Breummosley5631

astmilk.Wastewater-based disease surveillance is a promising approach for monitoring community outbreaks. Here we describe a nationwide campaign to monitor SARS-CoV-2 in the wastewater of 159 counties in 40 U.S. states, covering 13% of the U.S. population from February 18 to June 2, 2020. Out of 1,751 total samples analyzed, 846 samples were positive for SARS-CoV-2 RNA, with overall viral concentrations declining from April to May. Wastewater viral titers were consistent with, and appeared to precede, clinical COVID-19 surveillance indicators, including daily new cases. Wastewater surveillance had a high detection rate (>80%) of SARS-CoV-2 when the daily incidence exceeded 13 per 100,000 people. Detection rates were positively associated with wastewater treatment plant catchment size. To our knowledge, this work represents the largest-scale wastewater-based SARS-CoV-2 monitoring campaign to date, encompassing a wide diversity of wastewater treatment facilities and geographic locations. Our findings demonstrate that a national wastewater-based approach to disease surveillance may be feasible and effective.

There is considerable variability in COVID-19 outcomes amongst younger adults-and some of this variation may be due to genetic predisposition. We characterized the clinical implications of the major genetic risk factor for COVID-19 severity, and its age-dependent effect, using individual-level data in a large international multi-centre consortium.

The major common COVID-19 genetic risk factor is a chromosome 3 locus, tagged by the marker rs10490770. We combined individual level data for 13,424 COVID-19 positive patients (N=6,689 hospitalized) from 17 cohorts in nine countries to assess the association of this genetic marker with mortality, COVID-19-related complications and laboratory values. We next examined if the magnitude of these associations varied by age and were independent from known clinical COVID-19 risk factors.

We found that rs10490770 risk allele carriers experienced an increased risk of all-cause mortality (hazard ratio [HR] 1·4, 95% confidence interval [CI] 1·2-1·6) and COVID-19 related ciated with increased risks of morbidity and mortality-and these are more pronounced amongst individuals ≤ 60 years. The effect on COVID-19 severity was similar to, or larger than most established risk factors, suggesting potential implications for clinical risk management.

Funding was obtained by each of the participating cohorts individually.

Funding was obtained by each of the participating cohorts individually.While vaccines that protect against SARS-CoV-2 are being approved, the number of available doses is limited as it may take months until the production of vaccines can meet the actual demand. The majority of available SARS-CoV-2 vaccines elicits strong immune responses when administered as prime-boost regimens. Since the immunological response to the first ("prime") injection may provide already a substantial reduction in infectiousness and protection against severe disease, it may be more effective-under certain conditions-to vaccinate as many people as possible with only one shot, instead of administering a person a second ("boost") shot. Such a strategic vaccination campaign may help to more effectively slow down the spread of SARS-CoV-2, reduce hospitalizations, and reduce fatalities. Yet, the conditions which make single-dose vaccination favorable over prime-boost administrations are not well understood. Here, we formulate a model that helps explore these decisive conditions as a function of the various time scales and epidemiological mechanisms at work. We study how these conditions arise from disease prevalence, vaccination rates, basic reproduction number, prime and prime-boost efficacies, prime-boost intervals, and waning rates. GC7 nmr By combining epidemiological modeling, random sampling techniques, and decision tree learning, we find that prime-first vaccination is robustly favored over prime-boost vaccination campaigns, even for high vaccination rates, high disease prevalence, and a relatively low single-dose efficacy.

The viral entry of SARS-CoV-2 requires host-expressed TMPRSS2 to facilitate the viral spike (S) protein priming.

To test the hypothesis that Mg treatment leads to DNA methylation changes in

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This study is nested within the Personalized Prevention of Colorectal Cancer Trial (PPCCT), a double-blind 2×2 factorial randomized controlled trial, which enrolled 250 participants from Vanderbilt University Medical Center. Target doses for both Mg and placebo arms were personalized.

We found that 12-week of personalized Mg treatment significantly increased 5-mC methylation at cg16371860 (TSS1500, promoter) by 7.2% compared to placebo arm (decreased by 0.1%) in those aged < 65 years old. The difference remained statistically significant after adjusting for age, sex and baseline methylation as well as FDR correction (FDR-adjusted

=0.014). Additionally, Mg treatment significantly reduced 5-hmC level at cg26337277 (close proximity to TSS200 and 5'UTR, promoter) by 2.3% compared to increases by 7.1% in the modifying the phenotype of the TMPRSS2 genotype.

Covid-19 is a triphasic disorder first typified by a viral phase that lasts from the first onset of symptoms until seven days later. This is followed by a second and third phase, initially characterized by the appearance of lung infiltrates, followed in 20% by respiratory failure. The second phase is usually heralded by an elevation of serologic inflammatory markers including CRP, ferritin, IL-6, LDH as well as D-dimers. Approximately 20% proceed to the second phase and are usually then treated with dexamethasone, provided they are oxygen-dependent since these are the only cases that benefit from dexamethasone. If we had objective criteria to predict this 20% that develop severe illness, they could preemptively be treated with steroids. In this exploratory study we investigated the early use of preemptive steroids in the setting of early disease, in high-risk non-oxygen dependent cases.

