The Ministry of Health and Family Welfare has advocated an interim protocol in pediatric patients with COVID. This article focuses on WHO surveillance and diagnostic criteria for COVID in children, along with management protocol for mild, moderate, and severe disease, and MIS-C.

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Highlights of COVID-19 in children

It is well established that children are less likely to contract COVID infection and that the rest of those who do are asymptomatic or have mild symptoms. A limited proportion (10-20% ) of symptomatic children will need hospitalisation, and 1-3% of symptomatic children may develop serious illness necessitating intensive care admission. Direct transmission occurs via close contact, primarily via respiratory droplets released when an infected person coughs, sneezes, or speaks. Additionally, these droplets can land on surfaces where the virus is still viable.

The median period of incubation is 5.1 days (range 2 to 14 days). According to available data, the duration of infection begins two days prior to the onset of symptoms and lasts up to 8 days.

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Pathophysiology

The majority of patients with COVID-19 have a respiratory tract infection caused by SARS-CoV-2. Several of them can lead to serious and systemic illness, such as Acute Respiratory Distress Syndrome (ARDS), sepsis and septic shock, multiorgan failure, including acute kidney injury and acute cardiac injury.

Adult autopsy findings in China and Europe revealed endothelial injury to the pulmonary vasculature, microvascular thrombosis, and haemorrhage associated with severe alveolar and interstitial inflammation, which potentially results in pulmonary intravascular coagulopathy, hypercoagulability, reduced ventilation-perfusion, and Acute Respiratory Distress Syndrome. There is a paucity of data on kids.

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Clinical characteristics

The majority of kids infected with COVID are asymptomatic or have minor symptoms. Fever, asthma, breathlessness/shortness of breath, nausea, myalgia, rhinorrhoea, sore throat, diarrhoea, lack of smell, and loss of taste are all common symptoms. A few children may exhibit gastrointestinal symptoms as well as atypical symptoms. In children, a new condition termed multisystem inflammatory syndrome has been identified. Unremitting fever > 38°C, epidemiological correlation to SARS-CoV -2, and clinical features indicative of Multi-System Inflammatory Syndrome characterise such cases.

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Management of children with COVID-19 disease

Children infected with COVID-19 disease may be asymptomatic, slightly symptomatic, seriously sick or critically ill.

1. When family members are detected, asymptomatic children are typically identified through screening. These children do not need medication other than to be monitored for the progression of symptoms and only treated according to the severity measured.
2. Children with mild disease can present with a sore throat, rhinorrhoea, and cough but have no trouble breathing. A few children can even experience stomach symptoms. These children may not need further analysis. These children can be treated successfully at home through confinement and symptomatic care.
3. It is critical to test the feasibility of home isolation using the following steps:
   1. There is adequate separation capability at the child's home, as well as for quarantining family members.
   2. A parent or any caregiver who is capable of monitoring and caring for the child is present.
   3. If available, the Arogya Setu App should be downloaded
   4. The parent/caregiver has promised to track the child's welfare and to periodically remind the surveillance officer/doctor of his/her health status.
   5. The parent/caregiver has signed an undertaking on self-isolation and will adhere to home isolation/quarantine guidelines.
4. Children with underlying comorbidities such as congenital heart failure, chronic lung disease, chronic organ failure, and obesity (BMI> 2SD) can also be treated at home if they exhibit moderate disease characteristics and have better access to a healthcare facility in the event of decline. If appropriate arrangements for managing these children at home are not in place or if getting to a health centre is difficult, those children will be admitted.
5. Mild disease is treated symptomatically in home isolation.
6. Paracetamol 10-15 mg/kg/dose for fever (can repeat every 4-6 hours) can be prescribed.
7. In older children and teenagers, throat calming agents such as warm saline gargles can be used.
8. Fluids and feedstocks: The parent/caregiver should be advised to maintain hydration through oral fluids and a balanced diet.
9. Antibiotics are not recommended.
10. There is no role for hydroxychloroquine, favipiravir, ivermectin, lopinavir/ritonavir, remdesivir, or umifenovir, or immunomodulators such as tocilizumab, interferon beta 1a, convalescent plasma infusion, or dexamethasone.
11. At home, instruct parents/caretakers to maintain a monitoring chart that includes counting respiratory rates 2-3 times a day while the infant is not screaming, observing for chest indrawing, bluish discolouration of the body, cold extremities, urine output, oxygen saturation monitoring (using a hand-held pulse oximeter if possible), fluid intake, and activity level, especially for young children.
12. There should be routine contact with the physician or other healthcare professionals. Parents/caregivers should be informed on who to call in the event of an emergency.

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Moderate COVID-19 disease management in children

If a child with COVID-19 has the following symptoms, he or she is classified as having mild disease:

Under the age of 2 months: Respiratory rate >60/min

Between the ages of 2 and 12 months: Respiratory rate >50/min

Between the ages of 1 and 5: Respiratory rate >40/min

Over 5 years of age: Respiratory rate >30/min and oxygen saturation levels greater than 90%.

Children with moderate COVID-19 disease may have undiagnosed pneumonia. No laboratory tests are expected on a regular basis unless underlying co-morbid conditions suggest otherwise.

Children with moderate Covid-19 illness should be referred to a dedicated COVID health centre or a secondary level healthcare facility and their therapeutic progress should be closely tracked. Maintain an electrolyte and fluid balance. Increase oral ingestion (breastfeeding in infants); if oral intake is inadequate, intravenous fluid treatment should be started.

