DengueSeq: a pan-serotype whole genome amplicon sequencing protocol for dengue virus.

BACKGROUND: The increasing burden of dengue virus on public health due to more explosive and frequent outbreaks highlights the need for improved surveillance and control. Genomic surveillance of dengue virus not only provides important insights into the emergence and spread of genetically diverse serotypes and genotypes, but it is also critical to monitor the effectiveness of newly implemented control strategies. Here, we present DengueSeq, an amplicon sequencing protocol, which enables whole-genome sequencing of all four dengue virus serotypes. RESULTS: We developed primer schemes for the four dengue virus serotypes, which can be combined into a pan-serotype approach. We validated both approaches using genetically diverse virus stocks and clinical specimens that contained a range of virus copies. High genome coverage (>95%) was achieved for all genotypes, except DENV2 (genotype VI) and DENV 4 (genotype IV) sylvatics, with similar performance of the serotype-specific and pan-serotype approaches. The limit of detection to reach 70% coverage was 10-100 RNA copies/µL for all four serotypes, which is similar to other commonly used primer schemes. DengueSeq facilitates the sequencing of samples without known serotypes, allows the detection of multiple serotypes in the same sample, and can be used with a variety of library prep kits and sequencing instruments. CONCLUSIONS: DengueSeq was systematically evaluated with virus stocks and clinical specimens spanning the genetic diversity within each of the four dengue virus serotypes. The primer schemes can be plugged into existing amplicon sequencing workflows to facilitate the global need for expanded dengue virus genomic surveillance.

Introduction and Spread of Dengue Virus 3, Florida, USA, May 2022-April 2023.

During May 2022-April 2023, dengue virus serotype 3 was identified among 601 travel-associated and 61 locally acquired dengue cases in Florida, USA. All 203 sequenced genomes belonged to the same genotype III lineage and revealed potential transmission chains in which most locally acquired cases occurred shortly after introduction, with little sustained transmission.

Genomic epidemiology reveals multiple introductions of Zika virus into the United States.

Zika virus (ZIKV) is causing an unprecedented epidemic linked to severe congenital abnormalities. In July 2016, mosquito-borne ZIKV transmission was reported in the continental United States; since then, hundreds of locally acquired infections have been reported in Florida. To gain insights into the timing, source, and likely route(s) of ZIKV introduction, we tracked the virus from its first detection in Florida by sequencing ZIKV genomes from infected patients and Aedes aegypti mosquitoes. We show that at least 4 introductions, but potentially as many as 40, contributed to the outbreak in Florida and that local transmission is likely to have started in the spring of 2016-several months before its initial detection. By analysing surveillance and genetic data, we show that ZIKV moved among transmission zones in Miami. Our analyses show that most introductions were linked to the Caribbean, a finding corroborated by the high incidence rates and traffic volumes from the region into the Miami area. Our study provides an understanding of how ZIKV initiates transmission in new regions.

Zika virus evolution and spread in the Americas.

Although the recent Zika virus (ZIKV) epidemic in the Americas and its link to birth defects have attracted a great deal of attention, much remains unknown about ZIKV disease epidemiology and ZIKV evolution, in part owing to a lack of genomic data. Here we address this gap in knowledge by using multiple sequencing approaches to generate 110 ZIKV genomes from clinical and mosquito samples from 10 countries and territories, greatly expanding the observed viral genetic diversity from this outbreak. We analysed the timing and patterns of introductions into distinct geographic regions; our phylogenetic evidence suggests rapid expansion of the outbreak in Brazil and multiple introductions of outbreak strains into Puerto Rico, Honduras, Colombia, other Caribbean islands, and the continental United States. We find that ZIKV circulated undetected in multiple regions for many months before the first locally transmitted cases were confirmed, highlighting the importance of surveillance of viral infections. We identify mutations with possible functional implications for ZIKV biology and pathogenesis, as well as those that might be relevant to the effectiveness of diagnostic tests.

