Operational complexity versus design efficiency: challenges of implementing a phase IIa multiple parallel cohort targeted treatment platform trial in advanced breast cancer.

BACKGROUND: Platform trial designs are used increasingly in cancer clinical research and are considered an efficient model for evaluating multiple compounds within a single disease or disease subtype. However, these trial designs can be challenging to operationalise. The use of platform trials in oncology clinical research has increased considerably in recent years as advances in molecular biology enable molecularly defined stratification of patient populations and targeted therapy evaluation. Whereas multiple separate trials may be deemed infeasible, platform designs allow efficient, parallel evaluation of multiple targeted therapies in relatively small biologically defined patient sub-populations with the promise of increased molecular screening efficiency and reduced time for drug evaluation. Whilst the theoretical efficiencies are widely reported, the operational challenges associated with these designs (complexity, cost, regulatory, resource) are not always well understood. MAIN: In this commentary, we describe our practical experience of the implementation and delivery of the UK plasmaMATCH trial, a platform trial in advanced breast cancer, comprising an integrated screening component and multiple parallel downstream mutation-directed therapeutic cohorts. plasmaMATCH reported its primary results within 3 years of opening to recruitment. We reflect on the operational challenges encountered and share lessons learnt to inform the successful conduct of future trials. Key to the success of the plasmaMATCH trial was well co-ordinated stakeholder engagement by an experienced clinical trials unit with expert methodology and trial management expertise, a federated model of clinical leadership, a well-written protocol integrating screening and treatment components and including justification for the chosen structure and intentions for future adaptions, and an integrated funding model with streamlined contractual arrangements across multiple partners. Findings based on our practical experience include the importance of early engagement with the regulators and consideration of a flexible resource infrastructure to allow adequate resource allocation to support concurrent trial activities as adaptions are implemented in parallel to the continued management of patient safety and data quality of the ongoing trial cohorts. CONCLUSION: Platform trial designs allow the efficient reporting of multiple treatment cohorts. Operational challenges can be overcome through multidisciplinary engagement, streamlined contracting processes, rationalised protocol and database design and appropriate resourcing.

Highly Selective Aptamer-Molecularly Imprinted Polymer Hybrids for Recognition of SARS-CoV-2 Spike Protein Variants.

Virus recognition has been driven to the forefront of molecular recognition research due to the COVID-19 pandemic. Development of highly sensitive recognition elements, both natural and synthetic is critical to facing such a global issue. However, as viruses mutate, it is possible for their recognition to wane through changes in the target substrate, which can lead to detection avoidance and increased false negatives. Likewise, the ability to detect specific variants is of great interest for clinical analysis of all viruses. Here, a hybrid aptamer-molecularly imprinted polymer (aptaMIP), that maintains selective recognition for the spike protein template across various mutations, while improving performance over individual aptamer or MIP components (which themselves demonstrate excellent performance). The aptaMIP exhibits an equilibrium dissociation constant of 1.61 nM toward its template which matches or exceeds published examples of imprinting of the spike protein. The work here demonstrates that "fixing" the aptamer within a polymeric scaffold increases its capability to selectivity recognize its original target and points toward a methodology that will allow variant selective molecular recognition with exceptional affinity.

Results of the c-TRAK TN trial: a clinical trial utilising ctDNA mutation tracking to detect molecular residual disease and trigger intervention in patients with moderate and high-risk early stage triple negative breast cancer.

