Covid-19 Rates by Time since Vaccination during Delta Variant Predominance.

BACKGROUND: With the emergence of the delta variant, the United States experienced a rapid increase in Covid-19 cases in 2021. We estimated the risk of breakthrough infection and death by month of vaccination as a proxy for waning immunity during a period of delta variant predominance. METHODS: Covid-19 case and death data from 15 U.S. jurisdictions during January 3 to September 4, 2021 were used to estimate weekly hazard rates among fully vaccinated persons, stratified by age group and vaccine product. Case and death rates during August 1 to September 4, 2021 were presented across four cohorts defined by month of vaccination. Poisson models were used to estimate adjusted rate ratios comparing the earlier cohorts to July rates. RESULTS: During August 1 to September 4, 2021, case rates per 100,000 person-weeks among all vaccine recipients for the January to February, March to April, May to June, and July cohorts were 168.8 (95% confidence interval [CI], 167.5 to 170.1), 123.5 (95% CI, 122.8 to 124.1), 83.6 (95% CI, 82.9 to 84.3), and 63.1 (95% CI, 61.6 to 64.6), respectively. Similar trends were observed by age group for BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccine recipients. Rates for the Ad26.COV2.S (Janssen-Johnson & Johnson) vaccine were higher; however, trends were inconsistent. BNT162b2 vaccine recipients 65 years of age or older had higher death rates among those vaccinated earlier in the year. Protection against death was sustained for the mRNA-1273 vaccine recipients. Across age groups and vaccine types, people who were vaccinated 6 months ago or longer (January-February) were 3.44 (3.36 to 3.53) times more likely to be infected and 1.70 (1.29 to 2.23) times more likely to die from COVID-19 than people vaccinated recently in July 2021. CONCLUSIONS: Our study suggests that protection from SARS-CoV-2 infection among all ages or death among older adults waned with increasing time since vaccination during a period of delta predominance. These results add to the evidence base that supports U.S. booster recommendations, especially for older adults vaccinated with BNT162b2 and recipients of the Ad26.COV2.S vaccine. (Funded by the Centers for Disease Control and Prevention.).

Improvement in Anxiety Symptoms in Depressed Patients Treated With AXS-05 (DEXTROMETHORPHAN-BUPROPION): Results From the Evolve Open-Label, Long-Term Study

BackgroundInnovative therapies to treat individuals with MDD, especially those with comorbid anxiety, are urgently needed.AXS-05 (dextromethorphan HBr 45 mg-bupropion HCl 105 mg) is a novel, oral, investigational NMDA receptor antagonist with multimodal activity. The dextromethorphan component of AXS-05 is an NMDA receptor antagonist and a sigma-1 receptor agonist. The bupropion component of AXS-05 serves primarily to increase the bioavailability of dextromethorphan.ObjectiveTo evaluate the effects of AXS-05 on anxiety in MDD.MethodsEVOLVE was an open-label study, in which patients were treated with AXS-05 twice daily for up to 15 months. Subjects had either rolled in after a prior AXS-05 study or were directly enrolled and had a DSM-5 diagnosis of MDD, a MADRS score of ≥25, and had been treated with ≥ 1 antidepressant in the current major depressive episode. A total of 186 patients were enrolled. Efficacy endpoints included MADRS and HAM-A. Here we present the results for the directly enrolled patients (n =146).ResultsMean baseline HAM-A scores were 15.6. Reductions from baseline to Weeks 1, 2, and 6 were 3.4±5.34 (p< 0.001), 5.5±5.81 (p< 0.001), and 8.6±5.75 (p< 0.001), respectively. Improvements on the HAM-A were durable through Month 12 (-10.2±6.33;p< 0.001). Remission (HAM-A ≤7) rates on the HAM-A at Weeks 1, 2, and 6 were 19.9%, 36.0%, and 58.1%, respectively. Remission at Month 12 was 78.3%.Long-term treatment with AXS-05 was generally well tolerated. The most commonly reported adverse events were COVID-19 infection (8.9%), nausea (8.9%), headache (7.5%), dry mouth (6.2%), insomnia (5.5%), and dizziness (5.5%).ConclusionsThese data support the use of AXS-05 in patients with comorbid depression and anxiety.FundingAxsome Therapeutics