Omadacycline for a Carbapenem-Resistant Enterobacter cloacae-Associated Wound Infection.

Introduction: Carbapenem-resistant Enterobacteriaceae (CRE) are problematic pathogens because infections caused by these organisms are associated with significant morbidity and mortality. These organisms often harbor multiple resistance mechanisms, which makes it difficult to treat their associated infections. Treatment typically consists of intravenous antibiotics that are selected based on the specific susceptibility pattern for the pathogen. Data on the use of oral antibiotics for the treatment of infections caused by CRE are sparse. Case Presentation: In this case, a 62-year-old female presented with a chronic left leg wound infection. She previously underwent surgical debridement and skin grafting, which were unsuccessful. She was initially prescribed minocycline for the infection, but the wound got re-infected. At this time, the wound had significant surrounding erythema, drainage, and slough. A wound culture was obtained and demonstrated growth of carbapenem-resistant Enterobacter cloacae and methicillin-resistant Staphylococcus aureus. The patient was initiated on oral omadacycline, and she responded with resolution of the cellulitis and wound drainage. Conclusion: This case demonstrates that omadacycline may be beneficial as an oral medication for the treatment of complicated acute bacterial skin and skin structure infections caused by carbapenem-resistant Enterobacter cloacae.

Characteristics Associated With Household Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Ontario, Canada: A Cohort Study.

BACKGROUND: Within-household transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been identified as one of the main sources of spread of coronavirus disease 2019 (COVID-19) after lockdown restrictions and self-isolation guidelines are implemented. Secondary attack rates among household contacts are estimated to be 5-10 times higher than among non-household contacts, but it is unclear which individuals are more prone to transmit infection within their households. METHODS: Using address matching, a cohort was assembled of all individuals with laboratory-confirmed COVID-19 residing in private households in Ontario, Canada. Descriptive analyses were performed to compare characteristics of cases in households that experienced secondary transmission versus those that did not. Logistic regression models were fit to determine index case characteristics and neighborhood characteristics associated with transmission. RESULTS: Between January and July 2020, there were 26 714 individuals with COVID-19 residing in 21 226 households. Longer testing delays (≥5 vs 0 days; odds ratio [OR], 3.02; 95% confidence interval [CI], 2.53-3.60) and male gender (OR, 1.28; 95% CI, 1.18-1.38) were associated with greater odds of household secondary transmission, while being a healthcare worker (OR, .56; 95% CI, .50-.62) was associated with lower odds of transmission. Neighborhoods with larger average family size and a higher proportion of households with multiple persons per room were also associated with greater odds of transmission. CONCLUSIONS: It is important for individuals to get tested for SARS-CoV-2 infection as soon as symptoms appear, and to isolate away from household contacts; this is particularly important in neighborhoods with large family sizes and/or crowded households.

A cohort study of men infected with COVID-19 for presence of SARS-CoV-2 virus in their semen.

INTRODUCTION: Whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be detected in semen and transmitted sexually is a vital question that has, thus far, been inconclusive. Prior studies, with limited numbers, have included men in various stages of infection with most in the recovery phase of the illness. The timing of test results and severity of illness has made recruiting study participants a significant challenge. Our pilot study will examine semen from men with a recent diagnosis of COVID-19 as well as those in the convalescent phase to determine if SARS-CoV-2 can be detected and its relationship, if any, with the severity of the disease. METHODS: Eighteen men with a median age of 32 (range, 24-57) who tested positive for COVID-19 by rt-PCR analysis were enrolled and provided a semen sample. The study group demonstrated symptoms of COVID-19 ranging from asymptomatic to moderate and none required hospitalization. Samples were subjected to viral RNA extraction and then processed by real-time RT-PCR using the US Centers for Disease Control and Prevention (CDC, USA) panel of 2019-Novel Coronavirus (2019-nCoV) primers and probes to detect the presence of SARS-CoV-2 RNA. RESULTS: Length of time from diagnosis to providing a specimen ranged from 1 to 28 days (median, 6 days). Fifteen participants were symptomatic and three were asymptomatic, including recovering men, at the time of semen collection. No SARS-CoV-2 was detected in any of the semen samples. CONCLUSION: Based on these preliminary results and consistent with prior findings, we suggest SARS-CoV-2 is not present in semen during the acute or convalescent phase of COVID-19.

