COVID-19 Publications

24

Mar, 2021

SARS-CoV-2 infection and transmission in primary schools in England in June–December, 2020 (sKIDs): an active, prospective surveillance study

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Authors: Shamez N Ladhani, Frances Baawuah, Joanne Beckmann, Ifeanichukwu O Okike, Shazaad Ahmad, Joanna Garstang, Andrew J Brent, Bernadette Brent, Jemma Walker, Nick Andrews, Georgina Ireland, Felicity Aiano, Zahin Amin-Chowdhury, Louise Letley, Jessica Flood, Samuel E I Jones, Ray Borrow, Ezra Linley, Maria Zambon, John Poh, Vanessa Saliba, Gayatri Amirthalingam, Jamie Lopez Bernal, Kevin E Brown, Mary E Ramsay

Published in: The Lancet

 

Summary Background: Little is known about the risk of SARS-CoV-2 infection and transmission in educational settings. Public Health England initiated a study, COVID-19 Surveillance in School KIDs (sKIDs), in primary schools when they partially reopened from June 1, 2020, after the first national lockdown in England to estimate the incidence of symptomatic and asymptomatic SARS-CoV-2 infection, seroprevalence, and seroconversion in staff and students.

Methods: sKIDs, an active, prospective, surveillance study, included two groups: the weekly swabbing group and the blood sampling group. The swabbing group underwent weekly nasal swabs for at least 4 weeks after partial school reopening during the summer half-term (June to mid-July, 2020). The blood sampling group additionally underwent blood sampling for serum SARS-CoV-2 antibodies to measure previous infection at the beginning (June 1–19, 2020) and end (July 3–23, 2020) of the summer half-term, and, after full reopening in September, 2020, and at the end of the autumn term (Nov 23–Dec 18, 2020). We tested for predictors of SARS-CoV-2 antibody positivity using logistic regression. We calculated antibody seroconversion rates for participants who were seronegative in the first round and were tested in at least two rounds.

Findings: During the summer half-term, 11 966 participants (6727 students, 4628 staff, and 611 with unknown staff or student status) in 131 schools had 40 501 swabs taken. Weekly SARS-CoV-2 infection rates were 4·1 (one of 24463; 95% CI 0·1–21·8) per 100000 students and 12·5 (two of 16 038; 1·5–45·0) per 100000 staff. At recruitment, in 45 schools, 91 (11·2%; 95% CI 7·9–15·1) of 816 students and 209 (15·1%; 11·9–18·9) of 1381 staff members were positive for SARS-CoV-2 antibodies, similar to local community seroprevalence. Seropositivity was not associated with school attendance during lockdown (p=0·13 for students and p=0·20 for staff) or staff contact with students (p=0·37). At the end of the summer half-term, 603 (73·9%) of 816 students and 1015 (73·5%) of 1381 staff members were still participating in the surveillance, and five (four students, one staff member) seroconverted. By December, 2020, 55 (5·1%; 95% CI 3·8–6·5) of 1085 participants who were seronegative at recruitment (in June, 2020) had seroconverted, including 19 (5·6%; 3·4–8·6) of 340 students and 36 (4·8%; 3·4–6·6) of 745 staff members (p=0·60).

Interpretation: In England, SARS-CoV-2 infection rates were low in primary schools following their partial and full reopening in June and September, 2020.

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19

Mar, 2021

Vaccinating Children against Covid-19 — The Lessons of Measles

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Authors: Perri Klass, M.D. and Adam J. Ratner, M.D., M.P.H.

Published in: The New England Journal of Medicine

 

Introduction: Imagine a highly contagious virus circulating in the community. Many infected children have fever and some general misery but recover without incident. Rarely, devastating complications occur, leading to hospitalization, severe illness, and occasional deaths. Susceptible adults fare worse, with higher rates of poor outcomes. Would you want your child vaccinated against this disease?

You guessed we were talking about measles, right?

As the first SARS-CoV-2 vaccines are rolled out to the highest-risk groups, the current stage of the Covid-19 pandemic is pregnant with possibility. Even as cases multiply and new restrictions loom, we gaze longingly toward the next few months, hoping vaccines will deliver us. Vaccination could liberate us to return to school or work, celebrate holidays, eat in restaurants, travel, run marathons, and [fill in your own deprivations]. Early announcements of vaccine efficacy send stocks soaring, and suddenly everyone knows about phase 3 trials and cold-chain logistics. We look to vaccines to give us back our world.

