Imprinted antibody responses against SARS-CoV-2 Omicron sublineages

SARS-CoV-2 Omicron sublineages carry distinct spike mutations and represent an antigenic shift resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity or vaccine boosters result in potent plasma neutralizing activity against Omicron BA.1 and BA.2 and that breakthrough infections, but not vaccination-only, induce neutralizing activity in the nasal mucosa. Consistent with immunological imprinting, most antibodies derived from memory B cells or plasma cells of Omicron breakthrough cases cross-react with the Wuhan-Hu-1, BA.1 and BA.2 receptor-binding domains whereas Omicron primary infections elicit B cells of narrow specificity. While most clinical antibodies have reduced neutralization of Omicron, we identified an ultrapotent pan-variant antibody, that is unaffected by any Omicron lineage spike mutations and is a strong candidate for clinical development.

Analysis of severe illness after post-vaccination COVID-19 breakthrough among adults with and without HIV in the United States

ImportanceUnderstanding the severity of post-vaccination COVID-19 breakthrough illness among people with HIV (PWH) can inform vaccine guidelines and risk-reduction recommendations. ObjectiveEstimate the rate and risk of severe breakthrough illness among vaccinated PWH and people without HIV (PWoH) who experience a breakthrough infection. Design, setting, and participantsThe Corona-Infectious-Virus Epidemiology Team (CIVET-II) collaboration consists of four US longitudinal cohorts from integrated health systems and academic centers. Adults ([≥]18 years old), in-care, fully vaccinated by June 30, 2021 with HIV, and matched PWoH (on date fully vaccinated, age group, race/ethnicity, and sex) were the source population. Those who experienced a post-vaccination SARS-CoV-2 breakthrough infection were eligible. Severe COVID-19 breakthrough illness was defined as hospitalization due to COVID-19. Discrete time proportional hazards models estimated adjusted hazard ratios (aHR) and 95% confidence intervals ([,]) of severe breakthrough illness by HIV status adjusting for demographics, COVID-19 vaccine type, and clinical factors. The proportion of patients requiring mechanical ventilation or died was compared by HIV status. ExposureHIV infection OutcomeSevere COVID-19 breakthrough illness, defined as hospitalization within 28 days after a breakthrough SARS-CoV-2 infection with a primary or secondary COVID-19 discharge diagnosis. ResultsAmong 1,241 PWH and 2,408 PWoH with breakthrough infections, the cumulative incidence of severe illness in the first 28 days was low and comparable between PWoH and PWH (7.3% vs. 6.7%, respectively, risk difference=-0.67% [-2.58%, 1.23%]). The risk of severe breakthrough illness was 59% higher in PWH with CD4 counts <350 cells/mm3 compared with PWoH (aHR=1.59 [0.99, 2.46]). In multivariable analyses among PWH, being female, older, having a cancer diagnosis, and lower CD4 count increased the risk of severe breakthrough illness, while previous COVID-19 reduced the risk. Among all patients, 10% were mechanically ventilated and 8% died, with no difference by HIV status. Conclusions and RelevanceThe risk of severe COVID-19 breakthrough illness within 28 days of a breakthrough infection was low among vaccinated PWH and PWoH. However, PWH with moderate and severe immune suppression had a higher risk of severe breakthrough infection. Recommendations for additional vaccine doses and risk-reduction strategies for PWH with moderate immune suppression may be warranted. Key PointsO_ST_ABSQuestionC_ST_ABSIn 2021, among fully vaccinated people with COVID-19 breakthrough illness, was the risk of severe illness higher in people with HIV (PWH) compared to people without HIV (PWoH)? FindingsPWH with <350 cells/mm3 have a 59% increased risk of severe breakthrough illness compared to PWoH. MeaningVaccinations effectively reduce the risk of severe COVID-19 infection in both PWH and PWoH; however, PWH having a CD4 count <350 cells/mm3 are at higher risk of severe breakthrough infection compared to PWoH. PWH with moderate immune suppression should be considered for additional vaccine dosages and other risk-reduction measures.