BACKGROUND: Post-treatment detection of circulating tumour DNA (ctDNA) in early-stage triple negative breast cancer (TNBC) patients predicts high risk of relapse. c-TRAK-TN assessed the utility of prospective ctDNA surveillance in TNBC and the activity of pembrolizumab in patients with ctDNA detected (ctDNA+). PATIENTS AND METHODS: c-TRAK-TN, a multi-centre phase II trial, with integrated prospective ctDNA surveillance by digital PCR, enrolled patients with early-stage TNBC and residual disease following neoadjuvant chemotherapy, or, stage II/III with adjuvant chemotherapy. ctDNA surveillance comprised three monthly blood sampling to 12 months (18 months if samples were missed due to COVID), and ctDNA+ patients were randomised 2:1; intervention:observation. ctDNA results were blinded unless patients were allocated to intervention, when staging scans were done and those free of recurrence were offered pembrolizumab. A protocol amendment (16/09/2020) closed the observation group; all subsequent ctDNA+ patients were allocated to intervention. Co-primary endpoints were i) ctDNA detection rate ii) sustained ctDNA clearance rate on pembrolizumab (NCT03145961). RESULTS: 208 patients registered between 30/01/18 - 06/12/19, 185 had tumour sequenced, 171 (92·4%) had trackable mutations, and 161 entered ctDNA surveillance. Rate of ctDNA detection by 12 months was 27·3% (44/161,95%CI:20·6-34·9). Seven patients relapsed without prior ctDNA detection. 45 patients entered the therapeutic component (intervention n=31; observation n=14; 1 observation patient was re-allocated to intervention following protocol amendment). Of patients allocated intervention, 72% (23/32) had metastases on staging at time of ctDNA+, and 4 patients declined pembrolizumab. Of the five patients who commenced pembrolizumab, none achieved sustained ctDNA clearance. CONCLUSION: c-TRAK-TN is the first prospective study to assess whether ctDNA assays have clinical utility in guiding therapy in TNBC. Patients had a high rate of metastatic disease on ctDNA detection. Findings have implications for future trial design, emphasising the importance of commencing ctDNA testing early, with more sensitive and/or frequent ctDNA testing regimes.

The effect of COVID‐19 restrictions on sleep in individuals with cognitive impairment and their carers

Background COVID‐19 restrictions have been associated with apathy, anxiety and depression in individuals with cognitive impairment1‐3 and increased stress in caregivers4. But despite links between these restrictions and sleep impairment in the general population5, effects on sleep in this cohort are not widely reported. Here we determine overall sleep quality in these populations during the first UK lockdown, how this changed over time and explanatory factors associated with longitudinal change. Method Cognitively impaired group (CIG), carer group (CG) and older healthy participants completed online self‐reported validated questionnaires (PSQI, GAD‐7, PHQ‐8 and DBAS) alongside bespoke questions comprising the ‘SleepQuest' study at two comparable stringent lockdown periods within the UK [t1 – (29/4/20‐13/5/20) and t2 – (5/11/20‐2/12/20)]. Analysis utilised paired t‐tests with Bonferroni correction with 95% confidence intervals. Multivariable linear regression evaluated predictive factors. Result Within the CIG, baseline n = 79 [MCI, n = 33;AD, n = 19;Other, n = 27], mean age 68.7±9.7, with follow‐up data for n = 37. Within the CG, baseline n = 183, mean age 59.4±11.1, follow‐up n = 116. Overall sleep quality by PSQI Total was impaired at baseline (CIG = 7.8±4.3;CG = 7.9±4.0) compared to 6.6±3.6 for older healthy participants (n = 2354). There was a trend towards sleep quality deterioration from t1‐t2 in both groups (CIG ‐ Mean diff = 0.84, CI[‐0.20,1.84], p = 0.111;CG ‐ Mean diff = 0.51, CI[‐0.01,1.02], p = 0.053). PSQI subcomponent analysis revealed increasing sleep medication use in both groups (CIG – Mean diff = 0.83, CI[0.36,1.32], pcorr = 0.007;CG – Mean diff = 0.99, CI[0.81,1.17], pcorr<0.001). However, levels of daytime dysfunction improved in both groups (CIG – Mean diff = ‐0.54, CI[‐0.87,‐0.21], pcorr = 0.014;CG – Mean diff = ‐0.46, CI[‐0.61,‐0.30], pcorr<0.001). Within the CIG, affective and behavioural factors at t1 did not predict sleep at t2. Within carers, increased anxiety (total GAD‐7) at t1 predicted worse sleep at t2 (Est[normalised PSQI total] = 0.22, SE = 0.10, p = 0.041). Conclusion Overall sleep quality for individuals with cognitive impairment and their carers was poor at baseline and trended towards further deterioration, although daytime function improved. Within this cohort, potential compensatory strategies included increased use of sleep medication (associated with adverse outcomes). Given impaired sleep may accelerate progression of dementia neuropathology6,7, it is important to understand and ameliorate the impact of prolonged socio‐political stressors on people with dementia and their carers.

