key: cord-0059302-73sebxbf
authors: Mahendra, Malini; Mahendra, Vibha; Murugan, Shobana
title: Pediatric Patients and COVID-19
date: 2020-10-06
journal: Clinical Synopsis of COVID-19
DOI: 10.1007/978-981-15-8681-1_12
sha: dcf7bc209dcb4f409575c383b8692bf9407b8e4a
doc_id: 59302
cord_uid: 73sebxbf

The burden of illness in illness in pediatrics is much lower than what has been reported for adults, with <1% of pediatric patients requiring admission to the intensive care unit. Respiratory symptoms are the most common presentation of COVID-19. A minority of patients who are critically ill have presented with a hyperinflammatory shock that has been described as the pediatric multisystem inflammatory syndrome associated with COVID-19. Research suggests that differential expression of ACE2 receptors, difference in the immune response, and exposure to other viruses may be etiologies for why most children have milder forms of COVID-19 than adults. Precautions taken while caring for COVID-19-positive adults should also be applied to the pediatric patient. Strong consideration should be given to premedicating the child with COVID-19 preoperative to reduce crying and screaming (which may increase spread of the virus). At the time of writing, the World Health Organization and United States Centers for Disease Control do not recommend any specific treatment strategies in children because novel therapies have not been shown clear benefit.

The Novel Coronavirus Disease (COVID-19) the World Health Organization (WHO) declared a worldwide pandemic on March 11, 2020 [1] . Although the burden of COVID-19 has fallen largely on adults, there are unique pediatric considerations that clinicians should be aware of. In this section, we will review the impact of COVID-19 on the pediatric population, common disease presentation, physiology, anesthetic considerations, and critical care management of the illness.

The SARS CoV2 epidemic was first reported in Wuhan, China, in November 2019. The Chinese Center for Disease Control Chinese Center for Disease Control reported 2% of confirmed COVID cases were in patients <19 years of age. No deaths in children <9 years of age [2] . Similar findings were reported in the Italian outbreak [3] . The United States also reported similar findings with only 1.7% of COVID-19 cases in pediatric patients with a case fatality rate of 0.1%. However, the incidence of COVID-19 in pediatric patients with chronic illness is unknown. Additionally, like in adults, majority (57%) of cases were male and 91% of cases occurred after exposure at home or in the community [4] . Of pediatric patients with COVID-19, the hospitalization admission rate ranged between 5.7 and 20%. With 15% admitted to an ICU. Children aged <1 year accounted for the highest percentage (15-62%) of hospitalization among pediatric patients with COVID-19 [4] . Although nearly 5% of adults with COVID-19 require admission to the ICU, a case series suggested that 0.6% of pediatric patients had disease progression to acute respiratory distress syndrome or multiple organ dysfunction [5, 6] . The true incidence of the disease is unknown as some studies have reported that up to 10% of children are asymptomatic [7, 8] .

Case series have reported that the majority of neonatal and pediatric patients have been transmitted from infected family members [7] . Pediatric patients most frequently presented with fever, cough, and shortness of breath. The frequency of reported symptoms in pediatrics was less than what has been reported in adults [4] .

A minority of patients who are critically ill have presented with a hyperinflammatory shock that has been described as the pediatric multisystem inflammatory syndrome associated with COVID-19. The literature has commented on the similarity in presentation of this syndrome to Kawasaki disease. In a cohort of eight patients identified in the United Kingdom, patients presented with unrelenting fever, rash, conjunctivitis, peripheral edema, extremity pain, and significant GI symptoms.

Interestingly, all patients initially tested negative for COVID [9] . Most children in this case series did not present with respiratory symptoms but did require mechanical ventilation for hemodynamic support. All patients progressed to warm, vasoplegic shock. Common echocardiographic findings were echo bright coronary vessels, with one patient progressing to development of a giant coronary aneurysm. One patient suffered arrhythmias that required support with ECLS. The patient ultimately diedfrom a cerebrovascular infarct.

There is a growing body of literature that has suggested that the general pediatric population has been less severely affected by COVID-19 than adults. There are several hypotheses that have been proposed to explain this observation. Recent studies have proposed a correlation between the severity of COVID-19 disease with viral load or the duration of viral shedding [8, 10] . Differences in clinical presentation may be related to the differential expression of ACE2 receptors because SARS CoV2 is known to enter cells by binding to the ACE2 receptor. Data show that there is differential expression of the ACE2 receptor in the population: (1) ACE2 receptors are expressed more in adults than children; (2) there is increased expression of the ACE2 receptor in neonates compared to older children; and (3) circulating levels of ACE2 are higher in males than females. This differential expression may explain part of the reason why COVID-19 is more present in adults, males, and neonates [8] .