AXS-05 (DEXTROMETHORPHAN-BUPROPION) Improves Depressive Symptoms and Functioning in Patients With One Prior Treatment Failure: Results From the Evolve Long-Term, Open Label Study

BackgroundIn STAR*D, following non-remission with an SSRI, remission rates for second-line treatments were ~ 25%, regardless of the switch strategy employed. Antidepressants with novel mechanisms may improve outcomes in MDD. AXS-05 (dextromethorphan HBr 45 mg- bupropion HCl 105 mg) is a novel, oral, investigational, NMDA receptor antagonist with multimodal activity. The dextromethorphan component of AXS-05 is an NMDA receptor antagonist and a sigma-1 receptor agonist. The bupropion component of AXS-05 serves primarily to increase the bioavailability of dextromethorphan.MethodsEVOLVE was an open-label study, in which patients were treated with AXS-05 twice daily for up to 15 months. Subjects had either rolled in after a prior AXS-05 study or were directly enrolled and had a DSM-5 diagnosis of MDD, a MADRS score of ≥25, and had been treated with ≥1 antidepressant in the current major depressive episode (MDE). A total of 186 patients were enrolled. Here we present the results for the directly enrolled patients (n =146).ResultsMean change in MADRS total score from a baseline of 32.2 were -9.1±7.64, -13.3±8.58, and -20.4±7.79 points at Weeks 1, 2, and 6, respectively (p< 0.001 for all). Remission (MADRS ≤10) was achieved by 5.7%, 16.2%, and 46.0% of patients at Weeks 1, 2, and 6, respectively. Improvement in functioning, measured by the SDS, was seen starting at Week 1 (p < 0.001). Improvements in MADRS and SDS were sustained at Month 12.Long-term treatment with AXS-05 was generally well tolerated. The most commonly reported adverse events were COVID-19 infection (8.9%), nausea (8.9%), headache (7.5%), dry mouth (6.2%), insomnia (5.5%), and dizziness (5.5%).ConclusionsAXS-05 improved depression and functioning in patients who failed one prior antidepressant in the current MDE.FundingAxsome Therapeutics

COVID-19 Incidence and Mortality Among Unvaccinated and Vaccinated Persons Aged ≥12 Years by Receipt of Bivalent Booster Doses and Time Since Vaccination - 24 U.S. Jurisdictions, October 3, 2021-December 24, 2022.

On September 1, 2022, CDC recommended an updated (bivalent) COVID-19 vaccine booster to help restore waning protection conferred by previous vaccination and broaden protection against emerging variants for persons aged ≥12 years (subsequently extended to persons aged ≥6 months).* To assess the impact of original (monovalent) COVID-19 vaccines and bivalent boosters, case and mortality rate ratios (RRs) were estimated comparing unvaccinated and vaccinated persons aged ≥12 years by overall receipt of and by time since booster vaccination (monovalent or bivalent) during Delta variant and Omicron sublineage (BA.1, BA.2, early BA.4/BA.5, and late BA.4/BA.5) predominance.† During the late BA.4/BA.5 period, unvaccinated persons had higher COVID-19 mortality and infection rates than persons receiving bivalent doses (mortality RR = 14.1 and infection RR = 2.8) and to a lesser extent persons vaccinated with only monovalent doses (mortality RR = 5.4 and infection RR = 2.5). Among older adults, mortality rates among unvaccinated persons were significantly higher than among those who had received a bivalent booster (65-79 years; RR = 23.7 and ≥80 years; 10.3) or a monovalent booster (65-79 years; 8.3 and ≥80 years; 4.2). In a second analysis stratified by time since booster vaccination, there was a progressive decline from the Delta period (RR = 50.7) to the early BA.4/BA.5 period (7.4) in relative COVID-19 mortality rates among unvaccinated persons compared with persons receiving who had received a monovalent booster within 2 weeks-2 months. During the early BA.4/BA.5 period, declines in relative mortality rates were observed at 6-8 (RR = 4.6), 9-11 (4.5), and ≥12 (2.5) months after receiving a monovalent booster. In contrast, bivalent boosters received during the preceding 2 weeks-2 months improved protection against death (RR = 15.2) during the late BA.4/BA.5 period. In both analyses, when compared with unvaccinated persons, persons who had received bivalent boosters were provided additional protection against death over monovalent doses or monovalent boosters. Restored protection was highest in older adults. All persons should stay up to date with COVID-19 vaccination, including receipt of a bivalent booster by eligible persons, to reduce the risk for severe COVID-19.