COVID-19 Trials: Who Participates and Who Benefits?

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has disproportionately afflicted vulnerable populations. Older adults, particularly residents of nursing facilities, represent a small percentage of the population but account for 40% of mortality from COVID-19 in the United States. Racial and ethnic minority individuals, particularly Black, Hispanic, and Indigenous Americans have experienced higher rates of infection and death than the White population. Although there has been an unprecedented explosion of clinical trials to examine potential therapies, participation by members of these vulnerable communities is crucial to obtaining data generalizable to those communities. METHODS: We undertook an open-label, factorial randomized clinical trial examining hydroxychloroquine and/or azithromycin for hospitalized patients. RESULTS: Of 53 screened patients, 11 (21%) were enrolled. Ten percent (3/31) of Black patients were enrolled, 33% (7/21) of White patients, and 50% (6/12) of Hispanic patients. Forty-seven percent (25/53) of patients declined participation despite eligibility; 58%(18/31) of Black patients declined participation. Forty percent (21/53) of screened patients were from a nursing facility and 10% (2/21) were enrolled. Enrolled patients had fewer comorbidities than nonenrolled patients: median modified Charlson comorbidity score 2.0 (interquartile range 0-2.5), versus 4.0 (interquartile range 2-6) for nonenrolled patients (P = 0.006). The limitations of the study were the low participation rate and the multiple treatment trials concurrently recruiting at our institution. CONCLUSIONS: The high rate of nonparticipation in our trial of nursing facility residents and Black people emphasizes the concern that clinical trials for therapeutics may not target key populations with high mortality rates.

Landscape of coronavirus disease 2019 clinical trials: New frontiers and challenges.

BACKGROUND/AIM: The number of coronavirus disease 2019 deaths and cases continues to increase globally. Novel therapies are urgently needed to treat patients with coronavirus disease 2019. We sought to provide a critical review of trials designed during the coronavirus disease 2019 pandemic. Our primary goal was to provide a critical review of the landscape of clinical trials designed to address the coronavirus disease 2019 pandemic. Specifically, we were interested in assessing the design of phase II/III and phase III interventional trials. METHODS: We utilized the ClinicalTrials.gov database to include trials registered between 1 December 2019 and 11 April 2021 to survey the current landscape of clinical trials for coronavirus disease 2019. Variables extracted included: National Clinical Trial number, title, location, sponsor, study type, start date, completion date, gender group, age group, primary outcome, secondary outcome, overall status, and associated references. RESULTS: About 57% of studies were interventional, 14.5% were phase III trials, and the majority of the therapeutic trials included hospitalized patients. There were 52 primary composite outcomes and 285 unique interventions spanning 10 drug classes. The outcomes, disease severity, and comparators varied substantially across trials, and the trials were often too small to be definitive. CONCLUSION: These findings are relevant as we strongly advocate for global coordination of efforts through the use of common platforms that enable harmonizing of endpoints, collection of common key variables and clear definition of disease severity to have clinically meaningful results from clinical trials.

Evaluation of good grief festival, a public engagement initiative on grief and bereavement

