Background In general, children with COVID-19 have milder illness and better prognosis compared to adults. However, the neonatal population (from birth to 28 days of life) may be more vulnerable to severe COVID-19 disease due to the immaturity of neonatal immune system and possibility of in-utero infection from infected mothers. Comprehensive data on neonatal COVID-19 manifestations is currently lacking.
Objectives We aimed to determine the clinical manifestations and outcomes of neonates with COVID-19, and characterise these clinical characteristics based on illness severity.
Methods A systematic review (CRD42020183500) was conducted following the PRISMA guidelines with Embase, PubMed, and China Knowledge Resource Integrated (CNKI) databases until 1 August 2020. Additional studies were identified from references of included studies and the John Hopkins Centre for Humanitarian Health database. Studies reporting neonates (≤ 28 days old) who tested positive for SARS-CoV-2 by reverse transcriptase PCR (RT-PCR) were included. Descriptive statistics were used to compare mild-moderately ill neonates (non-severe group) with severely-critically ill neonates (severe group). This grouping was based on the World Health Organization’s definition. Continuous variables were analysed using Wilcoxon-Rank Sum Test. Dichotomous or categorical data were analysed with Chi-square and Fisher’s Exact Tests. Quality of the studies were reviewed with Newcastle-Ottawa Scale and Murad Tool.
Results Sixty-seven studies were included out of 199 full text articles screened. Studies comprised of case reports, case series or cohort studies. Of ninety-nine neonates with COVID-19 infection, 72 (72.7%) were symptomatic. Amongst the symptomatic neonates, respiratory symptoms were common: shortness of breath (36.1%), nasal symptoms (19.4%), cough (18.1%). Other symptoms included fever (55.6%), feeding problems (31.9%) and gastrointestinal (GI) symptoms (16.7%). Lymphopenia was present in 43.9% (18 of 41 neonates tested). Elevated C-reactive protein was only reported in 13.2% (5 of 38 neonates tested), while 65.4% (34 of 52 neonates) had chest radiographs suggestive of pneumonia. Thirty neonates (30.3%) had severe-critical illness (severe group), while 69 (69.9%) had mild-moderate illness (non-severe group). Compared with the non-severe group, more neonates in the severe group were symptomatic (100% vs 60.9%, p<0.001), had dyspnoea (66.7% vs 14.3%, p<0.001) and abnormal chest radiographic findings (84.6% vs 61.5%, p=0.038). Accordingly, more neonates in the severe group were admitted to the intensive care unit (91.7% vs 41.7%, p<0.001). On the contrary, mild-moderately ill neonates had increased incidence of fever (69.0% vs 36.7%, p=0.006), and GI symptoms (26.2% vs 3.33%, p=0.01). Ten out of 11 of mild-moderately ill neonates displaying GI symptoms did not have dyspnoea. Laboratory findings, duration of hospital stay, birth characteristics and age at COVID-19 diagnoses were similar between these two groups. No mortalities were reported.
Conclusions Prognosis of COVID-19 neonates were favourable. We postulate that GI symptoms alone predict a better prognosis, while GI symptoms with dyspnoea predict a worse prognosis, as observed in adults. However, our studies were of moderate quality, and clinical findings and investigation results were not completely reported. As the pandemic evolves, prospective studies and more systematic reporting of cases will improve our understanding of neonatal COVID-19 and verify utility of symptoms and laboratory tests in predicting the severity of disease.
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