Elana Shaw
A5043901977- COVID-19 Clinical Research Studies
- SARS-CoV-2 and COVID-19 Research
- Diabetes and associated disorders
- Immunodeficiency and Autoimmune Disorders
- Kawasaki Disease and Coronary Complications
- Adrenal Hormones and Disorders
- T-cell and B-cell Immunology
- Long-Term Effects of COVID-19
- Immune Cell Function and Interaction
- Macrophage Migration Inhibitory Factor
- IL-33, ST2, and ILC Pathways
- Viral Infections and Immunology Research
- Cancer Immunotherapy and Biomarkers
- Artificial Immune Systems Applications
- Polyomavirus and related diseases
- Tryptophan and brain disorders
- Herpesvirus Infections and Treatments
- Antibiotic Resistance in Bacteria
- Microbial Natural Products and Biosynthesis
- Hematological disorders and diagnostics
- Peptidase Inhibition and Analysis
- SARS-CoV-2 detection and testing
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Immune responses and vaccinations
- Blood disorders and treatments
National Institutes of Health
2020-2025
National Institute of Allergy and Infectious Diseases
2020-2025
Emory University
2020-2024
Johns Hopkins University
2023
Office of Extramural Research
2021
AID Atlanta
2020
Institut National d’Hygiène Publique
1989
Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 987 patients with life-threatening disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-ω (IFN-ω) (13 patients), 13 types IFN-α (36), or both (52) onset critical disease; a few also auto-Abs other three type I IFNs. The neutralize ability corresponding IFNs to block...
Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found about 10% patients with critical COVID-19 pneumonia, but not subjects asymptomatic infections. We detect auto-Abs 100-fold lower, more physiological, (100 pg/mL, 1/10 dilutions plasma) 13.6% 3,595 COVID-19, including 21% 374 > 80 years, and 6.5% 522 severe COVID-19. These antibodies also detected 18% the 1,124 deceased (aged 20 days-99 years; mean: 70...
Immune and inflammatory responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contribute disease severity of 2019 (COVID-19). However, the utility specific immune-based biomarkers predict clinical outcome remains elusive. Here, we analyzed levels 66 soluble in 175 Italian patients with COVID-19 ranging from mild/moderate critical assessed type I IFN–, II NF-κB–dependent whole-blood transcriptional signatures. A broad signature was observed, implicating activation various...
Patients with biallelic loss-of-function variants of AIRE suffer from autoimmune polyendocrine syndrome type-1 (APS-1) and produce a broad range autoantibodies (auto-Abs), including circulating auto-Abs neutralizing most type I interferons (IFNs). These were recently reported to account for at least 10% cases life-threatening COVID-19 pneumonia in the general population. We report 22 APS-1 patients 21 kindreds seven countries, aged between 8 48 yr infected SARS-CoV-2 since February 2020. The...
Significance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It important to estimate their quantitative impact on mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence these risk death increase with higher in men. Using an unvaccinated sample 1,261 deceased patients 34,159 individuals from general population, we found against IFNs strongly increased...
Type-I interferons (IFNs) mediate antiviral activity and have emerged as important immune mediators during coronavirus disease 19 (COVID-19). Several lines of evidence suggest that impaired type-I IFN signaling may predispose to severe COVID-19. However, the pathophysiologic mechanisms contribute illness severity remain unclear. In this study, our goal was gain insight into how IFNs influence outcomes in patients with To achieve goal, we compared clinical between 26 neutralizing...
Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to large group of RAG-mutated patients, we aimed at characterizing the immunopathology associated each phenotype. Although defective T B cell development is common all phenotypes, patients hypomorphic RAG variants generate cells signatures immune dysregulation produce autoantibodies broad range self-antigens, including type I interferons....
Binding levels and neutralization activity of anti-type 1 interferon autoantibodies peaked during acute coronavirus disease 2019 markedly decreased thereafter. Most patients maintained some ability to neutralize type into convalescence despite lower binding immunoglobulin G. Identifying these in healthy individuals before the development critical viral may be challenging.