Children also seem to have a different immune response to the SARS CoV2 virus than adults. Robustness of the immune response may decrease with age. With aging, T-cell distribution shifts from having naïve T cells to a population of mostly memory and effector T cells. This is associated with loss of co-stimulatory molecules that may increase susceptibility to infection [8] . Neonates also may be more susceptible to the SARS CoV2 virus because their immune response is skewed more to the Th2 rather than the pro-inflammatory Th1 response. When compared to younger macaques and mice, aging macaques and mice infected with SARS CoV2 had a more robust pro-inflammatory response associated with worse lung pathology. Because severe COVID-19 infection is associated with a massive proinflammatory response, cytokine storm, and multiorgan failure, it is proposed that differences in inflammatory response between the pediatric and adult patient may also contribute to differences in disease presentation [8] .

Although transmission of the SARS CoV2 virus is thought to occur primarily through respiratory droplets, there is concern that vertical transmission of the virus exists. There has been a case report of a neonate who tested positive via RT PCR at 16 h of life [11] . IgM antibodies have also been detected in the placenta, suggesting transplacental passage of the virus is possible. Testing is recommended for all neonates born to women with confirmed or suspected COVID-19 regardless of symptoms in the neonate via RT-PCR. Serologic testing is not recommended at this time to diagnose an acute infection in the neonate. Testing should occur at 24 h of life. If initial testing is negative or not available, testing should be repeated at 48 h of age [12] .

Postnatally, the AAP, ACOG, and Chinese experts have recommended separation of the newborn from COVID-19-positive mothers. However, the CDC recommends that the decision to separate and to breast feed the infant be a shared decision with the mother. If the decision is made to room in with the baby, mothers should wear facemask and practice social distancing as appropriate.

Transmission of aerosolized particles places anesthesiologists at high risk for transmission of the virus. Recorded rates of COVID-19 in healthcare workers range from 3 to 14% [13] . Precautions taken while caring for COVID-19-positive adults should also be applied to the pediatric patient. Because parents may not be able to accompany the child into the operating room, strong consideration should be given to premedicating the child to reduce crying and screaming (which may increase spread of the virus) [13] . Because the pediatric patient is at increased risk for tube dislodgement or obstruction while intubation and laryngospasm after extubation, effort should be taken to minimize the need to re-intubate patients [13] .

Early data has suggested that around 15% of COVID-19 pediatric patients had critical illness (defined as requiring mechanical ventilation or having ARDS, shock, systemic inflammatory response syndrome, or multiorgan failure) [14] . Seventythree percent of patients presented with respiratory symptoms, but the remainder of patients presented with other symptoms (circulatory collapse, seizures, vasoocclusive crisis of sickle cell, and DKA). Over 90% of patients admitted to the ICU had at least one comorbidity, with the most common comorbidity being long-term dependence on technological support. Over 1/3 of these patients required mechanical ventilation. Thirteen percent of patients required extracorporeal therapies. Reported case fatality rate was 4.2% at time of the report [14] .

Therapeutic management strategies stems from knowledge gained from treatment of other infectious diseases [15] . Treatment of critical illness has been largely supportive (nutrition, fluids, supplemental oxygen) [7] . Although the WHO and CDC do not recommend any specific treatment strategies in children because novel therapies have not been shown clear benefit, pediatric intensivists have used targeted therapy to COVID-19. The most common therapy received was hydroxychloroquine as a single agent. Azithromycin, remdisivir, and convalescent plasma were also used [14] . At the time of writing, there are no published guidelines on how to manage multisystem inflammatory syndrome. However, clinicians have used intravenous immunoglobulin, corticosteroids, and biologics such as infliximab and anakinra to treat patients [16] .

Most pediatric patients infected with SARS CoV2 present with mild symptoms. A minority of patients become critically ill and develop pediatric multisystem inflammatory syndrome. Differences in gene expression and the inflammatory response in neonatal and pediatric patients may explain differences in COVID-19 disease presentation. Supportive care is the recommended management strategy for patients with COVID-19 infections. No novel therapeutic strategies in children have been recommended as there is no clear evidence that there is benefit from use. Anesthetic management of the COVID-19-positive pediatric patient is similar to what has been described in the adult anesthetic literature.

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Paediatric early warning systems for detecting and responding to clinical deterioration in children: a systematic review

Coronavirus disease 2019 in critically ill children: a narrative review of the literature

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