Use of Rapid Antigen Tests to End Isolation in a University Setting: Observational Study.

BACKGROUND: COVID-19 isolation recommendations have evolved over the course of the pandemic. Initially, the US Centers for Disease Control and Prevention required 10 days of isolation after a positive test result. In December 2021, this was reduced to a minimum of 5 days with symptom improvement, followed by 5 days of mask wearing. As a result, several institutions of higher education, including the George Washington University, required persons testing positive for COVID-19 to either submit a negative rapid antigen test (RAT) with symptom resolution to leave isolation after 5 days or to maintain a 10-day isolation period in the absence of a negative RAT and the presence of continued symptoms. RATs are tools that can be used both to shorten isolation periods and to ensure that persons testing positive for COVID-19 remain in isolation if infectious. OBJECTIVE: The purpose of this analysis is to report on the experience of implementing RAT policies, examine the number of days that isolation was reduced via RAT testing, determine the factors that predicted uploading a RAT, and determine RAT positivity percentages to illustrate the utility of using RATs to end isolation. METHODS: In this study, 880 individuals in COVID-19 isolation at a university in Washington, DC, uploaded 887 RATs between February 21 and April 14, 2022. Daily positivity percentages were calculated, and multiple logistic regression analyses examined the odds of uploading a RAT by campus residential living status (ie, on or off campus), student or employee designation, age, and days in isolation. RESULTS: A total of 76% (669/880) of individuals in isolation uploaded a RAT during the study period. Overall, 38.6% (342/887) of uploaded RATs were positive. Uploaded RATs were positive 45.6% (118/259) of the time on day 5; 45.4% (55/121) on day 6; 47.1% (99/210) on day 7; and 11.1% (7/63) on day 10 or beyond. Adjusted logistic regression modeling indicated cases living on campus had increased odds of uploading a RAT (odds ratio [OR] 2.54, 95% CI 1.64-3.92), whereas primary student affiliation (OR 0.29, 95% CI 0.12-0.69) and days in isolation (OR 0.45, 95% CI 0.39-0.52) had decreased odds of uploading a RAT. Of the 545 cases with a negative RAT, 477 were cleared prior to day 10 of their isolation due to lack of symptoms and timely submission, resulting in a total of 1547 days of lost productivity saved compared to all being in isolation for 10 days. CONCLUSIONS: RATs are beneficial, as they can support a decision to release individuals from isolation when they have recovered and maintain isolation for people who may still be infectious. Future isolation policies should be guided by similar protocols and research to reduce the spread of COVID-19 and minimize lost productivity and disruption to individuals' lives.

A school of public health responds to the pandemic: A case study from Washington D.C.

The emergence of COVID-19 immediately affected higher education, and the closure of campuses at the start of the pandemic in March of 2020 forced educational institutions to quickly adapt to changing circumstances. Schools of public health faced challenges not only of shifting to remote learning and work environments, but also uniquely redirecting public health research and service efforts toward COVID-19. This paper offers a case study of how the Milken Institute School of Public Health at the George Washington University (GWSPH), the only school of public health in the nation's capital, initially adapted to the COVID-19 pandemic. Using a modified version of the Public Health Preparedness and Response Core Competency Model created by the Association of Schools and Programs of Public Health and the Centers for Disease Control and Prevention, we analyze how GWSPH worked in three areas-research, education, service/operations. We reviewed this initial response across four domains: model leadership; communication and management of information; planning and improving practice; and protecting worker (and student) health and safety. The adaptation of the model and the analysis of GWSPH's initial response to the pandemic can be useful to other schools of public health and health sciences in the United States and beyond, in preparing for all hazards. We hope that such analysis also informs the current concerns of schools such as return to in-person education as well as planning for future public health crises.

SARS-CoV-2 surveillance and outbreak response on an urban American college campus.

