Publications

17

Dec, 2021

Size of HIV-1 reservoir is associated with telomere shortening and immunosenescence in early-treated European children with perinatally acquired HIV-1

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Authors: A Dalzini, G Ballin, S Dominguez-Rodriguez, P Rojo , M.R Petrara, C Foster, N Cotugno, A Ruggiero, E Nastouli, N Klein, S Rinaldi, S Pahwa, P Rossi, C Giaquinto, P Palma , A De Rossi1, and on behalf of EPIICAL Consortium

Published in: Journal of the International AIDS Society

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9

Dec, 2021

Diaskin and tuberculin skin test as tuberculosis diagnostics in Russian children: comparative observational study

 

Authors: Fritschi N, Gureva T, Eliseev P, Crichton S ,Intira Jeannie Collins IJ, Turkova T, Mariandyshev A, Ritz N

Presented at: The 52nd Union World Conference On Lung Health 2021

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6

Dec, 2021

Characterisation of the HIV proviral and inducible reservoir in well- suppressed children on long-term ART

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Authors: Gärtner K, Byott M, Heaney J, Pagliuzza A, Spyer M.J Frampton D, Rossi A.D, Palmas P, Giaquinto C, Conejo P.R, Foster C,  Rossi P, Klein N, Chomont N, Nastouli E, for the EPIICAL consortium

Presented at: Keystone symposia on molecular and cellular biology

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3

Dec, 2021

Optimised versus standard dosing of vancomycin in infants with Gram-positive sepsis (NeoVanc): a multicentre, randomised, open-label, phase 2b, non-inferiority trial

 

Authors: Hill L.F, Clements M.N, Turner M.A, Donà D, Lutsar I, Jacqz-Aigrain E, Heath P.T, Roilides E, Rawcliffe L, Alonso-Diaz C, Baraldi E, Dotta A, Ilmoja M, Mahaveer A, Metsvaht T, Mitsiakos G,  Papaevangelou V, Sarafidis K, Walker A.S, Sharland M, on behalf of the NeoVanc Consortium

Published in: The Lancet

28

Sep, 2021

Dolutegravir-based ART is superior to NNRTI- and PI-based ART in infants, children and adolescents living with HIV (combined results of the main trial and the ‘under 14kg’ cohort)

 

Authors: Anna Turkova on behalf of the ODYSSEY trial team

Presented at: CHIVA 2021

 

Abstract

ODYSSEY

  • Internationalmulti-centre,randomised96-weeknon- inferiority trial
  • WeaimedtocompareefficacyandsafetyofDTG-basedART with standard-of-care in children and adolescents starting first-line ART (ODYSSEY A) or second-line (ODYSSEY B)

Main trial enrolled children≥14kg

  • Aim to enrol ≥700 children: 310 ODYSSEY A, 390 ODYSSEY B
  • Powered for efficacy (total population and A&B separately)
  • Once enrolment in the main trial was completed, the trial was opened for ‘under 14kg cohort’

‘Under 14kg’ cohort

  • Aim to enrol ≥20 children in each of the three lower WHO weight bands: 3-<6kg, 6-<10kg and 10-<14kg
  • To confirm efficacy, safety and the most practical dosing
  • Proportions of first- and second-line not pre-specified
  • Children in DTG arm did intensive PK

 

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15

Sep, 2021

Early Impact of SARS-CoV-2 on Pediatric Clinical Research: A Pan-European and Canadian Snapshot in Time

 

Authors: O L. Mantha, F. Flamein, M. Turner, R. M. Fernandes, R. Hankard, the Network of National Networks Study Group

Published in: The Journal od Pediatrics

 

Abstract

The article is meant to capture the early effects of the SARS-CoV-2 pandemic on pediatric clinical research.

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24

Aug, 2021

Causes of Microcephaly in the Zika Era in Argentina: A Retrospective Study

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Authors: G Berberian, R Bologna, MG Pérez, A Mangano, PhD, M Costa, MSc, S Calligaris, MA Morales, C Rugilo, E Ruiz-Burga, C Thorne

Published in: Sage Journals

 

