Therapeutic Plasma Exchange for Fibrinogen-Associated Hyperviscosity: Results of the COPLEX Randomized Controlled Trial.

Background: Therapeutic plasma exchange (TPE) is the primary intervention for treating symptomatic hyperviscosity from hypergammaglobulinemia, yet its efficacy for treating hyperviscosity related to hyperfibrinogenemia is unclear.

Objective: Define the safety and efficacy of TPE for critically ill COVID-19 patients with elevated blood viscosity from hyperfibrinogenemia.

Method: A prospective, randomized controlled trial in critically ill COVID-19 patients at a single US healthcare system.

Enhancing Apheresis Knowledge: An Educational Intervention for Non-Apheresis Medical Providers.

A knowledge gap exists between apheresis medicine (AM) physicians and providers who request the service, presenting challenges when coordinating care. We investigated an educational intervention consisting of a 40-min in-person evidence-based lecture for neurology residents, neurology attending physicians, and nephrology fellows. Pre-/post-testing demonstrated substantially improved understanding of apheresis mechanics, indications, complications, and patient consent.

Disease-associated B cells and immune endotypes shape adaptive immune responses to SARS-CoV-2 mRNA vaccination in human SLE.

Severe acute respiratory syndrome coronavirus 2 mRNA vaccination has reduced effectiveness in certain immunocompromised individuals. However, the cellular mechanisms underlying these defects, as well as the contribution of disease-induced cellular abnormalities, remain largely unexplored. In this study, we conducted a comprehensive serological and cellular analysis of patients with autoimmune systemic lupus erythematosus (SLE) who received the Wuhan-Hu-1 monovalent mRNA coronavirus disease 2019 vaccine.

Robust Meta-Model for Predicting the Likelihood of Receiving Blood Transfusion in Non-traumatic Intensive Care Unit Patients.

Blood transfusions, crucial in managing anemia and coagulopathy in intensive care unit (ICU) settings, require accurate prediction for effective resource allocation and patient risk assessment. However, existing clinical decision support systems have primarily targeted a particular patient demographic with unique medical conditions and focused on a single type of blood transfusion. This study aims to develop an advanced machine learning-based model to predict the probability of transfusion necessity over the next 24 h for a diverse range of non-traumatic ICU patients.

Mitigating the Prozone-Like Effect in HLA Antibody Testing: A Case Report of Therapeutic Plasma Exchange for Antibody-Mediated Rejection Post-Heart Transplantation.

Therapeutic plasma exchange (TPE) is a cornerstone treatment for antibody-mediated rejection (AMR) post-organ transplantation, aiming to eliminate pathogenic donor-specific HLA antibodies (DSA). However, limitations in HLA antibody interpretation due to the prozone-like effect (PLE) can lead to inaccurate assessment of treatment efficacy. We present a case of a heart transplant recipient with suspected AMR, where an unexpected increase in DSA levels post-TPE prompted investigation into PLE.

MENSA, a Media Enriched with Newly Synthesized Antibodies, to Identify SARS-CoV-2 Persistence and Latent Viral Reactivation in Long-COVID.

Post-acute sequelae of SARS-CoV-2 (SARS2) infection (PASC) is a heterogeneous condition, but the main viral drivers are unknown. Here, we use MENSA, Media Enriched with Newly Synthesized Antibodies, secreted exclusively from circulating human plasmablasts, to provide an immune snapshot that defines the underlying viral triggers. We provide proof-of-concept testing that the MENSA technology can capture the new host immune response to accurately diagnose acute primary and breakthrough infections when known SARS2 virus or proteins are present.

Patients taking benralizumab, dupilumab, or mepolizumab have lower postvaccination SARS-CoV-2 immunity.

Background: Biologic therapies inhibiting the IL-4 or IL-5 pathways are very effective in the treatment of asthma and other related conditions. However, the cytokines IL-4 and IL-5 also play a role in the generation of adaptive immune responses. Although these biologics do not cause overt immunosuppression, their effect in primary severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization has not been studied completely.

Post-transfusion biotin-labeled red blood cell survival studies in pediatric sickle cell disease with antibodies of uncertain significance.

Background: Red blood cell (RBC) antibodies are common in multiply transfused patients with sickle cell disease (SCD). Unlike RBC alloantibodies, the potential of autoantibodies to cause post-transfusion hemolysis may be uncertain. Biotin-labeling provides a direct measurement of red cell survival (RCS) over time, thus can be used to assess the clinical significance of RBC antibodies.

Comparison of RT-PCR and antigen test sensitivity across nasopharyngeal, nares, and oropharyngeal swab, and saliva sample types during the SARS-CoV-2 omicron variant.

Limited data highlight the need to understand differences in SARS-CoV-2 omicron (B.1.1.

Acute pulmonary injury in hematology patients supported with pathogen-reduced and conventional platelet components.

Patients treated with antineoplastic therapy often develop thrombocytopenia requiring platelet transfusion, which has potential to exacerbate pulmonary injury. This study tested the hypothesis that amotosalen-UVA pathogen-reduced platelet components (PRPCs) do not potentiate pulmonary dysfunction compared with conventional platelet components (CPCs). A prospective, multicenter, open-label, sequential cohort study evaluated the incidence of treatment-emergent assisted mechanical ventilation initiated for pulmonary dysfunction (TEAMV-PD).