Engagement of health workers and peer educators from the National Adolescent Health Programme-Rashtriya Kishor Swasthya Karyakram during the COVID-19 pandemic: Findings from a situational analysis.

BACKGROUND: To understand the impact of COVID-19 on implementation of the peer education programme of the National Adolescent Health Programme-Rashtriya Kishor Swasthya Karyakram (RKSK); repurposing of the RKSK health workers and Peer Educators (PEs) in COVID-19 response activities and effect on adolescents´ health and development issues. METHODS: Virtual in-depth interviews were conducted with stakeholders (n = 31) (aged 15 to 54 years) engaged in the implementation of the RKSK and peer education programme at state, district, block, and village levels in Madhya Pradesh and Maharashtra (India). These interviews were thematically coded and analysed to address the research objectives. RESULTS: Despite most peer education programme activities being stopped, delayed, or disrupted during the pandemic and subsequent lockdown, some communication networks previously established, helped facilitate public health communication regarding COVID-19 and RKSK, between health workers, PEs, and adolescents. There was repurposing of RKSK health workers and PEs' role towards COVID-19 response-related activities. PEs, with support from health workers, were involved in disseminating COVID-19 information, maintaining migrant and quarantine records, conducting household surveys for recording COVID-19 active cases and providing essential items (grocery, sanitary napkins, etc.) to communities and adolescents. CONCLUSION: PEs with support from community health workers are able to play a crucial role in meeting the needs of the communities during a pandemic. There is a need to further engage, involve and build the skills of PEs to support the health system. PEs can be encouraged by granting more visibility and incorporating their role more formally by paying them within the public health system in India.

THE DAWN OF A NEW ERA: ANTITRUST LAW VS. THE ANTIQUATED NCAA COMPENSATION MODEL PERPETUATING RACIAL INJUSTICE

Two crises in 2020 fueled the fire underlying a debate that has been smoldering for years: whether student athletes should be compensated. The COVID-19 pandemic coincided with the Black Lives Matter movement and drew unprecedented attention to systemic racism permeating society, including college sports that rely disproportionately on Black men risking physical harm to support an entire industry. The Supreme Court's decision in NCAA v. Alston opened the door for some athletic conferences to offer student athletes unlimited education-related benefits and called out the NCAA's business model that relies on not paying student athletes under the justification of amateurism. Alston asserted that the NCAA amateurism model is not exempt from antitrust law, and a scathing concurrence by Justice Brett Kavanaugh said in no uncertain terms that "[t]he NCAA is not above the law." In the context of the ever-evolving landscape of student-athlete compensation, this Note examines recent changes to the NCAA compensation model and suggests that antitrust law should be used as a vehicle to change the game by correcting racial inequities perpetuated by this business model. This Note asserts that the ball is now in Congress's court and advocates for federal legislation and collective bargaining to empower student athletes to seek the full value of their labor.

Seattle Children's Virtual Research Training Program: Pivoting to Remote Science Education for High School Students

Seattle Children's Research Institute has built a series of in-person education programs to inspire and empower students to explore futures in biomedical research and healthcare. The COVID-19 pandemic prevented us from offering an in-person laboratory program, forcing a rapid pivot to an online format. The Virtual Research Training Program (VRTP) was a one-week summer experience for high school students, including students from groups that are under-represented in STEM. The curriculum introduced topics such as biochemistry, immunology and immunotherapy, and global and public health. Also included were laboratory demonstrations to emphasize cutting-edge applications for healthcare and discussions regarding college and career preparation. Key challenges included converting the in-person curriculum into a digestible virtual format, becoming proficient with the technology to provide for a seamless end-user experience with equitable access, and establishing quantifiable metrics for evaluation. Students reported statistically significant gains with large effect sizes in knowledge about science concepts and laboratory procedures, and in preparation for college and future STEM careers. Students were also engaged by asking questions, indicating their active participation despite the online environment. This article discusses the adaptation of an in-person laboratory program into a virtual program as a potential model for increasing remote access to science education.

