ABSTRACT
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<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.ConclusionsPrognosis 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.
ABSTRACT
This is a prospective cohort study of 88 lactating women in Singapore who received two doses of BNT162b2 vaccination (Pfizer/BioNTech), whereby outcomes of mother-child dyads within 28 days after the second vaccine dose were determined through a structured questionnaire. Minimal effects related to breastfeeding were reported in this cohort; 3 of 88 (3.4%) women had mastitis with 1 of 88 (1.1%) women experiencing breast engorgement. We report an incidence of lymphadenopathy in our cohort at 5 of 88 (5.7%). Reassuringly, there was no change in reported breastmilk supply after vaccination. The most common side effect was pain/redness/swelling at the injection site, which was experienced by 57 of 88 (64.8%) women. There were no serious adverse events of anaphylaxis and hospital admissions. No adverse symptoms were reported in 67 of 88 (76.1%) breastfed children.
Subject(s)
Pain , Mastitis , Lymphatic Diseases , COVID-19 , AnaphylaxisABSTRACT
ImportanceTo examine the impact of SARS-CoV-2 vaccination of lactating mothers on human milk Objective(1) To quantify SARS-CoV-2-specific immunoglobulin A (IgA) and immunoglobulin G (IgG) in human milk of lactating mothers who received the BNT162b2 vaccine, with reference to a cohort convalescent from antenatal COVID-19, and healthy lactating mothers. (2) To detect and quantify vaccine mRNA in human milk after BNT162b2 vaccination. DesignGestational Immunity For Transfer 2 (GIFT-2) is a prospective cohort study of lactating mothers who were due to receive two doses of BNT162b2 vaccine, recruited between 5th February 2021 and 9th February 2021. SettingLactating healthcare workers living in Singapore ParticipantsConvenience sample of ten lactating healthcare workers. Human milk samples were collected at four time points: pre-vaccination, 1-3 days after dose one, 7-10 days after dose one, and 3-7 days after dose two of the BNT162b2 vaccine. ExposureTwo doses of the BNT162b2 vaccine 21 days apart. Main Outcome and Measure(i) SARS-CoV-2-specific IgA and IgG in human milk of lactating mothers who received BNT162b2 vaccine, (ii) Detection and quantification of vaccine mRNA in human milk after BNT162b2 vaccination. ResultsTen lactating healthcare workers aged 32.5 years (range 29 - 42) were recruited, with 40 human milk samples collected and analysed. SARS-CoV-2-specific IgA was predominant in human milk of lactating mothers who received BNT162b2 vaccine. The sharpest rise in antibody production was 3 -7 days after dose two of the BNT162b2 vaccine, with medians of 1110 picomolar of anti-SARS-CoV-2 spike and 374 picomolar of anti-Receptor Binding Domain IgA. Vaccine mRNA was detected only on rare occasions, at a maximum concentration of 2 ng/mL. Conclusions and RelevanceIn this cohort of ten lactating mothers following BNT162b2 vaccination, nine (90%) produced SARS-CoV-2 IgA, and ten (100%) produced IgG in human milk with minimal amounts of vaccine mRNA. Lactating individuals should continue breastfeeding in an uninterrupted manner after receiving mRNA vaccination for SARS-CoV-2. Trial RegistrationRegistered at clinicaltrials.gov (NCT04802278). Key PointsO_ST_ABSQuestionC_ST_ABSDoes BNT162b2 (i) induce the production and secretion of SARS-CoV-2 specific antibodies into human milk, and/or (ii) get secreted into human milk? FindingsIn this cohort that included ten lactating healthcare workers following BNT162b2 vaccination, 90% produced SARS-CoV-2 immunoglobulin A, and 100% produced immunoglobulin G in human milk, with minimal amounts of vaccine mRNA transfer. MeaningLactating individuals should continue breastfeeding in an uninterrupted manner after receiving SARS-CoV-2 mRNA vaccination.