Urban green space and the risks of dementia and stroke.

INTRODUCTION: It is unknown whether urban green space is associated with reduced risk of major neurological conditions, especially dementia and stroke. METHODS: Retrospective, population-based cohorts were created for each study outcome, including 1.7 and 4.3 million adults in Ontario, Canada for dementia and stroke, respectively. Residential green space was quantified using the satellite-derived Normalized Difference Vegetation Index. Incidence was ascertained using health administrative data with validated algorithms. Mixed-effects Cox models were used to estimate hazard ratios per interquartile range increase in green space exposure. RESULTS: Between 2001 and 2013, 219,013 individuals were diagnosed with dementia and 89,958 had a stroke. The hazard ratio per interquartile range increase in green space was 0.97 (95% CI: 0.96-0.98) for dementia and 0.96 (0.95-0.98) for stroke. Estimates remained generally consistent in sensitivity analyses. DISCUSSION: Increased exposure to urban green space was associated with reduced incidence of dementia and stroke. To our knowledge, this is the first population-based cohort study to assess these relationships.

Ambient air pollution and incidence of early-onset paediatric type 1 diabetes: A retrospective population-based cohort study.

BACKGROUND: Studies have reported increasing incidence rates of paediatric diabetes, especially among those aged 0-5 years. Epidemiological evidence linking ambient air pollution to paediatric diabetes remains mixed. OBJECTIVE: This study investigated the association between maternal and early-life exposures to common air pollutants (NO2, PM2.5, O3, and oxidant capacity [Ox; the redox-weighted average of O3 and NO2]) and the incidence of paediatric diabetes in children up to 6 years of age. METHODS: All registered singleton births in Ontario, Ca nada occurring between April 1st, 2006 and March 31st, 2012 were included through linkage from health administrative data. Monthly exposures to NO2, PM2.5, O3, and Ox were estimated across trimesters, the entire pregnancy period and during childhood. Random effects Cox proportional hazards models were used to assess the relationships with paediatric diabetes incidence while controlling for important covariates. We also modelled the shape of concentration-response (CR) relationships. RESULTS: There were 1094 children out of a cohort of 754,698 diagnosed with diabetes before the age of six. O3 exposures during the first trimester of pregnancy were associated with paediatric diabetes incidence (hazard ratio (HR) per interquartile (IQR) increase = 2.00, 95% CI: 1.04-3.86). The CR relationship between O3 during the first trimester and paediatric diabetes incidence appeared to have a risk threshold, in which there was little-to-no risk below 25 ppb of O3, while above this level risk increased sigmoidally. No other associations were observed. CONCLUSION: O3 exposures during a critical period of development were associated with an increased risk of paediatric diabetes incidence.

Travel surveillance uncovers dengue virus dynamics and introductions in the Caribbean.

Dengue is the most prevalent mosquito-borne viral disease in humans, and cases are continuing to rise globally. In particular, islands in the Caribbean have experienced more frequent outbreaks, and all four dengue virus (DENV) serotypes have been reported in the region, leading to hyperendemicity and increased rates of severe disease. However, there is significant variability regarding virus surveillance and reporting between islands, making it difficult to obtain an accurate understanding of the epidemiological patterns in the Caribbean. To investigate this, we used travel surveillance and genomic epidemiology to reconstruct outbreak dynamics, DENV serotype turnover, and patterns of spread within the region from 2009-2022. We uncovered two recent DENV-3 introductions from Asia, one of which resulted in a large outbreak in Cuba, which was previously under-reported. We also show that while outbreaks can be synchronized between islands, they are often caused by different serotypes. Our study highlights the importance of surveillance of infected travelers to provide a snapshot of local introductions and transmission in areas with limited local surveillance and suggests that the recent DENV-3 introductions may pose a major public health threat in the region.

