Defining a highly conserved B cell epitope in the receptor binding motif of SARS-CoV-2 spike glycoprotein.

SARS-CoV-2 mRNA vaccines induce robust and persistent germinal centre (GC) B cell responses in humans. It remains unclear how the continuous evolution of the virus impacts the breadth of the induced GC B cell response. Using ultrasound-guided fine needle aspiration, we examined draining lymph nodes of nine healthy adults following bivalent booster immunization.

Development of a metabolome-based respiratory infection prognostic during COVID-19 arrival.

In a new respiratory virus pandemic, optimizing allocation of scarce medical resources becomes an urgent challenge. Infection prognosis takes on particular importance when allocating scarce antiviral antibodies and drugs, which are most effective when administered before the onset of severe disease. During arrival of the COVID-19 pandemic to the United States in 2020, we conducted a prognostic biomarker discovery and validation effort based upon metabolomic profiling with a liquid-chromatography-mass spectrometer (LC-MS) type used clinically for rapid toxicology.

Lessons learned from the conduct of inpatient clinical trials in a pandemic.

Background: The COVID-19 pandemic amplified known challenges associated with the conduct of inpatient clinical trials, while also introducing new ones that needed to be addressed.

Methods: Stakeholders based in the United States who participated in the conduct of inpatient therapeutic trials for the treatment of COVID-19 as part of the Accelerating COVID-19 Therapeutic Interventions and Vaccines program identified challenges experienced in the conduct of these trials through a series of meeting to discuss and identify common themes. In addition, innovations developed to address these challenges and other potential solutions that may be utilized in future pandemics were highlighted.

Robust and persistent B-cell responses following SARS-CoV-2 vaccine determine protection from SARS-CoV-2 infection.

Introduction: A clear immune correlate of protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has not been defined. We explored antibody, B-cell, and T-cell responses to the third-dose vaccine and relationship to incident SARS-CoV-2 infection.

Methods: Adults in a prospective cohort provided blood samples at day 0, day 14, and 10 months after the third-dose SARS-CoV-2 vaccine.

Antiretroviral Therapy and Cardiovascular Risk in People With HIV in the United States-An Updated Analysis.

Background: Several antiretroviral therapy (ART) medications have been associated with increased cardiovascular risk, but less is known about the safety of modern ART. We sought to compare the risk of major adverse cardiac events (MACEs) among different ART regimens.

Methods: Using insurance claims databases from 2008 to 2020, we identified adults aged <65 years who newly initiated ART.

CD4 T cells exhibit distinct transcriptional phenotypes in the lymph nodes and blood following mRNA vaccination in humans.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and mRNA vaccination induce robust CD4 T cell responses. Using single-cell transcriptomics, here, we evaluated CD4 T cells specific for the SARS-CoV-2 spike protein in the blood and draining lymph nodes (dLNs) of individuals 3 months and 6 months after vaccination with the BNT162b2 mRNA vaccine. We analyzed 1,277 spike-specific CD4 T cells, including 238 defined using Trex, a deep learning-based reverse epitope mapping method to predict antigen specificity.

Immunoglobulin replacement products protect against SARS-CoV-2 infection in vivo despite poor neutralizing activity.

Immunoglobulin (IG) replacement products are used routinely in patients with immune deficiency and other immune dysregulation disorders who have poor responses to vaccination and require passive immunity conferred by commercial antibody products. The binding, neutralizing, and protective activity of intravenously administered IG against SARS-CoV-2 emerging variants remains unknown. Here, we tested 198 different IG products manufactured from December 2019 to August 2022.

Impact of Integrase Strand Transfer Inhibitors on Cognition in the HAILO Cohort.

Background: Integrase inhibitors (INSTIs) have been associated with poorer cognition in people with HIV (PWH). We examined the impact of switching to INSTIs on neuropsychological (NP) outcomes in PWH 40 years of age and older.

Methods: From the AIDS Clinical Trials Group observational cohort study, HAILO, we identified PWH who switched to INSTIs, had ≥2 NP assessments before and at least 1 after switch, and maintained viral suppression while on INSTIs.

