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Head injuries in children requiring hospitalisation two-fold higher during COVID-19

23rd May 2022

Head injuries leading to hospitalisation in children significantly increased during the COVID-19 period compared with pre-pandemic levels

Head injuries in children, and which resulted in hospitalisation, were more than two-fold higher during the COVID-19 pandemic compared with pre-pandemic levels, although the use of CT head scans was not appreciably different. This was the conclusion of a retrospective study by researchers from John Hopkin’s University, Baltimore, Maryland, USA.

Head injuries in children are a common cause for hospitalisation with a report by the US Centers for Disease Control and Prevention citing that in the US in 2016, 8.3% of boys and 5.6% of girls aged 3 –17 years had ever had a significant head injury in their lifetime. Head injuries are damage to the scalp, skull, or brain caused by trauma and in cases where this affects the brain, it is referred to as a traumatic brain injury. The most common causes of such head injuries are falls although other causes in older children are related to sports injuries or even motor vehicle accidents. Little is known about how the pandemic has impacted upon the incidence of head injuries in during during the pandemic although some work based on neuro-trauma admissions observed that while there was a decline in the number of head injury admissions during the pandemic, the severity of the injuries actually increased. However, no studies have compared the level of presentation during COVID-19 with the years prior to the pandemic.

For the present analysis, the US team retrospectively examined the proportion of emergency department visits for head injury in children and the severity of those injuries between March 2020 to June 2020. These data were then compared with data from between March 2019 – June 2019, i.e., pre-pandemic levels. For the analysis, researchers included anyone aged 0 to 21 and set the primary outcomes of interest as the presence of a medically attended head injury, hospital admission for the injury and the need for CT head scanning.

Head injuries in children and hospitalisations

There were a total of 8616 patients with a mean age of 7.4 years (51.4% male) seen with a head injury at the emergency department during the COVID-19 pandemic. This compared with 19,083 visits in the same period during 2019. Overall, there was a significant increase in the proportion of visits during COVID-19 (6.4% vs 5.5%, p = 0.004), for a head injury in children, giving an odds ratio (OR) of 1.2 (95% CI 1.1 – 1.4), even though the absolute number of visits was lower (1058 vs 553, pre-covid vs covid).

In addition, the proportion of visits requiring hospitalisation was more than two-fold higher (OR = 2.3, 95% CI 1.3 – 4.3), which was more likely in male patients (OR = 1.58). However, the need for a CT head scan was not significantly different (OR = 1.04, 955 CI 0.70 – 1.60). Interestingly, there was a lower level of hospital admissions associated with children aged < 2 years (OR = 0.3, 95% CI 0.2 – 0.6) which suggested that head injuries in this age group were less severe.

The authors concluded by suggesting that the higher level of head injuries in children observed during the pandemic period were potentially due to changes in certain factors including supervision and risk exposure in the home.

Citation
Satoskar S et al. Impact of the COVID-19 pandemic on pediatric emergency department utilization for head injuries J Investig Med 2022

Neurological manifestations seen in nearly half of children with COVID-19 and MIS-C

26th January 2022

Neurological manifestations have been found in nearly half of children hospitalised with COVID-19 or MIS-C according to a global study

A neurological manifestation has been found in 44% of children who had been hospitalised with either COVID-19 or multisystem inflammatory syndrome (MIS-C) according to researchers from the Global Consortium Study of Neurologic Dysfunction in COVID-19 (GCS-NeuroCOVID). This multinational research collaborative initiative was established in April 2020 and designed to collect information on the prevalence and outcomes of neurological manifestations associated with both acute infection with COVID-19 and those with MIS-C and the equivalent adult condition.

Among adults with COVID-19, neurological problems are common and in one study, 82% of patients reported experiencing such problems. In contrast, a study of 27 children with COVID-19 MISC-C, found that only four, previously healthy children, had new-onset neurological symptoms including encephalopathy, headaches, brainstem and cerebellar signs, muscle weakness, and reduced reflexes. However, all four children were admitted to an intensive care unit.