BackgroundGood Grief Festival was planned as a face-to-face festival to engage the public in multi-disciplinary research about grief and bereavement. Due to COVID-19, the festival was held online over 3 days in October 2020.AimTo evaluate the festival’s reach and impact.MethodsA pre/post evaluation was conducted via online surveys. Pre-festival surveys assessed reasons for attending and attitudes to bereavement across 4 items (being scared of saying the wrong thing, avoiding talking to someone bereaved, knowing what to do if someone bereaved was having trouble, knowing what kind of help/support to offer). Post-festival surveys evaluated audience experiences and the 4 attitude items.Results8500+ people attended, with most attending 2–5 events. Pre-festival survey participants (n=3785) were majority women (91%) and White (91%). 9% were from Black or minoritized ethnic communities. 14% were age ≥65 years, 16% age ≤34 years. 44% were members of the public. A third had been bereaved in the last year;6% had never been bereaved. People attended to learn about grief/bereavement (77%), be inspired (52%) and feel part of a community (49%). Post-festival participants (n=685) reported feeling part of a community (68%), learning about grief/bereavement (68%) and being inspired (66%). 89% rated the festival as excellent/very good, with a higher rating associated with attending a greater number of events. 75% agreed that through attending they felt more confident talking about grief. Post-festival attitudes were significantly higher across all 4 items (P<0.001). Free-text data showed appreciation e.g. for the online format, connection in the context of lockdown and ethnic diversity in speakers. Suggestions included improving registration, more interactive/arts-based events and reducing the volume of content.ConclusionGood Grief Festival was successful at reaching a large public audience, with data indicating benefit in terms of engagement and confidence. The evaluation was critical in shaping future events.

Age-Related Changes in the Nasopharyngeal Microbiome Are Associated With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection and Symptoms Among Children, Adolescents, and Young Adults.

BACKGROUND: Children are less susceptible to SARS-CoV-2 infection and typically have milder illness courses than adults, but the factors underlying these age-associated differences are not well understood. The upper respiratory microbiome undergoes substantial shifts during childhood and is increasingly recognized to influence host defense against respiratory pathogens. Thus, we sought to identify upper respiratory microbiome features associated with SARS-CoV-2 infection susceptibility and illness severity. METHODS: We collected clinical data and nasopharyngeal swabs from 285 children, adolescents, and young adults (<21 years) with documented SARS-CoV-2 exposure. We used 16S ribosomal RNA gene sequencing to characterize the nasopharyngeal microbiome and evaluated for age-adjusted associations between microbiome characteristics and SARS-CoV-2 infection status and respiratory symptoms. RESULTS: Nasopharyngeal microbiome composition varied with age (PERMANOVA, P < .001; R2 = 0.06) and between SARS-CoV-2-infected individuals with and without respiratory symptoms (PERMANOVA, P  = .002; R2 = 0.009). SARS-CoV-2-infected participants with Corynebacterium/Dolosigranulum-dominant microbiome profiles were less likely to have respiratory symptoms than infected participants with other nasopharyngeal microbiome profiles (OR: .38; 95% CI: .18-.81). Using generalized joint attributed modeling, we identified 9 bacterial taxa associated with SARS-CoV-2 infection and 6 taxa differentially abundant among SARS-CoV-2-infected participants with respiratory symptoms; the magnitude of these associations was strongly influenced by age. CONCLUSIONS: We identified interactive relationships between age and specific nasopharyngeal microbiome features that are associated with SARS-CoV-2 infection susceptibility and symptoms in children, adolescents, and young adults. Our data suggest that the upper respiratory microbiome may be a mechanism by which age influences SARS-CoV-2 susceptibility and illness severity.

Impact of COVID-19 pandemic on pharmacist-led allergy assessments and penicillin skin testing.

Allergy assessments and penicillin skin testing are associated with reductions in high-Clostridioides difficile infection (CDI)-risk antibiotic use and lower hospital-acquired CDI rates; however, these activities require substantial personnel and resource allocation. Recently, many antimicrobial stewardship programs' (ASPs) focus shifted towards supporting the COVID-19 pandemic response. We evaluated the impact of the COVID-19 pandemic on a pharmacist-led allergy assessment and penicillin skin testing program. Patients undergoing allergy assessment and/or penicillin skin testing (PST) from 1 January 2017 through 30 April 2021 were included for review. Monthly PST and allergy assessment rates were calculated and defined as the number of PSTs or allergy assessments per 1000 unique patient encounters for each month, respectively. The study used interrupted time series regression to assess potential level and slope changes in allergy assessments and PSTs during the pandemic. 200 058 total inpatient encounters by 188 867 unique patients occurred during the study period. ASP performed 918 allergy assessments and 204 PSTs. The local onset of the SARS-CoV-2 pandemic during March 2020 was associated with significant level reductions in allergy assessments and PSTs. Additional responsibilities added to the ASP team during the COVID-19 pandemic limited the ability to perform core antimicrobial stewardship activities with proven patient care benefits.