Mooreia alkaloidigena gen. nov., sp. nov. and Catalinimonas alkaloidigena gen. nov., sp. nov., alkaloid-producing marine bacteria in the proposed families Mooreiaceae fam. nov. and Catalimonadaceae fam. nov. in the phylum Bacteroidetes.

Bacterial strains CNX-216(T) and CNU-914(T) were isolated from marine sediment samples collected from Palmyra Atoll and off Catalina Island, respectively. Both strains were gram-negative and aerobic and produce deep-orange to pink colonies and alkaloid secondary metabolites. Cells of strain CNX-216(T) were short, non-motile rods, whereas cells of strain CNU-914(T) were short, curved rods with gliding motility. The DNA G+C contents of CNX-216(T) and CNU-914(T) were respectively 57.7 and 44.4 mol%. Strains CNX-216(T) and CNU-914(T) contained MK-7 as the predominant menaquinone and iso-C15 : 0 and C16 : 1ω5c as the major fatty acids. Phylogenetic analyses revealed that both strains belong to the order Cytophagales in the phylum Bacteroidetes. Strain CNX-216(T) exhibited low 16S rRNA gene sequence identity (87.1 %) to the nearest type strain, Cesiribacter roseus 311(T), and formed a well-supported lineage that is outside all currently described families in the order Cytophagales. Strain CNU-914(T) shared 97.6 % 16S rRNA gene sequence identity with 'Porifericola rhodea' N5EA6-3A2B and, together with 'Tunicatimonas pelagia' N5DB8-4 and four uncharacterized marine bacteria isolated as part of this study, formed a lineage that is clearly distinguished from other families in the order Cytophagales. Based on our polyphasic taxonomic characterization, we propose that strains CNX-216(T) and CNU-914(T) represent novel genera and species, for which we propose the names Mooreia alkaloidigena gen. nov., sp. nov. (type strain CNX-216(T)  = DSM 25187(T)  = KCCM 90102(T)) and Catalinimonas alkaloidigena gen. nov., sp. nov. (type strain CNU-914(T)  = DSM 25186(T)  = KCCM 90101(T)) within the new families Mooreiaceae fam. nov. and Catalimonadaceae fam. nov.

Anthracimycin, a potent anthrax antibiotic from a marine-derived actinomycete.

Licensed to kill: A new antibiotic, anthracimycin (see scheme), produced by a marine-derived actinomycete in saline culture, shows significant activity toward Bacillus anthracis, the bacterial pathogen responsible for anthrax infections. Chlorination of anthracimycin gives a dichloro derivative that retains activity against Gram-positive bacteria, such as anthrax, but also shows activity against selected Gram-negative bacteria.

Methodological changes implemented over time to support accurate and timely COVID-19 vaccine coverage estimates: Ontario, Canada.

The COVID-19 vaccination program implementation in Ontario, Canada has spanned multiple years and is ongoing. To meet the challenges of the program, Ontario developed and implemented a new electronic COVID-19 immunization registry, COVaxON, which captures individual-level data on all doses administered in the province enabling comprehensive coverage assessment. However, the need for ongoing COVID-19 vaccine coverage assessments over a multi-year vaccination program posed challenges necessitating methodological changes. This paper describes Ontario's COVID-19 immunization registry, the methods implemented over time to allow for the ongoing assessment of vaccine coverage by age, and the impact of those methodological changes. Throughout the course of the vaccination program, four different methodological approaches were used to calculate age-specific coverage estimates using vaccination data (numerator) obtained from COVaxON. Age-specific numerators were initially calculated using age at time of first dose (method A), but were updated to the age at coverage assessment (method B). Database enhancements allowed for the exclusion of deceased individuals from the numerator (method C). Population data (denominator) was updated to 2022 projections from the 2021 national census following their availability (method D). The impact was most evident in older age groups where vaccine uptake was high. For example, coverage estimates for individuals aged 70-79 years of age for at least one dose decreased from 104.9 % (method B) to 95.0 % (method D). Thus, methodological changes improved estimates such that none exceeded 100 %. Ontario's COVID-19 immunization registry has been transformational for vaccine program surveillance. The implementation of a single registry for COVID-19 vaccines was essential for comprehensive near real-time coverage assessment, and enabled new uses of the data to support additional components of vaccine program surveillance. The province is well positioned to build on what has been achieved as a result of the COVID-19 pandemic and expand the registry to other routine vaccination programs.

