Quantitative sensory testing for assessment of somatosensory function in children and adolescents: a scoping review.

Quantitative sensory testing (QST) refers to a group of noninvasive psychophysical tests that examine responses to a range of calibrated mechanical and thermal stimuli. Quantitative sensory testing has been used extensively in adult pain research and has more recently been applied to pediatric pain research. The aims of this scoping review were to map the current state of the field, to identify gaps in the literature, and to inform directions for future research. Comprehensive searches were run in 5 databases. Titles, abstracts, and full texts were screened by 2 reviewers. Data related to the study aims were extracted and analyzed descriptively. A total of 16,894 unique studies were identified, of which 505 were screened for eligibility. After a full-text review, 301 studies were retained for analysis. Date of publication ranged from 1966 to 2023. However, the majority of studies (61%) were published within the last decade. Studies included participants across the developmental trajectory (ie, early childhood to adolescence) and most often included a combination of school-age children and adolescents (49%). Approximately 23% of studies were conducted in healthy samples. Most studies (71%) used only one QST modality. Only 14% of studies reported using a standardized QST protocol. Quantitative sensory testing in pediatric populations is an emerging and rapidly growing area of pain research. Future work is needed using comprehensive, standardized QST protocols to harness the full potential that this procedure can offer to our understanding of pediatric pain.

Association between SARS-CoV-2 variants and post COVID-19 condition: findings from a longitudinal cohort study in the Belgian adult population.

BACKGROUND: While many studies on the determinants of post-COVID-19 conditions (PCC) have been conducted, little is known about the relationship between SARS-CoV-2 variants and PCC. This study aimed to assess the association between different SARS-CoV-2 variants and the probability of having PCC three months after the infection. METHODS: This study was a longitudinal cohort study conducted between April 2021 and September 2022 in Belgium. In total, 8,238 adults with a confirmed SARS-CoV-2 infection were followed up between the time of their infection and three months later. The primary outcomes were the PCC status three months post infection and seven PCC symptoms categories (neurocognitive, autonomic, gastrointestinal, respiratory, musculoskeletal, anosmia and/or dysgeusia, and other manifestations). The main exposure variable was the type of SARS-CoV-2 variants (i.e. Alpha, Delta, and Omicron), extracted from national surveillance data. The association between the different SARS-CoV-2 variants and PCC as well as PCC symptoms categories was assessed using multivariable logistic regression. RESULTS: The proportion of PCC among participants infected during the Alpha, Delta, and Omicron-dominant periods was significantly different and respectively 50%, 50%, and 37%. Participants infected during the Alpha- and Delta-dominant periods had a significantly higher odds of having PCC than those infected during the Omicron-dominant period (OR = 1.61, 95% confidence interval [CI] = 1.33-1.96 and OR = 1.73, 95%CI = 1.54-1.93, respectively). Participants infected during the Alpha and Delta-dominant periods were more likely to report neurocognitive, respiratory, and anosmia/dysgeusia symptoms of PCC. CONCLUSIONS: People infected during the Alpha- and Delta-dominant periods had a higher probability of having PCC three months after infection than those infected during the Omicron-dominant period. The lower probability of PCC with the Omicron variant must also be interpreted in absolute figures. Indeed, the number of infections with the Omicron variant being higher than with the Alpha and Delta variants, it is possible that the overall prevalence of PCC in the population increases, even if the probability of having a PCC decreases.

Outbreak of Corynebacterium diphtheriae among asylum seekers in Belgium in 2022: operational challenges and lessons learnt.

Since 2022, European countries have been facing an outbreak of mainly cutaneous diphtheria caused by toxigenic Corynebacterium diphtheriae among asylum seekers. In Belgium, between 1 March and 31 December 2022, 25 cases of toxigenic C. diphtheriae infection were confirmed among asylum seekers, mostly among young males from Afghanistan. Multi-locus sequence typing showed that most isolates belonged to sequence types 574 or 377, similar to the majority of cases in other European countries. The investigation and management of the outbreak, with many asylum seekers without shelter, required adjustments to case finding, contact tracing and treatment procedures. A test-and-treat centre was organised by non-governmental organisations, the duration of the antimicrobial treatment was shortened to increase compliance, and isolation and contact tracing of cases was not possible. A vaccination centre was opened, and mobile vaccination campaigns were organised to vaccinate a maximum of asylum seekers. No more cases were detected between end December 2022 and May 2023. Unfortunately, though, three cases of respiratory diphtheria, including one death, were reported at the end of June 2023. To prevent future outbreaks, specific attention and sufficient resources should be allocated to this vulnerable population, in Belgium and at international level.

