Estimated Childhood Lead Exposure From Drinking Water in Chicago.

Importance: There is no level of lead in drinking water considered to be safe, yet lead service lines are still commonly used in water systems across the US. Objective: To identify the extent of lead-contaminated drinking water in Chicago, Illinois, and model its impact on children younger than 6 years. Design, Setting, and Participants: For this cross-sectional study, a retrospective assessment was performed of lead exposure based on household tests collected from January 2016 to September 2023. Tests were obtained from households in Chicago that registered for a free self-administered testing service for lead exposure. Machine learning and microsimulation were used to estimate citywide childhood lead exposure. Exposure: Lead-contaminated drinking water, measured in parts per billion. Main Outcomes and Measures: Number of children younger than 6 years exposed to lead-contaminated water. Results: A total of 38 385 household lead tests were collected. An estimated 68% (95% uncertainty interval, 66%-69%) of children younger than 6 years were exposed to lead-contaminated water, corresponding to 129 000 children (95% uncertainty interval, 128 000-131 000 children). Ten-percentage-point increases in block-level Black and Hispanic populations were associated with 3% (95% CI, 2%-3%) and 6% (95% CI, 5%-7%) decreases in odds of being tested for lead and 4% (95% CI, 3%-6%) and 11% (95% CI, 10%-13%) increases in having lead-contaminated drinking water, respectively. Conclusions and Relevance: These findings indicate that childhood lead exposure is widespread in Chicago, and racial inequities are present in both testing rates and exposure levels. Machine learning may assist in preliminary screening for lead exposure, and efforts to remediate the effects of environmental racism should involve improving outreach for and access to lead testing services.

Epistasis regulates genetic control of cardiac hypertrophy.

The combinatorial effect of genetic variants is often assumed to be additive. Although genetic variation can clearly interact non-additively, methods to uncover epistatic relationships remain in their infancy. We develop low-signal signed iterative random forests to elucidate the complex genetic architecture of cardiac hypertrophy. We derive deep learning-based estimates of left ventricular mass from the cardiac MRI scans of 29,661 individuals enrolled in the UK Biobank. We report epistatic genetic variation including variants close to CCDC141, IGF1R, TTN, and TNKS. Several loci not prioritized by univariate genome-wide association analysis are identified. Functional genomic and integrative enrichment analyses reveal a complex gene regulatory network in which genes mapped from these loci share biological processes and myogenic regulatory factors. Through a network analysis of transcriptomic data from 313 explanted human hearts, we show that these interactions are preserved at the level of the cardiac transcriptome. We assess causality of epistatic effects via RNA silencing of gene-gene interactions in human induced pluripotent stem cell-derived cardiomyocytes. Finally, single-cell morphology analysis using a novel high-throughput microfluidic system shows that cardiomyocyte hypertrophy is non-additively modifiable by specific pairwise interactions between CCDC141 and both TTN and IGF1R. Our results expand the scope of genetic regulation of cardiac structure to epistasis.

Epistasis regulates genetic control of cardiac hypertrophy.

The combinatorial effect of genetic variants is often assumed to be additive. Although genetic variation can clearly interact non-additively, methods to uncover epistatic relationships remain in their infancy. We develop low-signal signed iterative random forests to elucidate the complex genetic architecture of cardiac hypertrophy. We derive deep learning-based estimates of left ventricular mass from the cardiac MRI scans of 29,661 individuals enrolled in the UK Biobank. We report epistatic genetic variation including variants close to CCDC141, IGF1R, TTN, and TNKS. Several loci not prioritized by univariate genome-wide association analysis are identified. Functional genomic and integrative enrichment analyses reveal a complex gene regulatory network in which genes mapped from these loci share biological processes and myogenic regulatory factors. Through a network analysis of transcriptomic data from 313 explanted human hearts, we show that these interactions are preserved at the level of the cardiac transcriptome. We assess causality of epistatic effects via RNA silencing of gene-gene interactions in human induced pluripotent stem cell-derived cardiomyocytes. Finally, single-cell morphology analysis using a novel high-throughput microfluidic system shows that cardiomyocyte hypertrophy is non-additively modifiable by specific pairwise interactions between CCDC141 and both TTN and IGF1R. Our results expand the scope of genetic regulation of cardiac structure to epistasis.

