Most downloaded biology preprints, all time
in category pediatrics
464 results found. For more information, click each entry to expand.
221,284 downloads medRxiv pediatrics
Since the first reports of novel coronavirus in the 2020, public health organizations have advocated preventative policies to limit virus, including stay-at-home orders that closed businesses, daycares, schools, playgrounds, and limited child learning and typical activities. Fear of infection and possible employment loss has placed stress on parents; while parents who could work from home faced chal-lenges in both working and providing full-time attentive childcare. For pregnant individuals, fear of at-tending prenatal visits also increased maternal stress, anxiety, and depression. Not surprising, there has been concern over how these factors, as well as missed educational opportunities and reduced interaction, stimulation, and creative play with other children might impact child neurodevelopment. Lev-eraging a large on-going longitudinal study of child neurodevelopment, we examined general childhood cognitive scores in 2020 and 2021 vs. the preceding decade, 2011-2019. We find that children born during the pandemic have significantly reduced verbal, motor, and overall cognitive performance com-pared to children born pre-pandemic. Moreover, we find that males and children in lower socioeconom-ic families have been most affected. Results highlight that even in the absence of direct SARS-CoV-2 infection and COVID-19 illness, the environmental changes associated COVID-19 pandemic is signifi-cantly and negatively affecting infant and child development.
26,036 downloads medRxiv pediatrics
There is increasing evidence that adult patients diagnosed with acute COVID-19 suffer from Long COVID initially described in Italy. To date, data on Long COVID in children are lacking. We assessed persistent symptoms in pediatric patients previously diagnosed with COVID-19. More than a half reported at least one persisting symptom even after 120 days since COVID-19, with 42.6% being impaired by these symptoms during daily activities. Symptoms like fatigue, muscle and joint pain, headache , insomnia, respiratory problems and palpitations were particularly frequent, as also described in adults. The evidence that COVID-19 can have long-term impact children as well, including those with asymptomatic/paucisymptomatic COVID-19, highlight the need for pediatricians, mental health experts and policy makers of implementing measures to reduce impact of the pandemic on child s health.
15,364 downloads medRxiv pediatrics
Background: Maternal vaccination for Influenza and TDaP have been well studied in terms of safety and efficacy for protection of the newborn by placental passage of antibodies. Similar newborn protection would be expected after maternal vaccination against SARS-CoV-2 (the virus responsible for COVID-19). There is a significant and urgent need for research regarding safety and efficacy of vaccination against SARS-CoV-2 during pregnancy. Here, we report the first known case of an infant with SARS-CoV-2 IgG antibodies detectable in cord blood after maternal vaccination. Case presentation: A vigorous, healthy, full-term female was born to a COVID-19 naive mother who had received a single dose of mRNA vaccine for SARS-CoV-2 three weeks prior to delivery. Cord blood antibodies (IgG) were detected to the S-protein of SARS-CoV-2 at time of delivery. Conclusion: Here, we report the first known case of an infant with SARS-CoV-2 IgG antibodies detectable in cord blood after maternal vaccination.
9,364 downloads medRxiv pediatrics
Jia Ming Low, Yue Gu, Melissa Shu Feng Ng, Amin Zubair, Le Ye Lee, Yvonne Peng Mei Ng, Bhuvaneshwari D/O Shunmuganathan, Yuxi Niu, Rashi Gupta, Paul Tambyah, Paul A Macary, Liang Wei Wang, Youjia Zhong
Importance: To 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. Design: Gestational 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. Setting: Lactating healthcare workers living in Singapore Participants: Convenience sample of ten lactating healthcare workers. Human milk samples were collected at four time points: pre-vaccination, 1 to 3 days after dose one, 7 to 10 days after dose one, and 3 to 7 days after dose two of the BNT162b2 vaccine. Exposure: Two 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. Results: Ten lactating healthcare workers aged 32.5 years (range 29 to 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 to 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. Infants had no reported adverse events, up to 28 days after ingestion of post-vaccination human milk. Conclusions and Relevance: In 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.
9,356 downloads medRxiv pediatrics
Several countries have recently approved the use of mRNA vaccines against COVID-19 under an emergency use authorization. However, no pregnant or lactating individuals were included in the Phase 3 clinical trials of these vaccines despite belonging to a group at high risk for severe complications of COVID-19 infection. We show here that the mRNA from anti-COVID vaccines is not detected in human breast milk samples collected 4-48 hours post-vaccine. These results strengthen the recommendation of ABM and WHO that lactating individuals who receive the anti-COVID-19 mRNA-based vaccine should continue to breastfeed their infants uninterrupted.