Classification of post COVID-19 condition symptoms: a longitudinal study in the Belgian population.

OBJECTIVES: Since the onset of the COVID-19 pandemic, most research has focused on its acute pathophysiology, yet some people tend to experience persisting symptoms beyond the acute phase of infection, referred to as post COVID-19 condition (PCC). However, evidence on PCC is still scarce. This study aimed to assess the distribution, classification of symptoms and associated factors of PCC in adults. DESIGN: Longitudinal online cohort study. SETTING: National study in Belgium. PARTICIPANTS: Participants were Belgian adults with a recent SARS-CoV-2 infection and were recruited when called up for contact tracing. A total of 3039 participants were included and completed an online questionnaire at the time of their infection and again 3 months later. OUTCOME MEASURES: The baseline questionnaire assessed the initial health status of the participants and their status during the acute phase of the infection. The follow-up questionnaire assessed their PCC status 3 months after infection. A latent class analysis (LCA) was performed to assess whether there are different classes of individuals with a similar set of self-reported PCC symptoms. RESULTS: Half of the participants reported PCC 3 months after infection (47%). The most frequent symptoms were fatigue (21%), headache (11%) and memory problems (10%). The LCA highlighted three different classes of PCC symptoms with different risk factors: (1) a combination of loss of smell and taste, (2) a combination of neurological symptoms and (3) other heterogeneous symptoms. CONCLUSIONS: With the increasing number of people who underwent COVID-19, PCC has become an important but complex public health problem due to the heterogeneity of its symptoms. The classification of symptoms performed in this study can help give insight into different aetiologies of PCC and better plan care according to the symptoms and needs of those affected.

Post COVID-19 condition and health-related quality of life: a longitudinal cohort study in the Belgian adult population.

BACKGROUND: Since the onset of the COVID-19 pandemic, most research has focused on the acute phase of COVID-19, yet some people experience symptoms beyond, referred to as post COVID-19 conditions (PCC). However, evidence on PCC and its impacts on health-related quality of life (HRQoL) is still scarce. This study aimed to assess the impact of COVID-19 and PCC on HRQoL. METHODS: This is a longitudinal cohort study of the Belgian adult population with recent SARS-CoV-2 infection. In total, 5,727 people were followed up between the time of their infection and three months later. HRQoL was measured with the EQ-5D-5L questionnaire before and during the infection and three months later. Linear mixed regression models were built to assess the longitudinal association between participants' characteristics and the evolution of their HRQoL. RESULTS: This study found a significant decline in HRQoL during the SARS-CoV-2 infection in comparison to the situation before (ß=-9.91, 95%CI=-10.13;-9.85), but no clinically important difference three months after the infection compared to the situation before, except among people reporting PCC (ß=-11.15, 95%CI=-11.72;-10.51). The main symptoms of PCC with a significant negative impact on the different dimensions of HRQoL were fatigue/exhaustion (21%), headache (11%), memory problems (10%), shortness of breath (9%), and joint (7%) or muscle pain (6%). The dimension of HRQoL most negatively affected by several PCC symptoms was pain/discomfort. CONCLUSIONS: With the growing number of people infected with SARS-CoV-2, PCC and its impact on HRQoL are becoming important public health issues. To allow people with PCC to recover and to limit its detrimental impact on HRQoL, it is essential to manage its various heterogeneous symptoms using a multidisciplinary approach.

A framework for individualized splice-switching oligonucleotide therapy.

