Real-world Effectiveness and Causal Mediation Study of BNT162b2 on Long COVID Risks in Children and Adolescents (preprint)

BackgroundThe impact of pre-infection vaccination on the risk of long COVID remains unclear in the pediatric population. Further, it is unknown if such pre-infection vaccination can mitigate the risk of long COVID beyond its established protective benefits against SARS-CoV-2 infection. ObjectiveTo assess the effectiveness of BNT162b2 on long COVID risks with various strains of the SARS-CoV-2 virus in children and adolescents, using comparative effectiveness methods. To disentangle the overall effectiveness of the vaccine on long COVID outcomes into its independent impact and indirect impact via prevention of SARS-CoV-2 infections, using causal mediation analysis. DesignReal-world vaccine effectiveness study and mediation analysis in three independent cohorts: adolescents (12 to 20 years) during the Delta phase, children (5 to 11 years) and adolescents (12 to 20 years) during the Omicron phase. SettingTwenty health systems in the RECOVER PCORnet electronic health record (EHR) Program. Participants112,590 adolescents (88,811 vaccinated) in the Delta period, 188,894 children (101,277 vaccinated), and 84,735 adolescents (37,724 vaccinated) in the Omicron period. ExposuresFirst dose of the BNT162b2 vaccine vs. no receipt of COVID-19 vaccine. MeasurementsOutcomes of interest include conclusive or probable diagnosis of long COVID following a documented SARS-CoV-2 infection, and body-system-specific condition clusters of post-acute sequelae of SARS-CoV-2 infection (PASC), such as cardiac, gastrointestinal, musculoskeletal, respiratory, and syndromic categories. The effectiveness was reported as (1-relative risk)*100 and mediating effects were reported as relative risks. ResultsDuring the Delta period, the estimated effectiveness of the BNT162b2 vaccine against long COVID among adolescents was 95.4% (95% CI: 90.9% to 97.7%). During the Omicron phase, the estimated effectiveness against long COVID among children was 60.2% (95% CI: 40.3% to 73.5%) and 75.1% (95% CI: 50.4% to 87.5%) among adolescents. The direct effect of vaccination, defined as the effect beyond their impact on SARS-CoV-2 infections, was found to be statistically non-significant in all three study cohorts, with estimates of 1.08 (95% CI: 0.75 to 1.55) in the Delta study among adolescents, 1.24 (95% CI: 0.92 to 1.66) among children and 0.91 (95% CI: 0.69 to 1.19) among adolescents in the Omicron studies. Meanwhile, the estimated indirect effects, which are effects through protecting SARS-CoV-2 infections, were estimated as 0.04 (95% CI: 0.03 to 0.05) among adolescents during Delta phase, 0.31 (95% CI: 0.23 to 0.42) among children and 0.21 (95% CI: 0.16 to 0.27) among adolescents during the Omicron period. LimitationsObservational study design and potentially undocumented infection. ConclusionsOur study suggests that BNT162b2 was effective in reducing risk of long COVID outcomes in children and adolescents during the Delta and Omicron periods. The mediation analysis indicates the vaccines effectiveness is primarily derived from its role in reducing the risk of SARS-CoV-2 infection. Primary Funding SourceNational Institutes of Health.

Vaccine Effectiveness Against Long COVID in Children: A Report from the RECOVER EHR Cohort (preprint)

Objective Vaccination reduces the risk of acute COVID-19 in children, but it is less clear whether it protects against long COVID. We estimated vaccine effectiveness (VE) against long COVID in children aged 5 to 17 years. Methods This retrospective cohort study used data from 17 health systems in the RECOVER PCORnet electronic health record (EHR) Program for visits between vaccine availability, and October 29, 2022. Conditional logistic regression was used to estimate VE against long COVID with matching on age group (5 to 11, 12 to 17) and time period and adjustment for sex, ethnicity, health system, comorbidity burden, and pre-exposure health care utilization. We examined both probable (symptom-based) and diagnosed long COVID in the year following vaccination. Results The vaccination rate was 56% in the cohort of 1,037,936 children. The incidence of probably long COVID was 4.5% among patients with COVID-19, while diagnosed long COVID was 0.7%. Adjusted vaccine effectiveness within 12 months was 35.4% (95 CI 24.5 - 44.5) against probable long COVID and 41.7% (15.0- 60.0) against diagnosed long COVID. VE was higher for adolescents 50.3% [36.3 - 61.0]) than children aged 5-11 (23.8% [4.9 -39.0]). VE was higher at 6 months (61.4% [51.0 - 69.6]), but decreased to 10.6% (-26.8 - 37.0%) at 18 months. Discussion This large retrospective study shows a moderate protective effect of SARS-CoV-2 vaccination against long COVID. The effect is stronger in adolescents, who have higher risk of long COVID, and wanes over time. Understanding VE mechanism against long COVID requires more study, including EHR sources and prospective data. Discussion This large retrospective study shows a moderate protective effect of SARS-CoV-2 vaccination against long COVID. The effect is stronger in adolescents, who have higher risk of long COVID, and wanes over time. Understanding VE mechanism against long COVID requires more study, including EHR sources and prospective data.

