SARS-CoV-2 detection in human milk: a systematic review.

PURPOSE: To synthesize the current evidence for the presence of SARS-CoV-2 RNA in the human milk of mothers with confirmed COVID-19 and its potential role in neonatal SARS-CoV-2 infection. MATERIALS AND METHODS: Using terms related to novel coronavirus 2019 and human milk, a systematic search was performed in three electronic databases (PubMed, EMBASE, and Web of Science) for studies published between December 2019 and 15 October 2020. Published peer-reviewed studies reporting the results of RT-PCR for SARS-CoV-2 RNA in human milk in mothers with confirmed COVID-19 were included. Proportion meta-analysis of case series and prospective cohort studies was performed using STATA version 14.2 (StataCorp, College Station, TX) and pooled estimate (with 95% confidence interval) of overall incidence of SARS-CoV-2 transmission was calculated. RESULTS: We identified 936 records, of which 34 studies (24 case-reports, 10 cohort studies) were eligible for this systematic review. A total of 116 confirmed COVID-19 lactating women (88 in cohort and 28 in case-reports) underwent RT-PCR testing in human milk, and 10 (six in case reports) were detected to have SARS-CoV-2 RNA. The overall pooled proportion (from cohort studies) for SARS-CoV-2 RNA detection in human milk was 2.16% (95% CI: 0.0-8.81%, I2: 0%). Four studies (six patients) also reported the presence of SARS-CoV-2 specific antibodies (along with RT-PCR) in human milk. CONCLUSIONS: The limited low-quality evidence suggests that SARS-CoV-2 RNA is detected in human milk in an extremely low proportion, however, based on current evidence no conclusion can be drawn about its infectivity and impact on the infants. In concordance with World Health Organization recommendations, exclusive breastfeeding should be considered in all cases unless any other contraindication exists.

Clinical characteristics & outcome of SARS-CoV-2 infected neonates presenting to paediatric emergency.

Background & objectives: Data on neonatal COVID-19 are limited to the immediate postnatal period, with a primary focus on vertical transmission in inborn infants. This study was aimed to assess the characteristics and outcome of COVID-19 in outborn neonates. Methods: All neonates admitted to the paediatric emergency from August 1 to December 31, 2020, were included in the study. SARS-CoV-2 reverse transcription- (RT)-PCR test was done on oro/nasopharyngeal specimens obtained at admission. The clinical characteristics and outcomes of SARS-CoV-2 positive and negative neonates were compared and the diagnostic accuracy of a selective testing policy was assessed. Results: A total of 1225 neonates were admitted during the study period, of whom SARS-CoV-2 RT-PCR was performed in 969. The RT-PCR test was positive in 17 (1.8%). Mean (standard deviation) gestation and birth weight of SARS-CoV-2-infected neonates were 35.5 (3.2) wk and 2274 (695) g, respectively. Most neonates (11/17) with confirmed COVID-19 reported in the first two weeks of life. Respiratory distress (14/17) was the predominant manifestation. Five (5/17, 29.4%) SARS-CoV-2 infected neonates died. Neonates with COVID-19 were at a higher risk for all-cause mortality [odds ratio (OR): 3.1; 95% confidence interval (CI): 1.1-8.9, P=0.03]; however, mortality did not differ after adjusting for lethal malformation (OR: 2.4; 95% CI: 0.7-8.7). Sensitivity, specificity, accuracy, positive and negative likelihood ratios (95% CI) of selective testing policy for SARS-CoV-2 infection at admission was 52.9 (28.5-76.1), 83.3 (80.7-85.6), 82.8 (80.3-85.1), 3.17 (1.98-5.07), and 0.56 (0.34-0.93) per cent, respectively. Interpretation & conclusions: SARS-CoV-2 positivity rate among the outborn neonates reporting to the paediatric emergency and tested for COVID-19 was observed to be low. The selective testing policy had poor diagnostic accuracy in distinguishing COVID-19 from non-COVID illness.

Relationship Between COVID-19 Lockdown and Epidemiology of Neonatal Sepsis.