Our immune system is critical for preventing and treating SARS-CoV-2 infections, but aberrant responses can have deleterious effects. While antibodies to glycans could recognize the virus influence clinical outcome, little known about their roles. Using a carbohydrate antigen microarray, we profiled serum in healthy control subjects COVID-19 patients from two separate cohorts. had numerous autoantibodies self-glycans, including antiganglioside that cause neurological disorders. Additionally,...
Patients with the monogenic immune dysregulatory syndrome autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), which is caused by loss-of-function mutations in regulator ( AIRE ) gene, uniformly carry neutralizing autoantibodies directed against type-I interferons (IFNs) and many develop pneumonitis, both of place them at high risk for life-threatening COVID-19 pneumonia. Bamlanivimab etesevimab are monoclonal antibodies (mAbs) that target SARS-CoV-2 spike protein block...
Natural products are important precursors for antibiotic drug design. These chemical scaffolds serve as synthetic inspiration chemists who leverage their structures to develop novel antibacterials and probes. We have previously studied carolacton, a natural product macrolactone fromSorangium cellulosum, discovered simplified derivative, A2, that maintained apparent biofilm inhibitory activity, although the biological target was unknown. Herein, we utilize affinity-based protein profiling...
Autoantibodies (autoAbs) that neutralize type 1 interferons (T1IFNs) are a major risk factor associated with developing critical COVID-19 disease and most commonly found in individuals over age 70 patients genetic or acquired thymic defects. Swift identification of autoAb-positive may allow targeted interventions to prevent disease. Herein, we provide workflow protocols aimed at rapidly identifying who autoAb positive from large cohort. Basic Protocol describes multiplex particle-based assay...
The Danger Model predicts that there are some molecules no immune system can ever be fully tolerant of, namely proteins only transiently expressed during times of stress, infection, or injury. Among these the danger/alarm signals themselves. Accordingly, a fleeting autoantibody response to danger is expected when they released. Depending on context, autoantibodies may serve beneficial "housekeeping" functions by removing surplus from circulation or, conversely, create an immunodeficiency....
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the pandemic infectious disease COVID-19.However, clinical manifestations and outcomes differ significantly among COVID-19 patients, ranging from asymptomatic to extremely severe, it remains unclear what drives these disparities.Here, we studied 159 sequentially enrolled hospitalized patients with COVID-19-associated pneumonia Brescia, Italy using VirScan phage-display method characterize circulating antibodies...
Abstract SARS-CoV-2 infection fatality rate (IFR) doubles with every five years of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ~20% deceased patients across groups. In the general population, they ~1% individuals aged 20-70 and >4% those >70 old. With a sample 1,261 34,159 uninfected individuals, we estimated both IFR relative risk death (RRD) groups for carrying type I IFNs, to non-carriers. For IFN-α2 or RRD was 17.0[95%...
Abstract Pediatric COVID-19 (pCOVID-19) is rarely severe, however a minority of SARS-CoV-2-infected children may develop MIS-C, multisystem inflammatory syndrome with significant morbidity. In this longitudinal multi-institutional study, we used multi-omics to identify novel time- and treatment-related immunopathological signatures in (n=105) MIS-C (n=76). pCOVID-19 was characterized by enhanced type I IFN responses, II IFN- NF-κB dependent matrisome activation, increased levels Spike...
Abstract Background Approximately 10-20% of patients with critical COVID-19 harbor neutralizing autoantibodies (auto-Abs) that target type I interferons (IFN), a family cytokines induce innate immune defense mechanisms upon viral infection. Studies to date indicate these auto-Abs are mostly detected in men over age 65. Methods We screened for IFN serum sera collected < 21 days post-symptom onset subset 103 inpatients and 24 outpatients drawn from large prospective cohort study...