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19

Mar, 2021

Virological and immunological features of SARS COV 2 infected children who who developed neutralizing antibodies

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Authors: Nicola Cotugno, Alessandra Ruggiero, Francesco Bonfante, Paolo Rossi, Anita De Rossi, Paolo Palma et al.

Published in: Cell Reports

 

Summary: As the global COVID-19 pandemic progresses, it is paramount to gain knowledge on adaptive immunity to SARS-CoV-2 in children to define immune correlates of protection upon immunization or infection. We analyzed anti-SARS-CoV-2 antibodies and their neutralizing activity (PRNT) in 66 COVID-19-infected children at 7 (±2) days after symptom onset. Individuals with specific humoral responses presented faster virus clearance and lower viral load associated with a reduced in vitro infectivity. We demonstrated that the frequencies of SARS-CoV-2-specific CD4+CD40L+ T cells and Spike-specific B cells were associated with the anti-SARS- CoV-2 antibodies and the magnitude of neutralizing activity. The plasma proteome confirmed the association between cellular and humoral SARS-CoV-2 immunity, and PRNT+ patients show higher viral signal transduction molecules (SLAMF1, CD244, CLEC4G). This work sheds lights on cellular and humoral anti-SARS-CoV-2 responses in children, which may drive future vaccination trial endpoints and quarantine measures policies.

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12

Mar, 2021

Sharing our understanding of the immune response of children living with HIV

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EPIICAL is proud to have presented four abstracts at the CROI conference this year, sharing updated information on viral decay and the immune response of children living with HIV who begin treatment early in life.

 

  • EFFECT OF HIV ON IMMUNE ACTIVATION AND EXHAUSTION IN CD4 AND CD8 T CELLS IN INFANTS Stefano Rinaldi, Vinh B. Dinh, Suresh Pallikkuth, Lesley D. Armas, Nadia Sitoe, Rajendra Pahwa, Nicola Cotugno, Paula Vaz, Paolo Palma, MariaGrazia Lain, Savita G. Pahwa
  • DYNAMICS OF INTACT PROVIRAL SEQUENCES IN EARLY TREATED HIV-1 CLADE C–INFECTED INFANTS Catherine K. Koofhethile, Stefano Rinaldi, Yelizaveta Rassadkina, Vinh B. Dinh, Ce Gao, Suresh Pallikkuth, Pilar Garcia-Broncano, Lesley D. Armas, Rajendra Pahwa, Nicola Cotugno, Maria Grazia Lain, Paolo Palma, Roger Shapiro, Savita G. Pahwa, Mathias Lichterfeld
  • VIRAL-RESERVOIR LANDSCAPE IN EARLY-TREATED VERTICALLY HIVINFECTED ADOLESCENTS Libera Sessa, Xiaodong Lian, Ce Gao, Nicola Cotugno, Alessandra Ruggiero, Xu G. Yu, Paolo Palma, Mathias Lichterfeld
  • FASTER INITIAL VIRAL DECAY IN FEMALE CHILDREN LIVING WITH HIV Sara Dominguez-Rodr.guez, Miquel Serna-Pascual, Caroline Foster, Paolo Palma, Eleni Nastouli, Anita De Rossi, Javier Seoane, Paolo Rossi, Carlo Giaquinto, Alfredo Tagarro, Pablo Rojo, for the EPIICAL Consortium

Follow this link to view the Abstract booklet

 

The CROI conference, which was held virtually from March 6-10, provided delegates with the opportunity to present new data on their HIV research and development studies. CROI is a long-standing conference that has provided a forum for scientists and investigators to present, discuss and critique research into human retroviruses and associated diseases. Over the years, the congress has facilitated the presentation of important discoveries and contributed to the acceleration in the understanding and progress in HIV/AIDS research.

The EPIICAL Consortium has successfully conducted studies on children living with HIV by setting up different well-characterized cohorts in Europe and Africa. The presented abstracts explored the factors that affect the immune response and the viral dynamics in children with a special focus on the early antiretroviral treatment. All these data are really informative and represent the basis to tailor immune therapeutic strategies in HIV infected children.

Thank you to all the authors for your invaluable contribution towards improving the understanding of HIV infection in children.

Learn more about EPIICAL here

Visit the EPIICAL website

11

Mar, 2021

ODYSSEY trial finds new drug is better for treating children living with HIV

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The anti-HIV drug Dolutegravir improves outcomes for children with HIV infection when given in a 3-drug combination. These results come from the ODYSSEY trial which was presented yesterday at the Conference on Retroviruses and Opportunistic Infections.