Protection against Omicron from Vaccination and Previous Infection in a Prison System.

BACKGROUND: Information regarding the protection conferred by vaccination and previous infection against infection with the B.1.1.529 (omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is limited. METHODS: We evaluated the protection conferred by mRNA vaccines and previous infection against infection with the omicron variant in two high-risk populations: residents and staff in the California state prison system. We used a retrospective cohort design to analyze the risk of infection during the omicron wave using data collected from December 24, 2021, through April 14, 2022. Weighted Cox models were used to compare the effectiveness (measured as 1 minus the hazard ratio) of vaccination and previous infection across combinations of vaccination history (stratified according to the number of mRNA doses received) and infection history (none or infection before or during the period of B.1.617.2 [delta]-variant predominance). A secondary analysis used a rolling matched-cohort design to evaluate the effectiveness of three vaccine doses as compared with two doses. RESULTS: Among 59,794 residents and 16,572 staff, the estimated effectiveness of previous infection against omicron infection among unvaccinated persons who had been infected before or during the period of delta predominance ranged from 16.3% (95% confidence interval [CI], 8.1 to 23.7) to 48.9% (95% CI, 41.6 to 55.3). Depending on previous infection status, the estimated effectiveness of vaccination (relative to being unvaccinated and without previous documented infection) ranged from 18.6% (95% CI, 7.7 to 28.1) to 83.2% (95% CI, 77.7 to 87.4) with two vaccine doses and from 40.9% (95% CI, 31.9 to 48.7) to 87.9% (95% CI, 76.0 to 93.9) with three vaccine doses. Incremental effectiveness estimates of a third (booster) dose (relative to two doses) ranged from 25.0% (95% CI, 16.6 to 32.5) to 57.9% (95% CI, 48.4 to 65.7) among persons who either had not had previous documented infection or had been infected before the period of delta predominance. CONCLUSIONS: Our findings in two high-risk populations suggest that mRNA vaccination and previous infection were effective against omicron infection, with lower estimates among those infected before the period of delta predominance. Three vaccine doses offered significantly more protection than two doses, including among previously infected persons.

Uptake of COVID-19 Vaccination Among Frontline Workers in California State Prisons.

Importance: Prisons and jails are high-risk environments for COVID-19. Vaccination levels among workers in many such settings remain markedly lower than those of residents and members of surrounding communities. The situation is troubling because prison staff are a key vector for COVID-19 transmission. Objective: To assess patterns and timing of staff vaccination in California state prisons and identify individual-level and community-level factors associated with remaining unvaccinated. Design Setting and Participants: This cohort study used data from December 22, 2020, through June 30, 2021, to quantify the fractions of staff and incarcerated residents who remained unvaccinated among 23 472 custody and 7617 health care staff who worked in roles requiring direct contact with residents at 33 of the 35 prisons operated by the California Department of Corrections and Rehabilitation. Multivariable probit regressions assessed demographic, community, and peer factors associated with staff vaccination uptake. Main Outcomes and Measures: Remaining unvaccinated throughout the study period. Results: Of 23 472 custody staff, 3751 (16%) were women, and 1454 (6%) were Asian/Pacific Islander individuals, 1571 (7%) Black individuals, 9008 (38%) Hispanic individuals, and 6666 (28%) White individuals. Of 7617 health care staff, 5434 (71%) were women, and 2148 (28%) were Asian/Pacific Islander individuals, 1201 (16%) Black individuals, 1409 (18%) Hispanic individuals, and 1771 (23%) White individuals. A total of 6103 custody staff (26%) and 3961 health care staff (52%) received 1 or more doses of a COVID-19 vaccine during the first 2 months vaccines were offered, but vaccination rates stagnated thereafter. By June 30, 2021, 14 317 custody staff (61%) and 2819 health care staff (37%) remained unvaccinated. In adjusted analyses, remaining unvaccinated was positively associated with younger age (custody staff: age, 18-29 years vs ≥60 years, 75% [95% CI, 73%-76%] vs 45% [95% CI, 42%-48%]; health care staff: 52% [95% CI, 48%-56%] vs 29% [95% CI, 27%-32%]), prior COVID-19 infection (custody staff: 67% [95% CI, 66%-68%] vs 59% [95% CI, 59%-60%]; health care staff: 44% [95% CI, 42%-47%] vs 36% [95% CI, 36%-36%]), residing in a community with relatively low rates of vaccination (custody staff: 75th vs 25th percentile:, 63% [95% CI, 62%-63%] vs 60% [95% CI, 59%-60%]; health care staff: 40% [95% CI, 39%-41%] vs 34% [95% CI, 33%-35%]), and sharing shifts with coworkers who had relatively low rates of vaccination (custody staff: 75th vs 25th percentile, 64% [95% CI, 62%-66%] vs 59% [95% CI, 57%-61%]; health care staff: 38% [95% CI, 36%-41%] vs 35% [95% CI, 31%-39%]). Conclusions and Relevance: This cohort study of California state prison custody and health care staff found that vaccination uptake plateaued at levels that posed ongoing risks of further outbreaks in the prisons and continuing transmission from prisons to surrounding communities. Prison staff decisions to forgo vaccination appear to be multifactorial, and vaccine mandates may be necessary to achieve adequate levels of immunity in this high-risk setting.