8,232 downloads medRxiv pediatrics
Background The COVID-19 pandemic created the need for very large scale, rapid testing to prevent and contain transmission of the SARS-CoV-2 virus. Lateral flow device (LFD) immunoassays meet this need by indicating the presence of SARS-CoV-2 antigen from nose/throat swab washings in 30 minutes without laboratory processing, and can be manufactured quickly at low cost. Since March 2021, UK schools have asked pupils without symptoms to test twice weekly. Pupils have posted on social media about using soft drinks to create positive results. The aim of this study was to systematically test a variety soft drinks to determine whether they can cause false false positive LFD results. Methods This study used 14 soft drinks and 4 artificial sweeteners to determine the outcome of misusing them as analyte for the Innova SARS-CoV-2 antigen rapid qualitative LFD. The pH value, sugar content and ingredients of each sample are described. The LFD results were double read and a subset was repeated using the same devices and fake analytes but differently sourced. Findings One sample (1/14; 7%), spring water, produced a negative result. Ten drinks (10/14; 71%) produced a positive or weakly positive result. Three samples (3/14; 21%) produced void results, mostly the fruit concentrate drinks. There was no apparent correlation between the pH value (pH 5.0 in 13/14, 93%; pH 6.5 in 1/14; 7%) or the sugar content (range 0-10.7 grams per 100mls) of the drinks and their LFD result. The 4 artificial sweeteners all produced negative results. A subset of the results was fully replicated with differently sourced materials. Interpretation Several soft drinks can be misused to give false positive SARS-CoV-2 LFD results. Daily LFD testing should be performed first thing in the morning, prior to the consumption of any food or drinks, and supervised where feasible. Funding This work was self-funded by author LO and the LFD were gifted for use in this study.
8,122 downloads medRxiv pediatrics
Objective: While pediatric population has largely remained free of severe COVID-19, in some cases SARS-CoV-2 infection has been associated with complications like Multiple Inflammatory Syndrome in children (MIS-C). We mention another unique presentation subsequent to asymptomatic infection of SARS-CoV-2, a unique form of hepatitis designated by us as COVID-19 Associated Hepatitis in Children (CAH-C). The contrasting clinical presentations, temporal association and viral parameters of CAH-C cases, to the MIS-C cases are presented here. Methods: As a retrospective and follow-up observational study we reviewed all children testing positive for SARS-CoV-2 during study period. Children presenting with sudden onset of hepatitis, elevated transaminases, non-obstructive jaundice, lacking marked inflammatory responses and without evidence of (a) other known causes of acute hepatitis or previous underlying liver disease (b) multi-system involvement were classified as CAH-C, are described here. Results: Among 475 children who tested positive, 47 patients presented with hepatitis, 37 patients who had features of CAH-C, having symptoms of hepatitis only, with un-elevated inflammatory markers and uneventful recovery following supportive treatment. Whereas remaining 10 MIS-C hepatitis had protracted illness, multiple system involvement, required admission to critical care, and had mortality of 30%. Conclusion: With the emergence of newer variants of concern (VOC) including the Delta variant which predominated the second wave of infections in India and has now spread to more than 142 countries with changing presentations, CAH-C might be one of them. Cases of such new entities need to be identified early and differentiated from other emerging syndromes in children during the ongoing pandemic for preventing adversities by timely intervention.
