Synthesis and systematic review of reported neonatal SARS-CoV-2 infections

Abstract

A number of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections have been reported in neonates. Here, we aim to clarify the transmission route, clinical features and outcomes of these infections. We present a meta-analysis of 176 published cases of neonatal SARS-CoV-2 infections that were defined by at least one positive nasopharyngeal swab and/or the presence of specific IgM. We report that 70% and 30% of infections are due to environmental and vertical transmission, respectively. Our analysis shows that 55% of infected neonates developed COVID-19; the most common symptoms were fever (44%), gastrointestinal (36%), respiratory (52%) and neurological manifestations (18%), and lung imaging was abnormal in 64% of cases. A lack of mother-neonate separation from birth is associated with late SARS-CoV-2 infection (OR 4.94 (95% CI: 1.98-13.08), p = 0.0002; adjusted OR 6.6 (95% CI: 2.6-16), p < 0.0001), while breastfeeding is not (OR 0.35 (95% CI: 0.09-1.18), p = 0.10; adjusted OR 2.2 (95% CI: 0.7-6.5), p = 0.148). Our findings add to the literature on neonatal SARS-CoV-2 infections.

Fig. 1. Study flow chart.

Flow chart prepared according to the PRISMA guidelines template for meta-analyses.

Fig. 2. Classification of neonatal SARS-CoV-2 infections according to the definition of maternal, fetal, and neonatal SARS-CoV-2 infections.

Classification is based on a system including several virological tests (on placental tissues, amniotic fluid, cord and newborn blood or nasopharyngeal swabs), as well as the presence of clinical manifestations. Cases are divided into: (1) congenital infections, (2) intrapartum acquired infections, or (3) postpartum acquired infections and into five mutually exclusive categories of the likelihood of infection: “confirmed”, “probable”, “possible”, “unlikely”, and “not infected”. Classification was applied to 122 cases (for 54 neonates, data needed to classify the infection were missing despite repeated requests to the authors of the articles). Areas in blue depict the infections confirmed or supposed to be environmentally acquired (i.e.: postpartum), while areas in brown depict confirmed or supposed to be vertically (either intrapartum or congenitally) transmitted infections; numbers represent the %.

Fig. 3. Effect of mother-neonate separation and breastfeeding on the occurrence of late SARS-CoV-2 infections.

Late infections are defined as those diagnosed after the first 72 h of life. Diamonds and horizontal lines represent the odds ratio (OR) and its 95% confidence interval (CI), respectively. Horizontal axis is on a log scale for better visualization; vertical hatched line represents OR = 1. Analysis was performed for 133 neonates for whom infection could have been classified as early- or late-onset. Figure illustrates OR 4.94 (95% CI: 1.98–13.08), p = 0.0002, for lack of mother-neonate separation from birth and OR 0.35 (95% CI: 0.09–1.18), p = 0.10 for breastfeeding. Analyses were performed with two-sided Fisher exact test.