Our search strategy resulted in a total of 5787 potential articles with COVID-19 related pediatric deaths. Following the removal of duplicates and screening of titles and abstracts, 199 full text articles were assessed for eligibility. 78 articles [11–88] ultimately met inclusion criteria and were utilized for analysis in this review. Our workflow is depicted in Fig. 1.
Of the 78 studies included in this review 24 were case reports, 10 were case series, 1 was case review, 2 were chart reviews, 1 was autopsy report, 1 was secondary analysis of epidemiological data, 2 were epidemiological studies, 20 were cohort studies, 9 were cross-sectional studies, and 8 were observational studies. Countries of publication include United States of America (n = 14), Brazil (n = 11), Iran (n = 10), Turkey (n = 10), India (n = 6), Saudi Arabia (n = 6), Mexico (n = 4), Spain (n = 5), United Kingdom (n = 5), Italy (n = 3), Pakistan (n = 3), Colombia (n = 2), Germany (n = 2), Algeria (n = 1), Argentina (n = 1), Austria (n = 1), Bangladesh (n = 1), Belgium (n = 1), Botswana (n = 1), Bulgaria (n = 1), Canada (n = 1), China (n = 1), Croatia (n = 1), Denmark (n = 1), France (n = 1), Indonesia (n = 1), Ireland (n = 1), Kuwait (n = 1), Lithuania (n = 1), Niger (n = 1), Portugal (n = 1), Slovenia (n = 1), Sweden (n = 1), Switzerland (n = 1). Four of the included studies included participants from multiple countries [12, 38, 45, 59]. Full study characteristics are listed in Supplementary Table 1.
Patient demographics
The Clinical characteristics of the 837 COVID-19 pediatric deaths were included in our review. Table 2 highlights the pooled findings for patients (findings by individual study are listed in Supplementary Table 2). Among these pediatric deaths, 109 were males and 93 were females, while 635 did not have their sex specified. The age of the patients included in our review ranges from 3 days old to 18 years old.
Table 2
Pooled analysis of case-fatality rate by risk factor
Risk factor | | Deaths | % |
Total | | 837 | 100.0 |
Sex | | | |
| Male | 109 | 13.0 |
| Female | 93 | 11.1 |
Symptoms | | | |
| Fever | 62 | 7.4 |
| Cough | 44 | 5.3 |
| Gastrointestinal symptoms (abdominal pain, vomiting, diarrhoea) | 34 | 4.1 |
Comorbidities | Malignancy | 252 | 30.1 |
| Cardiovascular diseases | 51 | 6.1 |
| Overweight/obesity | 26 | 3.1 |
| Other/ unspecified | 15 | 1.8 |
| | 160 | 19.1 |
Investigation | Ground-glass opacities imaging | | |
| | 27 | 3.2 |
Complications | PIMS-TS/ MIS-C | | |
| ARDS | 35 | 4.2 |
| | 18 | 2.2 |
Patients presented with a variety of symptoms including fever, cough, rhinorrhea, sore throat, shortness of breath or dyspnea, abdominal pain, vomiting, and diarrhea. Fever (62 patients) and cough (44 patients) were the two most common symptoms recorded, in 50 and 34 of the eligible studies respectively. 49 studies recorded at least one NICU or PICU admission among the pediatric deaths.
Comorbidities
252 out of 838 children (30.1%) who died from COVID-19 were known to have comorbidities, including a range of malignancies, cardiovascular diseases, overweight/obesity, neurological conditions (including epilepsy), renal disease, and hereditary and genetic disorders such as Down Syndrome. Malignancies were the most common comorbidities (51 patients, 22 studies), especially hematological malignancies, followed by cardiovascular diseases (26 patients, 16 studies), followed by overweight/ obesity (15 patients, 8 studies).
Investigation Findings and Treatments
Most studies have recorded abnormal blood counts (anemia, abnormal white blood cell count, and thrombocytopenia), elevated inflammatory markers (C-reactive protein and/or erythrocyte sedimentation rate), and abnormalities on chest imaging (Computed Tomography and/or X-ray). 15 studies have specifically recorded ground-glass opacities finding on imaging in a total of 27 patients.
A total of 32 studies recorded the use of antibiotics while 20 studies recorded the use of antivirals for treatment. The use of corticosteroids, including glucocorticoids such as prednisolone and dexamethasone, were recorded in 20 studies. The use of hydroxychloroquine and intravenous immunoglobulin for treatment were recorded in a total of 14 and 15 studies respectively. 37 studies reported the utilization of at least one type of respiratory support, including supplemental oxygen and intubation/mechanical ventilation. A total of 15 patients were managed on extracorporeal membrane oxygenation, recorded in 11 studies.
Complications
The most common complication seen was the pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). 16 studies have recorded the occurrence of PIMS-TS in a total of 35 patients. The second most common reported complication was acute respiratory distress syndrome (ARDS), recorded in 10 studies, in a total of 18 patients.