COVID-19 infections post-vaccination by HIV status in the United States

ImportanceRecommendations for additional doses of COVID vaccine are restricted to people with HIV who have advanced disease or unsuppressed HIV viral load. Understanding SARS-CoV-2 infection risk post-vaccination among PWH is essential for informing vaccination guidelines. ObjectiveEstimate the risk of breakthrough infections among fully vaccinated people with (PWH) and without (PWoH) HIV in the US. Design, setting, and participantsThe Corona-Infectious-Virus Epidemiology Team (CIVET)-II cohort collaboration consists of 4 longitudinal cohorts from integrated health systems and academic health centers. Each cohort identified individuals [≥]18 years old, in-care, and fully vaccinated for COVID-19 through 30 June 2021. PWH were matched to PWoH on date fully vaccinated, age group, race/ethnicity, and sex at birth. Incidence rates per 1,000 person-years and cumulative incidence of breakthrough infections with 95% confidence intervals ([,]) were estimated by HIV status. Cox proportional hazards models estimated adjusted hazard ratios (aHR) of breakthrough infections by HIV status adjusting for demographic factors, prior COVID-19 illness, vaccine type (BNT162b2, [Pfizer], mRNA-1273 [Moderna], Jansen Ad26.COV2.S [J&J]), calendar time, and cohort. Risk factors for breakthroughs among PWH, were also investigated. ExposureHIV infection OutcomeCOVID-19 breakthrough infections, defined as laboratory evidence of SARS-CoV-2 infection or COVID-19 diagnosis after an individual was fully vaccinated. ResultsAmong 109,599 individuals (31,840 PWH and 77,759 PWoH), the rate of breakthrough infections was higher in PWH versus PWoH: 44 [41, 48] vs. 31 [29, 33] per 1,000 person-years. Cumulative incidence at 210 days after date fully vaccinated was low, albeit higher in PWH versus PWoH overall (2.8% versus 2.1%, log-rank p<0.001, risk difference=0.7% [0.4%, 1.0%]) and within each vaccine type. Breakthrough infection risk was 41% higher in PWH versus PWoH (aHR=1.41 [1.28, 1.56]). Among PWH, younger age (18-24 versus 45-54), history of COVID-19 prior to fully vaccinated date, and J&J vaccination (versus Pfizer) were associated with increased risk of breakthroughs. There was no association of breakthrough with HIV viral load suppression or CD4 count among PWH. Conclusions and RelevanceCOVID-19 vaccination is effective against infection with SARS-CoV-2 strains circulating through 30 Sept 2021. PWH have an increased risk of breakthrough infections compared to PWoH. Recommendations for additional vaccine doses should be expanded to all PWH.

SARS-CoV-2 spike conformation determines plasma neutralizing activity

Numerous safe and effective COVID-19 vaccines have been developed that utilize various delivery technologies and engineering strategies. The influence of the SARS-CoV-2 spike (S) glycoprotein conformation on antibody responses induced by vaccination or infection in humans remains unknown. To address this question, we compared plasma antibodies elicited by six globally-distributed vaccines or infection and observed markedly higher binding titers for vaccines encoding a prefusion-stabilized S relative to other groups. Prefusion S binding titers positively correlated with plasma neutralizing activity, indicating that physical stabilization of the prefusion conformation enhances protection against SARS-CoV-2. We show that almost all plasma neutralizing activity is directed to prefusion S, in particular the S1 subunit, and that variant cross-neutralization is mediated solely by RBD-specific antibodies. Our data provide a quantitative framework for guiding future S engineering efforts to develop vaccines with higher resilience to the emergence of variants and longer durability than current technologies.

Delta breakthrough infections elicit potent, broad and durable neutralizing antibody responses

The SARS-CoV-2 Delta variant is currently responsible for most infections worldwide, including among fully vaccinated individuals. Although these latter infections are associated with milder COVID-19 disease relative to unvaccinated subjects, the specificity and durability of antibody responses elicited by Delta breakthrough cases remain unknown. Here, we demonstrate that breakthrough infections induce serum binding and neutralizing antibody responses that are markedly more potent, durable and resilient to spike mutations observed in variants of concern than those observed in subjects who were infected only or received only two doses of COVID-19 vaccine. However, wee show that Delta breakthrough cases, subjects who were vaccinated after SARS-CoV-2 infection and individuals vaccinated three times (without infection) have serum neutralizing activity of comparable magnitude and breadth indicate that multiple types of exposure or increased number of exposures to SARS-CoV-2 antigen(s) enhance spike-specific antibody responses. Neutralization of the genetically divergent SARS-CoV, however, was moderate with all four cohorts examined, except after four exposures to the SARS-CoV-2 spike, underscoring the importance of developing vaccines eliciting broad sarbecovirus immunity for pandemic preparedness.