OBJECTIVE: The George Washington University (GW) in Washington, D.C., USA established the Public Health Laboratory and Campus COVID-19 Support Team (CCST) to develop and implement its SARS-CoV-2 surveillance testing and outbreak response for the 2020-2021 academic year. PARTICIPANTS AND METHODS: Approximately 4,000 GW members had access to campus for living accommodations, limited in-person instruction, athletics, research, and university operations. The outbreak response included daily risk assessment surveys, weekly surveillance testing, symptomatic and voluntary testing, case investigation, and contact tracing. RESULTS: Between August 17 - November 24, 2020, 42,350 SARS-CoV-2 PCR tests were performed, and 194 (0.46%) of tests were positive. Surveillance testing identified 59 (30.4%); voluntary testing 97 (50%); and symptomatic testing 30 (15.5%) of the cases, respectively. CONCLUSIONS: Robust testing of asymptomatic people and rapid isolation and quarantine of members who are exposed or infected effectively limited the spread of SARS-CoV-2 during the Fall 2020 semester.

Methyl mercury, but not inorganic mercury, associated with higher blood pressure during pregnancy.

Prior studies addressing associations between mercury and blood pressure have produced inconsistent findings; some of this may result from measuring total instead of speciated mercury. This cross-sectional study of 263 pregnant women assessed total mercury, speciated mercury, selenium, and n-3 polyunsaturated fatty acids in umbilical cord blood and blood pressure during labor and delivery. Models with a) total mercury or b) methyl and inorganic mercury were evaluated. Regression models adjusted for maternal age, race/ethnicity, prepregnancy body mass index, neighborhood income, parity, smoking, n-3 fatty acids and selenium. Geometric mean total, methyl, and inorganic mercury concentrations were 1.40µg/L (95% confidence interval: 1.29, 1.52); 0.95µg/L (0.84, 1.07); and 0.13µg/L (0.10, 0.17), respectively. Elevated systolic BP, diastolic BP, and pulse pressure were found, respectively, in 11.4%, 6.8%, and 19.8% of mothers. In adjusted multivariable models, a one-tertile increase of methyl mercury was associated with 2.83mmHg (0.17, 5.50) higher systolic blood pressure and 2.99mmHg (0.91, 5.08) higher pulse pressure. In the same models, an increase of one tertile of inorganic mercury was associated with -1.18mmHg (-3.72, 1.35) lower systolic blood pressure and -2.51mmHg (-4.49, -0.53) lower pulse pressure. No associations were observed with diastolic pressure. There was a non-significant trend of higher total mercury with higher systolic blood pressure. We observed a significant association of higher methyl mercury with higher systolic and pulse pressure, yet higher inorganic mercury was significantly associated with lower pulse pressure. These results should be confirmed with larger, longitudinal studies.

Prenatal exposure to tobacco smoke leads to increased mitochondrial DNA content in umbilical cord serum associated to reduced gestational age.

We investigated if prenatal exposures to tobacco smoke lead to changes in mitochondrial DNA content (mtDNA) in cord serum and adversely affect newborns' health. Umbilical cord serum cotinine levels were used to determine in utero exposure to smoking. Cord serum mtDNA was measured by quantitative polymerase chain reaction analysis of the genes coding for cytochrome c oxidase1 (MT-CO1) and cytochrome c oxidase2 (MT-CO2). Log transformed levels of mtDNA coding for MT-CO1 and MT-CO2 were significantly higher among infants of active smokers with higher serum level of cotinine (p < 0.05) and inversely associated with gestational age (p = 0.08; p = 0.02). Structural equation modeling results confirmed a positive association between cotinine and MT-CO1 and2 (p < 0.01) and inverse associations with gestational age (p = 0.02) and IGF-1 (p < 0.01). We identified a dose-dependent increase in the level of MT-CO1 and MT-CO2 associated to increased cord serum cotinine and decreased gestational age.

Cord Blood Methylmercury and Fetal Growth Outcomes in Baltimore Newborns: Potential Confounding and Effect Modification by Omega-3 Fatty Acids, Selenium, and Sex.