The evidence of neurological manifestations in children to date is based on small samples. As a result, for the present study, the team made use of the GCS-NeuroCOVID) database and searched for children (i.e., those aged under 18 years of age) hospitalised with COVID-19 related condition which was either confirmed through testing or based on the presence of recognised clinical symptoms. The diagnosis of MIS-C was based on the Centers for Disease Control and Prevention (CDC) guidance. The primary outcome of the study was the frequency and type of neurological manifestations both overall, and due to COVID-19 and MIS-C.

Neurological manifestations identified

A total of 1,493 children with a median age of 8 (47% female) were included in the analysis, of whom 86% had COVID-19 and the remainder MIS-C.

Children with a pre-existing medical condition were more likely to become infected with COVID-19 than MIS-C (p < 0.001) although children with MIS-C were more likely to be admitted to intensive care units (69% vs 29%).

Overall, 44% of the whole cohort (40% of those with COVID-19 and 66% of those with MIS-C) had at least one neurological manifestation. The most common findings were headache (16% vs 47%, COVID-19 vs MIS-C) and acute encephalopathy (15% vs 22%) and for both conditions, this difference was statistically significant (p < 0.05). Other manifestations included seizures (8%), anosmia (4%) and ageusia (3.6%). Children with neurological manifestations were also more likely to require admission to ICU (51% vs 22%, p < 0.001).

Using regression analysis, the researchers identified that for the whole cohort, several factors including older age (adjusted odds ratio, aOR = 1.20, 95% CI 1.07 – 1.13), MIS-C (aOR = 2.16), neurologic (aOR = 3.48) and a pre-existing metabolic condition (aOR = 1.65) were all significantly (p < 0.05) associated with the presence of neurological manifestations.

Commenting on these results, the authors noted how the frequency of observed neurological manifestations in the cohort was fortunately much lower than that reported in adults, which was 80%. They concluded that neurological symptoms were a common problem in children hospitalised with COVID-19 and that the presence of such symptoms was much more likely in older children and those with pre-existing neurological and metabolic conditions.

Citation

Fink EL et al. Prevalence and Risk Factors of Neurologic Manifestations in Hospitalized Children Diagnosed with Acute SARS-CoV-2 or MIS-C Pediatr Neurol 2022

Add-on dupilumab therapy reduces exacerbations in children with moderate-to-severe asthma

21st December 2021

Add-on dupilumab therapy for children with uncontrolled moderate-to-severe asthma led to a significant reduction in disease exacerbations

Add-on dupilumab treatment in children with uncontrolled moderate-to-severe asthma produced a significant reduction in the number of exacerbations over a 52-week period, according to results of a Phase III, randomised, double-blind, placebo-controlled trial by researchers from the Division of Allergy, Immunology, and Pulmonary Medicine, Monroe Carell Jr. Children’s Hospital Nashville, US.

The global prevalence of asthma in children varies across the world with an estimated 10.8% of 6–7-year-old children having the disease although rates are lower rates in Northern and Eastern Europe (4.5%) but much higher in North America (20.0%) and Oceania (29.2%). While there are differences in the definition of ‘severe’ asthma, it has been suggested that prevalence of severe childhood asthma may be up to 5% and there is more concerning evidence indicating that childhood asthma increases the risk of COPD in adults.

Asthma appears, in part, to be a Th2-driven inflammatory process, characterised by the release of the cytokines interleukin (IL)-4, IL-5 and IL-13 and higher levels of Th2 inflammation are associated with greater airway hyper-responsiveness and more severe disease though only around 50% of patients have this endotype. The monoclonal antibody, dupilumab, blocks the action of IL-4 and IL-13 and has been approved for the treatment of adults and adolescents with asthma.

In Europe, the EMA has approved add-on dupilumab (brand name Dupixent) to ‘treat severe asthma in patients aged 12 years or over whose asthma is not properly controlled by a combination of high-dose corticosteroids taken by inhalation plus another medicine used for the prevention of asthma. Dupixent is only for use in patients with a type of inflammation of the airways called ‘type 2 inflammation’. 

For the present study, the US team recruited children aged 6 to 11 years with physician diagnosed moderate-to-severe asthma. Children were defined as those with type 2 inflammatory asthma phenotype defined by an eosinophil count of > 150 cells/cubic/ml or at least 300 cells/cubic/ml at baseline.