Gatekeeper training for vendors to reduce pesticide self-poisoning in rural South Asia: a study protocol for a stepped-wedge cluster randomised controlled trial.

INTRODUCTION: Pesticide self-poisoning kills an estimated 110 000-168 000 people worldwide annually. Data from South Asia indicate that in 15%-20% of attempted suicides and 30%-50% of completed suicides involving pesticides these are purchased shortly beforehand for this purpose. Individuals who are intoxicated with alcohol and/or non-farmers represent 72% of such customers. We have developed a 'gatekeeper' training programme for vendors to enable them to identify individuals at high risk of self-poisoning (gatekeeper function) and prevent such individuals from accessing pesticides (means restriction). The primary aim of the study is to evaluate the effectiveness of the gatekeeper intervention in preventing pesticide self-poisoning in Sri Lanka. Other aims are to identify method substitution and to assess the cost and cost-effectiveness of the intervention. METHODS AND ANALYSIS: A stepped-wedge cluster randomised trial of a gatekeeper intervention is being conducted in rural Sri Lanka with a population of approximately 2.7 million. The gatekeeper intervention is being introduced into 70 administrative divisions in random order at each of 30 steps over a 40-month period. The primary outcome is the number of pesticide self-poisoning cases identified from surveillance of hospitals and police stations. Secondary outcomes include: number of self-poisoning cases using pesticides purchased within the previous 24 hours, total number of all forms of self-harm and suicides. Intervention effectiveness will be estimated by comparing outcome measures between the pretraining and post-training periods across the divisions in the study area. The original study protocol has been adapted as necessary in light of the impact of the COVID-19. ETHICS AND DISSEMINATION: The Ethical Review Committee of the Faculty of Medicine and Allied Sciences, Rajarata University, Sri Lanka (ERC/2018/30), and the ACCORD Medical Research Ethics Committee, Edinburgh University (18-HV-053) approved the study. Results will be disseminated in scientific peer-reviewed journals. TRIAL REGISTRATION NUMBER: SLCTR/2019/006, U1111-1220-8046.

An Engineered Cytidine Deaminase for Biocatalytic Production of a Key Intermediate of the Covid-19 Antiviral Molnupiravir.

The Covid-19 pandemic highlights the urgent need for cost-effective processes to rapidly manufacture antiviral drugs at scale. Here we report a concise biocatalytic process for Molnupiravir, a nucleoside analogue recently approved as an orally available treatment for SARS-CoV-2. Key to the success of this process was the development of an efficient biocatalyst for the production of N-hydroxy-cytidine through evolutionary adaption of the hydrolytic enzyme cytidine deaminase. This engineered biocatalyst performs >85 000 turnovers in less than 3 h, operates at 180 g/L substrate loading, and benefits from in situ crystallization of the N-hydroxy-cytidine product (85% yield), which can be converted to Molnupiravir by a selective 5'-acylation using Novozym 435.

Functional antibody and T cell immunity following SARS-CoV-2 infection, including by variants of concern, in patients with cancer: the CAPTURE study.

Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study, integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2 positive, 94 were symptomatic and 2 died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies and 82% had neutralizing antibodies against wild type SARS-CoV-2, whereas neutralizing antibody titers against the Alpha, Beta and Delta variants were substantially reduced. S1-reactive antibody levels decreased in 13% of patients, whereas neutralizing antibody titers remained stable for up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment specific, but presented compensatory cellular responses, further supported by clinical recovery in all but one patient. Overall, these findings advance the understanding of the nature and duration of the immune response to SARS-CoV-2 in patients with cancer.

Risk factors for mortality and progression to severe COVID-19 disease in the Southeast region in the United States: A report from the SEUS Study Group.

