SARS-CoV-2 BA.2.86 enters lung cells and evades neutralizing antibodies with high efficiency.

BA.2.86, a recently identified descendant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2 sublineage, contains ∼35 mutations in the spike (S) protein and spreads in multiple countries. Here, we investigated whether the virus exhibits altered biological traits, focusing on S protein-driven viral entry. Employing pseudotyped particles, we show that BA.2.86, unlike other Omicron sublineages, enters Calu-3 lung cells with high efficiency and in a serine- but not cysteine-protease-dependent manner. Robust lung cell infection was confirmed with authentic BA.2.86, but the virus exhibited low specific infectivity. Further, BA.2.86 was highly resistant against all therapeutic antibodies tested, efficiently evading neutralization by antibodies induced by non-adapted vaccines. In contrast, BA.2.86 and the currently circulating EG.5.1 sublineage were appreciably neutralized by antibodies induced by the XBB.1.5-adapted vaccine. Collectively, BA.2.86 has regained a trait characteristic of early SARS-CoV-2 lineages, robust lung cell entry, and evades neutralizing antibodies. However, BA.2.86 exhibits low specific infectivity, which might limit transmissibility.

Rapid spread of the SARS-CoV-2 JN.1 lineage is associated with increased neutralization evasion.

In July/August 2023, the highly mutated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BA.2.86 lineage emerged and its descendant JN.1 is on track to become the dominant SARS-CoV-2 lineage globally. Compared to the spike (S) protein of the parental BA.2.86 lineage, the JN.1 S protein contains one mutation, L455S, which may affect receptor binding and antibody evasion. Here, we performed a virological assessment of the JN.1 lineage employing pseudovirus particles bearing diverse SARS-CoV-2 S proteins. Using this strategy, it was found that S protein mutation L455S confers increased neutralization resistance but reduces ACE2 binding capacity and S protein-driven cell entry efficiency. Altogether, these data suggest that the benefit of increased antibody evasion outweighs the reduced ACE2 binding capacity and further enabled the JN.1 lineage to effectively spread in the human population.

Evaluating the Feasibility, Acceptance, and Beneficial Effects of Online Occupational Therapy for Post-COVID-19 Condition: Protocol for a Randomized Controlled Trial (ErgoLoCo Study).

BACKGROUND: Post-COVID-19 syndrome (PCS; also known as "long COVID") is a relatively novel disease comprising physical, psychological, and cognitive complaints persisting several weeks to months after acute infection with SARS-CoV-2. Approximately 10% of patients with COVID-19 are affected by long-term symptoms. However, effective treatment strategies are lacking. The ErgoLoCo (Occupational Therapy [Ergotherapie] for Long COVID) study was designed to develop and evaluate a novel occupational therapy (OT) concept of online delivery of therapy for long COVID. OBJECTIVE: The primary study objective is to assess the feasibility of the online OT intervention in PCS. Secondary aims include the evaluation of online OT concerning cognitive problems, occupational performance, and social participation. METHODS: This randomized controlled interventional pilot study involves parallel mixed methods process analyses and a realist evaluation approach. A total of 80 clients with PCS aged at least 16 years will be recruited into two interventional groups. The control cohort (watch and wait) comprises 80 clients with long COVID. Treatment is provided through teletherapy (n=40) or delivery of prerecorded videos (n=40) using the same standardized OT concept twice weekly over 12 weeks. Analyses of quantitative questionnaires and qualitative interviews based on the theoretical framework of acceptability will be performed to assess feasibility. Focus group meetings will be used to assess how acceptable and helpful the intervention was to the participating occupational therapists. Standardized tests will be used to assess the initial efficacy of the intervention on neurocognitive performance; limitations in mobility, self-care, and everyday activities; pain; disabilities; quality of life (QoL); social participation; and anxiety and depression in PCS, and the possible effects of online OT on these complaints. RESULTS: The German Ministry of Education and Research provided funding for this research in March 2022. Data collection took place from October 2022 to August 31, 2023. Data analysis will be completed by the end of April 2024. We anticipate publishing the results in the fall of 2024. CONCLUSIONS: Despite the enormous clinical need, effective and scalable treatment options for OT clients who have PCS remain scarce. The ErgoLoCo study will assess whether online-delivered OT is a feasible treatment approach in PCS. Furthermore, this study will assess the effect of the intervention on cognitive symptoms, QoL, and occupational performance and participation in everyday life. Particular emphasis will be placed on the experiences of clients and occupational therapists with digitally delivered OT. This study will pave the way for novel and effective treatment strategies in PCS. TRIAL REGISTRATION: German Clinical Trial Registry DRKS00029990; https://drks.de/search/de/trial/DRKS00029990. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/50230.

Virological Traits of the SARS-CoV-2 BA.2.87.1 Lineage.

Transmissibility and immune evasion of the recently emerged, highly mutated SARS-CoV-2 BA.2.87.1 are unknown. Here, we report that BA.2.87.1 efficiently enters human cells but is more sensitive to antibody-mediated neutralization than the currently dominating JN.1 variant. Acquisition of adaptive mutations might thus be needed for efficient spread in the population.