These children were randomised 2:1 to receive subcutaneous dupilumab (or matching placebo) every two weeks for 52 weeks at a dose of 100 mg (if their weight was <30 kg) or 200 mg (if weighing >30 kg). The primary endpoint was the annualised rate of severe exacerbations during the treatment period, defined as a deterioration of asthma control requiring systemic glucocorticoids for at least 3 days, hospitalisation or an emergency department visit that resulted in systemic glucocorticoid use. A key secondary outcome was the change from baseline to week 12 in the percentage of predicted prebronchodilator FEV1 (ppFEV1).

Findings

A total of 408 children with type 2 inflammatory asthma and a mean age of 8.9 years (66.4% male) were randomised to add-on dupilumab therapy or placebo. Among these children, 43% used high-dose inhaled glucocorticoids and had an average of 2.2 severe asthma exacerbations in the past year. An additional 259 children with an eosinophil count > 300 were similarly matched to dupilumab and placebo.

In the type 2 inflammation group, the adjusted annualised rate of severe asthma exacerbations was 0.31 (95% CI 0.22 – 0.42) in the add-on dupilumab group and 0.75 (95% CI 0.54 – 1.03) in the placebo group, giving a relative risk reduction, RR of 59.3% (p < 0.001). Similarly, among those with eosinophil counts > 300, the adjusted annualised rate of severe exacerbations was 0.24 (dupilumab) and 0.67 (placebo).

Overall, the percentage of participants who had no exacerbations during the 52-week study period was 77.1% in the dupilumab group and 59.6% in the placebo group and 79% vs 58.3% in the eosinophil vs placebo groups.

The changes in ppFEV1 were also significantly better for those in the add-on dupilumab group for both asthma phenotypes.

The authors concluded that dupilumab led to a meaningful improvement through asthma exacerbations and improvements in lung function in 6 to 11 year olds with moderate-to-severe asthma.

Citation

Bacharier LB et al. Dupilumab in Children with Uncontrolled Moderate-to-Severe Asthma. N Engl J Med 2021

Analysis shows skin peanut allergy patch safe and well tolerated over 3-year period

1st December 2021

Viaskin, an epicutaneous peanut allergy patch, has been found to be safe and well tolerated when used by children over a three-year period

The use of Viaskin, an epicutaneous patch used for children with a peanut allergy appears to be safe and well tolerated according to a three-year analysis presented by at the American College of Allergy, Asthma and Immunology Conference, November 2021.

A peanut allergy is thought to affect around 2% of the general population and in a study of 3218 children, the incidence was found to be 24.8%. The presence of a peanut allergy is challenging for those affected and requires a high level of vigilance directed towards the avoidance of accidental ingestion of peanut-containing foods.

The use of viaskin represents ‘epicutaneous’ immunotherapy and according to the manufacturer, DBV Technologies, is a proprietary technology platform that enables the delivery of biologically active compounds to the immune system through the skin.

The data presented at the American College of Allergy, Asthma and Immunology Conference was based on the REALISE trial, which included children with documented histories of peanut anaphylaxis and who were randomised, 3:1, to either viaskin peanut 250mcg (which contains 1/1000th of the protein found in a single peanut) or a placebo for a period of 6 months. Once this initial phase was completed, all subjects continued to receive the active treatment in an open-label extension, for a period of three years. For the REALISE study, the primary outcome was set as adverse Events (AEs), treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) throughout the study period.

The 6-month safety data for viaskin has already been published and showed that the patch was well-tolerated.

Findings

REALISE recruited 393 children with a median age of 7 years (gender not reported) of whom, 14 (3.6%) had a history of severe anaphylaxis. Throughout the study period, most subjects experienced at least one TEAE although these were reported as being mild (97.4%) or moderate (70.4%) in severity and commonly consisted of application site erythema and pruritus which fortunately decreased over time.

Overall, 16 children experienced a total of 17 anaphylactic reactions (none severe) considered to be due to viaskin. In addition, there were 2 serious that were viakskin-related TEAEs (2 anaphylactic reactions: one leading to permanent study discontinuation). No difference in TEAEs in subjects with severe anaphylaxis history was apparent.