Evaluation of the gap in delivery of opioid agonist therapy among individuals with opioid-related health problems: a population-based retrospective cohort study.

AIMS: Although opioid-related harms have reached new heights across North America, the size of the gap in opioid agonist therapy (OAT) delivery for opioid-related health problems is unknown in most jurisdictions. This study sought to characterize the gap in OAT treatment using a cascade of care framework, and determine factors associated with engagement and retention in treatment. DESIGN: A population-based retrospective cohort study. SETTING: Ontario, Canada. PARTICIPANTS: Individuals who sought medical care for opioid-related health problems or died from an opioid-related cause between 2005 and 2019. MEASUREMENTS: Monthly treatment status for buprenorphine/naloxone or methadone OAT between 2013 and 2019 (i.e. 'off OAT', 'retained on OAT < 6 months', 'retained on OAT ≥ 6 months'). FINDINGS: Of 122 811 individuals in the cohort, 97 516 (79.4%) received OAT at least once during the study period. There was decreasing 6-month treatment retention over time. Model results indicated that males had higher odds of being on OAT each month [odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.23-1.28] but lower odds of OAT retention (OR = 0.90, 95% CI = 0.88-0.92), while the reverse was observed for older individuals (monthly: OR = 0.76 per 10-year increase, 95% CI = 0.76-0.77; retention: OR = 1.36 per 10-year increase, 95% CI = 1.34-1.38) and individuals with higher neighbourhood income (e.g. highest income quintile, monthly: OR = 0.79, 95% CI = 0.77-0.82; highest income quintile, retention: OR = 1.15, 95% CI = 1.11-1.20). Individuals residing in rural areas and with a history of mental health diagnoses had poorer outcomes overall, including lower odds of being on OAT each month (rural: OR = 0.75, 95% CI = 0.73-0.78; mental health: OR = 0.89, 95% CI = 0.87-0.92) and OAT retention (rural: OR = 0.79, 95% CI = 0.77-0.82; mental health: OR = 0.81, 95% CI = 0.78-0.83), as well as higher risk of starting/stopping OAT [rural, starting OAT: hazard ratio (HR) = 1.07, 95% CI = 1.05-1.10; mental health, starting OAT: HR = 1.20, 95% CI: 1.18-1.23; rural, stopping OAT: HR = 1.24, 95% CI: = 1.22-1.26; mental health, stopping OAT: HR = 1.11, 95% CI = 1.09-1.13]. Individuals with a history of mental health diagnoses also had a higher risk of death, regardless of OAT status (off OAT death: HR = 1.49, 95% CI = 1.33-1.66; on OAT death: HR = 1.20, 95% CI = 1.09-1.31). CONCLUSIONS: Factors influencing engagement and declining retention in treatment with opioid agonist therapy in Ontario's health system include age, sex and neighbourhood income, as well as mental health diagnoses or residing in rural regions.

DengueSeq: A pan-serotype whole genome amplicon sequencing protocol for dengue virus.