Stream Temperature Modeling and Fiber Optic Temperature Sensing to Characterize Groundwater Discharge.

The Ngongotaha Stream was used as a case study to assess the applicability of fiber optic distributed temperature sensing (FODTS) to identify the location of springs and quantify their discharge. Thirteen springs were identified, mostly located within a 115 m reach, five discharged from the right bank and eight from the left bank. To quantify groundwater discharge, a new approach was developed in which the one-dimensional transient heat transport model was fitted to the FODTS measurements, where the main calibration parameters of interest were the unknown spring discharges. The spatial disposition of the groundwater discharge estimation problem was constrained by two sources of information; first, the stream gains ∼500 L/s as determined by streamflow gauging. Second, the temperature profiles of the left and right banks provide the spatial disposition of springs and their relative discharges. FODTS was used to measure stream temperature near the left and right banks, which created two temperature datasets. A weighted average of the two datasets was then calculated, where the weights reflected the degree of mixing between the right and left banks downstream of a spring. The new approach in this study marks a departure from previous studies, in which the general approach was to use the steady-state thermal mixing model (Selker et al. 2006a; Westhoff et al. 2007; Briggs et al. 2012) to infer groundwater discharge, which is then used as an input into a transient model of the general form of equation to simulate stream temperature (Westhoff et al. 2007).

Regulação do profissional de saúde na Austrália: uma visão de antípodas / Health practitioner regulation in Australia: a view from the antipodes

Este artigo analisa a regulação dos profissionais de saúde na Austrália. Começa descrevendo os poderes constitucionais para regular os serviços de saúde na federação australiana e o sistema criado de direitos de acesso à saúde. O artigo examina a atual Lei Nacional de Regulação do Profissional de Saúde, que tenta criar um sistema regulatório uniforme para os profissionais de saúde na Austrália. O trabalho investiga o funcionamento desse sistema e os dados atuais sobre sua operação, concluindo com um olhar sobre seus desafios futuros.

Echinacea biotechnology: advances, commercialization and future considerations.

CONTEXT: Plants of the genus Echinacea (Asteraceae) are among the most popular herbal supplements on the market today. Recent studies indicate there are potential new applications and emerging markets for this natural health product (NHP). OBJECTIVE: This review aims to synthesize recent developments in Echinacea biotechnology and to identify promising applications for these advances in the industry. METHODS: A comprehensive survey of peer-reviewed publications was carried out, focusing on Echinacea biotechnology and impacts on phytochemistry. This article primarily covers research findings since 2007 and builds on earlier reviews on the biotechnology of Echinacea. RESULTS: Bioreactors, genetic engineering and controlled biotic or abiotic elicitation have the potential to significantly improve the yield, consistency and overall quality of Echinacea products. Using these technologies, a variety of new applications for Echinacea can be realized, such as the use of seed oil and antimicrobial and immune boosting feed additives for livestock. CONCLUSIONS: New applications can take advantage of the well-established popularity of Echinacea as a NHP. Echinacea presents a myriad of potential health benefits, including anti-inflammatory, anxiolytic and antibiotic activities that have yet to be fully translated into new applications. The distinct chemistry and bioactivity of different Echinacea species and organs, moreover, can lead to interesting and diverse commercial opportunities.

Preparing teachers for competency-based medical education: Fundamental teaching activities.

INTRODUCTION: The move to competency-based medical education has created new challenges for medical teachers, including the need to reflect on and further develop their own competencies as teachers. Guidance is needed to ensure comprehensive and coherent programs of faculty development to meet the needs of teachers. METHODS: The Working Group on Faculty Development of the College of Family Physicians of Canada developed a new concept, Fundamental Teaching Activities (FTAs), to describe the day-to-day work of teachers. These activities are intended to guide teacher professional development. Using task analysis and iterative reviews with teachers and educational leaders, these FTAs were organized into a framework for teachers to identify the actions involved in various teaching tasks, and to reflect on their teaching performance and next steps in personal development. RESULTS: In addition to use by teachers for personal development, the framework is being employed to guide the development of comprehensive faculty development offerings and curriculum, and to organize the beginnings of a national repository of teaching tools. CONCLUSIONS: Designed to support and aid teachers and those charged with faculty development, the Fundamental Teaching Activities Framework holds promise for all teachers in health sciences education.

