal pain, nausea, and anorexia. Children can present with gastrointestinal symptoms in the absence of respiratory symptoms.
• Cutaneous Findings

Clinical Course of COVID-19 in children.

• Asymptomatic presentation-
  • Children present with no clinical signs or symptoms with normal chest imaging.
  • Among 2143 children with COVID-19 infection 4% of children were asymptomatic.
  • According to one study 14.2% of children were asymptomatic. Another study showed 18% of asymptomatic children with COVID-19.
• Mild Disease
  • Children present with mild symptoms including fever, fatigue, myalgia, cough.
  • Among 2143 children with COVID-19 infection 51% of children had a mild disease of COVID-19.
  • A study showed 36.3% of children present with a mild form of the disease.
• Severe
  • Children present with dyspnea, central cyanosis, hypoxia.
  • Among 2143 children with COVID-19 infection 5% of children had a severe presentation.
  • 2.1% of children present with a severe form of COVID-19 disease.
  • Children with underlying comorbidities are more susceptible to getting severe COVID-19 disease.
• Critical
  • Children present with acute respiratory distress syndrome(ARDS), respiratory failure, shock, or multi-organ dysfunction.
  • Among 2143 children with COVID-19 infection, 0.6%% of children had a critical presentation.

Complications

Some of the complications associated with COVID-19 pediatric population are

• Multisystem Inflammatory Syndrome in Children (MISC-C)
• Exacerbation of the underlying conditions
• Sepsis
• Septic shock
• Secondary Bacterial infections.

Multisystem Inflammatory Syndrome in Children (MIS-C)

• It is a condition that causes inflammation of some parts of the body like heart, blood vessels, kidneys, digestive system, brain, skin, or eyes.
• According to recent evidence, it is suggested that children with MISC had antibodies against COVID-19 suggesting children had COVID-19 infection in the past.

Symptoms

• Fever lasting 24 hours or longer.
• Vomiting
• Diarrhea
• Abdominal pain
• Skin rash
• Red eyes
• Redness or swelling of the lips and tongue
• Lethargy
• Redness or swelling of the hands or feet

Emergency Warning Signs

• Difficulty Breathing
• Chest pain
• New onset confusion
• Lethargy
• Cyanosis
• Abdominal pain

Diagnosis

Preliminary WHO case definition: Children and adolescents

• 0–19 years of age with fever >3 days

AND

• Two of the following:

1. Rash or bilateral non-purulent conjunctivitis or muco-cutaneous inflammation signs (oral, hands or feet)
2. Hypotension or shock
3. Features of myocardial dysfunction, pericarditis, valvulitis, or coronary abnormalities (including ECHO findings or elevated Troponin/NT-proBNP)
4. Evidence of coagulopathy (by PT, PTT, elevated D-Dimers)
5. Acute gastrointestinal problems (diarrhea, vomiting, or abdominal pain)

AND

• Elevated markers of inflammation such as ESR, C-reactive protein, or procalcitonin

AND

• No other obvious microbial cause of inflammation, including bacterial sepsis, staphylococcal or streptococcal shock syndromes

AND

• Evidence of COVID-19 (RT-PCR, antigen test or serology-positive), or likely contact with patients with COVID-19

Prevention of MIS-C

• MIS-C can be prevented by reducing the risk of child exposure to COVID-19 infection.

Diagnosis

Most of the children with SARS-CoV-2 infection are either asymptomatic or produce mild symptoms. As asymptomatic patients do not get tested for COVID-19 and are potential carriers for viral transmission, high clinical suspicion is required to prevent such transmissions to a population at risk of developing severe disease. A pediatrician should be cautious to eliminate other causes of respiratory illnesses like seasonal influenza before any diagnostic tests. No diagnostic test is required for a kid with mild illness and no history of exposure to SARS-CoV-2.

Reverse-Transcriptase Polymerase Chain Reaction

U.S. Food and Drug Administration (FDA) has approved real-time Reverse-Transcription Polymerase Chain Reaction (RT-PCR) as the preferred test for diagnosing COVID-19 in children

• RT-PCR has high specificity and sensitivity of 66-80% in diagnosing SARS-CoV-2 infection
• The test is negative during the first 7-10 days of the infection and remains positive for several weeks after the infection subsides
• Swab contamination may produce false-positive results
• High levels of SARS-CoV-2 RNA were obtained in the samples from the upper respiratory tract in both symptomatic and asymptomatic patients
• Nasopharyngeal swabs and oropharyngeal swabs or throat swab are the preferred samples for the diagnostic test
• Nasopharyngeal swab is collected in children less than 2 years of age
• A throat swab is preferred for children above 2 years
• Due to the difficulty in obtaining samples and poor cooperation of children, it is advised to use saliva samples to diagnose SARS-CoV-2 infection
• Saliva samples reportedly showed higher positive rates than Nasopharyngeal swabs in adults. It is quick and non-invasive that deceases the risk of exposure and contamination
• In patients with a high risk of exposure, one negative test result does not exclude the infection. The test should be repeated or lower respiratory tract samples like Bronchoscopic Alveolar Lavage (BAL) should be used as a specimen in such patients
• Due to the increased risk of exposure for both patient and health care worker, bronchoscopy is not recommended to diagnose SARS-CoV-2 infection
• In patients on mechanical ventilation, bronchoscopic alveolar lavage fluid or endotracheal aspirates can be used
• The virus RNA was also detected in blood and stools specimen
• Real-time Fluorescent RT-PCR is used in children with atypical symptoms
• Alternatively, some researchers suggest using metagenomic next-generation sequencing (mNGS) of viral RNA for the diagnosis

Lab abnormalities

Studies reportedly showed following lab abnormalities in pediatric patients with COVID-19

• Leucocytosis(7.5%) or Leucopenia(16.6%)
• Increased (27.4%) or decreased (24%) neutrophils
• Lymphopenia (12.9%) or Lymphocytosis (11.7%)
• Increased (9.5%) or decreased (3.2%) platelets
• Increased CRP levels (19.3%)
• Increased procalcitonin levels (49.8%)
• Increased liver enzymes (19.2%)
• Increased Serum Creatinine (4%)
• Increased blood urea nitrogen (5%)
• Increased lactate dehydrogenase (LDH) levels (29%)
• Increased Creatine kinase levels (21%)
• Increased D-dimer levels (12%)

Co-infections

Co-infection with other pathogens were reported in 27% of cases. Some common microorganisms associated with SARS-CoV-2 infection in children are:

• Mycoplasma pneumoniae
• Influenza B virus
• Influenza A virus
• Respiratory syncytial virus (RSV)
• Cytomegalovirus (CMV)
• Enterobacter aerogenes

Radiological findings

CT chest is an important diagnostic modality in pediatric patients with COVID-19. Chest CT scans has reportedly shown higher positive rates in suspected patients than RT-PCR. It has better sensitivity. CT chest and a series of chest X-rays can be used to monitor the progression of the disease. Imaging findings reported in the studies are

• Local patchy shadows (18.7%)
• Bilateral patchy shadows (12.3%)
• Consolidation (33%)
• Ground glass opacities (28%)
• Interstitial abnormalities (1.2%)
• Pleural effusion was reported in a 2-month old child who had a co-infection with RSV along with SARS-CoV-2

Children are at increased risk of radiation and its effects, so CT scans and X-rays should be judiciously used in them. It is advised to perform Pulmonary Ultrasonography (USG) in newborns. It has better sensitivity and is safer than CT scans and Chest X-rays.