Splice-switching antisense oligonucleotides (ASOs) could be used to treat a subset of individuals with genetic diseases1, but the systematic identification of such individuals remains a challenge. Here we performed whole-genome sequencing analyses to characterize genetic variation in 235 individuals (from 209 families) with ataxia-telangiectasia, a severely debilitating and life-threatening recessive genetic disorder2,3, yielding a complete molecular diagnosis in almost all individuals. We developed a predictive taxonomy to assess the amenability of each individual to splice-switching ASO intervention; 9% and 6% of the individuals had variants that were 'probably' or 'possibly' amenable to ASO splice modulation, respectively. Most amenable variants were in deep intronic regions that are inaccessible to exon-targeted sequencing. We developed ASOs that successfully rescued mis-splicing and ATM cellular signalling in patient fibroblasts for two recurrent variants. In a pilot clinical study, one of these ASOs was used to treat a child who had been diagnosed with ataxia-telangiectasia soon after birth, and showed good tolerability without serious adverse events for three years. Our study provides a framework for the prospective identification of individuals with genetic diseases who might benefit from a therapeutic approach involving splice-switching ASOs.

Were SARS-CoV-2 self-tests used for their intended purpose? The experience in Belgium.

BACKGROUND: Self-testing has been promoted as a means of increasing COVID-19 test coverage. In Belgium, self-testing was recommended as a complement to the formal, provider-administered indications, such as out of courtesy before meeting others and when feared to be infected. More than a year after the introduction of self-testing their place in the test strategy was evaluated. METHODS: We assessed trends in the number of self-tests sold, the number of positive self-tests reported, the proportion sold self-tests/total tests, and the proportion of all positive tests that were confirmed self-tests. To evaluate the reason why people use self-tests, we used the results of two online surveys among members of the general population: one among 27,397 people, held in April 2021, and one among 22,354 people, held in December 2021. RESULTS: The use of self-tests became substantial from end 2021 onwards. In the period mid-November 2021 - end-of-June 2022, the average proportion of reported sold self-tests to all COVID-19 tests was 37% and 14% of all positive tests were positive self-tests. In both surveys, the main reported reasons for using a self-test were having symptoms (34% of users in April 2021 and 31% in December 2021) and after a risk contact (27% in both April and December). Moreover, the number of self-tests sold, and the number of positive self-tests reported closely followed the same trend as the provider-administered tests in symptomatic people and high risk-contacts, which reinforces the hypothesis that they were mainly used for these two indications. CONCLUSIONS: From end 2021 onwards, self-testing covered a significant part of COVID-19 testing in Belgium, which increased without doubt the testing coverage. However, the available data seem to indicate that self-testing was mostly used for indications outside of official recommendations. If and how this affected the control of the epidemic remains unknown.

Comparing the incidence of SARS-CoV-2 across age groups considering sampling biases - use of testing data of autumn 2021 in Belgium.

BACKGROUND: To design efficient mitigation measures against COVID-19, understanding the transmission dynamics between different age groups was crucial. The role of children in the pandemic has been intensely debated and involves both scientific and ethical questions. To design efficient age-targeted non-pharmaceutical interventions (NPI), a good view of the incidence of the different age groups was needed. However, using Belgian testing data to infer real incidence (RI) from observed incidence (OI) or positivity ratio (PR) was not trivial. METHODS: Based on Belgian testing data collected during the Delta wave of Autumn 2021, we compared the use of different estimators of RI and analyzed their effect on comparisons between age groups. RESULTS: We found that the RI estimator's choice strongly influences the comparison between age groups. CONCLUSION: The widespread implementation of testing campaigns using representative population samples could help to avoid pitfalls related to the current testing strategy in Belgium and worldwide. This approach would also allow a better comparison of the data from different countries while reducing biases arising from the specificities of each surveillance system.

Vaccine effectiveness against transmission of alpha, delta and omicron SARS-COV-2-infection, Belgian contact tracing, 2021-2022.

