Emergence of SARS-CoV-2 Delta Variant and Effect of Nonpharmaceutical Interventions, British Columbia, Canada.

In British Columbia, Canada, initial growth of the SARS-CoV-2 Delta variant was slower than that reported in other jurisdictions. Delta became the dominant variant (>50% prevalence) within ≈7-13 weeks of first detection in regions within the United Kingdom and United States. In British Columbia, it remained at <10% of weekly incident COVID-19 cases for 13 weeks after first detection on March 21, 2021, eventually reaching dominance after 17 weeks. We describe the growth of Delta variant cases in British Columbia during March 1-June 30, 2021, and apply retrospective counterfactual modeling to examine factors for the initially low COVID-19 case rate after Delta introduction, such as vaccination coverage and nonpharmaceutical interventions. Growth of COVID-19 cases in the first 3 months after Delta emergence was likely limited in British Columbia because additional nonpharmaceutical interventions were implemented to reduce levels of contact at the end of March 2021, soon after variant emergence.

Spike Mutation Profiles Associated With SARS-CoV-2 Breakthrough Infections in Delta Emerging and Predominant Time Periods in British Columbia, Canada.

Background: COVID-19 vaccination is a key public health measure in the pandemic response. The rapid evolution of SARS-CoV-2 variants introduce new groups of spike protein mutations. These new mutations are thought to aid in the evasion of vaccine-induced immunity and render vaccines less effective. However, not all spike mutations contribute equally to vaccine escape. Previous studies associate mutations with vaccine breakthrough infections (BTI), but information at the population level remains scarce. We aimed to identify spike mutations associated with SARS-CoV-2 vaccine BTI in a community setting during the emergence and predominance of the Delta-variant. Methods: This case-control study used both genomic, and epidemiological data from a provincial COVID-19 surveillance program. Analyses were stratified into two periods approximating the emergence and predominance of the Delta-variant, and restricted to primary SARS-CoV-2 infections from either unvaccinated individuals, or those infected ≥14 days after their second vaccination dose in a community setting. Each sample's spike mutations were concatenated into a unique spike mutation profile (SMP). Penalized logistic regression was used to identify spike mutations and SMPs associated with SARS-CoV-2 vaccine BTI in both time periods. Results and Discussion: This study reports population level relative risk estimates, between 2 and 4-folds, of spike mutation profiles associated with BTI during the emergence and predominance of the Delta-variant, which comprised 19,624 and 17,331 observations, respectively. The identified mutations cover multiple spike domains including the N-terminal domain (NTD), receptor binding domain (RBD), S1/S2 cleavage region, fusion peptide and heptad regions. Mutations in these different regions imply various mechanisms contribute to vaccine escape. Our profiling method identifies naturally occurring spike mutations associated with BTI, and can be applied to emerging SARS-CoV-2 variants with novel groups of spike mutations.

Rapid Increase in SARS-CoV-2 P.1 Lineage Leading to Codominance with B.1.1.7 Lineage, British Columbia, Canada, January-April 2021.

Several severe acute respiratory syndrome coronavirus 2 variants of concern (VOCs) emerged in late 2020; lineage B.1.1.7 initially dominated globally. However, lineages B.1.351 and P.1 represent potentially greater risk for transmission and immune escape. In British Columbia, Canada, B.1.1.7 and B.1.351 were first identified in December 2020 and P.1 in February 2021. We combined quantitative PCR and whole-genome sequencing to assess relative contribution of VOCs in nearly 67,000 infections during the first 16 weeks of 2021 in British Columbia. B.1.1.7 accounted for <10% of screened or sequenced specimens early on, increasing to >50% by week 8. P.1 accounted for <10% until week 10, increased rapidly to peak at week 12, and by week 13 codominated within 10% of rates of B.1.1.7. B.1.351 was a minority throughout. This rapid expansion of P.1 but suppression of B.1.351 expands our understanding of population-level VOC patterns and might provide clues to fitness determinants for emerging VOCs.

Impact of the adolescent pertussis booster dose on the incidence of pertussis in British Columbia and Quebec, Canada.