Adapting clinical skills volunteer patient recruitment and retention during COVID-19.

Implication Statement Institutions have been faced with the unique challenge of continuing to deliver medical education to students in a COVID-19 environment.1 , 2 Clinical skills teaching must be adapted to the pandemic environment, which begins with retaining Volunteer Patient (VP) engagement to facilitate the development of students' patient care aptitudes. The number of available VPs has been significantly reduced by the pandemic. We propose actionable solutions to recruit, engage, and retain VPs that can be easily adopted at any site. The SLIM-COVID framework can assist programs in altering curricula to deliver clinical skills with patient involvement in a pandemic environment. Énoncé des implications de la recherche Les établissements d'éducation médicale ont été confrontés au défi unique de continuer à assurer leurs services aux étudiants dans un environnement COVID-19.1 , 2 L'enseignement des habiletés cliniques doit être adapté au contexte de la pandémie, en premier lieu par le maintien de la participation des patients volontaires (PV) afin de faciliter le développement des aptitudes requises pour les soins aux patients. Le nombre de PV disponibles a considérablement baissé en raison de la pandémie. Nous proposons des solutions concrètes pour recruter, motiver et retenir les PV, ces solutions pouvant être facilement introduites dans tous les types de site. Le cadre SLIM-COVID peut faciliter l'adaptation des programmes d'études pour assurer la participation de patients dans l'enseignement des habiletés cliniques dans le contexte de la pandémie.

Assessment of Day-7 Postexposure Testing of Asymptomatic Contacts of COVID-19 Patients to Evaluate Early Release from Quarantine - Vermont, May-November 2020.

On May 8, 2020, the Vermont Department of Health (VDH) issued a Health Update* recommending shortening the duration of quarantine for persons exposed to SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). Exposed persons who were in quarantine could be tested by polymerase chain reaction (PCR) on or after quarantine day 7. Those who had remained asymptomatic throughout quarantine and who received a negative SARS-CoV-2 PCR test result on or after day 7 could end quarantine. This policy was based on a report suggesting that symptom onset occurs within this time frame in approximately three quarters of COVID-19 cases (1) and on consultation of the Vermont Health Commissioner with the U.S. Surgeon General. VDH implemented this policy to minimize restrictions on state residents, recognizing that some reduction could occur in the prevention benefit of quarantine to contain the spread of SARS-CoV-2. State-run SARS-CoV-2 testing sites were made available to increase access to no-cost testing and facilitate implementation of this policy. During August 1-December 1, among persons seeking testing at a VDH SARS-CoV-2 testing site, 36% stated that their reason for seeking testing was to end quarantine early (VDH, unpublished data, December 7, 2020), indicating that persons were aware of and following the policy and using the testing services provided. To assess the effectiveness of this policy, VDH analyzed testing data for contacts of persons with a COVID-19 diagnosis. During May 8-November 16, VDH identified 8,798 exposed contacts of COVID-19 patients; 3,983 (45%) had sought testing within 14 days of their exposure, with day 0 defined as the date of last exposure noted in the case investigation record. Among these persons, 2,200 (55%) who received testing on days 7-10 were included in this analysis; 977 (44.9%) of these contacts had a specimen collected for testing on day 7. Among these, 34 (3%) had test results that were positive, 940 (96%) had results that were negative, and three (<1%) had results that were indeterminate (Table). Among the 34 contacts who received a positive SARS-CoV-2 PCR test result on day 7 after exposure, 12 (35%) were asymptomatic. The remaining 22 contacts with positive test results were symptomatic at the time of testing; approximately one half had developed symptoms on days 4-7 after exposure. Among the 940 contacts who received negative test results on specimens collected on day 7 after exposure, 154 (16%) had a subsequent test within the next 7 days (i.e., days 8-14); among these, 152 (99%) had tests that remained negative, and two (1%) had results that were indeterminate.