Abstract
Background
The evidence base for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is nascent. We sought to characterize SARS-CoV-2 transmission within US households and estimate ...the household secondary infection rate (SIR) to inform strategies to reduce transmission.
Methods
We recruited patients with laboratory-confirmed SARS-CoV-2 infection and their household contacts in Utah and Wisconsin during 22 March 2020–25 April 2020. We interviewed patients and all household contacts to obtain demographics and medical histories. At the initial household visit, 14 days later, and when a household contact became newly symptomatic, we collected respiratory swabs from patients and household contacts for testing by SARS-CoV-2 real-time reverse-transcription polymerase chain reaction (rRT-PCR) and sera for SARS-CoV-2 antibodies testing by enzyme-linked immunosorbent assay (ELISA). We estimated SIR and odds ratios (ORs) to assess risk factors for secondary infection, defined by a positive rRT-PCR or ELISA test.
Results
Thirty-two (55%) of 58 households secondary infection among household contacts. The SIR was 29% (n = 55/188; 95% confidence interval CI, 23%–36%) overall, 42% among children (aged <18 years) of the COVID-19 patient and 33% among spouses/partners. Household contacts to COVID-19 patients with immunocompromised conditions and household contacts who themselves had diabetes mellitus had increased odds of infection with ORs 15.9 (95% CI, 2.4–106.9) and 7.1 (95% CI: 1.2–42.5), respectively.
Conclusions
We found substantial evidence of secondary infections among household contacts. People with COVID-19, particularly those with immunocompromising conditions or those with household contacts with diabetes, should take care to promptly self-isolate to prevent household transmission.
The 2 most widely used criteria to diagnose the metabolic syndrome (MS) are those developed by the United States Adult Treatment Panel III of the National Cholesterol Education Program (ATP III) and ...by the International Diabetes Federation (IDF). A major difference between these 2 sets of criteria is that the IDF places more emphasis on waist circumference. We compared the prevalence of MS using the ATP III and the IDF guidelines in 2 American (the Dallas Health Study and National Health and Nutrition Examination Survey) and 1 German (Prospective Cardiovascular Munster study) population samples. When the ATP III criteria were used, the prevalence of MS was higher in the United States than the German samples in both women (37% vs. 18%) and men (30% vs 25%), whereas when the IDF criteria were used, the prevalence of MS was 25% higher in the German than the American sample. Although in the United States both sets of criteria identified mostly the same people (concordance of about 90%), this was less true in Germany (concordance about 80%). To determine which criteria better predicted adverse cardiovascular outcomes, the incidence of coronary events associated with MS, as defined using the ATP III or the IDF criteria, were compared over a 10-year period among the middle-aged men in the German sample (n = 7,152). A total of 3.4% of men without MS developed an event. A much higher percentage of the men with MS defined by the ATP III criteria (10.7%) than the IDF criteria (5.5%) had a cardiovascular event. In conclusion, although the prevalence of MS was higher when the IDF criteria were used in the German sample, the IDF criteria have lower predictive power for coronary events.
•Checking vaccination status at school was reported by 77% of the countries in 2018•Individual home-based records were the most frequently checked document•Children were most often referred to health ...centers to receive missed vaccines•Checking vaccination status at school was infrequently monitored or evaluated
Checking vaccination status at school is widely recommended as a strategy to strengthen routine childhood vaccination coverage. Documentation of approaches, challenges, strengths, and impact of this strategy in a variety of contexts is key to enhancing adoption and implementation. However, there is limited information about the prevalence of policies and the implementation of checking vaccination status at school globally.
A one-time supplementary survey was circulated with the annual World Health Organization (WHO) and United Nations International Children’s Emergency Fund (UNICEF) Joint Reporting Form in 2019 to all WHO member states and non-member state reporting entities. Additional publicly available country-level data, including primary school enrollment, home-based record (HBR) ownership, and World Bank income classification were linked to the supplementary survey responses, which were descriptively analyzed.