OBJECTIVE: Identify risk factors that could increase progression to severe disease and mortality in hospitalized SARS-CoV-2 patients in the Southeast region of the United States. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, retrospective cohort including 502 adults hospitalized with laboratory-confirmed COVID-19 between March 1, 2020, and May 8, 2020 within 1 of 15 participating hospitals in 5 health systems across 5 states in the Southeast United States. METHODS: The study objectives were to identify risk factors that could increase progression to hospital mortality and severe disease (defined as a composite of intensive care unit admission or requirement of mechanical ventilation) in hospitalized SARS-CoV-2 patients in the Southeast United States. RESULTS: In total, 502 patients were included, and 476 of 502 (95%) had clinically evaluable outcomes. The hospital mortality rate was 16% (76 of 476); 35% (177 of 502) required ICU admission and 18% (91 of 502) required mechanical ventilation. By both univariate and adjusted multivariate analyses, hospital mortality was independently associated with age (adjusted odds ratio [aOR], 2.03 for each decade increase; 95% confidence interval [CI], 1.56--2.69), male sex (aOR, 2.44; 95% CI, 1.34-4.59), and cardiovascular disease (aOR, 2.16; 95% CI, 1.15-4.09). As with mortality, risk of severe disease was independently associated with age (aOR, 1.17 for each decade increase; 95% CI, 1.00-1.37), male sex (aOR, 2.34; 95% CI, 1.54-3.60), and cardiovascular disease (aOR, 1.77; 95% CI, 1.09-2.85). CONCLUSIONS: In an adjusted multivariate analysis, advanced age, male sex, and cardiovascular disease increased risk of severe disease and mortality in patients with COVID-19 in the Southeast United States. In-hospital mortality risk doubled with each subsequent decade of life.

Sleep quality, mental health, and circadian rhythms during COVID lockdown – results from the SleepQuest study

IntroductionBehavioural responses to COVID-19 lockdown will define the long-term impact of psychological stressors on sleep and brain health. Here, we tease apart factors that help protect against sleep disturbance. We capitalise on the unique restrictions during COVID-19 to understand how time of day of daylight exposure and outside exercise interact with chronotype and sleep quality.MethodsParticipants completed our online ‘SleepQuest’ Study between 29th April 2020- 13th May 2020 and were followed up between 5th November 2020 -2nd December 2020. The SleepQuest survey comprised a set of validated questionnaires probing sleep quality, depression, anxiety, and attitudes towards sleep alongside bespoke questions on the effect of COVID-19 lockdown on sleep, time spent outside and exercising and self-help sleep measures.Results3474 people from the UK (median age 62, range 18-91) completed the baseline data with 2781 participants followed up. Results showed sleep quality was negatively affected by the first UK lockdown restriction [mean PSQI at baseline 8.12 (2.92)] however from baseline to follow up, sleep quality improved (mean PSQI Difference=2.21;95% CI=[2.12,2.33.]) Factors that predicted poor prolonged sleep quality were baseline sleep quality (P<0.001), anxiety (P<0.001) and attitudes towards sleep (P<0.01). Better sleep quality was associated with going outside and exercising earlier, rather than later in the day. However, the benefit of being outside early is driven by improved sleep in ‘owl’ (p=0.0002) and not ‘lark’ (p=0.27) chronotype, whereas the benefit of early exercise (inside or outside) did not depend on chronotype.DiscussionWe have provided evidence to suggest anxiety and dysfunctional attitudes towards sleep predicted poorer prolonged sleep quality. Defining the interaction between chronotype, mental health and behaviour will be critical for targeted lifestyle adaptations to protect brain health through current and future crises.

Severe Acute Respiratory Syndrome Coronavirus 2 Infections Among Children in the Biospecimens from Respiratory Virus-Exposed Kids (BRAVE Kids) Study.