BACKGROUND: Methylmercury (MeHg) may affect fetal growth; however, prior research often lacked assessment of mercury speciation, confounders, and interactions. OBJECTIVE: Our objective was to assess the relationship between MeHg and fetal growth as well as the potential for confounding or interaction of this relationship from speciated mercury, fatty acids, selenium, and sex. METHODS: This cross-sectional study includes 271 singletons born in Baltimore, Maryland, 2004-2005. Umbilical cord blood was analyzed for speciated mercury, serum omega-3 highly unsaturated fatty acids (n-3 HUFAs), and selenium. Multivariable linear regression models controlled for gestational age, birth weight, maternal age, parity, prepregnancy body mass index, smoking, hypertension, diabetes, selenium, n-3 HUFAs, and inorganic mercury (IHg). RESULTS: Geometric mean cord blood MeHg was 0.94 µg/L (95% CI: 0.84, 1.07). In adjusted models for ponderal index, ßln(MeHg) = -0.045 (g/cm(3)) × 100 (95% CI: -0.084, -0.005). There was no evidence of a MeHg × sex interaction with ponderal index. Contrastingly, there was evidence of a MeHg × n-3 HUFAs interaction with birth length [among low n-3 HUFAs, ßln(MeHg) = 0.40 cm, 95% CI: -0.02, 0.81; among high n-3 HUFAs, ßln(MeHg) = -0.15, 95% CI: -0.54, 0.25; p-interaction = 0.048] and head circumference [among low n-3 HUFAs, ßln(MeHg) = 0.01 cm, 95% CI: -0.27, 0.29; among high n-3 HUFAs, ßln(MeHg) = -0.37, 95% CI: -0.63, -0.10; p-interaction = 0.042]. The association of MeHg with birth weight and ponderal index was affected by n-3 HUFAs, selenium, and IHg. For birth weight, ßln(MeHg) without these variables was -16.8 g (95% CI: -75.0, 41.3) versus -29.7 (95% CI: -93.9, 34.6) with all covariates. Corresponding values for ponderal index were -0.030 (g/cm(3)) × 100 (95% CI: -0.065, 0.005) and -0.045 (95% CI: -0.084, -0005). CONCLUSION: We observed an association of increased MeHg with decreased ponderal index. There is evidence for interaction between MeHg and n-3 HUFAs; infants with higher MeHg and n-3 HUFAs had lower birth length and head circumference. These results should be verified with additional studies.

Optimal Exposure Biomarkers for Nonpersistent Chemicals in Environmental Epidemiology.

We discuss considerations that are essential when evaluating exposure to nonpersistent, semivolatile environmental chemicals such as phthalates and phenols (e.g., bisphenol A). A biomarker should be chosen to best represent usual personal exposures and not recent, adventitious, or extraneous exposures. Biomarkers should be selected to minimize contamination arising from collection, sampling, or analysis procedures. Pharmacokinetics should be considered; for example, nonpersistent, semivolatile chemicals are metabolized quickly, and urine is the compartment with the highest concentrations of metabolites. Because these chemicals are nonpersistent, knowledge of intraindividual reliability over the biologic window of interest is also required. In recent years researchers have increasingly used blood as a matrix for characterizing exposure to nonpersistent chemicals. However, the biologic and technical factors noted above strongly support urine as the optimal matrix for measuring nonpersistent, semivolatile, hydrophilic environmental agents.

Paternal sperm DNA methylation associated with early signs of autism risk in an autism-enriched cohort.

BACKGROUND: Epigenetic mechanisms such as altered DNA methylation have been suggested to play a role in autism, beginning with the classical association of Prader-Willi syndrome, an imprinting disorder, with autistic features. OBJECTIVES: Here we tested for the relationship of paternal sperm DNA methylation with autism risk in offspring, examining an enriched-risk cohort of fathers of autistic children. METHODS: We examined genome-wide DNA methylation (DNAm) in paternal semen biosamples obtained from an autism spectrum disorder (ASD) enriched-risk pregnancy cohort, the Early Autism Risk Longitudinal Investigation (EARLI) cohort, to estimate associations between sperm DNAm and prospective ASD development, using a 12-month ASD symptoms assessment, the Autism Observation Scale for Infants (AOSI). We analysed methylation data from 44 sperm samples run on the CHARM 3.0 array, which contains over 4 million probes (over 7 million CpG sites), including 30 samples also run on the Illumina Infinium HumanMethylation450 (450K) BeadChip platform (∼485 000 CpG sites). We also examined associated regions in an independent sample of post-mortem human brain ASD and control samples for which Illumina 450K DNA methylation data were available. RESULTS: Using region-based statistical approaches, we identified 193 differentially methylated regions (DMRs) in paternal sperm with a family-wise empirical P-value [family-wise error rate (FWER)] <0.05 associated with performance on the Autism Observational Scale for Infants (AOSI) at 12 months of age in offspring. The DMRs clustered near genes involved in developmental processes, including many genes in the SNORD family, within the Prader-Willi syndrome gene cluster. These results were consistent among the 75 probes on the Illumina 450K array that cover AOSI-associated DMRs from CHARM. Further, 18 of 75 (24%) 450K array probes showed consistent differences in the cerebellums of autistic individuals compared with controls. CONCLUSIONS: These data suggest that epigenetic differences in paternal sperm may contribute to autism risk in offspring, and provide evidence that directionally consistent, potentially related epigenetic mechanisms may be operating in the cerebellum of individuals with autism.

