Aerosol delivery, but not intramuscular injection, of adenovirus-vectored tuberculosis vaccine induces respiratory-mucosal immunity in humans.

BackgroundAdenovirus-vectored (Ad-vectored) vaccines are typically administered via i.m. injection to humans and are incapable of inducing respiratory mucosal immunity. However, aerosol delivery of Ad-vectored vaccines remains poorly characterized, and its ability to induce mucosal immunity in humans is unknown. This phase Ib trial evaluated the safety and immunogenicity of human serotype-5 Ad-vectored tuberculosis (TB) vaccine (AdHu5Ag85A) delivered to humans via inhaled aerosol or i.m. injection.MethodsThirty-one healthy, previously BCG-vaccinated adults were enrolled. AdHu5Ag85A was administered by single-dose aerosol using Aeroneb Solo Nebulizer or by i.m. injection. The study consisted of the low-dose (LD) aerosol, high-dose (HD) aerosol, and i.m. groups. The adverse events were assessed at various times after vaccination. Immunogenicity data were collected from the peripheral blood and bronchoalveolar lavage samples at baseline, as well as at select time points after vaccination.ResultsThe nebulized aerosol droplets were < 5.39 µm in size. Both LD and HD of AdHu5Ag85A administered by aerosol inhalation and i.m. injection were safe and well tolerated. Both aerosol doses, particularly LD, but not i.m., vaccination markedly induced airway tissue-resident memory CD4+ and CD8+ T cells of polyfunctionality. While as expected, i.m. vaccination induced Ag85A-specific T cell responses in the blood, the LD aerosol vaccination also elicited such T cells in the blood. Furthermore, the LD aerosol vaccination induced persisting transcriptional changes in alveolar macrophages.ConclusionInhaled aerosol delivery of Ad-vectored vaccine is a safe and superior way to elicit respiratory mucosal immunity. This study warrants further development of aerosol vaccine strategies against respiratory pathogens, including TB and COVID-19.Trial registrationClinicalTrial.gov, NCT02337270.FundingThe Canadian Institutes for Health Research (CIHR) and the Natural Sciences and Engineering Research Council of Canada funded this work.

Scaling Up Patient-Centered Psychological Treatments for Perinatal Depression in the Wake of a Global Pandemic

There is a call to action to reduce the public health burden of perinatal depression worldwide. The COVID-19 pandemic has further highlighted significant gaps in perinatal mental health care, especially among women who identify as Black, Indigenous, People of Color (BIPOC). While psychotherapeutic (cognitive, behavioral and interpersonal) interventions are endorsed for perinatal mood disorders, barriers to access and uptake contribute to inequitable access to treatment at the population level. To effectively address these barriers and increase the scalability of psychotherapy among perinatal women, we suggest four pragmatic questions to be answered from a patient-centered lens;namely, “who,” “what,” “how,” and “when.” Promising avenues include task-sharing among mental health non-specialists, an emphasis on culturally sensitive care, web-based delivery of psychotherapy with some caveats, and a lifespan approach to perinatal mental health. Innovative research efforts are seeking to validate these approaches in diverse contexts across North America and the UK, lending optimism toward scalable and long-term solutions for equitable perinatal mental health care.

Adapting behavioral activation for perinatal depression and anxiety in response to the COVID-19 pandemic and racial injustice.

BACKGROUND: We examined the implementation of a brief, behavioural activation (BA) model, via telemedicine, for perinatal populations during a confluence of significant global events in 2020. We conducted a rigorous qualitative study to identify relevant barriers and facilitators from the perspectives of both perinatal participants and treatment providers. We also present two case studies where BA was used and adapted to provide patient-centered care. METHODS: Within the ongoing SUMMIT non-inferiority randomized controlled trial in Canada and USA, we interviewed a random selection of perinatal participants (n = 23) and all treatment providers (n = 28). A content analysis framework was developed to identify relevant barriers and facilitators and frequencies were calculated for each emergent theme within and across respondent groups. RESULTS: Key facilitators reported by participants receiving BA were that BA helped with support and social connection (73.9%), creative problem solving (26.1%) and attending to pandemic-related symptoms (21.7%). Key facilitators endorsed by providers delivering BA were the use of telemedicine (35.7%) and loosening of government restrictions (21.4%). Both participant groups reported similar barriers to BA during the pandemic such as a lack of privacy and limited activities due to pandemic restrictions. However, providers were more likely to endorse pandemic-related life stressors as a barrier to treatment delivery compared to participants (64.3% vs. 34.8%). Both participant groups experienced explicit discussion of race and the racial justice movements during sessions as beneficial and reported harms of not doing so to the therapeutic alliance. CONCLUSIONS: BA offers a person-centered model to facilitate social connection through creative problem-solving for women with perinatal depressive and anxiety symptoms within the context of the COVID-19 pandemic. Explicit discussion of race and racial injustice during sessions is an important and helpful aspect in psychological treatments.

Barriers and Facilitators to Resuming In-Person Psychotherapy with Perinatal Patients amid the COVID-19 Pandemic: A Multistakeholder Perspective.

During the COVID-19 pandemic, outpatient psychotherapy transitioned to telemedicine. This study aimed to examine barriers and facilitators to resuming in-person psychotherapy with perinatal patients as the pandemic abates. We conducted focus group and individual interviews with a sample of perinatal participants (n = 23), psychotherapy providers (n = 28), and stakeholders (n = 18) from Canada and the U.S. involved in the SUMMIT trial, which is aimed at improving access to mental healthcare for perinatal patients with depression and anxiety. Content analysis was used to examine perceived barriers and facilitators. Reported barriers included concerns about virus exposure in a hospital setting (77.8% stakeholders, 73.9% perinatal participants, 71.4% providers) or on public transportation (50.0% stakeholders, 26.1% perinatal participants, 25.0% providers), wearing a mask during sessions (50.0% stakeholders, 25.0% providers, 13.0% participants), lack of childcare (66.7% stakeholders, 46.4% providers, 43.5% perinatal participants), general transportation barriers (50.0% stakeholders, 47.8% perinatal participants, 25.0% providers), and the burden of planning and making time for in-person sessions (35.7% providers, 34.8% perinatal participants, 27.8% stakeholders). Reported facilitators included implementing and communicating safety protocols (72.2% stakeholders, 47.8% perinatal participants, 39.3% providers), conducting sessions at alternative or larger locations (44.4% stakeholders, 32.1% providers, 17.4% perinatal participants), providing incentives (34.8% perinatal participants, 21.4% providers, 11.1% stakeholders), and childcare and flexible scheduling options (31.1% perinatal participants, 16.7% stakeholders). This study identified a number of potential barriers and illustrated that COVID-19 has fostered and amplified barriers. Future interventions to facilitate resuming in-person sessions should focus on patient-centered strategies based on empathy regarding ongoing risk-aversion among perinatal patients despite existing safety protocols, and holistic thinking to make access to in-person psychotherapy easier and more accessible for perinatal patients.

Response to pegylated interferon in a COVID-19-positive elderly woman with primary myelofibrosis treated with ruxolitinib.

An 83-year-old female had asymptomatic SARS-CoV-2 infection while taking ruxolitinib. She remained RT-PCR positive for viral RNA for >120 days, and Pegylated interferon for 4 weeks led to viral RNA clearance. The observations support combination therapy of ruxolitinib + interferon for COVID-19.