OBJECTIVES: Vaccine effectiveness against transmission (VET) of SARS-CoV-2-infection can be estimated from secondary attack rates observed during contact tracing. We estimated VET, the vaccine-effect on infectiousness of the index case and susceptibility of the high-risk exposure contact (HREC). METHODS: We fitted RT-PCR-test results from HREC to immunity status (vaccine schedule, prior infection, time since last immunity-conferring event), age, sex, calendar week of sampling, household, background positivity rate and dominant VOC using a multilevel Bayesian regression-model. We included Belgian data collected between January 2021 and January 2022. RESULTS: For primary BNT162b2-vaccination we estimated initial VET at 96% (95%CI 95-97) against Alpha, 87% (95%CI 84-88) against Delta and 31% (95%CI 25-37) against Omicron. Initial VET of booster-vaccination (mRNA primary and booster-vaccination) was 87% (95%CI 86-89) against Delta and 68% (95%CI 65-70) against Omicron. The VET-estimate against Delta and Omicron decreased to 71% (95%CI 64-78) and 55% (95%CI 46-62) respectively, 150-200 days after booster-vaccination. Hybrid immunity, defined as vaccination and documented prior infection, was associated with durable and higher or comparable (by number of antigen exposures) protection against transmission. CONCLUSIONS: While we observed VOC-specific immune-escape, especially by Omicron, and waning over time since immunization, vaccination remained associated with a reduced risk of SARS-CoV-2-transmission.

Electroencephalographic delta and alpha oscillations reveal phase-amplitude coupling in paediatric patients undergoing sevoflurane-based general anaesthesia.

BACKGROUND: Sevoflurane-induced anaesthesia generates frontal alpha oscillations as early as 6 months of age, whereas strong delta oscillations are present at birth. In adults, delta oscillations and alpha oscillations are coupled: the phase of delta waves modulates the amplitude of alpha oscillations in a phenomenon known as phase-amplitude coupling. We hypothesise that delta-alpha phase-amplitude coupling exists in young children and is a feature of sevoflurane-based general anaesthesia distinct from emergence after anaesthesia. METHODS: Electroencephalographic data from 31 paediatric patients aged 10 months to 3 yr undergoing elective surgery with sevoflurane-based anaesthesia were analysed retrospectively. Delta-alpha phase-amplitude coupling was evaluated during maintenance of anaesthesia and during emergence. RESULTS: Delta-alpha phase-amplitude coupling was observed in the study population. Strength of phase-amplitude coupling, represented by the delta-alpha mean amplitude vector, was greater during general anaesthesia than during emergence (Wilcoxon paired signed-rank test, Z=3.107, P=0.002). Frontal alpha amplitude during anaesthesia was not uniformly distributed across all delta phases. During general anaesthesia, alpha power was restricted to the positive phase of the delta wave (omnibus circular uniformity, general anaesthesia: P<0.001, mean phase: 114º; 99% confidence interval: 90º-139º; emergence: P=0.35, mean phase 181º, 99% confidence interval: 110º-253º). CONCLUSIONS: Sevoflurane-based anaesthesia is associated with delta-alpha phase-amplitude coupling in paediatric patients. These findings improve our understanding of cortical dynamics in children undergoing general anaesthesia, which might improve paediatric intraoperative depth of anaesthesia monitoring techniques.

Quantitative Sensory Changes Following Posterior Spinal Fusion to Treat Adolescent Idiopathic Scoliosis.