Transforming ophthalmology in the digital century-new care models with added value for patients.

Ophthalmology faces many challenges in providing effective and meaningful eye care to an ever-increasing group of people. Even health systems that have so far been able to cope with the quantitative patient increase, due to their funding and the availability of highly qualified professionals, and improvements in practice routine efficiency, will be pushed to their limits. Further pressure on care will also be caused by new active substances for the largest group of patients with AMD, the so-called dry form. Treatment availability for this so far untreated group will increase the volume of patients 2-3 times. Without the adaptation of the care structures, this quantitative and qualitative expansion in therapy will inevitably lead to an undersupply.There is increasing scientific evidence that significant efficiency gains in the care of chronic diseases can be achieved through better networking of stakeholders in the healthcare system and greater patient involvement. Digitalization can make an important contribution here. Many technological solutions have been developed in recent years and the time is now ready to exploit this potential. The exceptional setting during the SARS-CoV-2 pandemic has shown many that new technology is available safely, quickly, and effectively. The emergency has catalyzed innovation processes and shown for post-pandemic time after that we are equipped to tackle the challenges in ophthalmic healthcare - ultimately for the benefit of patients and society.

Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine in children aged 6-17 years: a preliminary report of COV006, a phase 2 single-blind, randomised, controlled trial.

BACKGROUND: Vaccination of children and young people against SARS-CoV-2 is recommended in some countries. Scarce data have been published on immune responses induced by COVID-19 vaccines in people younger than 18 years compared with the same data that are available in adults. METHODS: COV006 is a phase 2, single-blind, randomised, controlled trial of ChAdOx1 nCoV-19 (AZD1222) in children and adolescents at four trial sites in the UK. Healthy participants aged 6-17 years, who did not have a history of chronic respiratory conditions, laboratory-confirmed COVID-19, or previously received capsular group B meningococcal vaccine (the control), were randomly assigned to four groups (4:1:4:1) to receive two intramuscular doses of 5 × 1010 viral particles of ChAdOx1 nCoV-19 or control, 28 days or 84 days apart. Participants, clinical investigators, and the laboratory team were masked to treatment allocation. Study groups were stratified by age, and participants aged 12-17 years were enrolled before those aged 6-11 years. Due to the restrictions in the use of ChAdOx1 nCoV-19 in people younger than 30 years that were introduced during the study, only participants aged 12-17 years who were randomly assigned to the 28-day interval group had received their vaccinations at the intended interval (day 28). The remaining participants received their second dose at day 112. The primary outcome was assessment of safety and tolerability in the safety population, which included all participants who received at least one dose of the study drug. The secondary outcome was immunogenicity, which was assessed in participants who were seronegative to the nucleocapsid protein at baseline and received both prime and boost vaccine. This study is registered with ISRCTN (15638344). FINDINGS: Between Feb 15 and April 2, 2021, 262 participants (150 [57%] participants aged 12-17 years and 112 [43%] aged 6-11 years; due to the change in the UK vaccination policy, the study terminated recruitment of the younger age group before the planned number of participants had been enrolled) were randomly assigned to receive vaccination with two doses of either ChAdOx1 nCoV-19 (n=211 [n=105 at day 28 and n=106 at day 84]) or control (n=51 [n=26 at day 28 and n=25 at day 84]). One participant in the ChAdOx1 nCoV-19 day 28 group in the younger age bracket