7,738 downloads medRxiv pediatrics
Joseph Ward, Rachel Harwood, Clare Smith, Simon E Kenny, Matthew Clark, Peter J Davis, Elizabeth S Draper, Dougal Hargreaves, Shamez Ladhani, Michael Linney, Karen Luyt, Elizabeth Whittaker, Lorna K Fraser, Russell M Viner
Identifying which children and young people (CYP) are vulnerable to severe disease following SARS-CoV-2 is important to guide shielding and vaccination policy. Methods We used data for all inpatient hospital admissions in England in CYP aged 0-17 between March 1st 2015 to Feb 28th 2021, linked to paediatric intensive care unit (PICU) admission, and SARS-CoV-2 PCR testing, and deaths. We calculated odds ratios and predicted probability of PICU admission using generalized estimation equations, and compared these between COVID-19, PIMS-TS, other admissions in 2020/21, all admissions in 2019/20, and admissions due to influenza in 20219/20. Findings There were 6,338 COVID-19 hospitalisations, 259 PICU admissions and 8 deaths as well as 712 PIMS-TS hospitalisations, 312 PICU admissions and <5 deaths. Odds of PICU admission were increased amongst neonates and decreased amongst 15-17 compared with 1-4 year olds with COVID-19, increased in older CYP and females with PIMS-TS, and increased for Black compared with White ethnicity for both conditions. Odds of PICU admission with COVID-19 were increased for CYP with any comorbidity and were highest for CYP with multiple medical problems. Comorbidities associated with PICU admission among COVID-19 patients were similar to overall PICU admissions in 2019/20 and to influenza PICU admissions in 2019/20, but with higher odds. Interpreting associations with comorbidities within PIMS-TS was complex due to the multisystem nature of the disease. Interpretation CYP were at very low risk of severe disease and death from COVID-19 or PIMS-TS. Patterns of vulnerability for severe COVID-19 appear to magnify background risk factors for serious illness in CYP.
7,141 downloads medRxiv pediatrics
Objective: To determine risk factors for SARS-CoV-2 infection and hospitalisation among children and adolescents. Design: Nationwide, population-based cohort study. Setting: Norway from 1 March 2020 to 31 April 2021. Participants: All Norwegian residents <18 years of age. Main outcome measures: Population-based health care and population registries were used to study risk factors for SARS-CoV-2 infection, including socioeconomic factors, country of origin, and pre-existing chronic comorbidities. All residents were followed until age 18, emigration, death, or end of follow-up. Hazard ratios (HR) estimated by Cox regression models were adjusted for testing frequency. Further, risk factors for admission to the hospital among the infected were investigated. Results: Of 1 182 796 residents, 22608 (1.9%) tested positive by polymerase chain reaction or lateral flow tests, of whom 107 (0.5%) were admitted to a hospital. Low family income (aHR 1.40, 95% confidence interval 1.36 to 1.46), crowded housing (1.35, 1.30 to 1.39), household size, age, and area of living were independent risk factors for infection. A non-Nordic country of origin was the strongest risk factor (aHR 2.37, 95% CI 2.30 to 2.49), whereas chronic comorbidity was not associated with the risk of infection. Chronic comorbidity was associated with hospitalisation (aHR 4.15, 2.63 to 6.56), in addition to age, whereas socioeconomic status and country of origin did not predict hospitalisation among those infected. Conclusions: Socioeconomic factors, country of origin, and area of living were associated with the risk of SARS-CoV-2 infection. However, these factors did not predict hospitalisation among those infected. Chronic comorbidity was associated with the risk of admission but not with the overall risk of acquiring SARS-CoV-2.
7,078 downloads medRxiv pediatrics
Rafael Heiss, Alexandra L Wagner, Lina Tan, Sandy Schmidt, Adrian P. Regensburger, Franziska Ewert, Dilbar Mammadova, Adrian Buehler, Jens Vogel-Claussen, Andreas Voskrebenzev, Oliver Rompel, Armin M Nagel, Simon Levy, Sebastian Bickelhaupt, Matthias S. May, Michael Uder, Markus Metzler, Regina Trollmann, Joachim Woelfle, Ferdinand Knieling
