S. Janna Bashar

Bio: S. Janna Bashar is an academic researcher from University of Wisconsin-Madison. The author has contributed to research in topics: Medicine & Antibody. The author has an hindex of 2, co-authored 4 publications receiving 8 citations.

Specific COVID-19 Symptoms Correlate with High Antibody Levels against SARS-CoV-2.

Abstract: Lasting immunity will be critical for overcoming COVID-19. However, the factors associated with the development of high titers of anti-SARS-CoV-2 Abs and how long those Abs persist remain incompletely defined. In particular, an understanding of the relationship between COVID-19 symptoms and anti-SARS-CoV-2 Abs is limited. To address these unknowns, we quantified serum anti-SARS- CoV-2 Abs in clinically diverse COVID-19 convalescent human subjects 5 wk (n = 113) and 3 mo (n = 79) after symptom resolution with three methods: a novel multiplex assay to quantify IgG against four SARS-CoV-2 Ags, a new SARS-CoV-2 receptor binding domain-angiotensin converting enzyme 2 inhibition assay, and a SARS-CoV-2 neutralizing assay. We then identified clinical and demographic factors, including never-before-assessed COVID-19 symptoms, that consistently correlate with high anti-SARS-CoV-2 Ab levels. We detected anti-SARS-CoV-2 Abs in 98% of COVID-19 convalescent subjects 5 wk after symptom resolution, and Ab levels did not decline at 3 mo. Greater disease severity, older age, male sex, higher body mass index, and higher Charlson Comorbidity Index score correlated with increased anti-SARS-CoV-2 Ab levels. Moreover, we report for the first time (to our knowledge) that COVID-19 symptoms, most consistently fever, body aches, and low appetite, correlate with higher anti-SARS-CoV-2 Ab levels. Our results provide robust and new insights into the development and persistence of anti-SARS-CoV-2 Abs.

Stimulating ideas for heart regeneration: the future of nerve-directed heart therapy

Abstract: Ischemic heart disease is the leading cause of death worldwide. The blockade of coronary arteries limits oxygen-rich blood to the heart and consequently there is cardiomyocyte (CM) cell death, inflammation, fibrotic scarring, and myocardial remodeling. Unfortunately, current therapeutics fail to effectively replace the lost cardiomyocytes or prevent fibrotic scarring, which results in reduced cardiac function and the development of heart failure (HF) in the adult mammalian heart. In contrast, neonatal mice are capable of regenerating their hearts following injury. However, this regenerative response is restricted to the first week of post-natal development. Recently, we identified that cholinergic nerve signaling is necessary for the neonatal mouse cardiac regenerative response. This demonstrates that cholinergic nerve stimulation holds significant potential as a bioelectronic therapeutic tool for heart disease. However, the mechanisms of nerve directed regeneration in the heart remain undetermined. In this review, we will describe the historical evidence of nerve function during regeneration across species. Specifically, we will focus on the emerging role of cholinergic innervation in modulating cardiomyocyte proliferation and inflammation during heart regeneration. Understanding the role of nerves in mammalian heart regeneration and adult cardiac remodeling can provide us with innovative bioelectronic-based therapeutic approaches for treatment of human heart disease.

Anti-membrane and anti-spike antibodies are long-lasting and together discriminate between past COVID-19 infection and vaccination

Abstract: The consequences of past COVID-19 infection for personal health and long-term population immunity are only starting to be revealed. Unfortunately, detecting past infection is currently a challenge, limiting clinical and research endeavors. Widely available anti-SARS-CoV-2 antibody tests cannot differentiate between past infection and vaccination given vaccine-induced anti-spike antibodies and the rapid loss of infection-induced anti-nucleocapsid antibodies. Anti-membrane antibodies develop after COVID-19, but their long-term persistence is unknown. Here, we demonstrate that anti-membrane IgG is a sensitive and specific marker of past COVID-19 infection and persists at least one year. We also confirm that anti-receptor binding domain (RBD) Ig is a long-lasting, sensitive, and specific marker of past infection and vaccination, while anti-nucleocapsid IgG lacks specificity and quickly declines after COVID-19. Thus, a combination of anti-membrane and anti-RBD antibodies can accurately differentiate between distant COVID-19 infection, vaccination, and naive states to advance public health, individual healthcare, and research goals.

Anti-membrane antibodies persist at least one year and discriminate between past COVID-19 infection and vaccination

Abstract: Abstract The consequences of past COVID-19 infection for personal and population health are emerging, but accurately identifying distant infection is a challenge. Anti-spike antibodies rise after both vaccination and infection and anti-nucleocapsid antibodies rapidly decline. We evaluated anti-membrane antibodies in COVID-19 naïve, vaccinated, and convalescent subjects to determine if they persist and accurately detect distant infection. We found that anti-membrane antibodies persist for at least a year and are a sensitive and specific marker of past COVID-19 infection. Thus, anti-membrane and anti-spike antibodies together can differentiate between COVID-19 convalescent, vaccinated, and naïve states to advance public health and research.