withdrew their consent before receiving a first dose. Of the participants who received ChAdOx1 nCoV-19, 169 (80%) of 210 participants reported at least one solicited local or systemic adverse event up to 7 days following the first dose, and 146 (76%) of 193 participants following the second dose. No serious adverse events related to ChAdOx1 nCoV-19 administration were recorded by the data cutoff date on Oct 28, 2021. Of the participants who received at least one dose of ChAdOx1 nCoV-19, there were 128 unsolicited adverse events up to 28 days after vaccination reported by 83 (40%) of 210 participants. One participant aged 6-11 years receiving ChAdOx1 nCoV-19 reported a grade 4 fever of 40·2°C on day 1 following first vaccination, which resolved within 24 h. Pain and tenderness were the most common local solicited adverse events for all the ChAdOx1 nCoV-19 and capsular group B meningococcal groups following both doses. Of the 242 participants with available serostatus data, 14 (6%) were seropositive at baseline. Serostatus data were not available for 20 (8%) of 262 participants. Among seronegative participants who received ChAdOx1 nCoV-19, anti-SARS-CoV-2 IgG and pseudoneutralising antibody titres at day 28 after the second dose were higher in participants aged 12-17 years with a longer interval between doses (geometric means of 73 371 arbitrary units [AU]/mL [95% CI 58 685-91 733] and 299 half-maximal inhibitory concentration [IC50; 95% CI 230-390]) compared with those aged 12-17 years who received their vaccines 28 days apart (43 280 AU/mL [95% CI 35 852-52 246] and 150 IC50 [95% CI 116-194]). Humoral responses were higher in those aged 6-11 years than in those aged 12-17 years receiving their second dose at the same 112-day interval (geometric mean ratios 1·48 [95% CI 1·07-2·07] for anti-SARS-CoV-2 IgG and 2·96 [1·89-4·62] for pseudoneutralising antibody titres). Cellular responses peaked after a first dose of ChAdOx1 nCoV-19 across all age and interval groups and remained above baseline after a second vaccination. INTERPRETATION: ChAdOx1 nCoV-19 is well tolerated and immunogenic in children aged 6-17 years, inducing concentrations of antibody that are similar to those associated with high efficacy in phase 3 studies in adults. No safety concerns were raised in this trial. FUNDING: AstraZeneca and the UK Department of Health and Social Care through the UK National Institute for Health and Care Research.

IDIOPATHIC MULTIFOCAL CHOROIDITIS WITH SERPIGINOUS-LIKE PERIPAPILLARY CHORIORETINAL ATROPHY.

PURPOSE: To report nine cases of multifocal choroiditis with serpiginous-like peripapillary chorioretinal atrophy. METHODS: A retrospective observational case series of eyes with multifocal choroiditis with serpiginous-like peripapillary chorioretinal atrophy. Multimodal imaging findings were reviewed and presented. RESULTS: Fifteen eyes of 9 patients (6 women and 3 men), with a mean age of 48.1 years (median, 46 years; range, 23-74 years), presented with multifocal choroiditis serpiginous-like peripapillary chorioretinal atrophy. All 15 eyes presented with serpiginoid peripapillary changes and had discrete patches of atrophy or punched-out scars in the posterior pole or periphery. Eleven eyes (73.3%) had cone-shaped retinal pigment epithelium elevations on optical coherence tomography, 10 eyes (66.7%) had mild vitritis, and 4 eyes (26.7%) had peripheral curvilinear streak lesions. Three eyes (20%) had choroidal neovascularization. All patients responded well to treatment with systemic immunosuppression, local corticosteroid injections, and/or intravitreal anti-vascular endothelial growth factor injections. CONCLUSION: Multifocal choroiditis may present with peripapillary chorioretinal changes resembling a serpiginous-like choroiditis in addition to the classic findings of patches of atrophy or punched-out scars in the posterior pole or periphery, cone-shaped retinal pigment epithelium elevated on optical coherence tomography and peripheral curvilinear streak lesions.

Injury-Related Pediatric Emergency Department Visits in the First Year of COVID-19.