BACKGROUND: Sensory changes surrounding the incision frequently develop after posterior spinal fusion (PSF) to treat adolescent idiopathic scoliosis (AIS). Anecdotally, patients may experience sensory changes on the chest wall. Such postsurgical sensory changes are not well described quantitatively. This study aims to evaluate the presence, intensity, and duration of mechanical sensory changes in AIS patients postoperatively. METHODS: A prospective cohort of AIS patients, 10 to 21 years old, was followed. Quantitative sensory testing (QST) included touch detection threshold [mechanical detection threshold (MDT)] and pain detection threshold (MPT), using VonFrey monofilaments and pinprick stimulators. QST was performed at 3 sites at T6: the right and left chest at the nipple line and adjacent to the incision below the inferior angle of the scapula. QST at the thenar eminence was the control. QST was collected at baseline, 3 days, 1, and 6 months postoperative. RESULTS: Thirty-four patients (21% males; mean age: 14.9 years old; median preoperative curve: 58 degrees) completed all testing. Mean deformity correction was 64% (SD: 10.4). Adjacent to the incision site, MDT was significantly higher compared with baseline at 3 days and 1 month ( P < 0.001) but not at 6 months ( P = 0.19), whereas MPT was significantly higher at 3 days, ( P < 0.001), 1 month ( P < 0.001), and 6 months ( P = 0.001). For the chest wall in all patients, MPT was higher on the left chest at 3 days ( P = 0.04) and on the right chest at 3 days ( P = 0.022) and 1 month ( P = 0.05). For patients with right-sided curves, MDT ( P = 0.01) and MPT ( P = 0.015) overall were significantly higher on the concave side (left) chest postoperatively. CONCLUSIONS: PSF is associated with sensory disturbances that are detectable within days, persist at 1 month, and improve at 6 months postoperatively adjacent to the incision and on the chest wall. We suspect that these sensory changes are transient. Describing postoperative sensory changes will help us better set postoperative expectations for patients undergoing PSF. LEVEL OF EVIDENCE: Level I.

Emerging functional connectivity patterns during sevoflurane anaesthesia in the developing human brain.

BACKGROUND: Spectral-based EEG is used to monitor anaesthetic state during surgical procedures in adults. Spectral EEG features that can resemble the patterns seen in adults emerge in children after the age of 10 months and cannot distinguish wakefulness and anaesthesia in the youngest children. There is a need to explore alternative EEG measures. We hypothesise that functional connectivity is one of the measures that can help distinguish between consciousness states in children. METHODS: An EEG data set of children undergoing sevoflurane general anaesthesia (age 0-3 yr) was reanalysed using debiased weighted phase lag index as a measure of functional connectivity in wakefulness (n=38) and anaesthesia (n=73). Network topology measures were compared between states in 0- to 6-, 6- to 10-, and >10-month-old children. RESULTS: Functional connectivity was reduced in anaesthesia vs wakefulness in delta band (n=cluster of 17 significant connections; P=0.013; 58% connections surviving thresholding in wakefulness and 49% in anaesthesia). Network density and node degree were lower in anaesthesia even in the youngest children (0.57 in wakefulness; 0.48 in anaesthesia; t [9]=3.39; P=0.029; G=0.98; confidence interval [CI] [0.25-1.77]). Modularity was higher in anaesthesia (0-6 months: 0.16 in wakefulness and 0.19 in anaesthesia, t [9]=-2.95, P=0.04, G=-0.85, CI [-1.60 to -0.16]; >10 months: 0.16 vs 0.21, t [13]=-6.45, P<0.001, G=-1.62, CI [-2.49 to -0.85]) and decreased with age (ρ [73]=-0.456; P<0.001). CONCLUSIONS: Anaesthesia modulates functional connectivity. Increased segregation into a more modular structure in anaesthesia decreases with age as adult-like features develop. These findings advance our understanding of the network architecture underlying the effects of anaesthesia on the developing brain.

Tactile sensitivity and motor coordination in infancy: Effect of age, prior surgery, anaesthesia & critical illness.

BACKGROUND: Tactile sensitivity in the infant period is poorly characterized, particularly among children with prior surgery, anaesthesia or critical illness. The study aims were to investigate tactile sensitivity of the foot and the associated coordination of lower limb motor movement in typically developing infants with and without prior hospital experience, and to develop feasible bedside sensory testing protocols. MATERIALS AND METHODS: A prospective, longitudinal study in 69 infants at 2 and 4 months-old, with and without prior hospital admission. Mechanical stimuli were applied to the foot at graded innocuous and noxious intensities. Primary outcome measures were tactile and nociceptive threshold (lowest force required to evoke any leg movement, or brisk leg withdrawal, respectively), and specific motor flexion threshold (ankle-, knee-, hip-flexion). Secondary analysis investigated (i) single vs multiple trials reliability, and (ii) the effect of age and prior surgery, anaesthesia, or critical illness on mechanical threshold. RESULTS: Magnitude of evoked motor activity increased with stimulus intensity. Single trials had excellent reliability for knee and hip flexion at age 1-3m and 4-7m (ICC range: 0.8 to 0.98, p >0.05). Nociceptive threshold varied as a function of age. Tactile sensitivity was independent of age, number of surgeries, general anaesthesia and ICU stay. CONCLUSIONS: This brief sensory testing protocol may reliably measure tactile and nociceptive reactivity in human infants. Age predicts nociceptive threshold which likely reflects ongoing maturation of spinal and supraspinal circuits. Prior hospital experience has a negligible global effect on sensory processing demonstrating the resilience of the CNS in adverse environments.

