Pediatric critical care and COVID19

Abstract

INTRODUCTION COVID-19, caused by SARS-CoV2, disproportionally affects adults (children <5% in most reports)1. Adult critical illness is characterized by acute hypoxemia, multi-organ failure, and high mortality2, 3. Reported risk factors for severe illness include age, cardiorespiratory comorbidities, obesity, and laboratory findings (lymphopenia and elevated D-dimer)2, 4. Pediatric reports describe low infection rates and infrequent pediatric intensive care unit (PICU) admission5, 6. The largest PICU report consists of 48 North American children7. It describes treatments and outcomes but not with adequate granularity to understand critical pediatric COVID-19. The CAKE (Critical Coronavirus And Kids Epidemiologic) Study was designed to specifically investigate severe cases and provide detailed data. It involves over 60 centers in nearly 20 countries from the Americas and Europe. This report provides preliminary insights into our first 17 patients. METHODS: CAKE is a cohort study of children <19 years old with severe or critical COVID-19. The study period runs from April through December 2020. For this report, we included patients enrolled through April 23. We defined critical COVID-19 as a positive SARS-CoV2 test and requiring ICU therapies [high flow nasal cannula (HFNC), noninvasive ventilation (NIV), invasive mechanical ventilation (IMV), vasoactive support, continuous renal replacement therapy (CRRT)]. Severe COVID-19 included those receiving mask or nasal oxygen exceeding the pediatric acute respiratory distress syndrome (ARDS) “at risk” threshold8. Deidentified data were collected using a modification of the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) form (https://isaric.tghn.org/COVID-19-CRF/). Local ethics approval was obtained with a waiver of need for consent. RESULTS: We enrolled 17 children from 10 PICUs in Chile, Colombia, Italy, Spain and USA. Detailed data are in the online supplement. Most were male (65%), young (median 4 years; range 0.08-18 years), and without known COVID-19 exposure (14/17). Comorbidities (Table 1; Supplemental Table 1) were common (71%) but variable. Symptoms were heterogenous with fever and cough being most frequent (Table 1; Supplemental Table 1). Most with gastrointestinal (GI) symptoms (4/6) were also diagnosed with myocarditis (Supplemental Table 2). All these were from Europe and without prior cardiovascular disease. Patients had frequent laboratory testing (Table 1; Supplemental Table 3). Common findings included leukocytosis, lymphopenia, plus elevated inflammatory markers, D-dimer, and troponin I. Four had viral or bacterial respiratory co-infection. Most subjects required respiratory support (Table 2; Supplemental Table 4), with nearly half requiring IMV. Five initially treated with HFNC needed no escalation; two were intubated. One initially treated with NIV was intubated. Pulmonary-specific adjuncts were uncommon. Most patients received antibiotics; fewer received antivirals (Table 2; Supplemental Table 4). Corticosteroids, hydroxychloroquine, and tocilizumab were each prescribed to nearly half. Intravenous immune globulin (IVIG) was prescribed exclusively for myocarditis. Pneumonia and ARDS were common diagnoses (Table 2; Supplemental Table 4). Vasoactive infusions were frequent, including three of four with myocarditis. Other organ support or complications were uncommon. Outcomes (minimum 3 weeks data) are shown in Table 4 and Supplemental Table 4. As of submission, 3 remained hospitalized, 1 in ICU, and 1 died. DISCUSSION: Our description exclusively about critical pediatric COVID-19 reveals an uncommon (17 patients, 60 centers) but heterogeneous disease. Children frequently had GI rather than respiratory symptoms after a brief illness and recovered quickly despite significant support. We found regional variability of diagnoses (myocarditis in Europe), treatments (remdesivir in North America), and age. Our findings parallel recent studies describing frequent comorbidities but a short PICU stay and low mortality, contrasting with adults2 3, 6, 7. Compared to the North American series, our study was international, younger, included only severe disease, and revealed a wider range of common symptoms7. We also provide critical COVID-19 laboratory findings. We found that three children had peri-intubation arrest, markedly higher than expected9. At least one resulted from unfamiliar protective equipment and intubation processes. Clinicians must consider the risks before intubating these children. Pediatric COVID-19 myocarditis has not been previously reported, although adult cases are described10. It is unclear why myocarditis was only identified in Europe, but pediatric clinicians should consider cardiac involvement, particularly in those with the GI complaints common in our myocarditis patients. This is a small case series and should be used to generate hypotheses for research rather than informing current treatment. Regional variations may limit our ability to identify outcome associations but do demonstrate regional differences. Finally, others use different definitions for COVID-19 severity, but their subjectivity could lead to patient misclassification6. Our definitions are simple, objective, and reflect clinically relevant distinctions. In summary, we provide early clinical and laboratory data about critical pediatric COVID-19, which suggest a variable disease but generally good outcomes compared to adults. Targets for research include the course of organ failure in pediatric critical COVID-19, laboratory findings for predicting illness course or complications, the inflammatory response and its role in pathophysiology, best treatments, and specific organ involvement, such as myocarditis.