COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major public health crisis threatening humanity at this point in time. Transmission of the infection occurs by inhalation of infected droplets or direct contact with soiled surfaces and fomites. It should be suspected in all symptomatic children who have undertaken international travel in the last 14 d, all hospitalized children with severe acute respiratory illness, and asymptomatic direct and high-risk contacts of a confirmed case. Clinical symptoms are similar to any acute respiratory viral infection with less pronounced nasal symptoms. Disease seems to be milder in children, but situation appears to be changing. Infants and young children had relatively more severe illness than older children. The case fatality rate is low in children. Diagnosis can be confirmed by Reverse transcriptase – Polymerase chain reaction (RT-PCR) on respiratory specimen (commonly nasopharyngeal and oropharyngeal swab). Rapid progress is being made to develop rapid diagnostic tests, which will help ramp up the capacity to test and also reduce the time to getting test results. Management is mainly supportive care. In severe pneumonia and critically ill children, trial of hydroxychloroquine or lopinavir/ritonavir should be considered. As per current policy, children with mild disease also need to be hospitalized; if this is not feasible, these children may be managed on ambulatory basis with strict home isolation. Pneumonia, severe disease and critical illness require admission and aggressive management for acute lung injury and shock and/or multiorgan dysfunction, if present. An early intubation is preferred over non-invasive ventilation or heated, humidified, high flow nasal cannula oxygen, as these may generate aerosols increasing the risk of infection in health care personnel. To prevent post discharge dissemination of infection, home isolation for 1–2 wk may be advised. As of now, no vaccine or specific chemotherapeutic agents are approved for children.
Investigations in Admitted Patients
Chest Imaging Chest X-ray (CXR) is usually the first-line investigation due to ease of availability. CXR findings are not described in detail in pediatric studies. Adult series of COVID-19 showed consolidation (47%) and ground glass opacities (GGO) (33%) as commonest parenchymal lesions with more peripheral (41%) and lower zone (50%) and frequently bilateral (50%) distribution. In pediatric series, common patterns on CT scan showed GGO (32.7%), local patchy shadow (18.7%), bilateral patchy shadow (12.3%), and interstitial abnormalities (1.2%). Another study of CT scan in children with COVID-19, showed more bilateral (50%) than unilateral involvement (30%). Common patterns of CT involvement were GGO, consolidation with surrounding halo sign, fresh mesh shadow and tiny nodules. These findings represent interstitial involvement of parenchyma. Chest X-rays should be considered in children requiring oxygen at admission or showing increase in respiratory distress or increase in requirement of respiratory support suggesting disease progression. This may suggest severe illness or early deterioration. Children not admitted to HDU or ICU may require a chest X-ray if they have worsening hypoxemia, particularly, if they have pre-existing conditions.
Other Investigations are needed in admitted patients. Complete blood counts is commonly performed. Extent of leukopenia, and lymphopenia is lesser in children with COVID-19 than adults. Median (IQR) of total leukocyte counts, lymphocytes and neutrophil counts in pediatric series were 6800 (5500, 8200) per cu mm, 2900 (2200, 4400) per cu mm, and 2500 (1800, 3700) per cu mm, respectively. Serum chemistry (liver and kidney function test), coagulogram and arterial blood gases, should be frequently monitored in sick children. Procalcitonin (64%) is more frequently elevated in children than C-reactive protein (19.7%). A bedside ultrasound of chest may be done if expertise is available.
Treatment
Approach to a child confirmed to be COVID-19 by RT-PCR or a suspected case in whom SARS-CoV-2 virus test is inconclusive or a severely ill patient whose RT-PCR results are awaited, is demonstrated in Fig. 2.
As per the protocol the management would be as follows.
Mild Illness: These Children Have No Respiratory Difficulty, Are Feeding Well, Have SpO2 > 92%
1.The current guidelines recommend admission in a isolation facility for all positive cases. If this is not feasible, then the child would have to be isolated at home and managed; in this scenario, teleconsultations may have a role.
2.Appropriate antibiotic may be prescribed, if respiratory rate is high.
3.Supportive care: Control of fever using paracetamol (10–15 mg/kg/ dose SOS/ q 4–6 hourly if required); avoid ibuprofen and other NSAIDs.
4.Ensure adequate hydration
5.Danger signs should be explained
6.The parent/ caregiver should take the necessary precautions, use appropriate PPE including a mask.
Duration of Isolation
Afebrile for 72 h AND at least 7 d after symptom resolution OR 2 negative samples 24 h apart.
Management of Hospitalized Cases
General Measures
Oxygen supplementation to maintain SpO2 > 92%.
Conservative fluid management is followed in mechanically ventilated patients (restrict fluid to 70–80% maintenance, if there is no evidence of hypovolemia).
Symptomatic treatment: Paracetamol for fever ((10–15 mg/kg/ dose SOS/ q 4–6 hourly if required); avoid ibuprofen and other NSAIDs
Blood culture sample should be sent at time of admission before starting anti-microbials.