The frequency and extent of persistent sequelae in children and adolescents after infection with SARS-CoV-2 still needs to be comprehensively determined. In this cross-sectional clinical trial, we used non-invasive, label-free morphologic and free-breathing phase-resolved functional low-field magnetic resonance imaging (LF-MRI) to identify pulmonary changes in children and adolescents from 5 to <18 years after previously PCR-confirmed SARS-CoV-2 infection. While morphological pathologies were less frequent in children, functional LF-MRI visualized widespread ventilation, perfusion and combined ventilation/perfusion defects compared to healthy controls. The loss of functional lung parenchyma was more pronounced in long Covid than recovered patients. While pulmonary dysfunction was persistent even month after primary infection, LF-MRI demonstrated high capability to visualize and detect these changes in children and adolescents. (Clinicaltrials.org ID NCT04990531)
6,809 downloads medRxiv pediatrics
Background: Aetiology of preterm birth (PTB) is heterogeneous and preventive strategies remain elusive. Socio-environmental measures implemented as Ireland s prudent response to the SARS-CoV-2 virus (COVID-19) pandemic represented, in effect, a national lockdown and have possibly influenced the health and wellbeing of pregnant women and unborn infants. Cumulative impact of such socio-environmental factors operating contemporaneously on PTB has never been assessed before. Methods: Regional PTB trends of very low birth weight (VLBW) infants in one designated health area of Ireland over two decades were analysed. Poisson regression and rate ratio analyses with 95% CI were conducted. Observed regional data from January to April 2020 were compared to historical regional and national data and forecasted national figures for 2020. Results: Poisson regression analysis found that the regional historical VLBW rate per 1000 live births for January to April, 2001 to 2019 was 8.18 (95% CI: 7.21, 9.29). During January to April 2020, an unusually low VLBW rate of just 2.17 per 1000 live births was observed. The rate ratio of 3.77 (95% CI: 1.21, 11.75), p = 0.022, estimates that for the last two decades there was, on average, 3.77 times the rate of VLBW, compared to the period January to April 2020 during which there is a 73% reduction. National Irish VLBW rate for 2020 is forecasted to be reduced to 400 per 60,000 births compared to historical 500 to 600 range. Conclusion: An unprecedented reduction in PTB of VLBW infants was observed in one health region of Ireland during the COVID-19 lockdown. Potential determinants of this unique temporal trend reside in the summative socio-environmental impact of the COVID-19 dictated lockdown. Our findings, if mirrored in other regions that have adopted similar measures to combat the pandemic, demonstrate the potential to evaluate these implicated interdependent behavioural and socio-environmental modifiers to positively influence PTB rates globally.
6,450 downloads medRxiv pediatrics
Gitte Hedermann, Paula L Hedley, Marie Baekvad-Hansen, Henrik Hjalgrim, Klaus Rostgaard, Porntiva Poorisrisak, Morten Breindahl, Mads Melbye, David Hougaard, Michael Christiansen, Ulrik Lausten-Thomsen
Objectives To explore the impact of COVID-19 lockdown on premature birth rates in Denmark Design Nationwide register-based prevalence proportion study. Participants 31,180 live singleton infants born in Denmark between March 12, and April 14, from 2015 to 2020 Main outcome measures The Main outcome measure was the odds ratio of premature birth, per preterm category, during the lockdown period compared with the calendar match period in the five previous years. Results A total of 31 180 newborns were included in the study period, of these 58 were born extremely premature (gestational age below 28 weeks). The distribution of gestational ages was significantly different (p = 0.004) during the lockdown period compared to the previous five years. The extremely premature birth rate during the lockdown was significantly lower than the corresponding mean rate for the same dates in the previous years (odds ratio 0.09 [95 % CI 0.01 - 0.04], p < 0.001). No significant difference between the lockdown and previous years was found for other gestational age categories. Conclusions The birth rate of extremely premature infants decreased significantly (~90 % reduction) during the Danish nationwide lockdown from a stable rate in the preceding five years. The reasons for this decrease are unclear. Identification of possible causal mechanisms might stimulate changes in clinical practice. Ideally, some cases of extreme prematurity are preventable which may decrease infant morbidity and mortality.