Protection against Omicron conferred by mRNA primary vaccine series, boosters, and prior infection.

B ackground: Prisons and jails are high-risk settings for Covid-19 transmission, morbidity, and mortality. We evaluate protection conferred by prior infection and vaccination against the SARS-CoV-2 Omicron variant within the California state prison system. M ethods: We employed a test-negative design to match resident and staff cases during the Omicron wave (December 24, 2021-April 14, 2022) to controls according to a case's test-week as well as demographic, clinical, and carceral characteristics. We estimated protection against infection using conditional logistic regression, with exposure status defined by vaccination, stratified by number of mRNA doses received, and prior infection, stratified by periods before or during Delta variant predominance. R esults: We matched 15,783 resident and 8,539 staff cases to 180,169 resident and 90,409 staff controls. Among cases, 29.7% and 2.2% were infected before or during the emergence of the Delta variant, respectively; 30.6% and 36.3% were vaccinated with two or three doses, respectively. Estimated protection from Omicron infection for two and three doses were 14.9% (95% Confidence Interval [CI], 12.3-19.7%) and 43.2% (42.2-47.4%) for those without known prior infections, 47.8% (95% CI, 46.6-52.8%) and 61.3% (95% CI, 60.7-64.8%) for those infected before the emergence of Delta, and 73.1% (95% CI, 69.8-80.1%) and 86.8% (95% CI, 82.1-92.7) for those infected during the period of Delta predominance. C onclusion: A third mRNA dose provided significant, additional protection over two doses, including among individuals with prior infection. Our findings suggest that vaccination should remain a priority-even in settings with high levels of transmission and prior infection.

Effectiveness of Coronavirus Disease 2019 (COVID-19) Vaccines Among Incarcerated People in California State Prisons: Retrospective Cohort Study.

BACKGROUND: Prisons and jails are high-risk settings for coronavirus disease 2019 (COVID-19). Vaccines may substantially reduce these risks, but evidence is needed on COVID-19 vaccine effectiveness for incarcerated people, who are confined in large, risky congregate settings. METHODS: We conducted a retrospective cohort study to estimate effectiveness of messenger RNA (mRNA) vaccines, BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna), against confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections among incarcerated people in California prisons from 22 December 2020 through 1 March 2021. The California Department of Corrections and Rehabilitation provided daily data for all prison residents including demographic, clinical, and carceral characteristics, as well as COVID-19 testing, vaccination, and outcomes. We estimated vaccine effectiveness using multivariable Cox models with time-varying covariates, adjusted for resident characteristics and infection rates across prisons. RESULTS: Among 60 707 cohort members, 49% received at least 1 BNT162b2 or mRNA-1273 dose during the study period. Estimated vaccine effectiveness was 74% (95% confidence interval [CI], 64%-82%) from day 14 after first dose until receipt of second dose and 97% (95% CI, 88%-99%) from day 14 after second dose. Effectiveness was similar among the subset of residents who were medically vulnerable: 74% (95% CI, 62%-82%) and 92% (95% CI, 74%-98%) from 14 days after first and second doses, respectively. CONCLUSIONS: Consistent with results from randomized trials and observational studies in other populations, mRNA vaccines were highly effective in preventing SARS-CoV-2 infections among incarcerated people. Prioritizing incarcerated people for vaccination, redoubling efforts to boost vaccination, and continuing other ongoing mitigation practices are essential in preventing COVID-19 in this disproportionately affected population.

