ACEP COVID-19 Field Guide

Author: Aisha T. Terry, MD, MPH, FACEP, Associate Professor of Emergency Medicine and Health Policy, George Washington University School of Medicine and Hospital, American College of Emergency Physicians, Board of Directors Member

The COVID-19 pandemic is rapidly evolving, as are the associated health care challenges. Despite the widespread global incidence and increasing number of cases, the epidemiology and clinical presentation of COVID-19 in pediatric patients is not well understood. The majority of children seen for emergency medical problems in the US are seen in general emergency departments, not pediatric-specific institutions, and this will likely continue with the current pandemic. Note that the information in this section is based on current evidence and evolving information. It is intended to assist in the evaluation and management of pediatric patients (not neonates) with suspected or confirmed COVID-19. 

Epidemiology

A significant proportion of pediatric cases appear to be associated with household contact. The incubation period averages 5 to 6 days, with a range of 2 to 14 days.¹ Pediatric patients appear to have the lowest rate of infection of all age groups, although the apparently low incidence may be due to a significant proportion of asymptomatic and mild cases in children that are not recognized and tested. Current reports suggest very low rates of hospitalization and critical disease (including ICU admission) in pediatric patients.^2,3 Of those patients considered to have critical disease, the majority were <1 year old.⁴ Similarly, the mortality rate in pediatric patients appears to be very low. The CDC (MMWR) reported no pediatric deaths related to COVID-19 in the US as of March 16, 2020.¹ Two epidemiological studies from China, the first with 965 pediatric patients (a subset of a larger study cohort) and the second with 2,143 pediatric patients (731 laboratory-confirmed cases; 1,412 suspected cases), reported only 1 death, respectively, in each cohort of patients.^3,4 There is very limited data on pediatric patients with chronic disease states and comorbid conditions. Patients with chronic disease states and comorbid conditions, particularly those with pulmonary or respiratory diseases and those considered immunosuppressed, whether congenital or acquired (including patients on chronic steroids), must be considered high risk for developing severe or critical disease.

Transmission

Person-to-person spread via respiratory droplets is thought to be the predominant means of transmission, although some emerging evidence suggests a potentially increasing role of spread via aerosols. It is presumed that transmission can also occur via contaminated fomites. At least one study has demonstrated that SARS-CoV-2 (the virus that causes COVID-19) may remain viable in aerosols for up to 3 hours, on cardboard for up to 24 hours, and on plastic and stainless steel for as long as 3 days.⁵ It is unclear whether infection can be spread via other body fluids (eg, blood, stool). However, SARS-CoV-2 RNA has been detected in stool specimens, and in pediatric patients, it has been demonstrated to persist longer in stool than in the nasopharynx.⁶ More information is available from the CDC’s “Clinical Questions about COVID-19: Questions and Answers” section.

Clinical presentation

A significant proportion of pediatric patients appear to be asymptomatic. In two early reports, the proportion of asymptomatic cases was 12.9% and 15.8%, respectively, in confirmed cases.^4,7,11 The most common clinical characteristics in symptomatic pediatric patients appear to be fever and cough. Other clinical characteristics include pharyngeal erythema, diarrhea, fatigue, rhinorrhea, nasal congestion, vomiting, and fatigue. Tachypnea and hypoxia have been identified in more severe cases.^7,8,9

Signs or symptoms of COVID-19 in children include:

• Fever
• Fatigue
• Headache
• Myalgia
• Cough
• Nasal congestion or rhinorrhea
• New loss of taste or smell
• Sore throat
• Shortness of breath or difficulty breathing
• Abdominal pain
• Diarrhea
• Nausea or vomiting
• Poor appetite or poor feeding

Testing and Recommendations for Isolation

Viral tests (nucleic acid or antigen) are recommended to diagnose acute infection with SARS-CoV-2. Testing strategies, including clinical criteria for considering testing and recommended specimen type, are the same for children and adults. CDC’s guidance for the evaluation and management of neonates at risk for COVID-19 details specific testing considerations for newborns.