Rapid Direct Detection of SARS-CoV-2 Aerosols in Exhaled Breath at the Point of Care.

Airborne transmission via virus-laden aerosols is a dominant route for the transmission of respiratory diseases, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Direct, non-invasive screening of respiratory virus aerosols in patients has been a long-standing technical challenge. Here, we introduce a point-of-care testing platform that directly detects SARS-CoV-2 aerosols in as little as two exhaled breaths of patients and provides results in under 60 s.

Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial.

Importance: Immune dysregulation contributes to poorer outcomes in COVID-19.

Objective: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia.

Design, Setting, And Participants: Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia.

SARS-CoV-2 Omicron boosting induces de novo B cell response in humans.

The primary two-dose SARS-CoV-2 mRNA vaccine series are strongly immunogenic in humans, but the emergence of highly infectious variants necessitated additional doses and the development of vaccines aimed at the new variants. SARS-CoV-2 booster immunizations in humans primarily recruit pre-existing memory B cells. However, it remains unclear whether the additional doses induce germinal centre reactions whereby re-engaged B cells can further mature, and whether variant-derived vaccines can elicit responses to variant-specific epitopes.

Persons with HIV Develop Spike-Specific Lymph Node Germinal Center Responses following SARS-CoV-2 Vaccination.

COVID-19 disproportionately affects persons with HIV (PWH) in worldwide locations with limited access to SARS-CoV-2 vaccines. PWH exhibit impaired immune responses to some, but not all, vaccines. Lymph node (LN) biopsies from PWH demonstrate abnormal LN structure, including dysregulated germinal center (GC) architecture.

HIV and obesity: updates in management strategies.

Purpose Of Review: Weight gain has emerged as an important problem in people with HIV (PWH). When dealing with obesity, PWH face additional challenges to those without HIV. Understanding the nature of the problem and the modern evidence is essential to optimize management and identify knowledge gaps.

SARS-CoV-2 booster vaccination rescues attenuated IgG1 memory B cell response in primary antibody deficiency patients.

Background: Although SARS-CoV-2 vaccines have proven effective in eliciting a protective immune response in healthy individuals, their ability to induce a durable immune response in immunocompromised individuals remains poorly understood. Primary antibody deficiency (PAD) syndromes are among the most common primary immunodeficiency disorders in adults and are characterized by hypogammaglobulinemia and impaired ability to mount robust antibody responses following infection or vaccination.

Methods: Here, we present an analysis of both the B and T cell response in a prospective cohort of 30 individuals with PAD up to 150 days following initial COVID-19 vaccination and 150 days post mRNA booster vaccination.

Plasma Aβ42/Aβ40 Ratios in Older People With Human Immunodeficiency Virus.

Background: As people with human immunodeficiency virus (HIV) (PWH) age, it remains unclear whether they are at higher risk for age-related neurodegenerative disorders-for example, Alzheimer disease (AD)-and, if so, how to differentiate HIV-associated neurocognitive impairment from AD. We examined a clinically available blood biomarker test for AD (plasma amyloid-β [Aβ] 42/Aβ40 ratio) in PWH who were cognitively normal (PWH_CN) or cognitively impaired (PWH_CI) and people without HIV (PWoH) who were cognitively normal (PWoH_CN) or had symptomatic AD (PWoH_AD).

Methods: A total of 66 PWH (age >40 years) (HIV RNA <50 copies/mL) and 195 PWoH provided blood samples, underwent magnetic resonance imaging, and completed a neuropsychological battery or clinical dementia rating scale.

The salivary and nasopharyngeal microbiomes are associated with SARS-CoV-2 infection and disease severity.

Emerging evidence suggests the oral and upper respiratory microbiota may play important roles in modulating host immune responses to viral infection. As the host microbiome may be involved in the pathophysiology of coronavirus disease 2019 (COVID-19), we investigated associations between the oral and nasopharyngeal microbiome and COVID-19 severity. We collected saliva (n = 78) and nasopharyngeal swab (n = 66) samples from a COVID-19 cohort and characterized the microbiomes using 16S ribosomal RNA gene sequencing.