Public health impacts of an imminent Red Sea oil spill.

The possibility of a massive oil spill in the Red Sea is increasingly likely. The Safer, a deteriorating oil tanker containing 1.1 million barrels of oil, has been deserted near the coast of Yemen since 2015 and threatens environmental catastrophe to a country presently in a humanitarian crisis. Here, we model the immediate public health impacts of a simulated spill. We estimate that all of Yemen's imported fuel through its key Red Sea ports would be disrupted and that the anticipated spill could disrupt clean-water supply equivalent to the daily use of 9.0-9.9 million people, food supply for 5.7-8.4 million people and 93-100% of Yemen's Red Sea fisheries. We also estimate an increased risk of cardiovascular hospitalization from pollution ranging from 5.8 to 42.0% over the duration of the spill. The spill and its potentially disastrous impacts remain entirely preventable through offloading the oil. Our results stress the need for urgent action to avert this looming disaster.

Suicide rates of migrants in United States immigration detention (2010-2020).

OBJECTIVE: We determined the annual suicide rate of migrants detained by U.S. Immigration and Customs Enforcement (ICE) in the past decade. METHODS: We performed a retrospective cohort analysis of the annual suicide rates for ICE detainees from federal fiscal years (FY) 2010-2020. Death date and cause of death were directly extracted from publicly available ICE Freedom of Information Act (FOIA) Library, ICE death reports, and ICE press releases. Annual suicide rates were calculated as suicides per 100,000 person-years and suicides per 100,000 admissions. RESULTS: From 2010-2019, the mean number of suicides per 100,000 person-years was 3.3 (standard deviation (SD): 2.6). In 2020, the suicide rate increased 5.3 times the prior 10-year average to 17.4 suicides per 100,000 person-years. When calculating suicide rate based on admissions per FY, the mean number of suicides from 2010-2019 per 100,000 admissions was 0.3 (SD: 0.3). In 2020, the suicide rate increased 11.0 times the prior 10-year average to 3.4 suicides per 100,000 admissions. CONCLUSION: In 2020, the detainee suicide rate increased substantially compared to the past decade. This may point to a worsening mental health crisis in ICE detention.

Outbreaks of COVID-19 variants in US prisons: a mathematical modelling analysis of vaccination and reopening policies.