Post COVID-19 condition and its physical, mental and social implications: protocol of a 2-year longitudinal cohort study in the Belgian adult population.

BACKGROUND: Since the onset of the COVID-19 pandemic, most research has focused on the pathophysiology and management of the acute symptoms of COVID-19, yet some people tend to experience symptoms beyond the acute phase of infection, that is, Post COVID-19 condition (PCC). However, evidence on the long-term health impacts of a COVID-19 infection are still scarce. The purpose of this paper is to describe the COVIMPACT study, which aims to set up a cohort of people who have been tested positive for COVID-19 and study the evolution of their physical, mental and social health over the medium (3 months) and long term (two years), and the factors associated with an (un)favorable evolution. METHODS: COVIMPACT is a longitudinal cohort study organised over a two-years period between April 2021 and April 2023. The eligible population is all people aged 18 years and older, living in Belgium, with a recent COVID-19 infection and contacted by the health authorities for contact tracing. Two questionnaires are used: a baseline questionnaire that aims to assess the initial health status of the participants and their status during the acute phase of the illness, and a follow-up questionnaire that is sent every three months after participants enter into the cohort. A matched non-COVID-19 control group was also selected. As of November 1, 2021, 10,708 people completed the baseline questionnaire (5% of the eligible population) and the follow-up participation rate was 79%. In total, 48% of the cohort participants appeared to fit the proposed case definition of PCC (i.e. report at least one symptom related to their COVID-19 infection three months afterwards). DISCUSSION: This study was designed to provide timely information on the short and long term impact of a COVID-19 infection, to stakeholders such as policymakers, health practitioners and people with PCC. Although the follow-up participation rate was good (79%), the participation rate of the eligible population was low (5%). Compared to other studies, this study has a large sample, of non-hospitalised and hospitalised people, who will be followed over a long period of 3 months to two years post infection, and with a global approach to their health.

Nusinersen for Patients With Spinal Muscular Atrophy: 1415 Doses via an Interdisciplinary Institutional Approach.

BACKGROUND: Spinal deformity and prior spinal fusion pose technical challenges to lumbar puncture (LP) for nusinersen administration for patients with spinal muscular atrophy (SMA). In this retrospective study over two study phases, we evaluated (1) factors associated with difficult LP or unscheduled requirement for image guidance and (2) effectiveness of a triage pathway for selective use of image guidance and nonstandard techniques, particularly for patients with spinal instrumentation/fusion to the sacrum. METHODS: With institutional review board approval, electronic health records, imaging, and administrative databases were analyzed for patients receiving nusinersen from January 2012 through September 2021. Descriptive statistics and univariate analyses were used. RESULTS: From January 2012 to March 2018 (phase 1), among 82 patients with SMA, 461 of 464 (99.4%) LP attempts were successful. Univariate analyses associated difficulty with prior spinal instrumentation, higher body mass index, and severity of the spinal deformity. Based on this experience, starting in April 2018 (phase 2), 125 patients were triaged selectively for ultrasound, fluoroscopy, or Dyna computed tomography. Patients with spinal instrumentation/fusion to the sacrum were treated primarily via intrathecal ports (137 doses) or transforaminal LP (55 doses). From April 2018 through September 2021, 704 of 709 (99.3%) LPs were successful. In total from January 2012 to September 2021, 1415 doses were administered. Over 50% of LPs were performed by neurology nurse practitioners without image guidance. Safety outcomes were excellent. CONCLUSIONS: A stratified approach resulted in successful intrathecal nusinersen delivery and efficient resource allocation for patients with SMA, with or without complex spinal anatomy.