Eligible patients were those 21 years or older with a diagnosis of Covid-19 and oxygen saturation ≥91%. For patients to so assessed.

In 76 patients, the expected number with respiratory failure was 30 (39.5%), yet only 4 (5.3%) developed that complication (p=.00001). Survival at 28 days was 98.6%.Improvement in inflammatory markers correlated with favorable outcome.

Our results are encouraging and suggest that this approach is both effective and safe.

Our results are encouraging and suggest that this approach is both effective and safe.Serological tests are an indispensable tool to understand the epidemiology of the SARS-CoV-2 pandemic, particularly in areas where molecular diagnostics are limited. Poor assay performance may hinder the utility of these tests, including high rates of false-positivity previously reported in sub-Saharan Africa. From 312 Malian samples collected prior to 2020, we measured antibodies to the commonly tested SARS-CoV-2 antigens and four other betacoronaviruses by ELISA, and assessed functional cross-reactivity in a subset by SARS-CoV-2 pseudovirus neutralization assay. We then evaluated the performance of an ELISA developed in the US, using two-antigen SARS-CoV-2 spike protein and receptor-binding domain. To optimize test performance, we compared single and two-antigen approaches using existing assay cutoffs and population-specific cutoffs for Malian control samples (positive and negative). Background reactivity to SARS-CoV-2 antigens was common in pre-pandemic samples compared to US controls (43.4% (135/311) for spike protein, 22.8% (71/312) for RBD, and 33.9% (79/233) for nucleocapsid protein). SARS-CoV-2 reactivity correlated weakly with other betacoronavirus reactivity, varied between Malian communities, and increased with age. No pre-pandemic samples demonstrated functional activity. Regardless of the cutoffs applied, specificity improved using a two-antigen approach. Test performance was optimal using a two-antigen assay with population-specific cutoffs derived from ROC curve analysis [Sensitivity 73.9% (51.6-89.8), Specificity 99.4% (97.7-99.9)]. In the setting of high background reactivity, such as sub-Saharan Africa, SARS-CoV-2 serological assays need careful qualification is to characterize the epidemiology of disease, prevent unnecessary harm, and allocate resources for targeted control measures.

To mitigate the COVID-19 pandemic and prevent overwhelming the healthcare system, social-distancing policies such as school closure, stay-at-home orders, and indoor dining closure have been utilized worldwide. These policies function by reducing the rate of close contact within populations and results in decreased human mobility. Adherence to social distancing can substantially reduce disease spread. Thus, quantifying human mobility and social-distancing compliance, especially at high temporal resolution, can provide great insight into the impact of social distancing policies.

We used the movement of individuals around New York City (NYC), measured via traffic levels, as a proxy for human mobility and the impact of social-distancing policies (i.e., work from home policies, school closure, indoor dining closure etc.). By data mining Google traffic in real-time, and applying image processing, we derived high resolution time series of traffic in NYC. We used time series decomposition and generalized additivel impact of large-scale traffic interventions such as congestion pricing policies.

We aimed to characterize the variability in the illness experience and recovery process from COVID-19. We conducted in-depth individual interviews with participants enrolled in the Long-term Immunological Impact of Novel Coronavirus (LIINC) cohort study in San Francisco, California from June through October of 2020. Participants were adults who had a previously confirmed positive SARV-CoV-2 nucleic acid amplification test result, had recovered or were recovering from acute infection, and underwent serial evaluations at our clinical research center. We purposefully sampled 24 English- and Spanish-speaking adults with asymptomatic, mild and severe symptomatic infection, including those who were hospitalized, and those with HIV co-infection. Half of our sample (50.0%) identified as Latinx/Hispanic and most of the participants were men (62.5%). We used thematic analysis to characterize the illness experience, recovery process, and mental health impact of experiencing COVID-19 and present clinical data for each participant. Emergent themes were (1) across symptom profiles and severity, experiencing COVID-19 was associated with psychological distress, (2) among participants with symptomatic infection, the illness experience was characterized by uncertainty in terms of managing symptoms and recovery, and (3) despite wide-ranging illness experiences, participants shared many common characteristics, including health information-seeking behavior facilitated by access to medical care, and uncertainty regarding the course of their illness and recovery. COVID-19 was associated with elevated levels of psychological distress, regardless of symptoms.

DNA methylation patterns of the human genome can be modified by environmental stimuli and provide dense information on gene regulatory circuitries. We studied genome-wide DNA methylation in nasal samples from infants (<6 months) applying whole-genome bisulfite sequencing (WGBS) to characterize epigenome response to 10 different respiratory viral infections including SARS-CoV-2.

We identified virus-specific differentially methylated regions (vDMR) with human metapneumovirus (hMPV) and SARS-CoV-2 followed by Influenza B (Flu B) causing the weakest vs. strongest epigenome response with 496 vs. 78541 and 14361 vDMR, respectively. We found a strong replication rate of FluB (52%) and SARS-CoV-2 (42%) vDMR in independent samples indicating robust epigenome perturbation upon infection. Among the FluB and SARS-CoV-2 vDMRs, around 70% were hypomethylated and significantly enriched among epithelial cell-specific regulatory elements whereas the hypermethylated vDMRs for these viruses mapped more frequently to immune cell regulatory elements, especially those of the myeloid lineage.