Background: The increasing burden of dengue virus on public health due to more explosive and frequent outbreaks highlights the need for improved surveillance and control. Genomic surveillance of dengue virus not only provides important insights into the emergence and spread of genetically diverse serotypes and genotypes, but it is also critical to monitor the effectiveness of newly implemented control strategies. Here, we present DengueSeq, an amplicon sequencing protocol, which enables whole-genome sequencing of all four dengue virus serotypes. Results: We developed primer schemes for the four dengue virus serotypes, which can be combined into a pan-serotype approach. We validated both approaches using genetically diverse virus stocks and clinical specimens that contained a range of virus copies. High genome coverage (>95%) was achieved for all genotypes, except DENV2 (genotype VI) and DENV 4 (genotype IV) sylvatics, with similar performance of the serotype-specific and pan-serotype approaches. The limit of detection to reach 70% coverage was 101-102 RNA copies/µL for all four serotypes, which is similar to other commonly used primer schemes. DengueSeq facilitates the sequencing of samples without known serotypes, allows the detection of multiple serotypes in the same sample, and can be used with a variety of library prep kits and sequencing instruments. Conclusions: DengueSeq was systematically evaluated with virus stocks and clinical specimens spanning the genetic diversity within each of the four dengue virus serotypes. The primer schemes can be plugged into existing amplicon sequencing workflows to facilitate the global need for expanded dengue virus genomic surveillance.

Travel surveillance uncovers dengue virus dynamics and introductions in the Caribbean.

Dengue is the most prevalent mosquito-borne viral disease in humans, and cases are continuing to rise globally. In particular, islands in the Caribbean have experienced more frequent outbreaks, and all four dengue virus (DENV) serotypes have been reported in the region, leading to hyperendemicity and increased rates of severe disease. However, there is significant variability regarding virus surveillance and reporting between islands, making it difficult to obtain an accurate understanding of the epidemiological patterns in the Caribbean. To investigate this, we used travel surveillance and genomic epidemiology to reconstruct outbreak dynamics, DENV serotype turnover, and patterns of spread within the region from 2009-2022. We uncovered two recent DENV-3 introductions from Asia, one of which resulted in a large outbreak in Cuba, which was previously under-reported. We also show that while outbreaks can be synchronized between islands, they are often caused by different serotypes. Our study highlights the importance of surveillance of infected travelers to provide a snapshot of local introductions and transmission in areas with limited local surveillance and suggests that the recent DENV-3 introductions may pose a major public health threat in the region.

Genetic complementation of the obligate marine actinobacterium Salinispora tropica with the large mechanosensitive channel gene mscL rescues cells from osmotic downshock.

Marine actinomycetes in the genus Salinispora fail to grow when seawater is replaced with deionized (DI) water in complex growth media. While bioinformatic analyses have led to the identification of a number of candidate marine adaptation genes, there is currently no experimental evidence to support the genetic basis for the osmotic requirements associated with this taxon. One hypothesis is that the lineage-specific loss of mscL is responsible for the failure of strains to grow in media prepared with DI water. The mscL gene encodes a conserved transmembrane protein that reduces turgor pressure under conditions of acute osmotic downshock. In the present study, the mscL gene from a Micromonospora strain capable of growth on media prepared with DI water was transformed into S. tropica strain CNB-440. The single-copy, chromosomal genetic complementation yielded a recombinant Salinispora mscL(+) strain that demonstrated an increased capacity to survive osmotic downshock. The enhanced survival of the S. tropica transformant provides experimental evidence that the loss of mscL is associated with the failure of Salinispora spp. to grow in low-osmotic-strength media.

Identifying the changing age distribution of opioid-related mortality with high-frequency data.