Identifying immunity gaps for measles using Belgian serial serology data.

Vaccine-preventable diseases, such as measles, have been re-emerging in countries with moderate to high vaccine uptake. It is increasingly important to identify and close immunity gaps and increase coverage of routine childhood vaccinations, including two doses of the measles-mumps-rubella vaccine (MMR). Here, we present a simple cohort model relying on a Bayesian approach to evaluate the evolution of measles seroprevalence in Belgium using the three most recent cross-sectional serological survey data collections (2002, 2006 and 2013) and information regarding vaccine properties. We find measles seroprevalence profiles to be similar for the different regions in Belgium. These profiles exhibit a drop in seroprevalence in birth cohorts that were offered vaccination at suboptimal coverages in the first years after routine vaccination has been started up. This immunity gap is observed across all cross-sectional survey years, although it is more pronounced in survey year 2013. At present, the COVID-19 pandemic could negatively impact the immunization coverage worldwide, thereby increasing the need for additional immunization programs in groups of children that are impacted by this. Therefore, it is now even more important to identify existing immunity gaps and to sustain and reach vaccine-derived measles immunity goals.

Vaccine effectiveness against onward transmission of SARS-CoV2-infection by variant of concern and time since vaccination, Belgian contact tracing, 2021.

BACKGROUND: During the first half of 2021, we observed high vaccine effectiveness (VE) against SARS-CoV2-infection. The replacement of the alpha-'variant of concern' (VOC) by the delta-VOC and uncertainty about the time course of immunity called for a re-assessment. METHODS: We estimated VE against transmission of infection (VET) from Belgian contact tracing data for high-risk exposure contacts between 26/01/2021 and 14/12/2021 by susceptibility (VEs) and infectiousness of breakthrough cases (VEi) for a complete schedule of Ad26.COV2.S, ChAdOx1, BNT162b2, mRNA-1273 as well as infection-acquired and hybrid immunity. We used a multilevel Bayesian model and adjusted for personal characteristics (age, sex, household), background exposure, calendar week, VOC and time since immunity conferring-event. FINDINGS: VET-estimates were higher for mRNA-vaccines, over 90%, compared to viral vector vaccines: 66% and 80% for Ad26COV2.S and ChAdOx1 respectively (Alpha, 0-50 days after vaccination). Delta was associated with a 40% increase in odds of transmission and a decrease of VEs (72-64%) and especially of VEi (71-46% for BNT162b2). Infection-acquired and hybrid immunity were less affected by Delta. Waning further reduced VET-estimates: from 81% to 63% for BNT162b2 (Delta, 150-200 days after vaccination). We observed lower initial VEi in the age group 65-84 years (32% vs 46% in the age group 45-64 years for BNT162b2) and faster waning. Hybrid immunity waned slower than vaccine-induced immunity. INTERPRETATION: VEi and VEs-estimates, while remaining significant, were reduced by Delta and waned over time. We observed faster waning in the oldest age group. We should seek to improve vaccine-induced protection in older persons and those vaccinated with viral-vector vaccines.

COVID-19 contact tracing in Belgium: main indicators and performance, January - September 2021.

BACKGROUND: Contact tracing is one of the main public health tools in the control of coronavirus disease 2019 (COVID-19). A centralized contact tracing system was developed in Belgium in 2020. We aim to evaluate the performance and describe the results, between January 01, 2021, and September 30, 2021. The characteristics of COVID-19 cases and the impact of COVID-19 vaccination on testing and tracing are also described. METHODS: We combined laboratory diagnostic test data (molecular and antigen test), vaccination data, and contact tracing data. A descriptive analysis was done to evaluate the performance of contact tracing and describe insights into the epidemiology of COVID-19 by contact tracing. RESULTS: Between January and September 2021, 555.181 COVID-19 cases were reported to the central contact center and 91% were contacted. The average delay between symptom onset and contact tracing initiation was around 5 days, of which 4 days corresponded to pre-testing delay. High-Risk Contacts (HRC) were reported by 49% of the contacted index cases. The mean number of reported HRC was 2.7. In total, 666.869 HRC were reported of which 91% were successfully contacted and 89% of these were tested at least once following the interview. The estimated average secondary attack rate (SAR) among the contacts of the COVID-19 cases who reported at least one contact, was 27% and was significantly higher among household HRC. The proportion of COVID-19 cases who were previously identified as HRC within the central system was 24%. CONCLUSIONS: The contact-tracing system contacted more than 90% of the reported COVID-19 cases and their HRC. This proportion remained stable between January 1 2021 and September 30 2021 despite an increase in cases in March-April 2021. We report high SAR, indicating that through contact tracing a large number of infections were prospectively detected. The system can be further improved by (1) reducing the delay between onset of illness and medical consultation (2) having more exhaustive reporting of HRC by the COVID-19 case.

