Improved evaluation of left ventricular hypertrophy using the spatial QRS-T angle by electrocardiography

Background: Conventional electrocardiographic (ECG) signs of left ventricular hypertrophy lack sensitivity, The aim was to identify LVH based on an abnormal spatial peaks QRS-T angle, and evaluate its diagnostic and prognostic performance compared to that of conventional ECG criteria for LVH. Methods: This was an observational study with four cohorts, all with a QRS duration <120 ms: (1) Healthy volunteers to define normality (n=921), (2) Separate healthy volunteers to compare test specificity (n=461), (3) Patients with at least moderate LVH by cardiac imaging (Imaging-LVH) to compare test sensitivity (n=225), and (4) Patients referred for cardiovascular magnetic resonance imaging to evaluate the combined outcome of hospitalization for heart failure or all-cause death (Clinical-Consecutive, n=783). Results: An abnormal spatial peaks QRS-T angle was defined as exceeding the upper limit of normal, which was found to be ≥40° for females and ≥55° for males. In healthy volunteers, the specificity of the QRS-T angle to detect LVH was 96% (females) and 98% (males). In Imaging-LVH, the QRS-T angle had a higher sensitivity to detect LVH than conventional ECG criteria (93-97% vs 13-56%, p<0.001 for all). In Clinical-Consecutive, of those who did not have any LVH, 238/556 (43%) had an abnormal QRS-T angle, suggesting it can occur even without LVH. There was an association with outcomes in univariable analysis for the QRS-T angle, Cornell voltage, QRS duration, and Cornell product (hazard ratios 1.68-2.5, p<0.01 for all) that persisted in multivariable analysis only for the QRS-T angle and QRS duration (p<0.001 for both). Conclusions: An increased QRS-T angle rarely occurred in healthy volunteers, was a mainstay of moderate or greater LVH, was common in clinical patients without LVH but with cardiac co-morbidities, associated with outcomes. Thus, an increased QRS-T angle identifies left ventricular electrical remodeling that can occur in the absence of LVH detected by imaging. The improved diagnostic and independent prognostic performance for the QRS-T angle suggests that it should be investigated when ECGs are evaluated.

High variability in transmission of SARS-CoV-2 within households and implications for control

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a high risk of transmission in close-contact indoor settings, which may include households. Prior studies have found a wide range of household secondary attack rates and may contain biases due to simplifying assumptions about transmission variability and test accuracy. Methods We compiled serological SARS-CoV-2 antibody test data and prior SARS-CoV-2 test reporting from members of 9,224 Utah households. We paired these data with a probabilistic model of household importation and transmission. We calculated a maximum likelihood estimate of the importation probability, mean and variability of household transmission probability, and sensitivity and specificity of test data. Given our household transmission estimates, we estimated the threshold of non-household transmission required for epidemic growth in the population. Results We estimated that individuals in our study households had a 0.41% (95% CI 0.32%– 0.51%) chance of acquiring SARS-CoV-2 infection outside their household. Our household secondary attack rate estimate was 36% (27%– 48%), substantially higher than the crude estimate of 16% unadjusted for imperfect serological test specificity and other factors. We found evidence for high variability in individual transmissibility, with higher probability of no transmissions or many transmissions compared to standard models. With household transmission at our estimates, the average number of non-household transmissions per case must be kept below 0.41 (0.33–0.52) to avoid continued growth of the pandemic in Utah. Conclusions Our findings suggest that crude estimates of household secondary attack rate based on serology data without accounting for false positive tests may underestimate the true average transmissibility, even when test specificity is high. Our finding of potential high variability (overdispersion) in transmissibility of infected individuals is consistent with characterizing SARS-CoV-2 transmission being largely driven by superspreading from a minority of infected individuals. Mitigation efforts targeting large households and other locations where many people congregate indoors might curb continued spread of the virus.

Trends in SARS-CoV-2 seroprevalence in Massachusetts estimated from newborn screening specimens