Dolutegravir has a number of potential advantages, including:

  • Few drug-to-drug interactions, making it easier to use when treating people who need treatment for other conditions such as tuberculosis
  • High potency at a low milligram dose, meaning tablets can be small
  • High genetic barrier to resistance
  • Low cost

Trials of dolutegravir in combination treatments in adults with HIV have shown that it is as good as or better than other drugs.  ODYSSEY is the first trial to look at whether treatment combinations based on dolutegravir are effective and safe for children living with HIV. Children who joined the trial were randomly allocated to receive either the current standard treatment combination or one that included dolutegravir. The ODYSSEY trial had two parts: ODYSSEY A was for children who were on first-line treatment. ODYSSEY B was for children whose previous treatment had stopped working and were now on second-line treatment.

The results presented yesterday are from over 700 children in ODYSSEY who weighed at least 14kg, and were aged between 3 and 17 years. Children were followed up for at least 96 weeks.

ODYSSEY found that dolutegravir-based HIV treatment combinations were superior to standard-of-care regimens in terms of preventing treatment failure for children living with HIV who weighed at least 14kg. Children in the dolutegravir arm were less likely to experience treatment failure than those on standard treatment combinations. An estimated 14% of children in the dolutegravir arm had experienced treatment failure by 96 weeks, compared to 22% in the standard treatment combination arm.

The ODYSSEY results were consistent with the same benefit of doultegravir-based ART in children starting first or second line ART. This was true at 48, 96 and 144 weeks. We also looked at other sub-groups including by age, weight or ART backbone and results suggested that all sub-groups were likely to benefit from dolutegravir-based ART.

Side-effect data from ODYSSEY were reassuring. Overall, there was no difference in the rate of side-effects between the arms. In particular excessive weight gain was not seen with dolutegravir (as observed in some adult trials) and blood lipid values were lower than in the control arms.

These results support the current World Health Organisation treatment guidelines, which recommend dolutegravir-based combinations for treating children living with HIV for whom there is an approved dolutegravir dosing.

Data from ODYSSEY on the efficacy and safety of dolutegravir-based ART for children weighing less than 14kg are still being collected and will be released later this year.

ODYSSEY has already had an impact, with simplified dosing data from the trial contributing to the licensing of using adult dolutegravir tablets for children weighing over 20kgs, and approval of 5mg tablets for younger children. ODYSSEY has also contributed data for the regulatory approval of a generic fixed-dose combination tablet suitable for children containing the drugs abacavir and 3TC in South Africa.

Overall, all these contributions from ODYSSEY are ensuring that children are not left behind and receive the best possible treatment alongside adults.

The ODYSSEY trial was sponsored by Penta, and coordinated by the MRC Clinical Trials Unit at UCL, as well as INSERM, PHPT and HIV-NAT-. 88% of children in this global trial were enrolled from Africa. The trial was funded by ViiV Healthcare and Penta. It took place in Uganda, Zimbabwe, South Africa, Thailand, and Penta centres in Germany, the UK, Portugal and Spain.

View abstract here

Visit the ODYSSEY trial website

Learn more about the ODYSSEY study

 

2

Mar, 2021

Johnson & Johnson has planned trials of its vaccine that will include infants.

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Johnson & Johnson plans to test its coronavirus vaccine in infants and even in newborns, as well as in pregnant women and in people who have compromised immune systems.

The bold plan for expanded clinical trials met with the approval of Dr. Ofer Levy, director of the Precision Vaccines Program at Harvard’s Boston Children’s Hospital and a member of the Food and Drug Administration advisory committee that reviewed the company’s vaccine data.

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19

Feb, 2021

ODYSSEY clinical trial design: a randomised global study to evaluate the efficacy and safety of dolutegravir-based antiretroviral therapy in HIV-positive children, with nested pharmacokinetic sub-studies to evaluate pragmatic WHO-weight-band based dolutegravir dosing

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Authors: Cecilia L. Moore, Anna Turkova , Hilda Mujuru , Adeodata Kekitiinwa, Abbas Lugemwa, Cissy M. Kityo, Linda N. Barlow-Mosha, et al, ODYSSEY trial team

Published in: BMC Infectious Diseases

 

Background: Dolutegravir (DTG)-based antiretroviral therapy (ART) is highly effective and well-tolerated in adults and is rapidly being adopted globally. We describe the design of the ODYSSEY trial which evaluates the efficacy and safety of DTG-based ART compared with standard-of-care in children and adolescents. The ODYSSEY trial includes nested pharmacokinetic (PK) sub-studies which evaluated pragmatic World Health Organization (WHO) weight-band-based DTG dosing and opened recruitment to children < 14 kg while dosing was in development.