Abstract

There are gaps in understanding the causes and consequences of microcephaly. This paper describes the epidemiological characteristics, clinical presentations, and etiologies of children presenting microcephaly during the Zika outbreak in Argentina. This observational retrospective study conducted in the pediatric hospital of Juan P. Garrahan reviewed the medical records of 40 children presenting microcephaly between March 2017 and November 2019. The majority (60%) were males and born full-term. At first evaluation, microcephaly was defined as congenital (31/40, 77%) and associated with other features (68%) such as seizures, developmental delay, non-progressive chronic encephalopathy, and West Syndrome. It was found manifestations restricted to central nervous system (55%), ocular (8/40, 20%), and acoustic (9/40, 23%) defects, and abnormal neuroimaging findings (31/39, 79%). Non-infectious diseases were the primary cause of isolated microcephaly (21/37, 57%), largely related to genetic diseases (13/21, 62%). Only 3 were children were diagnosed with Congenital Zika infection (3/16, 7.5%).

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19

Aug, 2021

Pre-activated antiviral innate immunity in the upper airways controls early SARS-CoV-2 infection in children

 

Authors: J. Loske, J. Röhmel, S. Lukassen, S. Stricker, V. G. Magalhães, J. Liebig, R. L. Chua, L. Thürmann, M. Messingschlager, A. Seegebarth, B. Timmermann, S. Klages, M. Ralser, B. Sawitzki, L. E. Sander, V. M. Corman, C. Conrad, S. Laudi, M. Binder, S. Trump, R. Eils, M. A. Mall and I. Lehmann

Published in: Nature Biotechnology

 

Abstract

Children have reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rates and a substantially lower risk for developing severe coronavirus disease 2019 compared with adults. However, the molecular mechanisms underlying protection in younger age groups remain unknown. Here we characterize the single-cell transcriptional landscape in the upper airways of SARS-CoV-2-negative (n = 18) and age-matched SARS-CoV-2-positive (n = 24) children and corresponding samples from adults (n = 44), covering an age range of 4 weeks to 77 years. Children displayed higher basal expression of relevant pattern recognition receptors such as MDA5 (IFIH1) and RIG-I (DDX58) in upper airway epithelial cells, macrophages and dendritic cells, resulting in stronger innate antiviral responses upon SARS-CoV-2 infection than in adults. We further detected distinct immune cell subpopulations including KLRC1 (NKG2A)+ cytotoxic T cells and a CD8+ T cell population with a memory phenotype occurring predominantly in children. Our study provides evidence that the airway immune cells of children are primed for virus sensing, resulting in a stronger early innate antiviral response to SARS-CoV-2 infection than in adults.

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16

Aug, 2021

Evaluation of mRNA-1273 SARS-CoV-2 Vaccine in Adolescents

 

Authors: K Ali, GBerman, H Zhou, W Deng, V Faughnan, M Coronado-Voges, B Ding, J Dooley, B Girard, W Hillebrand, R Pajon, JM. Miller, B Leav, and R McPhee

Published in: New England Journal of Medicine

 

Abstract

Background The incidence of coronavirus disease 2019 (Covid-19) among adolescents between 12 and 17 years of age was approximately 900 per 100,000 population from April 1 through June 11, 2021. The safety, immunogenicity, and efficacy of the mRNA-1273 vaccine in adolescents are unknown.

Methods In this ongoing phase 2–3, placebo-controlled trial, we randomly assigned healthy adolescents (12 to 17 years of age) in a 2:1 ratio to receive two injections of the mRNA-1273 vaccine (100 μg in each) or placebo, administered 28 days apart. The primary objectives were evaluation of the safety of mRNA-1273 in adolescents and the noninferiority of the immune response in adolescents as compared with that in young adults (18 to 25 years of age) in a phase 3 trial. Secondary objectives included the efficacy of mRNA-1273 in preventing Covid-19 or asymptomatic severe acute respiratory syndrome coronavirus 2 infection.

Results A total of 3732 participants were randomly assigned to receive mRNA-1273 (2489 participants) or placebo (1243 participants). In the mRNA-1273 group, the most common solicited adverse reactions after the first or second injections were injection-site pain (in 93.1% and 92.4%, respectively), headache (in 44.6% and 70.2%, respectively), and fatigue (in 47.9% and 67.8%, respectively); in the placebo group, the most common solicited adverse reactions after the first or second injections were injection-site pain (in 34.8% or 30.3%, respectively), headache (in 38.5% and 30.2%, respectively), and fatigue (in 36.6% and 28.9%, respectively). No serious adverse events related to mRNA-1273 or placebo were noted. The geometric mean titer ratio of pseudovirus neutralizing antibody titers in adolescents relative to young adults was 1.08 (95% confidence interval [CI], 0.94 to 1.24), and the absolute difference in serologic response was 0.2 percentage points (95% CI, −1.8 to 2.4), which met the noninferiority criterion. No cases of Covid-19 with an onset of 14 days after the second injection were reported in the mRNA-1273 group, and four cases occurred in the placebo group.