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Children with mild COVID-19 disease should receive the following:

1. Paracetamol 10-15 mg/kg/dose for fever; repeat every 4-6 hours (temperature greater than 38°C, or 100.4°F).
2. If there is evidence/strong suspicion of bacterial infection, amoxycillin should be prescribed.
3. If the SpO2 level falls below 94 per cent, oxygen supplementation is essential.

Corticosteroids can be used intravenously in patients with rapidly progressing disease. It is not necessary for all children with mild illness, especially within the first few days. Children with comorbid illnesses, if any, should be offered supportive treatment.

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Severe COVID-19 disease management in children

Children with a SpO2 value less than 90% are considered to have a severe case of COVID-19 infection. These children may be suffering from extreme pneumonia, Acute Respiratory Distress Syndrome (ARDS), septic shock, multi-organ failure syndrome (MODS), or pneumonia with cyanosis.

Clinically, such children can exhibit grunting, extreme chest retraction, lethargy, somnolence, and seizures. These children should be sent to a COVID-designated hospital or a secondary/tertiary level healthcare centre. Few children can need treatment in these facilities' HDU/ICU areas. They should be evaluated for thrombosis, haemophagocytic lymphohistiocytosis (HLH), and organ dysfunction.

Inquiries: Complete blood counts, liver and kidney function scans, and chest X-rays are also routine procedures.

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Management

1. Intravenous fluid treatment is recommended.
2. Corticosteroids: Dexamethasone 0.15 mg/kg per dose (maximum of 6 mg) twice daily is preferred. For 5 to 14 days, an equivalent dosage of methylprednisolone can be used, based on the results of continuous clinical evaluation.
3. Antivirals: Remdesivir is an antiviral. There are insufficient statistics on the protection and effectiveness of children younger than 19 years of age. Randomised trials in adults above the age of 18 years have not shown major survival advantages for this drug. Children have been issued an emergency usage permit. Before more data is available, it can be used cautiously in children with serious disease within 3 days of onset of symptoms, after ensuring that the child's renal and liver processes are normal and that the child is checked for medication-related side effects.
   1. Suggested doses for individuals weighing more than 40 kg: 200 mg on the first day, followed by 100 mg every daily for four days
   2. If bodyweight is between 3.5 kg and 4 kg: 5 mg/kg may be taken on the first day and 2.5 mg/kg every day for four days
4. Hydroxychloroquine, Favipiravir, Ivermectin, lopinavir/ritonavir, and umifenovir have no role.
5. In the event of organ failure, children may require organ support, such as Renal Replacement Therapy.
   1. Acute Respiratory Distress Syndrome (ARDS) Management: The medical principles are identical to those for ARDS caused by some other underlying condition.
   2. Mild ARDS: High Flow Nasal Oxygenation can be used, as well as non-invasive ventilation.
   3. Severe ARDS: Mechanical ventilation with a low tidal volume (6 mL/kg and a high positive end-expiratory pressure) can be administered.
6. If the child's health condition does not change by then, recommend (if available) High-Frequency Oscillatory Ventilation or Extracorporeal Membrane Oxygenation (ECMO).
7. If older hypoxemic children accept it, the awake prone position can be suggested.

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Shock Management

1. If the infant experiences septic shock or myocardial dysfunction, he or she can need crystalloid bolus administration- 10 to 20 ml/kg over 30 to 60 minutes; proceed with caution if cardiac dysfunction exists.
2. As for any other source of shock, early inotrope assistance should be combined with monitoring of fluid overload.

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Multi-system inflammatory syndrome in children and teens along with COVID-19 (MIS-C) management

Multi-system inflammatory syndrome is a recent syndrome that has been identified in children. Unremitting fever >38°C, epidemiological correlation to SARS-CoV-2, and clinical features indicative of Multi-System Inflammatory Syndrome characterise such cases.

Investigations: As described previously in standards and investigations to elucidate common differential diagnoses.

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MIS-C Treatment

Drugs to be used in children with Multi-System Inflammatory Syndrome whether the infant has heart dysfunction, shock, coronary artery involvement, or multiple organ dysfunction:

• Methylprednisolone 1–2 mg/kg daily
• Intravenous immunoglobulin at a dose of 2 g/kg over a 24-48-hour period
• Antimicrobials

The child requires adequate supportive care, preferably in the intensive care unit. In the absence of heart dysfunction, shock, coronary artery involvement, or multi-organ dysfunction, steroids or IVIG can be used. If the child does not recover or deteriorates after the aforementioned procedure, the following treatments are available:

1. Repetition of IVIg
2. Corticosteroid at a high dosage (methylprednisolone 10–30 mg/kg/day for 3–5 days)
3. Aspirin: 3 mg/kg/day to 5 mg/kg/day, maximum 81 mg/day (if thrombosis or coronary aneurysm score is greater than 2.5)
4. Molecules with low molecular weight heparin:
   1. Enoxaparin: 1 mg/kg subcutaneously twice daily
   2. Clotting Factor Xa should be between 0.5 and 1 (if the patient has a thrombosis/coronary aneurysm score of greater than 10 or an LVEF of less than 30%).

Steroids must be tapered over a 2- to 3-week period when inflammatory markers are monitored. Repeat ECG 48 hours a day in children with heart involvement; repeat ECHO at 7 to 14 days, 4 to 6 weeks, and 1 year if original ECHO was abnormal.

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