Consensus recommendations for use of long-acting antiretroviral medications in the treatment and prevention of HIV-1: Endorsed by the American Academy of HIV Medicine, American College of Clinical Pharmacy, Canadian HIV and Viral Hepatitis Pharmacists Network, European AIDS Clinical Society, and Society of Infectious Diseases Pharmacists: An executive summary.

Five long-acting (LA) antiretrovirals (ARVs) are currently available in a limited number of countries worldwide for HIV-1 prevention or treatment - cabotegravir, rilpivirine, lenacapavir, ibalizumab, and dapivirine. Implementing use of LA ARVs in routine clinical practice requires significant changes to the current framework of HIV-1 prevention, treatment, and service provision. Given the novelty, complexity, and interdisciplinary requirements of safe and optimal use of LA ARVs, consensus recommendations on the use of LA ARVs will assist clinicians in optimizing use of these agents. The purpose of these recommendations is to provide guidance for the clinical use of LA ARVs for HIV-1 treatment and prevention. In addition, future areas of research are identified and discussed.

Consensus recommendations for use of long-acting antiretroviral medications in the treatment and prevention of HIV-1: Endorsed by the American Academy of HIV Medicine, American College of Clinical Pharmacy, Canadian HIV and Viral Hepatitis Pharmacists Network, European AIDS Clinical Society, and Society of Infectious Diseases Pharmacists.

Five long-acting (LA) antiretrovirals (ARVs) are currently available in a limited number of countries worldwide for HIV-1 prevention or treatment-cabotegravir, rilpivirine, lenacapavir, ibalizumab, and dapivirine. Implementing use of LA ARVs into routine clinical practice requires significant changes to the current framework of HIV-1 prevention, treatment, and service provision. Given the novelty, complexity, and interdisciplinary requirements needed to safely and optimally utilize LA ARVs, consensus recommendations on the use of LA ARVs will assist clinicians in optimizing use of these agents. The purpose of these recommendations is to provide guidance for the clinical use of LA ARVs for HIV-1 treatment and prevention. In addition, future areas of research are also identified and discussed.

Systems biology analysis reveals distinct molecular signatures associated with immune responsiveness to the BNT162b COVID-19 vaccine.

BACKGROUND: Human immune responses to COVID-19 vaccines display a large heterogeneity of induced immunity and the underlying immune mechanisms for this remain largely unknown. METHODS: Using a systems biology approach, we longitudinally profiled a unique cohort of female high and low responders to the BNT162b vaccine, who were known from previous COVID-19 vaccinations to develop maximum and minimum immune responses to the vaccine. We utilized high dimensional flow cytometry, bulk and single cell mRNA sequencing and 48-plex serum cytokine analyses. FINDINGS: We revealed early, transient immunological and molecular signatures that distinguished high from low responders and correlated with B and T cell responses measured 14 days later. High responders featured a distinct transcriptional activity of interferon-driven genes and genes connected to enhanced antigen presentation. This was accompanied by a robust cytokine response related to Th1 differentiation. Both transcriptome and serum cytokine signatures were confirmed in two independent confirmatory cohorts. INTERPRETATION: Collectively, our data contribute to a better understanding of the immunogenicity of mRNA-based COVID-19 vaccines, which might lead to the optimization of vaccine designs for individuals with poor vaccine responses. FUNDING: German Center for Infection Research, German Center for Lung Research, German Research Foundation, Excellence Strategy EXC 2155 "RESIST" and European Regional Development Fund.

Prevalence of infectious diseases, immunity to vaccine-preventable diseases and chronic medical conditions among Ukrainian refugees in Germany - A cross sectional study from the German Network University Medicine (NUM).

BACKGROUND: Vulnerability to infectious diseases in refugees is dependent on country of origin, flight routes, and conditions. Information on specific medical needs of different groups of refugees is lacking. We assessed the prevalence of infectious diseases, immunity to vaccine-preventable diseases, and chronic medical conditions in children, adolescents, and adult refugees from Ukraine who arrived in Germany in 2022. METHODS: Using different media, we recruited Ukrainian refugees at 13 sites between 9-12/2022. An antigen test for acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, serologies for a range of vaccine-preventable diseases, as well as interferon gamma release assays (IGRAs) for tuberculosis (TB), and SARS-CoV-2 were performed. We assessed personal and family history of chronic medical conditions, infectious diseases, vaccination status, and conditions during migration. RESULTS: Overall, 1793 refugees (1401 adults and 392 children/adolescents) were included. Most participants were females (n = 1307; 72·3%) and from Eastern or Southern Ukraine. TB IGRA was positive in 13% (n = 184) of the adults and in 2% (n = 7) of the children. Serology-based immunological response was insufficient in approximately 21% (360/1793) of the participants for measles, 32% (572/1793) for diphtheria, and 74% (1289/1793) for hepatitis B. CONCLUSIONS: We show evidence of low serological response to vaccine-preventable infections and increased LTBI prevalence in Ukrainian refugees. These findings should be integrated into guidelines for screening and treatment of infectious diseases in migrants and refugees in Germany and Europe. Furthermore, low immunity for vaccine-preventable diseases in Ukrainians independent of their refugee status, calls for tailor-made communication efforts.