Immune phenotypes that are associated with subsequent COVID-19 severity inferred from post-recovery samples.

Severe COVID-19 causes profound immune perturbations, but pre-infection immune signatures contributing to severe COVID-19 remain unknown. Genome-wide association studies (GWAS) identified strong associations between severe disease and several chemokine receptors and molecules from the type I interferon pathway. Here, we define immune signatures associated with severe COVID-19 using high-dimensional flow cytometry.

Abatacept for Treatment of Adults Hospitalized with Moderate or Severe Covid-19.

Background: We investigated whether abatacept, a selective costimulation modulator, provides additional benefit when added to standard-of-care for patients hospitalized with Covid-19.

Methods: We conducted a master protocol to investigate immunomodulators for potential benefit treating patients hospitalized with Covid-19 and report results for abatacept. Intravenous abatacept (one-time dose 10 mg/kg, maximum dose 1000 mg) plus standard of care (SOC) was compared with shared placebo plus SOC.

Hydroxychloroquine/chloroquine for the treatment of hospitalized patients with COVID-19: An individual participant data meta-analysis.

Background: Results from observational studies and randomized clinical trials (RCTs) have led to the consensus that hydroxychloroquine (HCQ) and chloroquine (CQ) are not effective for COVID-19 prevention or treatment. Pooling individual participant data, including unanalyzed data from trials terminated early, enables more detailed investigation of the efficacy and safety of HCQ/CQ among subgroups of hospitalized patients.

Methods: We searched ClinicalTrials.

Infliximab for Treatment of Adults Hospitalized with Moderate or Severe Covid-19.

Background: Immune dysregulation contributes to poorer outcomes in severe Covid-19. Immunomodulators targeting various pathways have improved outcomes. We investigated whether infliximab provides benefit over standard of care.

SARS-CoV-2 Omicron boosting induces de novo B cell response in humans.

The primary two-dose SARS-CoV-2 mRNA vaccine series are strongly immunogenic in humans, but the emergence of highly infectious variants necessitated additional doses of these vaccines and the development of new variant-derived ones . SARS-CoV-2 booster immunizations in humans primarily recruit pre-existing memory B cells (MBCs) . It remains unclear, however, whether the additional doses induce germinal centre (GC) reactions where reengaged B cells can further mature and whether variant-derived vaccines can elicit responses to novel epitopes specific to such variants.

Metabolic syndrome in people with HIV from Guatemala: analysis of components and risk factors.

Background: People with HIV (PWH) in Latin America are at a greater risk of developing comorbidities due to the increasing burden of obesity and metabolic syndrome in the region. We explored the associations between social, cardiovascular and HIV-related risk factors with metabolic syndrome in PWH from Guatemala.

Methods: Cross-sectional study analyzing demographic, clinical and laboratory data from PWH.

Loss of Pfizer (BNT162b2) Vaccine-Induced Antibody Responses against the SARS-CoV-2 Omicron Variant in Adolescents and Adults.

Emerging variants, especially the recent Omicron variant, and gaps in vaccine coverage threaten mRNA vaccine mediated protection against SARS-CoV-2. While children have been relatively spared by the ongoing pandemic, increasing case numbers and hospitalizations are now evident among children. Thus, it is essential to better understand the magnitude and breadth of vaccine-induced immunity in children against circulating viral variant of concerns (VOCs).

mRNA vaccine boosting enhances antibody responses against SARS-CoV-2 Omicron variant in individuals with antibody deficiency syndromes.

Individuals with primary antibody deficiency (PAD) syndromes have poor humoral immune responses requiring immunoglobulin replacement therapy. We followed individuals with PAD after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination by evaluating their immunoglobulin replacement products and serum for anti-spike binding, Fcγ receptor (FcγR) binding, and neutralizing activities. The immunoglobulin replacement products tested have low anti-spike and receptor-binding domain (RBD) titers and neutralizing activity.