The authors concluded that ‘over 36-months, Viaskin Peanut was generally well tolerated, with decreasing frequency and intensity of local and systemic treatment-related AEs over time.’

The product is yet to be approved by the FDA, which has requested more data or the EMA.

Citation

Brown-Whitehorn T et al. D030 REALISE (REAL-LIFE USE AND SAFETY OF EPIT) STUDY: 3 YEAR RESULTS IN PEANUT-ALLERGIC CHILDREN. Ann Allergy Asthma Immunol 2021

Non-urgent attendances represent a substantial number of children’s emergency care visits

8th November 2021

Non-urgent attendances for younger children account for a fifth of all emergency care visits and which could be managed in other care setting.

A substantial number of emergency care (EC) visits for young children represent non-urgent attendance (NUA). This is the conclusion of a retrospective analysis of hospital database by a team from the School of Health and Related Research, The University of Sheffield, Sheffield, UK.

Data for the UK show that in 2018-19, there were 24.8 million attendances at accident and emergency (A&E) departments, which represents a 4% increase on the previous year and a 21% increase since 2009-10. While much attention has focused on adult attendance at A&E, visits by children and young people has been less well studied despite the fact that children make more frequent visits to A&E. For example, in 2015/16 there were 425 A&E attendances for every 1000 children and young people an 345 A&E attendances for every 1000 adults aged 25 and over.

Research suggests that non-urgent attendance to EC can vary between 20 and 40% and there is evidence that younger age is one of several associated factors, though specific data on characterising NUA in children is limited. For the present study, the Sheffield team sought to define the proportion of NUA by children which were amenable to treatment or management elsewhere, how these non-urgent attendances varied by patient age as well as the impact on waiting times in the EC department. Patient characteristics such as as age, gender, date of attendance, disposal, type of treatment etc were extracted from a hospital database containing information for more than a tenth of England’s population over a 3-year period. The team defined a non-urgent attendance as one in which there was no treatment/investigations or referrals that required the facilities of an EC department.

Findings

A total of 1,068,598 EC attendances from children aged 0 – 15 years were identified and included in the analysis. Overall, the proportion of visits deemed NUA was 21.4% (208,788). Compared to visits for children less than 1 years of age, the odds ratio for a NUA was much more likely in children aged 1 – 4 years (odds ratio, OR = 0.82, 95% CI 0.80 – 0.83). However, NUA decreased with increasing age, for example, among children aged 10 – 14 years, the proportion of NUA was 14.6% (OR = 0.40) compared with 20.5% (OR = 0.61) for those aged 5 – 9 years. The odds of a patient presenting with a NUA was also significantly higher (OR = 1.19, 95% CI 1.18 – 1.20) for those attending out of hours compared to in hours (i.e., 8 am to 6 pm, Monday to Friday).

The researchers also found that for a NUA, the mean waiting, treatment and department times were all lower compared with urgent cases. Extrapolating their findings, the authors estimated up to 1 million non-urgent attendance visits across England in 2018-19 for ages 14 years and under.

They concluded that targeting groups such as those age under 5 years, particularly in providing accessible, timely care outside of usual community care opening hours would be of benefit.

Citation

Simpson RM et al. Non-urgent emergency department attendances in children: a retrospective observational analysis. Emerg J Med 2021

Similar factors associated with COVID-19 severity in children and adults

21st September 2021

A US study has found that as with adults, the same clinical factors affect COVID-19 severity and hospitalisation in children and adolescents.

The available evidence clearly shows that infection with COVID-19 is disproportionately higher in adults compared with children. Nevertheless, emerging data suggests that in children infection with COVID-19 can induce multisystem inflammatory syndrome and lead to serious illness. While the pandemic has revealed how several clinical factors such as older age, various co-morbidities and ethnicity, are all associated with a higher level of COVID-19 severity, much less is known about which factors lead to more severe disease in children.