BACKGROUND: We compared the hospital-based epidemiology of neonatal sepsis after the coronavirus disease 2019 lockdown (LD) versus historical epochs and the LD period versus phases of unlocking. METHODS: This retrospective cohort study was conducted in a level 3 neonatal unit. We compared neonates born in three 24-week periods-Group LD: 22 March 2020 to 5 September 2020-the reference group, Group pre-LD: 29 September 2019 to 14 March 2020 and Group temporally corresponding to LD in 2019 (corres-LD): 24 March 2019 to 7 September 2019. We also studied linear trends from LD phase 1.0 until Unlock 4.0. The key outcome was culture-positive sepsis. RESULTS: There were 1622, 2744 and 2700 subjects in groups LD, pre-LD and corres-LD, respectively. The incidence of any culture-positive sepsis in pre-LD was higher than LD [odds ratio (95% CI) = 1.61 (1.02-2.56)]. This was mainly due to a statistically significant reduction in Acinetobacter baumannii sepsis, with incidence rate differences of pre-LD versus LD [0.67 (95% CI: 0.37-0.97), P = 0.0001] and corres-LD versus LD [0.40 (95% CI: 0.16-0.64), P = 0.0024]. Groups pre-LD and corres-LD had higher proportion of multi-drug resistant (MDR)/extreme drug resistance/pan drug resistance sepsis than LD [77%, 77% and 44%, respectively (P values of both groups vs. LD = 0.01)]. From LD 1.0 to unlock 4.0, there were fewer episodes of MDR sepsis (Plinear trends = 0.047). On multivariable analysis, group pre-LD (vs. reference group LD), male sex, birth weight and Apgar score independently predicted culture-positive sepsis. CONCLUSIONS: LD favorably impacted the epidemiology of neonatal sepsis in a hospital setting, with less A. baumannii and MDR sepsis, which persisted during unlocking.

Efficacy and safety of hydroxychloroquine/chloroquine against SARS-CoV-2 infection: A systematic review and meta-analysis.

INTRODUCTION: Hydroxychloroquine (HCQ)/Chloroquine (CQ) has been evaluated for treatment and prophylaxis against SARS-CoV-2 infection in various studies with conflicting results. We performed a systematic review to synthesize the currently available evidence over the efficacy and safety of HCQ/CQ therapy alone against SARS-CoV-2 infection. METHODS: We searched Embase, PubMed, Web of Science, and Cochrane central for randomized controlled trials (RCTs) and prospective cohort studies published until October 15, 2020 and assessing the efficacy of HCQ alone against SARS-CoV-2 infection. We included studies evaluating HCQ/CQ alone as intervention and placebo/standard care as a control group. Retrospective studies and studies using other drugs (namely azithromycin, corticosteroids, immunomodulators, etc.) we excluded. Thirteen RCTs and three prospective cohort studies were included in this review. We pooled data using a random-effect model. RESULTS: Pooled data from 12 studies (9917 participants) showed that HCQs increase mortality as compared to placebo/standard of care (RR 1.10; 95% CI:1.00-1.20). Hydroxychloroquine did not reduce the need for hospitalization in out-patients (RR 0.57; 95% CI 0.31-1.02). HCQ group has a significantly higher rate of any adverse event (RR 2.68; 95% CI 1.55-4.64), as compared to the control group. Also, using HCQ for prophylaxis against SARS-CoV-2 infection did not reduce the risk of acquiring SARS-CoV-2 infection (RR 1.04; 95% CI 0.58-1.88). CONCLUSIONS: HCQ therapy for COVID-19 is associated with an increase in mortality and other adverse events. The negative effects are more pronounced in hospitalized patients. Therefore, with the available evidence, HCQ should not be used in prophylaxis or treatment of patients with COVID-19.

Clinical Features and Outcome of SARS-CoV-2 Infection in Neonates: A Systematic Review.

