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Within the span of a few months, the coronavirus disease 2019 (COVID-19) has rapidly spread globally, becoming a pandemic, and primarily affecting elderly individuals and those with underlying chronic conditions. Cases of infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were only observed in 2% of the population aged <20 years.1
However, in light of recent reports, the novel coronavirus may be associated with a pediatric multisystem inflammatory syndrome.2
We spoke with Mary Beth Son, MD, director of the rheumatology program at Boston Children’s Hospital in Boston, Massachusetts, who provided insight on the potential association between the Kawasaki-like inflammatory disease and COVID-19.
Dr Son highlighted that there have been several observations of clusters of pediatric patients with a range of symptoms, some of which have been severe. “This has been reported in Spain, Italy, France, the United Kingdom, and most recently the United States, primarily on the east coast but cases have also been reported in [other parts of the country]. Children with febrile illnesses are being admitted with hypotension, some of whom had features of Kawasaki disease and others with signs of cytokine storm. Many children have showed preceding gastrointestinal symptoms; however, respiratory symptoms have not been widely reported. Testing for SARS CoV-2 has also varied, [producing both positive and negative results]; some children who tested negative for COVID-19 have had confirmed exposures with the virus.”
On the topic of why these pediatric cases were emerging or being reported now, she noted, “This has been a distressing and unexpected development. It is not clear if some of these children who [tested as] polymerase chain reaction-positive have Kawasaki disease in the setting of a viral trigger, a scenario that we are well familiar with. For many children, it seems likely that their clinical presentation is caused by a postinfectious immune mediated response. However, we are still very early into this, and we need more data and research to determine what is causing this spectrum of phenotypes.”
Case Reports: Identifying the Kawasaki-Like Disease in COVID-19
#A report by Jones and colleagues1 published in April 2020 described the case of a 6-month-old infant who presented to a pediatric urgent care unit and was subsequently diagnosed with Kawasaki disease on the basis of a classical presentation of illness on day 5 post-symptom onset. She received intravenous immunoglobulin (IVIG) and high-dose aspirin after which her clinical symptoms subsided; observations on echocardiogram demonstrated no abnormalities. Prior to discharge, a reverse transcriptase polymerase chain reaction test returned positive for infection with SARS-CoV-2; the authors of the case report noted that the patient’s course of illness with COVID-19 was mild. The patient was discharged 48 hours after her IVIG infusion and was recommended to quarantine for 14 days.
Researchers concluded that this case report may be useful in understanding patterns of clinical presentations in pediatric patients with COVID-19; however, they noted, “Further description of the clinical course of pediatric patients diagnosed with COVID-19 remains necessary, particularly regarding the potential association with [Kawasaki disease].”1
#Another study published in Pediatrics described the case of a 12-year-old girl who presented with fever, cough, and vomiting.3 Laboratory examinations demonstrated severe thrombocytopenia and elevated markers of inflammation, and chest radiograph showed bilateral diffuse airspace opacities and small pleural effusion; the patient subsequently developed respiratory failure, and required mechanical ventilation. On hospital day 4, testing of a nasopharyngeal swab sample returned positive for SARS-CoV-2. Investigators observed an improvement in thrombocytopenia symptoms on treatment with IVIG and steroids; ventilation and inhaled nitric oxide were administered for the management of severe acute respiratory distress syndrome. Following failed treatment with azithromycin and hydroxychloroquine, the patient received a regimen of tocilizumab and remdesivir that demonstrated clinical benefit.
Investigators of this case report concluded, “Given that severe pediatric COVID-19 is rare, we hope to inform pediatric providers on the clinical course and management considerations as this pandemic continues to spread.”3
#As of May 6, 2020, 64 patients with suspected multisystem inflammatory syndrome associated with COVID-19 were reported from hospitals in New York City. Some patients showed features similar to Kawasaki disease and toxic shock syndrome, including elevated inflammatory markers, fever, and abdominal symptoms.2 Furthermore, although Kawasaki disease may affect the heart or the blood vessels of children, symptoms typically resolve in 5 to 6 weeks and patients make a full recovery. However, in some cases, coronary artery damage persists, making Kawasaki disease the most common cause of acquired heart disease in developing countries, as observed by experts at the American Heart Association.4
Guidance for Testing and Reporting of COVID-19-Related Inflammation
The New York Department of Health issued guidance for clinicians that includes early recognition and prompt referral to pediatricians and in-patient specialists; providing critical care to these patients; and eliciting recent history of patients with infection with COVID-19 or symptomatic patients with the Kawasaki-like disease associated with COVID-19 who were in close contact. The health advisory specifically advises hospitals to immediately report cases of pediatric multisystem inflammatory syndrome associated with COVID-19 in patients aged <21 years and perform diagnostic and serologic tests for SARS-CoV-2.2
When asked about how clinicians can better screen patients for Kawasaki disease and COVID-19, Dr Son noted, “Children who are persistently febrile and/or ill should be evaluated in a tertiary care setting for signs of Kawasaki disease (conjunctival injection, red, cracked lips and/or erythematous oropharynx, rash, redness and swelling of the hands and feet or a swollen cervical lymph node), and cytokine storm. Many of these children have myocarditis, so an echocardiogram to look at the heart’s function as well as the coronary arteries is important to evaluate children with clinical signs of hemodynamic instability.”
In their report, the American Heart Association also added that because some children are progressing to severe illness rapidly, their symptoms should be evaluated quickly and they must be transferred to pediatric cardiac intensive care units for care. For patients who present with fever and inflammation without severe illness, elevated C-reactive protein levels and white blood cells must be monitored.3
Dr Son advised clinicians to emphasize to patients and their families that these cases have only occurred among a very small number of children. She added “… having children evaluated in an appropriate care setting with a multidisciplinary team is recommended to provide cohesive care.”
References
1. Jones VG, Mills M, Suarez D, et al. COVID-19 and Kawasaki disease: novel virus and novel case [published April 7, 2020]. Hosp Pediatr. doi:10.1542/hpeds.2020-0123
2. New York Department of Health. Health advisory: pediatric multi-system inflammatory syndrome potentially associated with coronavirus disease (COVID-19) in children. Published May 6, 2020. Accessed May 8, 2020. https://www.health.ny.gov/press/releases/2020/docs/2020-05-06_covid19_pediatric_inflammatory_syndrome.pdf
3. Patel PA, Chandrakasan, S, Mickells GE, Yildirim I, Kao CM, Bennett CM. Severe pediatric COVID-19 presenting with respiratory failure and severe thrombocytopenia [published May 4, 2020]. Pediatr. doi:10.1542/peds.2020-1437
4. American Heart Association. Kids with Kawasaki disease symptoms possibly linked to COVID-19; coronavirus infection leading to critical illness in children remains very infrequent. Published May 6, 2020. Accessed May 8, 2020. https://newsroom.heart.org/news/kids-with-kawasaki-disease-symptoms-possibly-linked-to-covid-19-coronavirus-infection-leading-to-critical-illness-in-children-remains-very-infrequent