Background. Estimating the cumulative incidence of SARS-CoV-2 is essential for setting public health policies. We leveraged de-identified Massachusetts newborn screening specimens to generate an accessible, retrospective source of maternal antibodies for estimating statewide SARS-CoV-2 seroprevalence in a non-test-seeking population. Methods. We analyzed 72,117 newborn dried blood spots collected from November 2019 through December 2020, representing 337 towns and cities across Massachusetts. Seroprevalence was estimated for the general Massachusetts population after correcting for imperfect test specificity and nonrepresentative sampling using Bayesian multilevel regression and poststratification. Results. Statewide seroprevalence was estimated to be 0.03% (90% credible interval (CI) [0.00, 0.11]) in November 2019 and rose to 1.47% (90% CI [1.00, 2.13]) by May 2020, following sustained SARS-CoV-2 transmission in the spring. Seroprevalence plateaued from May onwards, reaching 2.15% (90% CI [1.56, 2.98]) in December 2020. Seroprevalence varied substantially by community and was particularly associated with community percent non-Hispanic Black (β = 0.024, 90% CI [0.004, 0.044]); i.e., a 10% increase in community percent non-Hispanic Black was associated with a 27% higher odds of seropositivity. Seroprevalence estimates had good concordance with reported case counts and wastewater surveillance for most of 2020, prior to the resurgence of transmission in winter. Conclusions. Cumulative incidence of SARS-CoV-2 protective antibody in Massachusetts was low as of December 2020, indicating that a substantial fraction of the population was still susceptible. Maternal seroprevalence data from newborn screening can inform longitudinal trends and identify cities and towns at highest risk, particularly in settings where widespread diagnostic testing is unavailable.

A community detection study: Two replicated distinct subgroups in autistic adults

Psychiatric conditions, such as Autism Spectrum Condition (ASC) are marked by large heterogeneity, which complicates providing tailored support and prognosis. In this study, we aim to identify homogeneous subgroups in autistic adults using community detection. We included 14 variables related to aging with ASC (i.e., demographic, psychological and lifestyle), measured by questionnaires. Community detection analysis was used for subgroup identification in 133 autistic adults and 62 non-autistic comparisons (age 31-89 years). We replicated our findings in a separate sample (Nautistic = 277; Ncomparisons=384; age 30-92 years). For more insight into heterogeneity within ASC, we performed separate community detection analyses in the ASC subsamples. To test the external validity of the ASC subgroups, we compared them on cognitive failures, quality of life, and psychological difficulties. To test specificity, we repeated the community detection analysis after adding 62 adults with ADHD. The ASC and COMP groups formed distinct subgroups. Within the ASC group, we identified three subgroups, of which two were replicated. We identified a “High social, High Grip” subgroup and a “Low social, low grip” subgroup. The “Low social, low grip” reported the most cognitive failures, lowest quality of life, and most psychological difficulties. Addition of an ADHD group did not alter the subgrouping results. Autistic adults are distinct from comparisons on the considered variables. Within autistic adults, one subgroup seems to have less grip on life and could in the long-term benefit from more support, although this must be confirmed in longitudinal and intervention studies.

Development and evaluation of an indirect ELISA for detection of Teladorsagia circumcincta infection in sheep

Background The gastrointestinal helminth, Teladorsagia circumcincta, is one of the major health risks and production-limiting diseases in small ruminant populations, particularly in temperate regions. With the increasing importance of disease management and recruited anthelmintic resistant types, accurate approaches are needed for the diagnosis of the infection in the host. Due to uncertain results using faecal examinations, the ELISA method was indicated for the detection of nematode antigenic materials. Despite some promising results, problems were described in terms of test specificity and cross-reactions. Therefore, this study aimed to evaluate the IgG response to worm somatic and excretory/secretory (ES) products using western blot analysis and an indirect ELISA for the detection of T. circumcincta infection in sheep. Results Based on the immuno-reactivity analysis, immunogenic fractions with molecular weights (MWs) of approximately 60, 75 and 100 kDa were detected in somatic content and two antigens of about 63 and 75 kDa in ES material. Accordingly, a specific product at 75 kDa had the strongest reaction and appeared as the most common antigenic protein. In ELISA, all the sera from the infected sheep revealed the OD rates above the calculated cut-off value with about two-fold greater average. Negative control samples were also specifically recognized with the mean OD rate of about 1/3 of the estimated cut-off value. The cross-reaction test, using rabbit anti-T. circumcincta IgG, did not show reactivity with the ES antigens of other prevalent nematodes including Haemonchus contortus, Protostrongylus rufescens and Marshallagia marshalli. In contrast, a strong positive reaction was observed with the somatic antigens of M. marshalli. Conclusions The results of this study indicated that the indirect ELISA method using the ES content enables distinguishing the T. circumcincta infected sheep with high specificity. Those antigenic ES peptides with 63 and particularly 75 kDa MWs should be further investigated due to the potential for serological diagnostic methods and immunoprotective targets in the host.