Methods: ODYSSEY (Once-daily DTG based ART in Young people vS. Standard thErapY) is an open-label, randomised, non-inferiority, basket trial comparing the efficacy and safety of DTG + 2 nucleos(t) ides (NRTIs) versus standard-of-care (SOC) in HIV-infected children < 18 years starting first-line ART (ODYSSEY A) or switching to second-line ART (ODYSSEY B). The primary endpoint is clinical or virological failure by 96 weeks.

Results: Between September 2016 and June 2018, 707 children weighing ≥14 kg were enrolled; including 311 ARTnaïve children and 396 children starting second-line. 47% of children were enrolled in Uganda, 21% Zimbabwe, 20% South Africa, 9% Thailand, 4% Europe. 362 (51%) participants were male; median age [range] at enrolment was 12.2 years [2.9–18.0]. 82 (12%) children weighed 14 to < 20 kg, 135 (19%) 20 to < 25 kg, 206 (29%) 25 to < 35 kg, 284 (40%) ≥35 kg. 128 (18%) had WHO stage 3 and 60 (8%) WHO stage 4 disease. Challenges encountered include: (i) running the trial across high- to low-income countries with differing frequencies of standard-of-care viral load monitoring; (ii) evaluating pragmatic DTG dosing in PK sub-studies alongside FDA- and EMA-approved dosing and subsequently transitioning participants to new recommended doses; (iii) delays in dosing information for children weighing 3 to < 14 kg and rapid recruitment of ART-naïve older/heavier children, which led to capping recruitment of participants weighing ≥35 kg in ODYSSEY A and extending recruitment (above 700) to allow for ≥60 additional children weighing between 3 to < 14 kg with associated PK; (iv) a safety alert associated with DTG use during pregnancy, which required a review of the safety plan for adolescent girls.

Conclusions: By employing a basket design, to include ART-naïve and -experienced children, and nested PK substudies, the ODYSSEY trial efficiently evaluates multiple scientific questions regarding dosing and effectiveness of DTG-based ART in children.

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21

Jan, 2021

EU grants Marketing Authorisation to first-ever dispersible-tablet dolutegravir

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On 12 January 2021, the European Medicine Agency approved the use of dolutegravir 5mg dispersible tablets for treating HIV in young children living in Europe. This decision was based, in part, on data from our ODYSSEY trial, which we are conducting in close collaboration with the MRC CTU at the University College London.

The EMA also authorised updating dosing recommendations for dolutegravir film-coated tablets (10mg, 25mg and 50mg) for children six years and older and weighing at least 14kg, bringing these in line with the World Health Organization weight bands.

This decision enables European children to now have access to age-appropriate formulations of HIV medicine and reduces the gap between the treatment options available for adults and children.

The Marketing Authorisation of dolutegravir dispersible tablets by the European Medicine Agency follows the US Food and Drug Administration (FDA) approval in June 2020.

Requests of regulatory approval are ongoing in other countries globally, to ensure that these new HIV treatments become available to children wherever they are needed.

 

Read the Press Release by ViiV Healthcare.

20

Jan, 2021

Why schools probably aren’t COVID hotspots

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Data gathered worldwide are increasingly suggesting that schools are not hotspots for coronavirus infections. Despite fears, COVID-19 infections did not surge when schools and day-care centres reopened after pandemic lockdowns eased. And when outbreaks do occur, they mostly result in only a small number of people becoming ill.

However, research also shows that children can catch the virus and shed viral particles, and older children are more likely than very young kids to pass it on to others. Scientists say that the reasons for these trends are unclear, but they have policy implications for older children and teachers.

Globally, COVID-19 infections are still much lower in children than among adults, says Walter Haas, an infectious-diseases epidemiologist at the Robert Koch Institute in Berlin. “They seem rather to follow the situation than to drive it.”

Read the full article by Dyani Lewis here

10

Dec, 2019

Human Rights Day

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Today we celebrate Human’s Right Day: this year’s theme is “Youth Standing Up for Human Rights”.
School HIV-prevention campaigns in Africa are often designed to frighten children. However, we believe this should be done differently. By providing children with information about HIV we can help prevent fear and ensure children are educated.

Peer-support groups play an important role in providing children and adolescents with information they need about HIV.

Watch the full video by Picturing Health here.

#StandUp4HumanRights #HumanRightsDay

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