Testing, Isolation, and Quarantine for School-Aged Children

School-aged children should be prioritized for viral testing if they have:

• Signs or symptoms of COVID-19 and
• close contact (within 6 feet of someone for a total of 15 minutes or more) with a person with laboratory-confirmed or probable SARS-CoV-2 infection or
• increased likelihood for exposure (which includes living in or traveling to a community with substantial transmission as defined by the local public health department and described in CDC’s Community Mitigation Framework)
• No symptoms but have had close contact (within 6 feet of someone for a total of 15 minutes or more) with a person with laboratory-confirmed or probable SARS-CoV-2 infection.

Children with symptoms of an infectious disease should not attend school, but the length of time the child should stay home depends on the most likely etiology of illness (COVID-19 or not). Return to school policies for children with COVID-19 should be based on CDC’s recommendation for discontinuation of home isolation. A negative test or doctor’s note should not be required for return to school upon completion of the 10 days of isolation with improvement of symptoms.

Management

No specific therapeutic drugs for COVID-19 are currently approved by the FDA. Initial management priorities should include infection control measures and supportive treatment as indicated. Although several potential therapeutic agents are currently being investigated, none are currently recommended by the CDC for treating pediatric patients with COVID-19. According to the NIH COVID 19 Guidelines, there are insufficient data to recommend for or against the use of specific antivirals or immunomodulatory agents for the treatment of COVID-19 in pediatric patients. More information regarding investigational therapeutics is provided in the CDC’s “Interim Clinical Guidance for Management of Patients with Confirmed Coronavirus Disease (COVID-19).” Additionally, information regarding specific clinical trials is available at the NIH’s clinicaltrials.gov website. Pediatric patients with asymptomatic or mild disease, who are not high-risk patients (eg, immunosuppressed) and for which admission is not clinically indicated, may not require transfer to a pediatric center. The decision to admit a patient to the hospital or continue observation at home must be made on a case-by-case basis. As a significant proportion of pediatric patients appear to have a mild disease course associated with COVID-19, it is likely that many will be candidates for outpatient management. Pediatric patients managed on an outpatient basis must be provided clear information and instructions regarding infection spread control, potential progression of signs and symptoms, and return precautions. Parents who care for pediatric patients being quarantined due to having a confirmed diagnosis of COVID-19, COVID-19 exposure, or awaiting COVID-19 test results should wear appropriate PPE to prevent transmission.

Information for Healthcare Providers about Multisystem Inflammatory Syndrome in Children (MIS-C)

As described in the CDC Health Advisory, “Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19,” the case definition for MIS-C is:

• An individual aged <21 years presenting with fever*, laboratory evidence of inflammation**, and evidence of clinically severe illness requiring hospitalization, with multisystem (>2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic or neurological); AND
• No alternative plausible diagnoses; AND
• Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or exposure to a suspected or confirmed COVID-19 case within the 4 weeks prior to the onset of symptoms.

*Fever >38.0°C for ≥24 hours, or report of subjective fever lasting ≥24 hours

**Including, but not limited to, one or more of the following: an elevated C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen, procalcitonin, d-dimer, ferritin, lactic acid dehydrogenase (LDH), or interleukin 6 (IL-6), elevated neutrophils, reduced lymphocytes and low albumin

Additional comments:

• Some individuals may fulfill full or partial criteria for Kawasaki disease but should be reported if they meet the case definition for MIS-C.
• Consider MIS-C in any pediatric death with evidence of SARS-CoV-2 infection.

Clinical Presentation

• Patients with MIS-C usually present with persistent fever, abdominal pain, vomiting, diarrhea, skin rash, mucocutaneous lesions and, in severe cases, with hypotension and shock. 
• They have elevated laboratory markers of inflammation (e.g., CRP, ferritin), and in a majority of patients laboratory markers of damage to the heart (e.g., troponin; B-type natriuretic peptide (BNP) or proBNP). 
• Some patients develop myocarditis, cardiac dysfunction, and acute kidney injury. 
• Not all children will have the same signs and symptoms, and some children may have symptoms not listed here. 
• MIS-C may begin weeks after a child is infected with SARS-CoV-2. The child may have been infected from an asymptomatic contact and, in some cases, the child and their caregivers may not even know they had been infected.