6,186 downloads medRxiv pediatrics
Hanna Renk, Alex Dulovic, Matthias Becker, Dorit Fabricius, Maria Zernickel, Daniel Junker, Alina Seidel, Ruediger Gross, Alexander Hilger, Sebastian Bode, Linus Fritsch, Pauline Frieh, Anneke Haddad, Tessa Goerne, Jonathan Remppis, Tina Ganzenmueller, Andrea Dietz, Daniela Huzly, Hartmut Hengel, Klaus Kaier, Susanne Weber, Eva-Maria Jacobsen, Philipp Kaiser, Bjoern Traenkle, Ulrich Rothbauer, Maximilian Stich, Burkhard Toenshoff, Georg Friedrich Hoffmann, Barbara Mueller, Bernd Jahrsdoerfer, Carolin Ludwig, Hubert Schrezenmeier, Andreas Peter, Sebastian Hoerber, Thomas Iftner, Jan Muench, Thomas Stamminger, Martin Wolkewitz, Corinna Engel, Marta Rizzi, Hans-Juergen Gross, Axel Franz, Philipp Henneke, Klaus-Michael Debatin, Nicole Schneiderhan-Marra, Ales Janda, Roland Elling
Background: Long-term persistence of antibodies against SARS-CoV-2, particularly the SARS-CoV-2 Spike Trimer, determines individual protection against infection and potentially viral spread. The quality of children's natural humoral immune response following SARS-CoV-2 infection is yet incompletely understood but crucial to guide pediatric SARS-CoV-2 vaccination programs. Methods: In this prospective observational multi-center cohort study, we followed 328 households, consisting of 548 children and 717 adults, with at least one member with a previous laboratory-confirmed SARS-CoV-2 infection. The serological response was assessed at 3-4 months and 11-12 months after infection using a bead-based multiplex immunoassay for 23 human coronavirus antigens including SARS-CoV-2 and its Variants of Concern (VOC) and endemic human coronaviruses (HCoVs), and additionally by three commercial SARS-CoV-2 antibody assays. Results: Overall, 33.76% of SARS-CoV-2 exposed children and 57.88% adults were seropositive. Children were five times more likely to have seroconverted without symptoms compared to adults. Despite the frequently asymptomatic course of infection, children had higher specific antibody levels, and their antibodies persisted longer than in adults (96.22% versus 82.89% still seropositive 11-12 months post infection). Of note, symptomatic and asymptomatic infections induced similar humoral responses in all age groups. In symptomatic children, only dysgeusia was found as diagnostic indicator of COVID-19. SARS-CoV-2 infections occurred independent of HCoV serostatus. Antibody binding responses to VOCs were similar in children and adults, with reduced binding for the Beta variant in both groups. Conclusions: The long-term humoral immune response to SARS-CoV-2 infection in children is robust and may provide long-term protection even after asymptomatic infection. (Study ID at German Clinical Trials Register: 00021521)
4,752 downloads medRxiv pediatrics
ContextThe coronavirus disease 2019 (COVID-19) outbreak is an unprecedented global public health challenge, leading to thousands of deaths every day worldwide. Despite the epidemiological importance, clinical patterns of children with COVID-19 remain unclear. ObjectiveTo describe the clinical, laboratorial and radiological characteristics of children with COVID-19. Data SourcesThe Medline database was searched between December 1st 2019 and March 30th 2020. Study SelectionInclusion criteria were: (1) studied patients younger than 18 years old; presented original data from cases of COVID-19 confirmed by reverse-transcription polymerase chain reaction; and (3) contained descriptions of clinical manifestations, laboratory tests or radiological examinations. Data ExtractionNumber of cases, gender, age, clinical manifestations, laboratory tests, radiological examinations and outcomes. ResultsA total of 34 studies (1,118 cases) were included. From all the cases, 1,111 had their severity classified: 14.3% were asymptomatic, 36.4% were mild, 46.0% were moderate, 2.2% were severe and 1.2% were critical. The most prevalent symptom was fever (16.3%), followed by cough (14.4%), nasal symptoms (3.6%), diarrhea (2.7%) and nausea/vomiting (2.5%). One hundred forty-five (12.9%) children were diagnosed with pneumonia and 43 (3.8%) upper airway infections were reported. Reduced lymphocyte count were reported in 13.1% of cases. Abnormalities on computed tomography were reported in 62.7% of cases. The most prevalent abnormalities reported were ground glass opacities, patchy shadows and consolidations. Only one death was reported. ConclusionsClinical manifestations of children with COVID-19 differ widely from adults cases. Fever and respiratory symptoms should not be considered a hallmark of COVID-19 in children.
4,426 downloads medRxiv pediatrics
Background South Africa reported a notable increase in COVID-19 cases from mid-November 2021 onwards, starting in Tshwane District, linked to rapid community spread of the Omicron variant. This coincided with a rapid rise in paediatric COVID-19-associated hospitalisations. Methods We synthesized data from five sources to describe the impact of Omicron on clinical manifestations and outcomes of hospitalized children ([≤]19 years) with positive SARS-CoV-2 tests in Tshwane District from 31 October to 11 December 2021, including: 1) COVID-19 line lists; 2) collated SARS-CoV-2 testing data; 3) SARS-CoV-2 genomic sequencing data; 4) COVID-19 hospitalisation surveillance; and 5) clinical data of public sector paediatric ([≤]13 years) COVID-19 hospitalisations. Findings During the six-week period 6,287 paediatric ([≤]19 years) COVID-19 cases were recorded in Tshwane District, of these 462 (7.2%) were hospitalized in 42 hospitals (18% of overall admissions). The number of paediatric cases was higher than in the prior 3 waves, uncharacteristically preceding adult hospitalisations. Of the 75 viral specimens sequenced from the district, 99% were Omicron. Detailed clinical information obtained from 139 of 183 (76%) admitted children ([≤]13 years; including all public sector hospitalisations) indicated that young children (0-4 years) were most affected (62%). Symptoms included fever (47%), cough (40%), vomiting (24%), difficulty breathing (23%), diarrhoea (20%) and convulsions (20%). Length of hospital stay was short (mean 3.2 days), and in 44% COVID-19 was the primary diagnosis. Most children received standard ward care (92%), with 31 (25%) receiving oxygen therapy. Seven children (6%) were ventilated; four children died, all related to complex underlying co-pathologies. All children and majority of parents for whom data were available were unvaccinated. Interpretation Rapid increases in paediatric COVID-19 cases and hospitalisations mirror high community transmission of SARS-CoV-2 (Omicron variant) in Tshwane District, South Africa. Continued monitoring is needed to understand the long-term impact of the Omicron variant on children.