OBJECTIVES: To describe the epidemiology of pediatric injury-related visits to children's hospital emergency departments (EDs) in the United States during early and later periods of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. METHODS: We conducted a cross-sectional study using the Pediatric Health Information System, an administrative database to identify injury-related ED visits at 41 United States children's hospitals during the SARS-CoV-2 pandemic period (March 15, 2020 to March 14, 2021) and a 3 year comparator period (March 15-March 14, 2017-2020). For these 2 periods, we compared patient characteristics, injury type and severity, primary discharge diagnoses, and disposition, stratified by early (March 15, 2020 to June 30, 2020), middle (July 1, 2020 to October 31, 2020), and late (November 1, 2020 to March 14, 2021) pandemic periods. RESULTS: Overall, ED injury-related visits decreased by 26.6% during the first year of the SARS-CoV-2 pandemic, with the largest decline observed in minor injuries. ED injury-related visits resulting in serious-critical injuries increased across the pandemic (15.9% early, 4.9% middle, 20.6% late). Injury patterns with the sharpest relative declines included superficial injuries (41.7% early) and sprains/strains (62.4% early). Mechanisms of injury with the greatest relative increases included (1) firearms (22.9% early; 42.8% middle; 37% late), (2) pedal cyclists (60.4%; 24.9%; 32.2%), (3) other transportation (20.8%; 25.3%; 17.9%), and (4) suffocation/asphyxiation (21.4%; 20.2%; 28.4%) and injuries because of suicide intent (-16.2%, 19.9%, 21.8%). CONCLUSIONS: Pediatric injury-related ED visits declined in general. However, there was a relative increase in injuries with the highest severity, which warrants further investigation.

Child Opportunity Index and Changes in Pediatric Acute Care Utilization in the COVID-19 Pandemic.

BACKGROUND: Pediatric acute care utilization decreased dramatically during the coronavirus disease 2019 (COVID-19) pandemic. This study examined the association between the Child Opportunity Index (COI), a multidimensional neighborhood measure of childhood opportunity, and changes in acute care utilization at US pediatric hospitals during the COVID-19 pandemic compared with the previous 3 years. METHODS: This observational study used administrative data across 41 US-based pediatric hospitals. Children aged 0 to 17 years with emergency department (ED) encounters during the study period were included. The COVID-19 pandemic time period (March 15, 2020-March 14, 2021) was the primary exposure. The primary outcome was the relative volume drop in ED encounters and observation/inpatient admissions through the ED by COI quintile. RESULTS: Of 12 138 750 encounters, 3 705 320 (30.5%) were among the very low COI quintile. Overall, there was a 46.8% relative volume reduction in the pandemic period compared with the prepandmic period. This drop in volume occurred disproportionately among the very low COI quintile (51.1%) compared with the very high COI quintile (42.8%). The majority of clinical diagnosis groups demonstrated larger relative volume drops among the very low COI quintile. CONCLUSIONS: Acute care utilization decreased the most among children from very low COI neighborhoods, narrowing previously described acute care utilization disparities. Additional study of patient perspectives on health care needs and access during this period is required to understand these changes.

Weekly iron and folic acid supplementation and nutrition education for adolescent girls in Africa and Asia

ASIA & AFRICA. What this article is about: This article outlines the activities carried out by Nutrition International since 2015, providing weekly iron and folic acid (IFA) supplementation to adolescents residing in six separate high-risk countries. Key messages: * Despite regional supply chain challenges and the complications due to the COVID-19 pandemic, weekly programmes were successful in supporting governments to increase IFA supplementation coverage. * There remains a paucity of data on adolescent health outcomes which makes the design, implementation and monitoring of adolescent health projects particularly difficult. * Although school-based delivery models are effective at the population level, reaching adolescents who do not attend school - who are often at higher risk - remains a significant challenge. Governments should prioritise reaching these isolated groups in order to meet public health policy objectives.

Presidential Home Style: Trump in the Era of COVID-19

In Homestyle: House Members in their Districts (1978) Richard Fenno argued that members of Congress utilize different “home styles” when communicating with various segments of their constituency. These tailored, face-to-face interactions help build trust, are essential to the reelection effort, and shape member behavior once in office. In this paper, we reconfigure and extend Fenno’s theory to help explain presidential (in)action in the digital age. By analyzing President Trump’s daily press briefings and social media presence during the early days of the COVID-19 pandemic, we argue that just as a representative’s home style carries over into governance, the same can be said for a president in what we have called “presidential home styles.” We find that the characteristics that made Trump a successful campaigner in the 2016 election are not conducive to effective governance, especially during a crisis.