Evaluation

Laboratory Testing

• Testing aimed at identifying laboratory evidence of inflammation is warranted.
• Similarly, SARS-CoV-2 detection by RT-PCR or antigen test is indicated.
• Where feasible, SARS-CoV-2 serologic testing is suggested, even in the presence of positive results from RT-PCR or antigen testing. Any serologic testing should be performed prior to administering intravenous immunoglobulin (IVIG) or any other exogenous antibody treatments.

Other Evaluations

• Given the frequent association of MIS-C with cardiac involvement, many centers are performing cardiac testing including, but not limited to:
• echocardiogram;
• electrocardiogram;
• cardiac enzyme or troponin testing (per the center’s testing standards); and
• B-type natriuretic peptide (BNP) or NT-proBNP.

Other testing to evaluate multisystem involvement should be directed by patient signs or symptoms. Additionally, testing to evaluate for other potential diagnoses should be directed by patient signs or symptoms.

Treatment

Treatments have consisted primarily of supportive care and directed care against the underlying inflammatory process. Supportive measures have included:

• fluid resuscitation;
• inotropic support;
• respiratory support; and
• in rare cases, extracorporeal membranous oxygenation (ECMO).

Anti-inflammatory measures have included the frequent use of IVIG and steroids. The use of other anti-inflammatory medications and the use of anti-coagulation treatments have been variable. Aspirin has commonly been used due to concerns for coronary artery involvement, and antibiotics are routinely used to treat potential sepsis while awaiting bacterial cultures. Thrombotic prophylaxis is often used given the hypercoagulable state typically associated with MIS-C.

Additional Information:

• CDC Information for Healthcare Providers about Multisystem Inflammatory Syndrome in Children (MIS-C)
• The American College of Rheumatology has developed clinical guidance for pediatric patients diagnosed with MIS-C associated with SARS-CoV-2.
• The American Academy of Pediatrics has published interim guidance  on multisystem inflammatory syndrome in children (MIS-C).

References

1. Zimmerman P, Curtis, N. Coronavirus infections in children including COVID-19: an overview of the epidemiology, clinical features, diagnosis, treatment and prevention options in children [volume online first]. Pediatr Infect Dis J. 2020 Mar 12. doi: 10.1097/INF.0000000000002660 
2. CDC COVID-19 Response Team. Severe outcomes among patients with coronavirus disease 2019 (COVID-19) - United States, February 12-March 16, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(12):343-346. Published 2020 Mar 27. doi:10.15585/mmwr.mm6912e2 
3. The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team. The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) — China, 2020[J]. China CDC Weekly. 2020;2(8):113-122.
4. Dong Y, Mo X, Hu Y, et al. Epidemiology of COVID-19 among children in China [published online ahead of print, 2020 Mar 16]. Pediatrics. 2020;e20200702. doi:10.1542/peds.2020-0702 
5. van Doremalen N, Bushmaker T, Morris DH, et al. Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1 [published online ahead of print, 2020 Mar 17]. N Engl J Med. 2020;NEJMc2004973. doi:10.1056/NEJMc2004973 
6. Xu Y, Xufang L, Bing Z, et al. Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding. Nat Med. 2020 Mar 13.
7. Lu X, Zhang L, Du H, et al. SARS-CoV-2 infection in children [published online ahead of print, 2020 Mar 18]. N Engl J Med. 2020;NEJMc2005073. doi:10.1056/NEJMc2005073 
8. Chen ZM, Fu JF, Shu Q, et al. Diagnosis and treatment recommendations for pediatric respiratory infection caused by the 2019 novel coronavirus [published online ahead of print, 2020 Feb 5]. World J Pediatr. 2020;10.1007/s12519-020-00345-5. doi:10.1007/s12519-020-00345-5  
9. Liu W, Zhang Q, Chen J, et al. Detection of Covid-19 in children in early January 2020 in Wuhan, China. N Engl J Med. 2020;382(14):1370–1371. doi:10.1056/NEJMc2003717 
10. Pediatric Emergency Medicine Committee of the American College of Emergency Physicians Florida Chapter.
11. Castagnoli R, Votto M, Licari A, et al. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents: a systematic review [published online ahead of print, 2020 Apr 22]. JAMA Pediatr. 2020;10.1001/jamapediatrics.2020.1467. doi:10.1001/jamapediatrics.2020.1467