Diagnostic accuracy of the Cepheid 3-gene host response fingerstick blood test in a prospective, multi-site study: interim results

Background The development of a fast and accurate, non-sputum-based point-of-care triage test for tuberculosis (TB) would have a major impact on combating the TB burden worldwide. A new fingerstick blood test has been developed by Cepheid (the Xpert-MTB-Host Response (HR)-Prototype), which generates a ‘TB score’ based on mRNA expression of 3 genes. Here we describe the first prospective findings of the MTB-HR prototype. Methods Fingerstick blood from adults presenting with symptoms compatible with TB in South Africa, The Gambia, Uganda and Vietnam was analysed using the Cepheid GeneXpert MTB-HR prototype. Accuracy of the Xpert MTB-HR cartridge was determined in relation to GeneXpert Ultra results and a composite microbiological score (GeneXpert Ultra and liquid culture) with patients classified as having TB or other respiratory diseases (ORD). Results When data from all sites (n=75 TB, 120 ORD) were analysed, the TB score discriminated between TB and ORD with an AUC of 0·94 (CI, 0·91-0·97), sensitivity of 87% (CI, 77-93%) and specificity of 94% (88-97%). When sensitivity was set at 90% for a triage test, specificity was 86% (CI, 75-97%). These results were not influenced by HIV status or geographical location. When evaluated against a composite microbiological score (n=80 TB, 111 ORD), the TB score was able to discriminate between TB and ORD with an AUC of 0·88 (CI, 0·83-0·94), 80% sensitivity (CI, 76-85%) and 94% specificity (CI, 91-96%). Conclusions Our interim data indicate the Cepheid MTB-HR cartridge reaches the minimal target product profile for a point of care triage test for TB using fingerstick blood, regardless of geographic area or HIV infection status.

Comparative analyses of all FDA EUA-approved rapid antigen tests and RT-PCR for COVID-19 quarantine and surveillance-based isolation

Rapid antigen (RA) tests are being increasingly employed to detect COVID-19 infections in quarantine and surveillance. We conducted a comparative analysis of quarantine durations, testing frequencies, and false-positive rates for all of the 18 RA tests with emergency use authorization (EUA) from the FDA, and an RT-PCR test. For each test, we employed a mathematical model of imminent infections to calculate the effective reproductive number in the context of the test used for quarantine or serial testing. We informed the model with data on test specificity, temporal diagnostic sensitivity, and COVID-19 infectiousness. Our results demonstrate that the relative effectiveness of RA and RT-PCR tests in reducing post-quarantine transmission depends on the quarantine duration and the turnaround time of testing results. For quarantines shorter than five days, RA test on entry to and on exit from quarantine reduced onward transmission more than a single RT-PCR test conducted upon exit. Conducting surveillance via serial RT-PCR testing with a 24-h turnaround time, the minimum testing frequency paired with isolation of positives that is required to suppress the effective reproduction number (RE) below one was found to be every six days. RA tests reduce RE below one when conducted at a minimum frequency that ranges from every six days to every eight days. Our analysis also highlights that the risk of onward transmission during serial testing increases with the delay in obtaining the results. These RA test-specific results are an important component of the tool set for policy decision-making, and demonstrate that judicious selection of an appropriate RA test can supply a viable alternative to RT-PCR in efforts to control the spread of disease.

Specificity of SARS-CoV-2 antibody-detection assays against S and N protein among pre-COVID-19 sera from patients with protozoan and helminth parasitic infections

Background: We aimed to assess the specificity of SARS-CoV-2 antibody detection assays among people with known tissue-borne parasitic infections. Methods: We tested three SARS-CoV-2 antibody-detection assays (cPass SARS-CoV-2 Neutralization Antibody Detection Kit, Abbott SARS-CoV-2 IgG assay, and STANDARD Q COVID-19 IgM/IgG Combo Rapid Test) among 559 pre-COVID-19 sera. Results: The specificity of assays was 95-98% overall. However, lower specificity was observed among sera from patients with protozoan infections of the reticuloendothelial system, such as human African trypanosomiasis (Abbott Architect; 88% [95%CI 75-95]), visceral leishmaniasis (SD RDT IgG; 80% [95%CI 30-99]), and from patients with recent malaria from a holoendemic area of Senegal (ranging from 91% for Abbott Architect and SD RDT IgM to 98-99% for cPass and SD RDT IgG). For specimens from patients with evidence of past or present helminth infection overall, test specificity estimates were all ≥ 96%. Sera collected from patients clinically suspected of parasitic infections that tested negative for these infections yielded a specificity of 98-100%. The majority (>85%) of false-positive results were positive by only one assay. Conclusions: The specificity of SARS-CoV-2 serological assays among sera from patients with tissue-borne parasitic infections was below the threshold required for decisions about individual patient care. Specificity is markedly increased by the use of confirmatory testing with a second assay. Finally, the SD RDT IgG proved similarly specific to laboratory-based assays and provides an option in low-resource settings when detection of anti-SARS-CoV-2 IgG is indicated.