Using bioinformatic protein sequence similarity to investigate if SARS CoV-2 infection could cause an ocular autoimmune inflammatory reactions?

Although severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infection have emerged globally, findings related to ocular involvement and reported cases are quite limited. Immune reactions against viral infections are closely related to viral and host proteins sequence similarity. Molecular Mimicry has been described for many different viruses; sequence similarities of viral and human tissue proteins may trigger autoimmune reactions after viral infections due to similarities between viral and human structures. With this study, we aimed to investigate the protein sequence similarity of SARS CoV-2 with retinal proteins and retinal pigment epithelium (RPE) surface proteins. Retinal proteins involved in autoimmune retinopathy and retinal pigment epithelium surface transport proteins were analyzed in order to infer their structural similarity to surface glycoprotein (S), nucleocapsid phosphoprotein (N), membrane glycoprotein (M), envelope protein (E), ORF1ab polyprotein (orf1ab) proteins of SARS CoV-2. Protein similarity comparisons, 3D protein structure prediction, T cell epitopes-MHC binding prediction, B cell epitopes-MHC binding prediction and the evaluation of the antigenicity of peptides assessments were performed. The protein sequence analysis was made using the Pairwise Sequence Alignment and the LALIGN program. 3D protein structure estimates were made using Swiss Model with default settings and analyzed with TM-align web server. T-cell epitope identification was performed using the Immune Epitope Database and Analysis (IEDB) resource Tepitool. B cell epitopes based on sequence characteristics of the antigen was performed using amino acid scales and HMMs with the BepiPred 2.0 web server. The predicted peptides/epitopes in terms of antigenicity were examined using the default settings with the VaxiJen v2.0 server. Analyses showed that, there is a meaningful similarities between 6 retinal pigment epithelium surface transport proteins (MRP-4, MRP-5, RFC1, SNAT7, TAUT and MATE) and the SARS CoV-2 E protein. Immunoreactive epitopic sites of these proteins which are similar to protein E epitope can create an immune stimulation on T cytotoxic and T helper cells and 6 of these 9 epitopic sites are also vaxiJen. These result imply that autoimmune cross-reaction is likely between the studied RPE proteins and SARS CoV-2 E protein. The structure of SARS CoV-2, its proteins and immunologic reactions against these proteins remain largely unknown. Understanding the structure of SARS CoV-2 proteins and demonstration of similarity with human proteins are crucial to predict an autoimmune response associated with immunity against host proteins and its clinical manifestations as well as possible adverse effects of vaccination.

Pediatric Emergency Department Visits at US Children's Hospitals During the COVID-19 Pandemic.

BACKGROUND AND OBJECTIVES: The impact of the coronavirus disease 2019 (COVID-19) pandemic on pediatric emergency department (ED) visits is not well characterized. We aimed to describe the epidemiology of pediatric ED visits and resource use during the pandemic. METHODS: We conducted a cross-sectional study using the Pediatric Health Information System for ED visits to 27 US children's hospitals during the COVID-19 pandemic period (March 15, 2020, to August 31, 2020) and a 3-year comparator period (March 15 to August 31, 2017-2019). ED visit rates, patient and visit characteristics, resource use, and ED charges were compared between the time periods. We specifically evaluated changes in low-resource-intensity visits, defined as ED visits that did not result in hospitalization or medication administration and for which no laboratory tests, diagnostic imaging, or procedures were performed. RESULTS: ED visit rates decreased by 45.7% (average 911 026 ED visits over 2017-2019 vs 495 052 visits in 2020) during the pandemic. The largest decrease occurred among visits for respiratory disorders (70.0%). The pandemic was associated with a relative increase in the proportion of visits for children with a chronic condition from 23.7% to 27.8% (P < .001). The proportion of low-resource-intensity visits decreased by 7.0 percentage points, and total charges decreased by 20.0% during the pandemic period. CONCLUSIONS: The COVID-19 pandemic was associated with a marked decrease in pediatric ED visits across a broad range of conditions; however, the proportional decline of poisoning and mental health visits was less pronounced. The impact of decreased visits on patient outcomes warrants further research.