We received survey responses from 130 of the 194 (67%) WHO member states and 15 non-member state reporting entities. Almost half (46%) of the respondents reported having a law requiring proof of vaccination to enter at least one level of education, and 60% of the respondents reported having a law that requires checking vaccination status at school in 2018. Three-quarters of the respondents (77%) reported the practice of routinely checking vaccination status at school. Both laws and the practice of checking were more common in the WHO Region of the Americas and the WHO European Region, and in high- and upper-middle-income countries. Individual HBR was the document most frequently checked. Catch-up vaccination occurred most frequently at health centers. Evaluation of checking vaccination status at school to determine what has worked and its effect was infrequently reported.
Despite widespread implementation of checking vaccination status at school in 2018, documentation of the experiences in planning and implementing this strategy, and its effects remains sparse, particularly in low- and middle-income countries.
Limited data exist on severe acute respiratory syndrome coronavirus 2 in children. We described infection rates and symptom profiles among pediatric household contacts of individuals with coronavirus ...disease 2019.
We enrolled individuals with coronavirus disease 2019 and their household contacts, assessed daily symptoms prospectively for 14 days, and obtained specimens for severe acute respiratory syndrome coronavirus 2 real-time reverse transcription polymerase chain reaction and serology testing. Among pediatric contacts (<18 years), we described transmission, assessed the risk factors for infection, and calculated symptom positive and negative predictive values. We compared secondary infection rates and symptoms between pediatric and adult contacts using generalized estimating equations.
Among 58 households, 188 contacts were enrolled (120 adults; 68 children). Secondary infection rates for adults (30%) and children (28%) were similar. Among households with potential for transmission from children, child-to-adult transmission may have occurred in 2 of 10 (20%), and child-to-child transmission may have occurred in 1 of 6 (17%). Pediatric case patients most commonly reported headache (79%), sore throat (68%), and rhinorrhea (68%); symptoms had low positive predictive values, except measured fever (100%; 95% confidence interval CI: 44% to 100%). Compared with symptomatic adults, children were less likely to report cough (odds ratio OR: 0.15; 95% CI: 0.04 to 0.57), loss of taste (OR: 0.21; 95% CI: 0.06 to 0.74), and loss of smell (OR: 0.29; 95% CI: 0.09 to 0.96) and more likely to report sore throat (OR: 3.4; 95% CI: 1.04 to 11.18).
Children and adults had similar secondary infection rates, but children generally had less frequent and severe symptoms. In two states early in the pandemic, we observed possible transmission from children in approximately one-fifth of households with potential to observe such transmission patterns.
Abstract
Background
Improved understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spectrum of disease is essential for clinical and public health interventions. There are ...limited data on mild or asymptomatic infections, but recognition of these individuals is key as they contribute to viral transmission. We describe the symptom profiles from individuals with mild or asymptomatic SARS-CoV-2 infection.
Methods
From 22 March to 22 April 2020 in Wisconsin and Utah, we enrolled and prospectively observed 198 household contacts exposed to SARS-CoV-2. We collected and tested nasopharyngeal specimens by real-time reverse-transcription polymerase chain reaction (rRT-PCR) 2 or more times during a 14-day period. Contacts completed daily symptom diaries. We characterized symptom profiles on the date of first positive rRT-PCR test and described progression of symptoms over time.
Results
We identified 47 contacts, median age 24 (3–75) years, with detectable SARS-CoV-2 by rRT-PCR. The most commonly reported symptoms on the day of first positive rRT-PCR test were upper respiratory (n = 32 68%) and neurologic (n = 30 64%); fever was not commonly reported (n = 9 19%). Eight (17%) individuals were asymptomatic at the date of first positive rRT-PCR collection; 2 (4%) had preceding symptoms that resolved and 6 (13%) subsequently developed symptoms. Children less frequently reported lower respiratory symptoms (21%, 60%, and 69% for <18, 18–49, and ≥50 years of age, respectively; P = .03).