Performance of the Xpert™ Mpox PCR assay with oropharyngeal, anorectal, and cutaneous lesion swab specimens.

Anorectal and oropharyngeal exposures are implicated in sexual transmission of mpox, but authorized assays in the United States are only validated with cutaneous lesion swabs. Diagnostic assays for anorectal and oropharyngeal swabs are needed to address potential future outbreaks. The Cepheid Xpert® Mpox is the first point-of-care assay to receive FDA emergency use authorization in the United States and would be a valuable tool for evaluating these sample types.

Clinical Utility of SARS-CoV-2 Serological Testing and Defining a Correlate of Protection.

Herein, we review established clinical use cases for SARS-CoV-2 antibody measures, which include diagnosis of recent prior infection, isolating high titer convalescent plasma, diagnosing multisystem inflammatory syndrome in children (MIS-C), and booster dosing in the immunosuppressed and other populations. We then address whether an antibody correlate of protection (CoP) for SARS-CoV-2 has been successfully defined with the following considerations: Antibody responses in the immunocompetent, vaccine type, variants, use of binding antibody tests vs. neutralization tests, and endpoint measures.

Rapid, high throughput, automated detection of SARS-CoV-2 neutralizing antibodies against Wuhan-WT, delta and omicron BA1, BA2 spike trimers.

Traditional cellular and live-virus methods for detection of SARS-CoV-2 neutralizing antibodies (nAbs) are labor- and time-intensive, and thus not suited for routine use in the clinical lab to predict vaccine efficacy and natural immune protection. Here, we report the development and validation of a rapid, high throughput method for measuring SARS-CoV-2 nAbs against native-like trimeric spike proteins. This assay uses a blockade of human angiotensin converting enzyme 2 (hACE-2) binding (BoAb) approach in an automated digital immunoassay on the Quanterix HD-X platform.

Mechanisms by which the cystic fibrosis transmembrane conductance regulator may influence SARS-CoV-2 infection and COVID-19 disease severity.

Patients with cystic fibrosis (CF) exhibit pronounced respiratory damage and were initially considered among those at highest risk for serious harm from SARS-CoV-2 infection. Numerous clinical studies have subsequently reported that individuals with CF in North America and Europe-while susceptible to severe COVID-19-are often spared from the highest levels of virus-associated mortality. To understand features that might influence COVID-19 among patients with cystic fibrosis, we studied relationships between SARS-CoV-2 and the gene responsible for CF (i.

Sensitivity of rapid antigen tests against SARS-CoV-2 Omicron and Delta variants.

Rapid antigen tests (RATs) have become an invaluable tool for combating the COVID-19 pandemic. However, concerns have been raised regarding the ability of existing RATs to effectively detect emerging SARS-CoV-2 variants. We compared the performance of 10 commercially available, emergency use authorized RATs against the Delta and Omicron SARS-CoV-2 variants using both individual patient and serially diluted pooled clinical samples.

Light chain of a public SARS-CoV-2 class-3 antibody modulates neutralization against Omicron.

The pairing of antibody genes IGHV2-5/IGLV2-14 is established as a public immune response that potently cross-neutralizes SARS-CoV-2 variants, including Omicron, by targeting class-3/RBD-5 epitopes in the receptor binding domain (RBD). LY-CoV1404 (bebtelovimab) exemplifies this, displaying exceptional potency against Omicron sub-variants up to BA.5.

Effect of swab pooling on the Accula point-of-care RT-PCR for SARS-CoV-2 detection.

Introduction: Swab pooling may allow for more efficient use of point-of-care assays for SARS-CoV-2 detection in settings where widespread testing is warranted, but the effects of pooling on assay performance are not well described.

Methods: We tested the Thermo-Fisher Accula rapid point-of-care RT-PCR platform with contrived pooled nasal swab specimens.

Results: We observed a higher limit of detection of 3,750 copies/swab in pooled specimens compared to 2,250 copies/swab in individual specimens.

COVID-19 vaccine induced poor neutralization titers for SARS-CoV-2 omicron variants in maternal and cord blood.

Introduction: Maternally derived antibodies are crucial for neonatal immunity. Understanding the binding and cross-neutralization capacity of maternal and cord antibody responses to SARS-CoV-2 variants following COVID-19 vaccination in pregnancy can inform neonatal immunity.

Methods: Here we characterized the binding and neutralizing antibody profile at delivery in 24 pregnant individuals following two doses of Moderna mRNA-1273 or Pfizer BNT162b2 vaccination.

Poor immunogenicity upon SARS-CoV-2 mRNA vaccinations in autoimmune SLE patients is associated with pronounced EF-mediated responses and anti-BAFF/Belimumab treatment.

Novel mRNA vaccines have resulted in a reduced number of SARS-CoV-2 infections and hospitalizations. Yet, there is a paucity of studies regarding their effectiveness on immunocompromised autoimmune subjects. In this study, we enrolled subjects naïve to SARS-CoV-2 infections from two cohorts of healthy donors (HD, n=56) and systemic lupus erythematosus (SLE, n=69).

Blood group A enhances SARS-CoV-2 infection.

Among the risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), ABO(H) blood group antigens are among the most recognized predictors of infection. However, the mechanisms by which ABO(H) antigens influence susceptibility to COVID-19 remain incompletely understood. The receptor-binding domain (RBD) of SARS-CoV-2, which facilitates host cell engagement, bears significant similarity to galectins, an ancient family of carbohydrate-binding proteins.