Prenatal mercury concentration is associated with changes in DNA methylation at TCEANC2 in newborns.

BACKGROUND: Human exposure to the widespread environmental contaminant mercury is a known risk factor for common diseases such as cancer, cardiovascular disease and neurological disorders through poorly characterized mechanisms. Evidence suggests mercury exposure may alter DNA methylation levels, but to date, the effects in early life on a genome-wide scale have not been investigated. METHODS: A study sample of 141 newborns was recruited in Baltimore, MD, USA and total mercury and methylmercury were measured in cord blood samples. We quantified genome-wide DNA methylation data using CHARM 2.0, an array-based method, and used region-finding analyses to identify concentration-associated differentially methylated regions (DMRs). To test for replication of these identified DMRs in the pilot, or Vanguard, phase of the National Children's Study (NCS), we compared bisulfite-pyrosequenced DNA at candidate regions from 85 whole cord blood samples with matched first trimester maternal mercury concentration measures. RESULTS: Total mercury concentration was associated with methylation at DMRs inside ANGPT2 and near PRPF18 genes [false discovery rate (FDR) < 0.05], as well as DMRs near FOXD2 and within TCEANC2 (FDR< 0.1) genes. Methylmercury concentration was associated with an overlapping DMR within TCEANC2 (FDR< 0.05). In NCS replication analyses, methylation levels at three of four cytosine-guanine DNA dinucleotides (CpG sites) within the TCEANC2 DMR were associated with total mercury concentration (P < 0.05), and this association was diminished after adjusting for estimated cell proportions. CONCLUSIONS: Evidence for an association between mercury and DNA methylation at the TCEANC2 region was found, which may represent a mercury-associated shift in cord blood cell composition or a change in methylation within blood cell types. Further confirmatory studies are needed.

Elucidating the molecular basis of adverse health effects from exposure to anthropogenic polyfluorinated compounds using toxicoproteomic approaches.

Linear, short-chain polyfluorinated and perfluorinated alkyl compounds, often referred to as PFCs, have been in worldwide use as surfactants and polymer precursors for decades, and environmental dispersal of these highly persistent compounds represents a public health threat. Whereas ubiquitous low-level exposure to these compounds has been demonstrated in human populations from around the world, the exact mechanisms of toxicity and their toxic potency remain subject to investigation and scientific dispute. As with other environmental exposures, a major hurdle for gaining a better understanding of their human health impacts is the limited utility of cell culture and animal models serving as convenient, yet imperfect proxies to human physiology and disease. The present communication provides a brief overview of the current understanding of potential health effects of PFC exposure and examines how new toxicoproteomic methodologies can provide insight into the molecular mechanism of PFC exposure. Furthermore, we showcase an exemplary data set to illustrate how toxicoproteomic, population-wide studies might overcome limitations of animal models to more fully understand the metabolism and effects of PFCs and other environmental stressors where it matters most, in human populations experiencing real-world, chronic, low-level exposures.

Chemical safety, health care costs and the Affordable Care Act.

On May 22, 2013, the late Senator Frank Lautenberg (D-NJ), Senator David Vitter (R-LA) and 19 of their colleagues introduced bipartisan chemical safety legislation in the US Senate, "The Chemical Safety Improvement Act of 2013." The bill's purpose is to protect human health and the environment against the hazards of toxic chemicals, by requiring the US Environmental Protection Agency (EPA) to examine the safety of all chemicals in consumer products. The bill is currently before the Senate Committee on Environment and Public Works, chaired by Senator Barbara Boxer (D-CA). This legislation is critically important for physicians and healthcare organizations because it creates significant new opportunities to prevent disease and cut healthcare costs.