BACKGROUND: Child with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection typically have mild symptoms that do not require medical attention, leaving a gap in our understanding of the spectrum of SARS-CoV-2-related illnesses that the viruses causes in children. METHODS: We conducted a prospective cohort study of children and adolescents (aged <21 years) with a SARS-CoV-2-infected close contact. We collected nasopharyngeal or nasal swabs at enrollment and tested for SARS-CoV-2 using a real-time polymerase chain reaction assay. RESULTS: Of 382 children, 293 (77%) were SARS-CoV-2-infected. SARS-CoV-2-infected children were more likely to be Hispanic (P < .0001), less likely to have asthma (P = .005), and more likely to have an infected sibling contact (P = .001) than uninfected children. Children aged 6-13 years were frequently asymptomatic (39%) and had respiratory symptoms less often than younger children (29% vs 48%; P = .01) or adolescents (29% vs 60%; P < .001). Compared with children aged 6-13 years, adolescents more frequently reported influenza-like (61% vs 39%; P < .001) , and gastrointestinal (27% vs 9%; P = .002), and sensory symptoms (42% vs 9%; P < .0001) and had more prolonged illnesses (median [interquartile range] duration: 7 [4-12] vs 4 [3-8] days; P = 0.01). Despite the age-related variability in symptoms, wWe found no difference in nasopharyngeal viral load by age or between symptomatic and asymptomatic children. CONCLUSIONS: Hispanic ethnicity and an infected sibling close contact are associated with increased SARS-CoV-2 infection risk among children, while asthma is associated with decreased risk. Age-related differences in clinical manifestations of SARS-CoV-2 infection must be considered when evaluating children for coronavirus disease 2019 and in developing screening strategies for schools and childcare settings.

Social Disadvantage, Politics, and Severe Acute Respiratory Syndrome Coronavirus 2 Trends: A County-level Analysis of United States Data.

BACKGROUND: Understanding the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for public health control efforts. Social, demographic, and political characteristics at the United States (US) county level might be associated with changes in SARS-CoV-2 case incidence. METHODS: We conducted a retrospective analysis of the relationship between the change in reported SARS-CoV-2 case counts at the US county level during 1 June-30 June 2020 and social, demographic, and political characteristics of the county. RESULTS: Of 3142 US counties, 1023 were included in the analysis: 678 (66.3%) had increasing and 345 (33.7%) nonincreasing SARS-CoV-2 case counts between 1 June and 30 June 2020. In bivariate analysis, counties with increasing case counts had a significantly higher Social Deprivation Index (median, 48 [interquartile range {IQR}, 24-72]) than counties with nonincreasing case counts (median, 40 [IQR, 19-66]; P = .009). Counties with increasing case counts were significantly more likely to be metropolitan areas of 250 000-1 million population (P < .001), to have a higher percentage of black residents (9% vs 6%; P = .013), and to have voted for the Republican presidential candidate in 2016 by a ≥10-point margin (P = .044). In the multivariable model, metropolitan areas of 250 000-1 million population, higher percentage of black residents, and a ≥10-point Republican victory were independently associated with increasing case counts. CONCLUSIONS: Increasing case counts of SARS-CoV-2 in the US during June 2020 were associated with a combination of sociodemographic and political factors. Addressing social disadvantage and differential belief systems that may correspond with political alignment will play a critical role in pandemic control.

Asymptomatic or mild symptomatic SARS-CoV-2 infection elicits durable neutralizing antibody responses in children and adolescents.

As SARS-CoV-2 continues to spread globally, questions have emerged regarding the strength and durability of immune responses in specific populations. In this study, we evaluated humoral immune responses in 69 children and adolescents with asymptomatic or mild symptomatic SARS-CoV-2 infection. We detected robust IgM, IgG, and IgA antibody responses to a broad array of SARS-CoV-2 antigens at the time of acute infection and 2 and 4 months after acute infection in all participants. Notably, these antibody responses were associated with virus-neutralizing activity that was still detectable 4 months after acute infection in 94% of children. Moreover, antibody responses and neutralizing activity in sera from children and adolescents were comparable or superior to those observed in sera from 24 adults with mild symptomatic infection. Taken together, these findings indicate that children and adolescents with mild or asymptomatic SARS-CoV-2 infection generate robust and durable humoral immune responses that can likely contribute to protection from reinfection.