Impact of an adolescent tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine program was assessed in the provinces of British Columbia and Quebec, Canada. In both provinces, the Tdap booster has been in place since 2004, targeting Grade 9 students (14-15-years-of-age). Incidence rate ratios (IRRs) standardizing notification rates among teens 15-19-years-old to infants <1-year-old decreased following introduction of the Tdap program and were significantly halved during the 2009-2012 post-Tdap versus 2000-2003 pre-Tdap period. This program impact, however, is tempered by the observation that pertussis incidence among 15-19-year-olds was already lower than any other pediatric age group, following gradual decline from pre-teen rates even before the Tdap program. The risk of hospitalization among adolescents 15-19-years-old was also low throughout at <1/100,000. Furthermore, IRRs increased in 2013-2017 when an increasing proportion of 15-19-year-olds were primed with acellular pertussis vaccine only, suggesting short-lived Tdap booster-dose effectiveness that warrants further monitoring.

Neurocognitive risk markers in pediatric obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) has complex genetic underpinnings, particularly in its early-onset form, which places siblings at a 10-fold increased risk of developing the disorder. Examination for neurocognitive markers preceding pediatric OCD onset has not been conducted, although markers have been identified in adult OCD. This study compared neurocognition across groups of OCD-affected youth (n = 87), unaffected siblings of those with early-onset OCD (n = 67), and healthy controls (HC; n = 79). METHODS: A total of 233 participants aged 6-18 years old completed standardized neurocognitive tests of cognitive flexibility, decision making, planning, response inhibition, spatial working memory, attention, recognition nonverbal memory, and intelligence. They were administered the Anxiety Disorders Interview Schedule-Parent version (ADIS-P) and completed self-report anxiety and OCD questionnaires. Linear mixed-effects models tested for differences between groups, adjusting for age, gender, IQ, state anxiety, and ethnicity, and accounting for random effects of family membership. RESULTS: OCD-affected youth and unaffected siblings performed significantly worse on planning in comparison to HCs (Cohen's d = 0.74; 95% CI = [0.11, 1.36]; Cohen's d = 0.75; 95% CI = [0.12, 1.38], respectively; omnibus group effect p = .007). No other significant between-group differences were identified. CONCLUSIONS: Neurocognitive performance differences between groups identified planning as a preexisting trait marker of pediatric OCD, while no other domain presented as a marker of pediatric OCD. This differs from adult OCD, which is associated with broader cognitive impairments. Investigating longitudinal trajectories and predictive significance of neurocognition in those affected by, and at risk for, early-onset OCD is warranted. Ideally, this will enhance individualized risk stratification and inform future prevention and early intervention strategies.

The Change in Living Kidney Donation in Women and Men in the United States (2005-2015): A Population-Based Analysis.

The factors underlying the decline in living kidney donation in the United States since 2005 must be understood to inform strategies to ensure access to this option for future patients. Population-based estimates provide a better assessment of donation activity than do trends in the number of living donor transplants. Using data from the Scientific Registry of Transplant Recipients and the United States Census, we determined longitudinal changes in living kidney donation between 2005 and 2015, focusing on the effect of sex and income. We used multilevel Poisson models to adjust for differences in age, race, the incidence of ESRD, and geographic factors (including population density, urbanization, and daily commuting). During the study period, the unadjusted rate of donation was 30.1 and 19.3 per million population in women and men, respectively, and the adjusted incidence of donation was 44% higher in women (incidence rate ratio [IRR], 1.44; 95% confidence interval [95% CI], 1.39 to 1.49). The incidence of donation was stable in women (IRR, 0.95; 95% CI, 0.84 to 1.07) but declined in men (IRR, 0.75; 95% CI, 0.68 to 0.83). Income was associated with longitudinal changes in donation in both sexes, yet donation was stable in the highest two population income quartiles in women but only in the highest income quartile in men. In both sexes, living related donations declined, irrespective of income. In conclusion, living donation declined in men but remained stable in women between 2005 and 2015, and income appeared to have a greater effect on living donation in men.

Variation in Dialysis Exposure Prior to Nonpreemptive Living Donor Kidney Transplantation in the United States and Its Association With Allograft Outcomes.