This lack of information prompted a group of US researchers from the Division of Hospital Medicine, Monroe Carell Jr, Children’s Hospital, Vanderbilt, Nashville, Tennessee, US, to undertake a retrospective cohort study across 45 US children’s hospitals to assess factors associated with COVID-19 severity in paediatric patients. The researchers included patients as young as 30 days old to 18 years of age, discharged from either an emergency department (ED) or inpatient setting with a primary diagnosis of COVID-19. The researcher collected demographic data and information on the presence of any co-morbidities, particularly those which appeared to result in a worse prognosis among adults. The outcome of interest was COVID-19 severity which was categorised as mild (i.e., ED discharge), moderate (in-patient admission) and severe (intensive care (ICU) admission) and very severe (ICU admission with mechanical ventilation, shock or death). The results were analysed using regression analysis and presented as odds ratios adjusted for various factors including ethnicity and co-morbidities.

Findings
The study included 19,976 ED encounters of children with a median age of 6 years (51.2% male) with the most common ethnicities being Hispanic (48.8%) and non-Hispanic White (21.1%). In the majority of cases (79.9%) COVID-19 severity was mild (79.7%) and these individuals were discharged from the ED. However, among the 4063 (20.3%) patients who were hospitalised, the majority had moderate COVID-19 severity (79.3%) with 11.3% classed as severe and 9.4% as very severe. When compared with those who were discharged from the ED, the clinical factors associated with an increased odds of hospitalisation included obesity/type 2 diabetes (adjusted Odds ratio, aOR = 10.4, 95% CI 8.90 – 13.3), asthma (aOR = 1.40, 95% CI 1.3 – 1.60), cardiovascular disease (aOR = 5.0), an immunocompromised condition (aOR = 5.9) and pulmonary disease (aOR = 3.2). Only Black ethnicity impacted on the risk of hospitalisation compared to those of White ethnicity, (aOR = 1.52, 95% CI 1.20 – 1.93). With respect to age, compared to children aged 0 – 4 years, the risk of hospitalisation was lower among those aged 5 – 11 years (aOR = 0.50, 95% CI 0.45 – 56) and 12 – 17 years (aOR = 0.75, 95% CI 0.69 – 0.82). However, once hospitalised, the risk of higher COVID-19 severity increased in both groups: 5 – 11 group (aOR = 2.66) and 12 – 17 years (aOR = 2.09).
The authors concluded that while older children were at a lower risk of hospitalisation with COVID-19, once hospitalised, they appeared to be a higher risk of more severe disease. In addition, as with adults, similar co-morbidities were associated with a greater risk of hospitalisation and higher COVID-19 severity once admitted.

Citation
Antoon JW et al. Factors associated with COVID-19 disease severity in US children and adolescents. J Hosp Med 2021

Monitoring adalimumab levels valuable for assessing remission in children with Crohn’s disease

9th June 2021

Adalimumab is effective for children with Crohn’s disease but little is known about the impact of therapeutic monitoring on clinical outcomes.

The clinical symptoms of Crohn’s disease (CD) are similar in adults and children although there is evidence that cases of paediatric CD are on the rise, with one study estimating that the highest incidence, at 23 per 100,000 person-years occurred in Europe. Endoscopic evidence of mucosal healing is a valuable therapeutic goal that decreases the risk of disease relapse although little is known about the association between mucosal healing and therapeutic levels of biological treatments such as adalimumab. This prompted a team from the Department of Paediatrics, Samsung Medical Centre, Korea, to examine the relationship between therapeutic drug monitoring of adalimumab and mucosal healing and clinical remission in paediatric patients with CD. The team prospectively recruited paediatric patients with CD receiving adalimumab maintenance therapy and who underwent routine endoscopic evaluation of mucosal healing and therapeutic drug monitoring. Monitoring assessments were made at 4 months and then at years 1, 2 and 3.