Conclusions The mRNA-1273 vaccine had an acceptable safety profile in adolescents. The immune response was similar to that in young adults, and the vaccine was efficacious in preventing Covid-19. (Funded by Moderna and the Biomedical Advanced Research and Development Authority; Teen COVE ClinicalTrials.gov number, NCT04649151. opens in new tab.)

 

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12

Aug, 2021

Illness duration and symptom profile in symptomatic UK school-aged children tested for SARS-CoV-2

 

Authors: E Molteni, CH Sudre, LS Canas, SS Bhopal, RC Hughes, M Antonelli, B Murray, K Kläser, E Kerfoot, L Chen, J Deng, C Hu, Somesh Selvachandran, Kenneth Read, Joan Capdevila Pujol, Prof Alexander Hammers, Prof Tim D Spector, Prof Sebastien Ourselin, Claire J Steves, Marc Modat, Michael Absoud, Prof Emma L Duncan

Published in: The Lancet

 

Abstract 

Background In children, SARS-CoV-2 infection is usually asymptomatic or causes a mild illness of short duration. Persistent illness has been reported; however, its prevalence and characteristics are unclear. We aimed to determine illness duration and characteristics in symptomatic UK school-aged children tested for SARS-CoV-2 using data from the COVID Symptom Study, one of the largest UK citizen participatory epidemiological studies to date.

Methods In this prospective cohort study, data from UK school-aged children (age 5–17 years) were reported by an adult proxy. Participants were voluntary, and used a mobile application (app) launched jointly by Zoe Limited and King’s College London. Illness duration and symptom prevalence, duration, and burden were analysed for children testing positive for SARS-CoV-2 for whom illness duration could be determined, and were assessed overall and for younger (age 5–11 years) and older (age 12–17 years) groups. Children with longer than 1 week between symptomatic reports on the app were excluded from analysis. Data from symptomatic children testing negative for SARS-CoV-2, matched 1:1 for age, gender, and week of testing, were also assessed.

Findings 258 790 children aged 5–17 years were reported by an adult proxy between March 24, 2020, and Feb 22, 2021, of whom 75 529 had valid test results for SARS-CoV-2. 1734 children (588 younger and 1146 older children) had a positive SARS-CoV-2 test result and calculable illness duration within the study timeframe (illness onset between Sept 1, 2021, and Jan 24, 2021). The most common symptoms were headache (1079 [62·2%] of 1734 children), and fatigue (954 [55·0%] of 1734 children). Median illness duration was 6 days (IQR 3–11) versus 3 days (2–7) in children testing negative, and was positively associated with age (Spearman’s rank-order rs 0·19, p<0·0001). Median illness duration was longer for older children (7 days, IQR 3–12) than younger children (5 days, 2–9). 77 (4·4%) of 1734 children had illness duration of at least 28 days, more commonly in older than younger children (59 [5·1%] of 1146 older children vs 18 [3·1%] of 588 younger children; p=0·046). The commonest symptoms experienced by these children during the first 4 weeks of illness were fatigue (65 [84·4%] of 77), headache (60 [77·9%] of 77), and anosmia (60 [77·9%] of 77); however, after day 28 the symptom burden was low (median 2 symptoms, IQR 1–4) compared with the first week of illness (median 6 symptoms, 4–8). Only 25 (1·8%) of 1379 children experienced symptoms for at least 56 days. Few children (15 children, 0·9%) in the negatively tested cohort had symptoms for at least 28 days; however, these children experienced greater symptom burden throughout their illness (9 symptoms, IQR 7·7–11·0 vs 8, 6–9) and after day 28 (5 symptoms, IQR 1·5–6·5 vs 2, 1–4) than did children who tested positive for SARS-CoV-2.

Interpretation Although COVID-19 in children is usually of short duration with low symptom burden, some children with COVID-19 experience prolonged illness duration. Reassuringly, symptom burden in these children did not increase with time, and most recovered by day 56. Some children who tested negative for SARS-CoV-2 also had persistent and burdensome illness. A holistic approach for all children with persistent illness during the pandemic is appropriate.

 

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