Conclusions
Household contacts with laboratory-confirmed SARS-CoV-2 infection reported mild symptoms. When assessed at a single timepoint, several contacts appeared to have asymptomatic infection; however, over time all developed symptoms. These findings are important to inform infection control, contact tracing, and community mitigation strategies.
Optimized symptom-based COVID-19 case definitions that guide public health surveillance and individual patient management in the community may assist pandemic control.
We assessed diagnostic ...performance of existing cases definitions (e.g. influenza-like illness, COVID-like illness) using symptoms reported from 185 household contacts to a PCR-confirmed case of COVID-19 in Wisconsin and Utah, United States. We stratified analyses between adults and children. We also constructed novel case definitions for comparison.
Existing COVID-19 case definitions generally showed high sensitivity (86-96%) but low positive predictive value (PPV) (36-49%; F-1 score 52-63) in this community cohort. Top performing novel symptom combinations included taste or smell dysfunction and improved the balance of sensitivity and PPV (F-1 score 78-80). Performance indicators were generally lower for children (< 18 years of age).
Existing COVID-19 case definitions appropriately screened in household contacts with COVID-19. Novel symptom combinations incorporating taste or smell dysfunction as a primary component improved accuracy. Case definitions tailored for children versus adults should be further explored.
It has been long believed that long-term potentiation (LTP) and long-term depression (LTD) are the primary mechanisms for encoding memory. However, causal evidence of this has thus far been elusive. ...Here we demonstrate a causal relationship between these mechanisms of plasticity and associative fear memory in rats. Using optogenetic targeting of auditory inputs to the lateral amygdala, an associative memory can be formed through light stimulation paired with foot-shock. Following this conditioning, fear memory can be activated through light stimulation as demonstrated by freezing and avoidance of a strongly rewarding task. LTD induction through low frequency stimulus leads to removal of this memory, demonstrated by continued reward task activity during light stimulation. Subsequent LTP induction through high frequency stimulation leads to restoration of the memory, as shown by restored freezing and award task avoidance during light stimulation. Using this simple series of experiments we have demonstrated the removal and reinstatement of a memory using LTD and LTP, thus demonstrating a causal relationship between these synaptic processes and memory.
This thesis addresses using haplotypes to detect disease predisposing chromosomal regions based on a Bayesian hierarchical model for case-control data. By utilizing the Stochastic Search Variable ...Selection (SSVS) procedure of George and McCulloch (1997), the number of parameters is riot constrained by the sample size, as are the frequentist methods. Haplotype information is used in the form of estimated haplotype frequencies, and using these values in the model as if they were the true population frequencies. A Bayesian hierarchical probit model was developed by estimating the distribution of haplotype pairs for an individual based on these estimated populaltion frequencies and using SSVS to make decisions about model selection. To date, Bayesian models for haplotype based case-control data assume either the haplotypes are known, or that haplotypes can be clustered such that every haplotype within a cluster has the same effect on disease status. A simulation was performed analyzing the testing properties of this Bayesian model and comparing it to a popular frequentist method (Schaid, 2002). Both real genotype data from the Dallas Heart Study (DHS) and simulated data were used to study the operating characteristics of the new model The Bayesian method is shown to have higher power than Schaid's frequentist method when there are a limited number of common haplotypes in a region, a situation that appears to be common (Gabriel, 2002). An approach based on the maximum of Chi-squared statistics at each marker locus performed suprisingly well against both haplotype methods in various cases. These simulations contribute to the ongoing debate on the efficacy of haplotype methods. The most suprising result was the ability of the genotype methods to outperform the haplotype methods in various instances where there were cis-acting interactions. The Bayesian haplotype method performed better in comparison when dealing with low penetrance in highly conserved blocks. Additionally, a set of simulations were based on a number of genes from the DHS data set with multiple haplotype block regions. This demonstrated the similarities of the haplotype methods and the added flexibility when analyzing posterior distributions. We also demonstrate that interactions between loci in separate blocks can be detected without having interaction terms in the regression model. Future work should focus on more efficient methods of detecting these and other complex interactions.
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