Modified Sensory Testing in Non-verbal Patients Receiving Novel Intrathecal Therapies for Neurological Disorders.

Several neurological disorders may be amenable to treatment with gene-targeting therapies such as antisense oligonucleotides (ASOs) or viral vector-based gene therapy. The US FDA has approved several of these treatments; many others are in clinical trials. Preclinical toxicity studies of ASO candidates have identified dose-dependent neurotoxicity patterns. These include degeneration of dorsal root ganglia, the cell bodies of peripheral sensory neurons. Quantitative sensory testing (QST) refers to a series of standardized mechanical and/or thermal measures that complement clinical neurologic examination in detecting sensory dysfunction. QST primarily relies on patient self-report or task performance (i.e., button-pushing). This brief report illustrates individualized pragmatic approaches to QST in non-verbal subjects receiving early phase investigational intrathecal drug therapies as a component of clinical trial safety protocols. Three children with neurodevelopmental disorders that include Neuronal Ceroid Lipofuscinosis Type 7, Ataxia-Telangiectasia, and Epilepsy of Infancy with Migrating Focal Seizures are presented. These case studies discuss individualized testing protocols, accounting for disease presentation, cognitive and motor function. We outline specific considerations for developing assessments for detecting changes in sensory processing in diverse patient groups and safety monitoring trials of early phase investigational intrathecal drug therapies. QST may complement information obtained from the standard neurologic examination, electrophysiologic studies, skin biopsies, and imaging. QST has limitations and challenges, especially in non-verbal subjects, as shown in the three cases discussed in this report. Future directions call for collaborative efforts to generate sensory datasets and share data registries in the pediatric neurology field.

Long-term alterations in somatosensory functioning in survivors of childhood cancer.

ABSTRACT: Cancer and its treatment can have lasting consequences on somatosensation, including pain, which is often underrecognized and undertreated. Research characterizing the impact of cancer on pain and sensory processing in survivors of childhood cancer is scarce. This study aimed to quantify generalized differences in pain and sensory processing in survivors of childhood cancer compared with reference data using a standardized thermal and mechanical quantitative sensory testing (QST) protocol. The association between demographic, clinical (eg, leukemia vs other cancers and treatment exposures), and psychosocial (eg, anxiety and pain catastrophizing) variables and sensitivity to pain and sensory stimuli were also evaluated. Participants were 56 survivors of various types of childhood cancer (52% male, Mage = 13.5 years, SD = 3.2, range = 8-17 years). On average, children were 7 years (SD = 4.1, range = 1.2-16.5) post treatment. Almost all participants (86%) had at least 1 abnormal QST parameter compared with age- and sex-matched reference data; however, few participants self-reported the presence of sensory abnormalities. Generally, participants exhibited reduced sensitivity across the QST parameters examined (Ps < 0.05, ds = 0.40-3.45). A significant minority (45%) also exhibited pain sensitization (P <0.001, d = 0.42). Several risk factors for changes in sensory processing were identified, including current age, history of leukemia, certain treatment exposures (eg, vincristine cumulative dose, major surgery, and bone marrow or stem cell transplant), time off treatment, and higher anxiety and pain catastrophizing scores. Overall, this study demonstrated that somatosensory changes are prevalent in survivors of childhood cancer years after the completion of treatment. Future research is needed to understand long-term implications of altered somatosensation in this complex population.