Empirical antimicrobials (e.g., Ceftriaxone) within 1 h of admission in case of suspected sepsis and septic shock.
Oseltamivir may be considered after sending appropriate investigation if influenza is suspected.
Systemic corticosteroids are not recommended, unless indicated for any other reason.
MDI with spacer is preferred for administration of inhaled medication over nebulization, as nebulization is associated with increased risk of aerosolization.
Close monitoring for worsening clinical status is of paramount importance. Children who have significant distress may be managed in a HDU setting; those needing intubation and mechanical ventilation or other organ support should be managed in an ICU
Respiratory Support
Low flow oxygen cannula is utilized with flows up to 1–2 L/min in infants, 2–4 L/min in young children and 4–6 L/min in older children and adolescents. Heated humidified high flow nasal cannula (HHHFNC) is not favoured as there are concerns of an increased aerosol formation. Similarly use of NIV is discouraged in view of potential for aerosol generation, though clinical evidence is not definitive. If HHHFNC or NIV are used, HCP should wear personal protective equipment (PPE) for aerosol transmission, and separate negative pressure isolation room should be provided to the child. A medical mask should be secured on face of the child receiving oxygen therapy with nasal prong or HHHFNC, if the child tolerates. Child should be monitored frequently including for SpO2, change in respiratory rate and heart rate, hemodynamic parameters, sensorium and urine output. Respiratory support should be promptly hiked to mechanical ventilation if there is no benefit of NIV trial on respiratory rate, heart rate and respiratory efforts, or respiratory status worsens
Specific Therapy
No specific antivirals have been proven to be effective as per currently available data. Hydroxychloroquine and chloroquine have been demonstrated to have anti-SARS-CoV-2 activity in in-vitro studies. Mechanisms for anti-viral activity of hydroxychloroquine include inhibiting membrane fusion by increasing pH of endosome/lysosome, inhibiting virus entry by changing glycosylation of ACE2 receptor and spike protein, and immune-modulation. In an open-labelled uncontrolled trial in adults, there was significant reduction in viral load with hydroxychloroquine and azithromycin therapy compared to routine care. Clinical trial of Lopinavir/Ritonavir (protease inhibitors impairing virus assembly) in adults was not associated with improved 28-d mortality (19.2% vs. 25.0%; difference, −5.8 percentage points; 95% CI, − 17.3 to 5.7). But the study only included the most severe patients. Starting the therapy early, before multi-organ dysfunction sets in, might be more appropriate approach. It is to be seen if early therapy with these drugs would have any impact on disease progression and need for mechanical ventilation. Currently there are no pediatric studies. Clinical indications for starting virus-suppressive therapy (either Hydroxychloroquine or Lopinavir/Ritonavir) include patients with suspected or confirmed COVID-19 with “severe pneumonia” or “critically ill patients”.
Hydroxychloroquine 7–8 mg/kg/dose twice daily for Day 1 and then Day 2–5, 7–8 mg/kg once a day.
Lopinavir/Ritonavir: Suggested dose of LPV/r is 10 mg/2.5 mg per kg twice daily for maximum 14 d; maximum dose is 400 mg/100 mg twice daily. Choose appropriate formulation to deliver the calculated dose (Syp LPV/r 80 mg/20 mg per ml; Tablet LPV/r 100 mg/25 mg; Tablet LPV/r 200 mg/50 mg).
These recommendations are based on a recent guidance issued by ICMR for adults. As the dosing studies are not yet available, the doses mentioned above have been extrapolated from the doses recommended for adults. HCPs should be aware about common side effects of hydroxychloroquine including headache, dizziness, ringing sensation in ears; nausea, vomiting, abdominal pain; loss of appetite, weight loss; mood changes, feeling nervous or irritable; skin rash or itching; low heart rate, hypoglycemia, etc. Lopinavir/ritonavir use can be associated with skin rash, gastrointestinal symptoms, hepatitis, metabolic derangements (hypercholesterolemia, hyperglycemia), neutropenia, thrombocytopenia, and prolonged QT.
Caution Do NOT co-administer Lopinavir/ritonavir and Hydroxychloroquine due to drug interaction which may cause increased Hydroxychloroquine levels and subsequent toxicity (e.g., QT prolongation, hypoglycemia).