Rheumatoid Factor and Anti–Modified Protein Antibody Reactivities Converge on IgG Epitopes

Abstract: Rheumatoid arthritis (RA) patients often develop rheumatoid factors (RFs), antibodies that bind IgG Fc, and anti–modified protein antibodies (AMPAs), multireactive autoantibodies that commonly bind citrullinated, homocitrullinated, and acetylated antigens. Recently, antibodies that bind citrulline‐containing IgG epitopes were discovered in RA, suggesting that additional undiscovered IgG epitopes could exist and that IgG could be a shared antigen for RFs and AMPAs. This study was undertaken to reveal new IgG epitopes in rheumatic disease and to determine if multireactive AMPAs bind IgG.

A Third Dose of SARS-CoV-2 Vaccine Increases Neutralizing Antibodies Against Variants of Concern in Solid Organ Transplant Recipients

Abstract: Vaccine-induced SARS-CoV-2 antibody responses are attenuated in solid organ transplant recipients (SOTRs) and breakthrough infections are more common. Additional SARS-CoV-2 vaccine doses increase anti-spike IgG in some SOTRs, but it is uncertain whether neutralization of variants of concern (VOCs) is enhanced. We tested 47 SOTRs for clinical and research anti-spike IgG, pseudoneutralization (ACE2 blocking), and live-virus neutralization (nAb) against VOCs before and after a third SARS-CoV-2 vaccine dose (70% mRNA, 30% Ad26.COV2.S) with comparison to 15 healthy controls after two mRNA vaccine doses. We used correlation analysis to compare anti-spike IgG assays and focused on thresholds associated with neutralizing activity. A third SARS-CoV-2 vaccine dose increased median anti-spike (1.6-fold) and receptor-binding domain (1.5-fold) IgG, as well as pseudoneutralization against VOCs (2.5-fold versus Delta). However, IgG and neutralization activity were significantly lower than healthy controls (p 4 AU on the clinical assay and >10^4 AU on the research assay. These findings highlight benefits of a third vaccine dose for some SOTRs and the need for alternative strategies to improve protection in a significant subset of this population.

The landscape of antibody binding in SARS-CoV-2 infection.

Abstract: The search for potential antibody-based diagnostics, vaccines, and therapeutics for pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has focused almost exclusively on the spike (S) and nucleocapsid (N) proteins. Coronavirus membrane (M), ORF3a, and ORF8 proteins are humoral immunogens in other coronaviruses (CoVs) but remain largely uninvestigated for SARS-CoV-2. Here, we use ultradense peptide microarray mapping to show that SARS-CoV-2 infection induces robust antibody responses to epitopes throughout the SARS-CoV-2 proteome, particularly in M, in which 1 epitope achieved excellent diagnostic accuracy. We map 79 B cell epitopes throughout the SARS-CoV-2 proteome and demonstrate that antibodies that develop in response to SARS-CoV-2 infection bind homologous peptide sequences in the 6 other known human CoVs. We also confirm reactivity against 4 of our top-ranking epitopes by enzyme-linked immunosorbent assay (ELISA). Illness severity correlated with increased reactivity to 9 SARS-CoV-2 epitopes in S, M, N, and ORF3a in our population. Our results demonstrate previously unknown, highly reactive B cell epitopes throughout the full proteome of SARS-CoV-2 and other CoV proteins.

Large Animal Models of Cell-Free Cardiac Regeneration.

Abstract: The adult mammalian heart lacks the ability to sufficiently regenerate itself, leading to the progressive deterioration of function and heart failure after ischemic injuries such as myocardial infarction. Thus far, cell-based therapies have delivered unsatisfactory results, prompting the search for cell-free alternatives that can induce the heart to repair itself through cardiomyocyte proliferation, angiogenesis, and advantageous remodeling. Large animal models are an invaluable step toward translating basic research into clinical applications. In this review, we give an overview of the state-of-the-art in cell-free cardiac regeneration therapies that have been tested in large animal models, mainly pigs. Cell-free cardiac regeneration therapies involve stem cell secretome- and extracellular vesicles (including exosomes)-induced cardiac repair, RNA-based therapies, mainly regarding microRNAs, but also modified mRNA (modRNA) as well as other molecules including growth factors and extracellular matrix components. Various methods for the delivery of regenerative substances are used, including adenoviral vectors (AAVs), microencapsulation, and microparticles. Physical stimulation methods and direct cardiac reprogramming approaches are also discussed.

Heart regeneration: beyond new muscle and vessels.

Abstract: The most striking consequence of a heart attack is the loss of billions of heart muscle cells, alongside damage to the associated vasculature. The lost cardiovascular tissue is replaced by scar formation, which is non-functional and results in pathological remodelling of the heart and ultimately heart failure. It is, therefore, unsurprising that the heart regeneration field has centred efforts to generate new muscle and blood vessels through targeting cardiomyocyte proliferation and angiogenesis following injury. However, combined insights from embryological studies and regenerative models, alongside the adoption of -omics technology, highlight the extensive heterogeneity of cell types within the forming or re-forming heart and the significant crosstalk arising from non-muscle and non-vessel cell types. In this review, we focus on the roles of fibroblasts, immune cells, conduction system and nervous system cell populations during heart development and we consider the latest evidence supporting a function for these diverse lineages in contributing to regeneration following heart injury. We suggest that the emerging picture of neurologically, immunologically and electrically coupled cell function calls for a wider-ranging combinatorial approach to heart regeneration.