Findings
In total, 31 children with a mean age of 14.8 years (74% male) were included in the analysis. After 1 year of treatment, 26 (83.9%) had achieved clinical remission and 17 (54.8%) had complete mucosal healing. The mean adalimumab trough levels were higher in patients who had achieved remission compared to those with active disease (7.6 mcg/ml vs 5.1 mcg/ml, remission vs active disease). Similarly, trough levels of adalimumab were significantly higher in those who achieved mucosal healing after 1 year (14.2 mcg/ml vs 7.8mcg/ml, mucosal healing vs non-healed, p = 0.03). Although only 23 children were evaluated after 3 years, adalimumab trough levels remained above 10 mcg/ml and a similar proportion of children maintained mucosal healing (64.3%) and clinical remission (92.9%). Using receiver operating curves, authors calculated that the optimal cut-off adalimumab trough levels to achieve mucosal healing was 8.18 mcg/ml.

In discussing their findings, the authors commented on the results demonstrated that mucosal healing rates increased when adalimumab was used over the longer term and that the drug maintained its efficacy. They concluded that there was merit in using therapeutic drug monitoring to guide proactive optimisation of drug levels to achieve the goal of mucosal healing.

Citation
Kim MJ et al. Therapeutic Drug Monitoring of Adalimumab During Long-term Follow-up in Paediatric Patients with Crohn Disease. JPGN 2021;72:870-6.

Only a quarter of children with COVID-19 have typical symptoms

3rd June 2021

Children account for a smaller proportion of COVID-19 infections but a large US study has found among those with the virus, the majority do not present with the usual symptoms.

Data have suggested that the risks of adverse outcomes among children infected with COVID-19 are far less than those of adults. Moreover, the classic COVID-19 symptoms such as cough and fever has been found to occur in only half of children infected with the virus. With the reopening of schools and the subsequent increased risk of community transmission, a team from the Division of Cardiovascular Disease, University of Alabama, Alabama, US, investigated the clinical characteristics of children infected with COVID-19 using information derived from a multi-centre healthcare network electronic health database. The authors included paediatric patients with a positive PCR test, aged < 18 years and stratified the population based on their age and ethnicity. Information was also included on past medical history and if hospitalised, whether individuals required mechanical ventilation or other forms of critical care. The PCR positive individuals were propensity matched on sex and ethnicity.

Findings
The retrospective analysis included 12,306 children, 672 (5.5%) of whom were hospitalised with a mean age of 9 years (51% male). Interestingly, only 25.1% of the sample had at least one of the classic COVID-19 symptoms (i.e., fever, cough or shortness of breath). The range of symptoms observed included respiratory symptoms (16.5%) such as cough or dyspnoea, gastrointestinal symptoms (13.9%) e.g., nausea, vomiting, skin rashes (8.1%) non-specific symptoms (18.8%) including fever, malaise, myalgia or disturbances of taste and smell. Among those hospitalised, 17.6% required critical care and 4.1% mechanical ventilation and there were fewer than 10 deaths. The risk of hospitalisation was higher in non-Hispanic black children compared with those of white ethnicity (relative risk, RR = 1.97 95% CI 1.49 – 2.61).

The authors described how they had observed a wide range of non-specific clinical symptoms and that only a quarter of those with a positive PCR test actually had the classic COVID-19 symptoms. They suggested that this warranted a need for increased vigilance among healthcare professionals when seeing school-aged children who might be infected with the virus. They concluded that while children can develop severe illness after infection with COVID-19, fortunately this is uncommon.

Citation
Parcha V et al. A retrospective cohort study of 12,306 pediatric COVID?19 patients in the United States. Sci Rep 2021

Malaria vaccine candidate achieves 77% efficacy in children

27th April 2021

With only a single malaria vaccine with limited efficacy, the search continues for more effective agents.