BACKGROUND: Opioid-related mortality continues to rise across North America, and mortality rates have been further exacerbated by the COVID-19 pandemic. This study sought to provide an updated picture of trends of opioid-related mortality for Ontario, Canada between January 2003 and December 2020, in relation to age and sex. METHODS: Using mortality data from the Office of the Chief Coroner for Ontario, we applied Bayesian Poisson regression to model age/sex mortality per 100,000 person-years, including random walks to flexibly capture age and time effects. Models were also used to explore how trends might continue into 2022, considering both pre- and post-COVID-19 courses. RESULTS: From 2003 to 2020, there were 11,633 opioid-related deaths in Ontario. A shift in the age distribution of mortality was observed, with the greatest mortality rates now among younger individuals. In 2003, mortality rates reached maximums at 5.5 deaths per 100,000 person-years (95% credible interval: 4.0-7.6) for males around age 44 and 2.2 deaths per 100,000 person-years (95% CI: 1.5-3.2) for females around age 51. As of 2020, rates have reached maximums at 67.2 deaths per 100,000 person-years (95% CI: 55.3-81.5) for males around age 35 and 16.8 deaths per 100,000 person-years (95% CI: 12.8-22.0) for females around age 37. Our models estimate that opioid-related mortality among the younger population will continue to grow, and that current conditions could lead to male mortality rates that are more than quadruple those of pre-pandemic estimations. CONCLUSIONS: This analysis may inform a refocusing of public health strategy for reducing rising rates of opioid-related mortality, including effectively reaching both older and younger males, as well as young females, with health and social supports such as treatment and harm reduction measures.

Association of Age and Pediatric Household Transmission of SARS-CoV-2 Infection.

Importance: As a result of low numbers of pediatric cases early in the COVID-19 pandemic, pediatric household transmission of SARS-CoV-2 remains an understudied topic. Objective: To determine whether there are differences in the odds of household transmission by younger children compared with older children. Design, Setting, and Participants: This population-based cohort study took place between June 1 and December 31, 2020, in Ontario, Canada. Private households in which the index case individual of laboratory-confirmed SARS-CoV-2 infection was younger than 18 years were included. Individuals were excluded if they resided in apartments missing suite information, in households with multiple index cases, or in households where the age of the index case individual was missing. Exposures: Age group of pediatric index cases categorized as 0 to 3, 4 to 8, 9 to 13, and 14 to 17 years. Main Outcomes and Measures: Household transmission, defined as households where at least 1 secondary case occurred 1 to 14 days after the pediatric index case. Results: A total of 6280 households had pediatric index cases, and 1717 households (27.3%) experienced secondary transmission. The mean (SD) age of pediatric index case individuals was 10.7 (5.1) years and 2863 (45.6%) were female individuals. Children aged 0 to 3 years had the highest odds of transmitting SARS-CoV-2 to household contacts compared with children aged 14 to 17 years (odds ratio, 1.43; 95% CI, 1.17-1.75). This association was similarly observed in sensitivity analyses defining secondary cases as 2 to 14 days or 4 to 14 days after the index case and stratified analyses by presence of symptoms, association with a school/childcare outbreak, or school/childcare reopening. Children aged 4 to 8 years and 9 to 13 years also had increased odds of transmission (aged 4-8 years: odds ratio, 1.40; 95% CI, 1.18-1.67; aged 9-13 years: odds ratio, 1.13; 95% CI, 0.97-1.32). Conclusions and Relevance: This study suggests that younger children may be more likely to transmit SARS-CoV-2 infection compared with older children, and the highest odds of transmission was observed for children aged 0 to 3 years. Differential infectivity of pediatric age groups has implications for infection prevention within households, as well as schools/childcare, to minimize risk of household secondary transmission. Additional population-based studies are required to establish the risk of transmission by younger pediatric index cases.

Design Principles of Lipid-like Ionic Liquids for Gene Delivery.

We developed lipid-like ionic liquids, containing 2-mercaptoimidazolium and 2-mercaptothiazolinium headgroups tethered to two long saturated alkyl chains, as carriers for in vitro delivery of plasmid HEK DNA into 293T cells. We employed a combination of modular design, synthesis, X-ray analysis, and computational modeling to rationalize the self-assembly and desired physicochemical and biological properties. The results suggest that thioamide-derived ionic liquids may serve as a modular platform for lipid-mediated gene delivery. This work represents a step toward understanding the structure-function relationships of these amphiphiles with long-range ordering and offering insight into design principles for synthetic vectors based on self-assembly behavior.