BACKGROUND: Residents of prisons have experienced disproportionate COVID-19-related health harms. To control outbreaks, many prisons in the USA restricted in-person activities, which are now resuming even as viral variants proliferate. This study aims to use mathematical modelling to assess the risks and harms of COVID-19 outbreaks in prisons under a range of policies, including resumption of activities. METHODS: We obtained daily resident-level data for all California state prisons from Jan 1, 2020, to May 15, 2021, describing prison layouts, housing status, sociodemographic and health characteristics, participation in activities, and COVID-19 testing, infection, and vaccination status. We developed a transmission-dynamic stochastic microsimulation parameterised by the California data and published literature. After an initial infection is introduced to a prison, the model evaluates the effect of various policy scenarios on infections and hospitalisations over 200 days. Scenarios vary by vaccine coverage, baseline immunity (0%, 25%, or 50%), resumption of activities, and use of non-pharmaceutical interventions (NPIs) that reduce transmission by 75%. We simulated five prison types that differ by residential layout and demographics, and estimated outcomes with and without repeated infection introductions over the 200 days. FINDINGS: If a viral variant is introduced into a prison that has resumed pre-2020 contact levels, has moderate vaccine coverage (ranging from 36% to 76% among residents, dependent on age, with 40% coverage for staff), and has no baseline immunity, 23-74% of residents are expected to be infected over 200 days. High vaccination coverage (90%) coupled with NPIs reduces cumulative infections to 2-54%. Even in prisons with low room occupancies (ie, no more than two occupants) and low levels of cumulative infections (ie, <10%), hospitalisation risks are substantial when these prisons house medically vulnerable populations. Risks of large outbreaks (>20% of residents infected) are substantially higher if infections are repeatedly introduced. INTERPRETATION: Balancing benefits of resuming activities against risks of outbreaks presents challenging trade-offs. After achieving high vaccine coverage, prisons with mostly one-to-two-person cells that have higher baseline immunity from previous outbreaks can resume in-person activities with low risk of a widespread new outbreak, provided they maintain widespread NPIs, continue testing, and take measures to protect the medically vulnerable. FUNDING: Horowitz Family Foundation, National Institute on Drug Abuse, Centers for Disease Control and Prevention, National Science Foundation, Open Society Foundation, Advanced Micro Devices.

Effectiveness of COVID-19 Vaccines among Incarcerated People in California State Prisons: A Retrospective Cohort Study.

BACKGROUND: Prisons and jails are high-risk settings for COVID-19 transmission, morbidity, and mortality. COVID-19 vaccines may substantially reduce these risks, but evidence is needed of their effectiveness for incarcerated people, who are confined in large, risky congregate settings. METHODS: We conducted a retrospective cohort study to estimate effectiveness of mRNA vaccines, BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna), against confirmed SARS-CoV-2 infections among incarcerated people in California prisons from December 22, 2020 through March 1, 2021. The California Department of Corrections and Rehabilitation provided daily data for all prison residents including demographic, clinical, and carceral characteristics, as well as COVID-19 testing, vaccination status, and outcomes. We estimated vaccine effectiveness using multivariable Cox models with time-varying covariates that adjusted for resident characteristics and infection rates across prisons. FINDINGS: Among 60,707 residents in the cohort, 49% received at least one BNT162b2 or mRNA-1273 dose during the study period. Estimated vaccine effectiveness was 74% (95% confidence interval [CI], 64-82%) from day 14 after first dose until receipt of second dose and 97% (95% CI, 88-99%) from day 14 after second dose. Effectiveness was similar among the subset of residents who were medically vulnerable (74% [95% CI, 62-82%] and 92% [95% CI, 74-98%] from 14 days after first and second doses, respectively), as well as among the subset of residents who received the mRNA-1273 vaccine (71% [95% CI, 58-80%] and 96% [95% CI, 67-99%]). CONCLUSIONS: Consistent with results from randomized trials and observational studies in other populations, mRNA vaccines were highly effective in preventing SARS-CoV-2 infections among incarcerated people. Prioritizing incarcerated people for vaccination, redoubling efforts to boost vaccination and continuing other ongoing mitigation practices are essential in preventing COVID-19 in this disproportionately affected population. FUNDING: Horowitz Family Foundation, National Institute on Drug Abuse, Centers for Disease Control and Prevention, National Science Foundation, Open Society Foundation, Advanced Micro Devices.

COVID-19 in the California State Prison System: an Observational Study of Decarceration, Ongoing Risks, and Risk Factors.