OBJECTIVE: The objective of this study is to systematically synthesize the currently available literature on various modes of transmission (congenital, intrapartum, and postpartum), clinical features and outcomes of SARS-CoV-2 infection in neonates. METHODS: We conducted a comprehensive literature search using PubMed, EMBASE, and Web of Science until 9 June 2020. A combination of keywords and MeSH terms, such as COVID-19, coronavirus, SARS-CoV-2, 2019-nCoV, severe acute respiratory syndrome coronavirus 2, neonates, newborn, infant, pregnancy, obstetrics, vertical transmission, maternal-foetal transmission and intrauterine transmission, were used in the search strategy. We included studies reporting neonatal outcomes of SARS-CoV-2 proven pregnancies or neonatal cases diagnosed with SARS-CoV-2 infection. RESULTS: Eighty-six publications (45 case series and 41 case reports) were included in this review. Forty-five case series reported 1992 pregnant women, of which 1125 (56.5%) gave birth to 1141 neonates. A total of 281 (25%) neonates were preterm, and caesarean section (66%) was the preferred mode of delivery. Forty-one case reports describe 43 mother-baby dyads of which 16 were preterm, 9 were low birth weight and 27 were born by caesarean section. Overall, 58 neonates were reported with SARS-CoV-2 infection (4 had a congenital infection), of which 29 (50%) were symptomatic (23 required ICU) with respiratory symptoms being the predominant manifestation (70%). No mortality was reported in SARS-CoV-2-positive neonates. CONCLUSION: The limited low-quality evidence suggests that the risk of SARS-CoV-2 infections in neonates is extremely low. Unlike children, most COVID-positive neonates were symptomatic and required intensive care. Postpartum acquisition was the commonest mode of infection in neonates, although a few cases of congenital infection have also been reported.

Radiological Findings of COVID-19 in Children: A Systematic Review and Meta-Analysis.

BACKGROUND: The majority of the children with SARS-CoV-2 infection present with respiratory symptoms, hence various chest imaging modalities have been used in the management. Knowledge about the radiological findings of coronavirus disease (COVID-19) in children is limited. Hence, we systematically synthesized the available data that will help in better management of COVID-19 in children. METHODS: Four different electronic databases (MEDLINE, EMBASE, Web of Science and CENTRAL) were searched for articles reporting radiological findings in children with COVID-19. Studies reporting thoracic radiological findings of COVID-19 in patients aged <19 years were included. A random-effect meta-analysis (wherever feasible) was performed to provide pooled estimates of various findings. RESULTS: A total of 1984 records were screened of which forty-six studies (923 patients) fulfilled the eligibility criteria and were included in this systematic review. A chest computed tomography (CT) scan was the most frequently used imaging modality. While one-third of the patients had normal scans, a significant proportion (19%) of clinically asymptomatic children had radiological abnormalities too. Unilateral lung involvement (55%) was frequent when compared with bilateral and ground-glass opacities were the most frequent (40%) definitive radiological findings. Other common radiological findings were non-specific patchy shadows (44%), consolidation (23%), halo sign (26%), pulmonary nodules and prominent bronchovascular marking. Interstitial infiltration being the most frequent lung ultrasound finding. CONCLUSION: CT scan is the most frequently used imaging modality for COVID-19 in children and can detect pneumonia before the appearance of clinical symptoms. Undefined patchy shadows, grand-glass opacities and consolidation are commonly observed imaging findings in COVID-19 pneumonia.

Clinical Features and Outcome of SARS-CoV-2 Infection in Children: A Systematic Review and Meta-analysis.

OBJECTIVE: Knowledge about COVID-19 in children is limited due to the paucity of reported data. The pediatric age group comprises only less than 5% of total COVID-19 worldwide, therefore, large studies in this population are unlikely in the immediate future. Hence, we planned to synthesize the current data that will help in a better understanding of COVID-19 in children. EVIDENCE ACQUISITION: Four different electronic databases (MEDLINE, EMBASE, Web of Science, and CENTRAL) were searched for articles related to COVID-19 in the pediatric population. We included studies reporting disease characteristics and outcomes of COVID-19 in patients aged less than 19 years. We performed a random-effect meta-analysis to provide pooled estimates of various disease characteristics. RESULTS: 27 studies (4857 patients) fulfilling the eligibility criteria were included in this systematic review, from a total of 883 records. About half of the patients had each of fever and cough, 11% (6-17%) had fast breathing, and 6-13% had gastrointestinal manifestations. Most of the patients had mild to moderate disease, and only 4% had a severe or critical illness. Leukopenia was the commonest reported laboratory abnormality. CONCLUSIONS: Even among the symptomatic COVID-19 cases, severe manifestations are seen in very few children. Though fever and respiratory symptoms are most common, many children also have gastrointestinal manifestations.