BACKGROUND: The impact of dialysis exposure before nonpreemptive living donor kidney transplantation on allograft outcomes is uncertain. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adult first-time recipients of kidney-only living donor transplants in the United States who were recorded within the Scientific Registry of Transplant Recipients for 2000 to 2016. FACTORS: Duration of pretransplantation dialysis exposure. OUTCOMES: Kidney transplant failure from any cause including death, death-censored transplant failure, and death with allograft function. RESULTS: Among the 77,607 living donor transplant recipients studied, longer pretransplantation dialysis exposure was independently associated with progressively higher risk for transplant failure from any cause, including death beginning 6 months after transplantation. Compared with patients with 0.1 to 3.0 months of dialysis exposure, the HR for transplant failure from any cause including death increased from 1.16 (95% CI, 1.07-1.31) among patients with 6.1 to 9.0 months of dialysis exposure to 1.60 (95% CI, 1.43-1.79) among patients with more than 60.0 months of dialysis exposure. Pretransplantation dialysis exposure varied markedly among centers; median exposures were 11.0 and 18.9 months for centers in the 10th and 90th percentiles of dialysis exposure, respectively. Centers with the highest proportions of living donor transplantations had the shortest pretransplantation dialysis exposures. In multivariable analysis, patients of black race, with low income, with nonprivate insurance, with less than high school education, and not working for income had longer pretransplantation dialysis exposures. Dialysis exposure in patients with these characteristics also varied 2-fold between transplantation centers. LIMITATIONS: Why longer dialysis exposure is associated with transplant failure could not be determined. CONCLUSIONS: Longer pretransplantation dialysis exposure in nonpreemptive living donor kidney transplantation is associated with increased risk for allograft failure. Pretransplantation dialysis exposure is associated with recipients' sociodemographic and transplantation centers' characteristics. Understanding whether limiting pretransplantation dialysis exposure could improve living donor transplant outcomes will require further study.

Use and Outcomes of Kidneys from Donation after Circulatory Death Donors in the United States.

Donation after circulatory death (DCD) donors are an important source of kidneys for transplantation, but DCD donor transplantation is less common in the United States than in other countries. In this study of national data obtained between 2008 and 2015, recovery of DCD kidneys varied substantially among the country's 58 donor service areas, and 25% of DCD kidneys were recovered in only four donor service areas. Overall, 20% of recovered DCD kidneys were discarded, varying from 3% to 33% among donor service areas. Compared with kidneys from neurologically brain dead (NBD) donors, DCD kidneys had a higher adjusted odds ratio of discard that varied from 1.25 (95% confidence interval [95% CI], 1.16 to 1.34) in kidneys with total donor warm ischemic time (WIT) of 10-26 minutes to 2.67 (95% CI, 2.34 to 3.04) in kidneys with total donor WIT >48 minutes. Among the 12,831 DCD kidneys transplanted, kidneys with WIT≤48 minutes had survival similar to that of NBD kidneys. DCD kidneys with WIT>48 minutes had a higher risk of allograft failure (hazard ratio, 1.23; 95% CI, 1.07 to 1.41), but this risk was limited to kidneys with cold ischemia time (CIT) >12 hours. We conclude that donor service area-level variation in the recovery and discard of DCD kidneys is large. Additional national data collection is needed to understand the potential to increase DCD donor transplantation in the United States. Strategies to minimize cold ischemic injury may safely allow increased use of DCD kidneys with WIT>48 minutes.

Cold ischemia time up to 16 hours has little impact on living donor kidney transplant outcomes in the era of kidney paired donation.

In living donor transplantation, cold ischemia time is a concern in transplants involving kidney paired donation. The impact of cold ischemia time over eight hours is unknown. Here we examined the association of cold ischemia time with delayed graft function and allograft loss among 48,498 living recipients in the Scientific Registry of Transplant Recipients registry. The incidence of delayed graft function was low but significantly higher among patients with longer cold ischemia times (0-2.0 hours: 3.3%; 2.1-4.0 hours: 3.9%; 4.1-8.0 hours: 4.3%; 8.1-16.0 hours: 5.5%). In multivariate analyses, only those with cold ischemia times of 8.1-16.0 hours had increased odds of delayed graft function (odds ratio 1.47; 95% confidence interval 1.05-2.05) compared to patients with times of 0-2.0 hours. In multivariate time-to-event analyses, cold ischemia times of 16 hours or less were not associated with allograft loss from any cause including death or death-censored graft loss with hazard ratios for cold ischemia times between 8.0-16.0 hours of 0.97 (95% confidence interval 0.74-1.26) and 1.09 (0.81-1.48) compared to patients with times of 0-2.0 hours). The results were consistent in paired and non-kidney paired donation transplants and in those with living donors over 50 years of age. In subgroup analysis restricted to kidney paired donation recipients, there was no difference in the risk of delayed graft function with an odds ratio of 1.40 (0.88, 2.40) or all-cause graft loss with a hazard ratio of 0.89 (0.62, 1.30) in transplant recipients who received kidneys that were shipped versus not shipped. Thus, a cold ischemia time up to 16 hours has limited impact on living donor outcomes. These findings may help expand living donor transplantation through kidney paired donation.