BACKGROUND: Correctional institutions nationwide are seeking to mitigate COVID-19-related risks. OBJECTIVE: To quantify changes to California's prison population since the pandemic began and identify risk factors for COVID-19 infection. DESIGN: For California state prisons (March 1-October 10, 2020), we described residents' demographic characteristics, health status, COVID-19 risk scores, room occupancy, and labor participation. We used Cox proportional hazard models to estimate the association between rates of COVID-19 infection and room occupancy and out-of-room labor, respectively. PARTICIPANTS: Residents of California state prisons. MAIN MEASURES: Changes in the incarcerated population's size, composition, housing, and activities. For the risk factor analysis, the exposure variables were room type (cells vs. dormitories) and labor participation (any room occupant participating in the prior 2 weeks) and the outcome variable was incident COVID-19 case rates. KEY RESULTS: The incarcerated population decreased 19.1% (119,401 to 96,623) during the study period. On October 10, 2020, 11.5% of residents were aged ≥60, 18.3% had high COVID-19 risk scores, 31.0% participated in out-of-room labor, and 14.8% lived in rooms with ≥10 occupants. Nearly 40% of residents with high COVID-19 risk scores lived in dormitories. In 9 prisons with major outbreaks (6,928 rooms; 21,750 residents), dormitory residents had higher infection rates than cell residents (adjusted hazard ratio [AHR], 2.51 95% CI, 2.25-2.80) and residents of rooms with labor participation had higher rates than residents of other rooms (AHR, 1.56; 95% CI, 1.39-1.74). CONCLUSION: Despite reductions in room occupancy and mixing, California prisons still house many medically vulnerable residents in risky settings. Reducing risks further requires a combination of strategies, including rehousing, decarceration, and vaccination.

Routine asymptomatic testing strategies for airline travel during the COVID-19 pandemic: a simulation study.

BACKGROUND: Routine viral testing strategies for SARS-CoV-2 infection might facilitate safe airline travel during the COVID-19 pandemic and mitigate global spread of the virus. However, the effectiveness of these test-and-travel strategies to reduce passenger risk of SARS-CoV-2 infection and population-level transmission remains unknown. METHODS: In this simulation study, we developed a microsimulation of SARS-CoV-2 transmission in a cohort of 100 000 US domestic airline travellers using publicly available data on COVID-19 clinical cases and published natural history parameters to assign individuals one of five health states of susceptible to infection, latent period, early infection, late infection, or recovered. We estimated a per-day risk of infection with SARS-CoV-2 corresponding to a daily incidence of 150 infections per 100 000 people. We assessed five testing strategies: (1) anterior nasal PCR test within 3 days of departure, (2) PCR within 3 days of departure and 5 days after arrival, (3) rapid antigen test on the day of travel (assuming 90% of the sensitivity of PCR during active infection), (4) rapid antigen test on the day of travel and PCR test 5 days after arrival, and (5) PCR test 5 days after arrival. Strategies 2 and 4 included a 5-day quarantine after arrival. The travel period was defined as 3 days before travel to 2 weeks after travel. Under each scenario, individuals who tested positive before travel were not permitted to travel. The primary study outcome was cumulative number of infectious days in the cohort over the travel period without isolation or quarantine (population-level transmission risk), and the key secondary outcome was the number of infectious people detected on the day of travel (passenger risk of infection). FINDINGS: We estimated that in a cohort of 100 000 airline travellers, in a scenario with no testing or screening, there would be 8357 (95% uncertainty interval 6144-12831) infectious days with 649 (505-950) actively infectious passengers on the day of travel. The pre-travel PCR test reduced the number of infectious days from 8357 to 5401 (3917-8677), a reduction of 36% (29-41) compared with the base case, and identified 569 (88% [76-92]) of 649 actively infectious travellers on the day of flight; the addition of post-travel quarantine and PCR reduced the number of infectious days to 2520 days (1849-4158), a reduction of 70% (64-75) compared with the base case. The rapid antigen test on the day of travel reduced the number of infectious days to 5674 (4126-9081), a reduction of 32% (26-38) compared with the base case, and identified 560 (86% [83-89]) actively infectious travellers; the addition of post-travel quarantine and PCR reduced the number of infectious days to 3124 (2356-495), a reduction of 63% (58-66) compared with the base case. The post-travel PCR alone reduced the number of infectious days to 4851 (3714-7679), a reduction of 42% (35-49) compared with the base case. INTERPRETATION: Routine asymptomatic testing for SARS-CoV-2 before travel can be an effective strategy to reduce passenger risk of infection during travel, although abbreviated quarantine with post-travel testing is probably needed to reduce population-level transmission due to importation of infection when travelling from a high to low incidence setting. FUNDING: University of California, San Francisco.