As the pandemic is evolving, research is ongoing for more effective therapy for seriously ill patients. Remdesivir (prodrug of remdesivir triphosphate, an adenosine analogue) has been shown as a potent inhibitor of SARS-CoV-2 in-vitro and is undergoing clinical trial in adults with COVID-19. In critically ill patient with hyper-inflammatory response, anti-IL-6 receptor antibodies (Tocilizumab, Sarilumab) are another promising therapies under investigation. Recently, a case series of 5 adults with ARDS with high viral load were treated with convalescent plasma transfusion (SARS-CoV-2 specific IgG titer greater than 1:1000) with favourable clinical outcome. Other drugs described for SARS-CoV-2 without proven efficacy include antiviral (interferons, ribavirin) and anti-inflammatory (azithromycin) agents. In treatment refractory patients, therapy can be individualized with one of these agents on case-to-case basis. With ongoing research in therapeutics against SARS-CoV-2, treatment algorithms are likely to evolve drastically
Criteria for ICU Admission
Requiring mechanical ventilation
Shock requiring vasopressor support
Worsening mental status
Multi-organ dysfunction syndrome
Indications for Intubation
Severe respiratory distress; exhaustion.
Not able to maintain SpO2 > 90% on non-invasive oxygen supplementation
PaO2/FiO2 < 200.
PaO2/FiO2 < 300 with hypotension requiring vasopressor support
GCS < 8 with threatened airway
Decision to intubate should be taken on a case by case basis based on the clinician’s discretion
How to Intubate
Pre-oxygenation with 100% FiO2 with non-rebreathing mask or nasal prongs.
Try to avoid bag and mask ventilation (risk of aerosol generation). If needed, can be used by connecting a viral filter.
The most skilled member of the team should be identified at the beginning of each shift for performing intubations.
If readily available, intubation should be performed using a video-laryngoscope.
Cuffed endotracheal tubes should be used to avoid peri-tubal leak and dissemination of secretions.
Rapid sequence intubation should be done.
During induction, monitor for hemodynamic instability and use fluids and vasopressors, if required.
Get X-ray chest to confirm correct position of tube.
After intubation, appropriate cleaning/disinfection of equipment and environment should be done
Management Strategies for ARDS The general principles of management of child with ARDS apply to a child with COVID-19 related ARDS. The principles include lung protective ventilation: appropriate high PEEP; and low tidal volume (4–6 ml/kg). Children with refractory hypoxemia may benefit from ventilation in prone position. For more details, readers may refer to management protocols. Care of Ventilated Patient
Fresh, preferably disposable ventilator circuit to be used for every new patient.
Use viral filter in expiratory limb of the circuit
Heat and moisture exchanger (HME) to be changed every 48 h or when visibly soiled
Use closed suctioning technique and avoid routine suctioning Appropriate sedation should be ensured and intermittent muscle relaxants may be used.
Special Considerations during Resuscitation
Chest compression and bag and mask ventilation should be started only after wearing PPE for aerosol transmission protection.
Minimize the number of people inside the room during high aerosol generating events like cardiopulmonary resuscitation.
One airway specialist, one nurse/doctor for chest compression and one nurse for administering medications are essential.
Other assistants may remain outside the room and may enter only if necessary, after donning full PPE.
Hand bagging needs to be avoided; if essential use a viral filter with the bag.
Septic Shock
Recognize septic shock in children with any hypotension [systolic blood pressure (SBP) < 5th centile or < 2 SD below normal for age] or two or more of the following: altered mental state; bradycardia or tachycardia (Heart rate < 90/min or > 160/min in infants, and < 70/min or > 150/min in children); prolonged capillary refill (> 2 s) or feeble pulses; tachypnea; mottled or cold skin or petechial or purpuric rash; increased lactate; oliguria; hyperthermia or hypothermia.
Management should be as per Surviving Sepsis Campaign Guidelines. For more details, refer to management protocols.
Supportive Treatment in Critically Ill Children
Head end elevation; avoid if child has poor perfusion/ shock
Oral hygiene with antiseptic mouthwash
Glycemic control to maintain blood glucose in range of 100–180 mg/dl
Foley’s catheter for accurate urine output monitoring
Ryle’s tube for enteral feeds/ medications
Central venous catheter
Bedsore prevention by position change every 2 h
For more details, refer to management protocols. Discharge Criteria On resolution of symptoms
Suspected case– If the laboratory results for SARS-CoV-2 are negative, discharge is to be decided as per discretion of the treating physician based on his provisional/confirmed diagnosis.
Confirmed case– Resolution of symptoms, radiological improvement with a documented virological clearance in 2 samples at least 24 h apart.
Instructions for SARS-CoV-2 Positive Mothers who are Breastfeeding their Infants A SARS-CoV-2 positive mother who is breastfeeding her infant should continue breastfeeding the infant if her medical condition permits; she should use a medical face mask secured appropriately.
Advice for Parents/ Adults who have COVID-19 and are Staying at Home with a Child
The affected person should stay in a separate room.
The affected person should use a 3-ply surgical mask.
Household members should stay in a different room and be separated from the person as much as possible.
Only an assigned family member should be tasked with taking care of the person and should help with groceries, prescriptions and other personal needs.
Avoid shaking the soiled linen or direct contact with skin.
Use disposable gloves when cleaning the surfaces or handling soiled linen.
Wash hands after removing gloves and before and after eating, drinking and using the washroom with soap and water (at least 20 s) or with alcohol-based hand