4,251 downloads medRxiv pediatrics
Clare Smith, David Odd, Rachel Harwood, Joseph Ward, Michael Linney, Matthew Clark, Dougal Hargreaves, Shamez Ladhani, Elizabeth S Draper, Peter J Davis, Simon E Kenny, Elizabeth Whittaker, Karen Luyt, Russell M Viner, Lorna K Fraser
Background Deaths in children and young people (CYP) following SARS-CoV-2 infection are rare. Quantifying the risk of mortality is challenging because of high relative prevalence of asymptomatic and non-specific disease manifestations. Therefore, it is important to differentiate between CYP who have died of SARS-CoV-2 and those who have died of an alternative disease process but coincidentally tested positive. Methods During the pandemic, the mandatory National Child Mortality Database (NCMD) was linked to Public Health England (PHE) testing data to identify CYP (<18 years) who died with a positive SARS-CoV-2 test. A clinical review of all deaths from March 2020 to February 2021 was undertaken to differentiate between those who died of SARS-CoV-2 infection and those who died of an alternative cause but coincidentally tested positive. Then, using linkage to national hospital admission data, demographic and comorbidity details of CYP who died of SARS-CoV-2 were compared to all other deaths. Absolute risk of death was estimated where denominator data were available. Findings 3105 CYP died from all causes during the first pandemic year in England. 61 of these deaths occurred in CYP who tested positive for SARS-CoV-2. 25 CYP died of SARS-CoV-2 infection; 22 from acute infection and three from PIMS-TS. 99.995% of CYP with a positive SARS-CoV-2 test survived. The 25 CYP who died of SARS-CoV-2 equates to a mortality rate of 2/million for the 12,023,568 CYP living in England. CYP >10 years, of Asian and Black ethnic backgrounds, and with comorbidities were over-represented compared to other children. Interpretation SARS-CoV-2 is very rarely fatal in CYP, even among those with underlying comorbidities. These findings are important to guide families, clinicians and policy makers about future shielding and vaccination.
4,245 downloads medRxiv pediatrics
Camila Rosat Consiglio, Nicola Cotugno, Fabian Sardh, Christian Pou, Donato Amodio, Sonia Zicari, Alessandra Ruggiero, Giuseppe Rubens Pascucci, Lucie Rodriguez, Veronica Santilli, Tessa Campbell, Yenan Bryceson, Ziyang Tan, Daniel Eriksson, Jun Wang, Tadepally Lakshmikanth, Alessandra Marchesi, Andrea Campana, Alberto Villani, Paolo Rossi, the CACTUS study team, Nils Landegren, Paolo Palma, Petter Brodin
SARS-CoV2 infection is typically very mild and often asymptomatic in children. A complication is the rare Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19, presenting 4-6 weeks after infection as high fever and organ dysfunction and strongly elevated markers of inflammation. The pathogenesis is unclear but has overlapping features with Kawasaki disease suggestive of vasculitis and a likely autoimmune etiology. We apply systems-level analyses of blood immune cells, cytokines and autoantibodies in healthy children, children with Kawasaki disease enrolled prior to COVID-19, children infected with SARS-CoV2 and children presenting with MIS-C. We find that the inflammatory response in MIS-C differs from the cytokine storm of severe acute COVID-19, is more similar to Kawasaki disease, but also differ from this with respect to T-cell subsets, IL-17A and biomarkers associated with arterial damage. Finally, autoantibody profiling suggests endoglin, an endothelial glycoprotein as one of several candidate targets of autoantibodies in MIS-C.
