BackgroundIn 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.ObjectivesWe aimed to determine the clinical manifestations and outcomes of neonates with COVID-19, and characterise these clinical characteristics based on illness severity.MethodsA 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.ResultsSixty-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