The parasite Plasmodium falciparum (P. falciparum) is responsible for malaria and which is a leading cause of both morbidity and mortality across the globe. RTS,S, brand name Mosquirix, is the only vaccine available to treat malaria and was approved by the EMA in 2015. Sporozoites are the form of the parasite that enter the body and Mosquirix contains part of the P. falciparum circumsporozoite protein (CSP) and leads to the generation of anti-circumsporozoite antibodies. However, in children, the vaccine efficacy is only 56% whereas the World Health Organization’s strategic goal is for a malaria vaccine to have an efficacy of 75%. This led researchers from the Jenner Institute, University of Oxford to undertake a double-blind, randomised, controlled trial using a vaccine named R21, which is a novel pre-erythrocytic candidate that also targets part of the CSP. The vaccine combines R21 with Matrix-M (MM), an adjuvant which increases immunogenicity. The team recruited children aged 5–17 months in the catchment area of Nanoro, Burkina Faso (West Africa) and which represents a high area of malaria transmission, especially between June and November. All children were randomised to one of three groups; group 1 received a lower dose of MM (i.e., 5 mcg R21/25mcg MM); group 2, a higher dose of MM (5 mcg R21/50mcg MM); and a control group (group 3) who received a control vaccine (rabies). Three doses were administered at 4-week intervals prior to the main malaria season (early May to August) and all participants received a fourth booster dose 12 months after their third vaccination. The primary outcome assessed was protective efficacy from 14 days after the third vaccination to 6 months and clinical malaria was defined in terms of an axillary temperature greater than 37.5 degrees centigrade and a P. falciparum density of greater than 5000 parasites/micro-litre.

Findings
A total of 450 children were included in the trial with a mean age of 11.6 months and 222 female participants. Moreover, there were 186 cases of clinical malaria, 43 in group 1, 38 in group 2 and 105 in group 3 (control). Using a Cox regression model which compared group 1 to 3, vaccine efficacy was 74% (95% CI 63 – 82, p < 0.001) and between group 2 and 3, the efficacy was 77% (95% CI 67 – 84, p < 0.0001). Efficacy was also assessed after 12 months at which point, the efficacy was 71% (group 1 vs group 3) and 77% (group 2 vs group 3). The authors calculated that the number of cases averted by the group 1 regime over 12 months would be a rate reduction of 1393 cases per 1000 children years.

The authors observed, however, that antibody levels in groups 1 and 2 decreased over the 12-month period but were boosted back to the levels achieved after the third dose, 28 days after the 4th dose.

Although this is the first study to report on the vaccine, the trial is continuing for a second malaria season to determine the durability of this high level of vaccine efficacy.

Citation
Datoo MS et al. High efficacy of a low dose candidate malaria vaccine, R21 in adjuvant Matrix-MTM, with seasonal administration to children in Burkina Faso. Lancet 2021

Differences in immune and clotting functioning may explain less severe COVID-19 in children

7th December 2020

The lower incidence of severe COVID-19 in children has prompted much speculation. In reviewing various hypotheses, researchers believe that changes in endothelial cells and clotting functions is a likely reason for the disparity.

A consistent finding of infection with COVID-19 is that the virus is less severe in children, most of whom are asymptomatic, with a mild fever, cough and changes in taste or smell. Whether or not children are less likely to become infected is an ongoing debate but overall, only between 1 and 2% of cases involve children, suggesting that as a group, children are less likely to become infected, even when exposed to similar viral loads.

In a review of all the currently available evidence, a team from the Faculty of Science and Medicine, University of Fribourg, Switzerland, have examined the various potential physiological differences between adults and children and how these might account for the variation in rates of infection.

While there are still no definite answers, the authors suggest that infection of endothelial cells, leading to vasculitis and the formation of microthrombi, is more problematic in adults, especially in the presence of comorbidities such as hypertension and diabetes, both of which affect endothelial cell functioning. While children are less likely to have comorbidities and are therefore at lower risk, immunosuppressed children or those with cancer, do not appear to be at any higher risk from COVID-19. Another possible protector is that children have a stronger innate immune and adaptive immune system with higher number of natural killer cells and both B and T cells, whereas ageing is associated with immunosenescence, i.e., a gradual decline of both immune systems. Other proposed differences which might be protective in children are higher levels of melatonin and the microbiota in the nasopharynx in children which is more heavily colonised in children compared with adults.

The authors conclude that with the exception of the endothelial/clotting function disparities, none of the currently proposed hypotheses are able to account for the differences in susceptibility to infection between adults and children.

Citation
Zimmerman P, Curtis N. Why is COVID-19 less severe in children? A review of the proposed mechanisms underlying the age-related difference in severity of SARS-CoV-2 infections. Arch Dis Child 2020 doi:10.1136/archdischild-2020-320338