Optimizing Stony Coral Tissue Loss Disease (SCTLD) Intervention Treatments on Montastraea cavernosa in an Endemic Zone

Stony coral tissue loss disease (SCTLD) has persisted since 2014 in the Southeast Florida Coral Reef Ecosystem Conservation Area (ECA) where it was first discovered. Most of the highly susceptible corals have perished, leaving Montastraea cavernosa as the most abundant reef-building species with high SCTLD prevalence. Disease interventions (DI) have been conducted throughout Florida’s Coral Reef to save the remaining corals and reduce the disease prevalence with varying degrees of success. The two main treatments were chlorinated (Chl) epoxy and an antibiotic paste. The antibiotic paste was highly effective in the Florida Keys, but its effectiveness in the Coral ECA was questionable. Therefore, we compared the effectiveness of the antibiotic paste and Chl epoxy treatments on M. cavernosa to optimize DI efforts on this species in the Coral ECA. Significant differences were found between the treatment materials and applications related to the proportion of quiesced lesions and corals where antibiotic paste (91.2% success) outperformed Chl epoxy (20% success). By day 351, 50.6% of the antibiotic paste disease-break tissue was fully healed compared to 2.2% of the total Chl epoxy-filled disease-break area. During the study, new lesions occurred on previously treated colonies, as well as colonies not previously treated and new lesion rates varied through time, indicating revisitation is necessary to eliminate disease. Most margin treatments failed within the first nine days, however, most disease-breaks failed before 44 days. Considering the high treatment success of the antibiotic paste and the conditional variation of new lesion rates, about one month is a good practical re-visitation time for retreating failures and any new lesions. DI using antibiotic paste is currently the most effective way to intervene the SCTLD epidemic, but this is only effective as a stopgap measure while the larger causative agents are identified and remediated. Conducting DI at a reef-scape scale is time consuming and requires extensive person-power and resources, making it very expensive. But this expense pales in comparison to the current cost to restore the diversity and live tissue saved with DI. This method comes with the risk of introducing antibiotics into reef environments, which may have unintended outcomes.

Racial, Ethnic, and Geographic Disparities in Novel Coronavirus (Severe Acute Respiratory Syndrome Coronavirus 2) Test Positivity in North Carolina.

BACKGROUND: Emerging evidence suggests that black and Hispanic communities in the United States are disproportionately affected by coronavirus disease 2019 (COVID-19). A complex interplay of socioeconomic and healthcare disparities likely contribute to disproportionate COVID-19 risk. METHODS: We conducted a geospatial analysis to determine whether individual- and neighborhood-level attributes predict local odds of testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We analyzed 29 138 SARS-CoV-2 tests within the 6-county catchment area for Duke University Health System from March to June 2020. We used generalized additive models to analyze the spatial distribution of SARS-CoV-2 positivity. Adjusted models included individual-level age, gender, and race, as well as neighborhood-level Area Deprivation Index, population density, demographic composition, and household size. RESULTS: Our dataset included 27 099 negative and 2039 positive unique SARS-CoV-2 tests. The odds of a positive SARS-CoV-2 test were higher for males (odds ratio [OR], 1.43; 95% credible interval [CI], 1.30-1.58), blacks (OR, 1.47; 95% CI, 1.27-1.70), and Hispanics (OR, 4.25; 955 CI, 3.55-5.12). Among neighborhood-level predictors, percentage of black population (OR, 1.14; 95% CI, 1.05-1.25), and percentage Hispanic population (OR, 1.23; 95% CI, 1.07-1.41) also influenced the odds of a positive SARS-CoV-2 test. Population density, average household size, and Area Deprivation Index were not associated with SARS-CoV-2 test results after adjusting for race. CONCLUSIONS: The odds of testing positive for SARS-CoV-2 were higher for both black and Hispanic individuals, as well as within neighborhoods with a higher proportion of black or Hispanic residents-confirming that black and Hispanic communities are disproportionately affected by SARS-CoV-2.