4,222 downloads medRxiv pediatrics
Erika Molteni, Carole Helene Sudre, Liane S Canas, Sunil S Bhopal, Robert C Hughes, Liyuan Chen, Jie Deng, Benjamin Murray, Eric Kerfoot, Michela S Antonelli, Mark S Graham, Kerstin Klaser, Anna May, Christina Hu, Joan Capdevila Pujol, Jonathan Wolf, Alexander Hammers, Timothy Spector, Sebastien Ourselin, Marc Modat, Claire J Steves, Michael Absoud, Emma L Duncan
Background The Delta (B.1.617.2) SARSCoV2 variant became the predominant UK circulating strain in May 2021. Whether COVID19 from Delta infection differs to infection with other variants in children is unknown. Methods Through the prospective COVID Symptom Study, 109,626 UK school-aged children were proxy-reported between December 28, 2020 and July 8, 2021. We selected all symptomatic children who tested positive for SARS-CoV-2 and were proxy-reported at least weekly, within two timeframes: December 28, 2020 to May 6, 2021 (Alpha (B.1.1.7) the main UK circulating variant); and May 26 to July 8, 2021 (Delta the main UK circulating variant). We assessed illness profiles (symptom prevalence, duration, and burden), hospital presentation, and presence of long (>28 day) illness; and calculated odds ratios for symptoms presenting within the first 28 days of illness. Findings 694 (276 younger [5 11 years], 418 older [12 17 years]) symptomatic children tested positive for SARS-CoV-2 with Alpha infection and 706 (227 younger and 479 older) children with Delta infection. Median illness duration was short with either variant (overall cohort: 5 days (IQR 2 9.75) with Alpha, 5 days (IQR 2 9) with Delta). The seven most prevalent symptoms were common to both variants. Symptom burden over the first 28 days was slightly greater with Delta compared with Alpha infection (in younger children, 3 (IQR 2 5) with Alpha, 4 (IQR 2 7) with Delta; in older children 5 (IQR 3 8) with Alpha and 6 (IQR 3 9) with Delta infection in older children). The odds of several symptoms were higher with Delta than Alpha infection, including headache and fever. Few children presented to hospital, and long illness duration was uncommon, with either variant. Interpretation COVID-19 in UK school-aged children due to SARSCoV2 Delta strain B.1.617.2 resembles illness due to the Alpha variant B.1.1.7., with short duration and similar symptom burden.
3,905 downloads medRxiv pediatrics
Anjali Ramaswamy, Nina N. Brodsky, Tomokazu S. Sumida, Michela Comi, Hiromitsu Asashima, Kenneth B Hoehn, Ningshan Li, Yunqing Liu, Aagam Shah, Neal G. Ravindra, Jason Bishai, Alamzeb Khan, William Lau, Brian Sellers, Neha Bansal, Rachel Sparks, Avraham Unterman, Victoria Habet, Andrew J. Rice, Jason Catanzaro, Harsha Chandnani, Merrick Lopez, Naftali Kaminski, Charles S. Dela Cruz, John S Tsang, Zuoheng Wang, Xiting Yan, Steven H. Kleinstein, David van Dijk, Richard Pierce, David A. Hafler, Carrie L. Lucas
Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening post-infectious complication occurring unpredictably weeks after mild or asymptomatic SARS-CoV2 infection in otherwise healthy children. Here, we define immune abnormalities in MIS-C compared to adult COVID-19 and pediatric/adult healthy controls using single-cell RNA sequencing, antigen receptor repertoire analysis, unbiased serum proteomics, and in vitro assays. Despite no evidence of active infection, we uncover elevated S100A-family alarmins in myeloid cells and marked enrichment of serum proteins that map to myeloid cells and pathways including cytokines, complement/coagulation, and fluid shear stress in MIS-C patients. Moreover, NK and CD8 T cell cytotoxicity genes are elevated, and plasmablasts harboring IgG1 and IgG3 are expanded. Consistently, we detect elevated binding of serum IgG from severe MIS-C patients to activated human cardiac microvascular endothelial cells in culture. Thus, we define immunopathology features of MIS-C with implications for predicting and managing this SARS-CoV2-induced critical illness in children.
3,522 downloads medRxiv pediatrics
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.
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