Nitrate removal, communities of denitrifiers and adverse effects in different carbon substrates for use in denitrification beds.

Denitrification beds are containers filled with wood by-products that serve as a carbon and energy source to denitrifiers, which reduce nitrate (NO(3)(-)) from point source discharges into non-reactive dinitrogen (N(2)) gas. This study investigates a range of alternative carbon sources and determines rates, mechanisms and factors controlling NO(3)(-) removal, denitrifying bacterial community, and the adverse effects of these substrates. Experimental barrels (0.2 m(3)) filled with either maize cobs, wheat straw, green waste, sawdust, pine woodchips or eucalyptus woodchips were incubated at 16.8 °C or 27.1 °C (outlet temperature), and received NO(3)(-) enriched water (14.38 mg N L(-1) and 17.15 mg N L(-1)). After 2.5 years of incubation measurements were made of NO(3)(-)-N removal rates, in vitro denitrification rates (DR), factors limiting denitrification (carbon and nitrate availability, dissolved oxygen, temperature, pH, and concentrations of NO(3)(-), nitrite and ammonia), copy number of nitrite reductase (nirS and nirK) and nitrous oxide reductase (nosZ) genes, and greenhouse gas production (dissolved nitrous oxide (N(2)O) and methane), and carbon (TOC) loss. Microbial denitrification was the main mechanism for NO(3)(-)-N removal. Nitrate-N removal rates ranged from 1.3 (pine woodchips) to 6.2 g N m(-3) d(-1) (maize cobs), and were predominantly limited by C availability and temperature (Q(10) = 1.2) when NO(3)(-)-N outlet concentrations remained above 1 mg L(-1). The NO(3)(-)-N removal rate did not depend directly on substrate type, but on the quantity of microbially available carbon, which differed between carbon sources. The abundance of denitrifying genes (nirS, nirK and nosZ) was similar in replicate barrels under cold incubation, but varied substantially under warm incubation, and between substrates. Warm incubation enhanced growth of nirS containing bacteria and bacteria that lacked the nosZ gene, potentially explaining the greater N(2)O emission in warmer environments. Maize cob substrate had the highest NO(3)(-)-N removal rate, but adverse effects include TOC release, dissolved N(2)O release and substantial carbon consumption by non-denitrifiers. Woodchips removed less than half of NO(3)(-) removed by maize cobs, but provided ideal conditions for denitrifying bacteria, and adverse effects were not observed. Therefore we recommend the combination of maize cobs and woodchips to enhance NO(3)(-) removal while minimizing adverse effects in denitrification beds.

Adoption of open-access scheduling in an academic family practice.

PROBLEM ADDRESSED: Patients have to wait too long to see their family physicians. Open access, a new approach to office scheduling, has shown promise in reducing patient wait times to see primary care physicians. OBJECTIVE OF PROGRAM: To offer same-day appointments to most patients who call the office, thus reducing wait times as measured by the third available appointment. Reductions in no-show rates have also been reported by those who have adopted the open-access system. PROGRAM DESCRIPTION: Following extensive preparation, a 2-site academic practice in Halifax, NS, adopted open-access booking in October 2008. Data on third available appointment times, no-show appointments, and patient volumes were tracked before and during the yearlong implementation. CONCLUSION: The clinics recorded a substantial, sustained reduction in third available appointment time, indicating improved patient access. There was also a decline in no-show appointments. Patient volumes were unaffected.

Cinderella revisited.

OBJECTIVE: To examine the references to Cinderella in medical literature. DESIGN: Analysis of papers published in the past 50 years that mention Cinderella. RESULTS: The trend for use of Cinderella as a metaphor in medical publications is increasing exponentially. Five separate themes emerged: neglect, identity, transformation, exhaustion, and the mixed metaphor. CONCLUSIONS: The medical use of the Cinderella fable is growing in popularity.