Joshua Rosenheim
A5035555442- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Mycobacterium research and diagnosis
- vaccines and immunoinformatics approaches
- Tuberculosis Research and Epidemiology
- Respiratory viral infections research
- Diagnosis and treatment of tuberculosis
- Long-Term Effects of COVID-19
- Single-cell and spatial transcriptomics
- interferon and immune responses
- Immune responses and vaccinations
- T-cell and B-cell Immunology
- COVID-19 epidemiological studies
- Immune Cell Function and Interaction
- Immunodeficiency and Autoimmune Disorders
- Liver Disease Diagnosis and Treatment
- SARS-CoV-2 detection and testing
- Viral gastroenteritis research and epidemiology
- Animal Virus Infections Studies
University College London
2020-2024
Institute of Infection and Immunity
2022-2023
Abstract Individuals with potential exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) do not necessarily develop PCR or antibody positivity, suggesting that some individuals may clear subclinical infection before seroconversion. T cells can contribute the rapid clearance of SARS-CoV-2 and other infections 1–3 . Here we hypothesize pre-existing memory cell responses, cross-protective against (refs. 4–11 ), would expand in vivo support viral control, aborting infection....
Understanding the nature of immunity following mild/asymptomatic infection with SARS-CoV-2 is crucial to controlling pandemic. We analyzed T cell and neutralizing antibody responses in 136 healthcare workers (HCW) 16-18 weeks after United Kingdom lockdown, 76 whom had captured by serial sampling. Neutralizing antibodies (nAb) were present 89% previously infected HCW. tended be lower asymptomatic than those reporting case-definition symptoms COVID-19, while nAb titers maintained irrespective...
Abstract Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis children have been reported worldwide, including 278 the UK 1 . Here we report an investigation 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination genomic, transcriptomic, proteomic immunohistochemical methods. We detected high levels adeno-associated virus 2 (AAV2) DNA liver, blood, plasma or stool from 27 28 cases....
BackgroundWe hypothesised that host-response biomarkers of viral infections might contribute to early identification individuals infected with SARS-CoV-2, which is critical breaking the chains transmission. We aimed evaluate diagnostic accuracy existing candidate whole-blood transcriptomic signatures for infection predict positivity nasopharyngeal SARS-CoV-2 PCR testing.MethodsWe did a nested case-control study among prospective cohort health-care workers (aged ≥18 years) at St Bartholomew's...
Effective control of SARS-CoV-2 infection on primary exposure may reveal correlates protective immunity to future variants, but we lack insights into immune responses before or at the time virus is first detected. We use blood transcriptomics, multiparameter flow cytometry, and T cell receptor (TCR) sequencing spanning incident non-severe in unvaccinated virus-naive individuals identify rapid type 1 interferon (IFN) common other acute respiratory viruses proliferation that discriminate from...
In vivo IL-17A activity is elevated in active tuberculosis and may be a therapeutic target to attenuate disease-associated immunopathology.
Abstract Individuals with likely exposure to the highly infectious SARS-CoV-2 do not necessarily develop PCR or antibody positivity, suggesting some may clear sub-clinical infection before seroconversion. T cells can contribute rapid clearance of and other coronavirus infections 1–5 . We hypothesised that pre-existing memory cell responses, cross-protective potential against 6–12 , would expand in vivo mediate viral control, potentially aborting infection. studied replication transcription...
T cell responses precede antibody and may provide early control of infection. We analyzed the clonal basis this rapid response following SARS-COV-2 applied receptor (TCR) sequencing to define trajectories individual clones immediately. In PCR+ individuals, a wave TCRs strongly but transiently expand, frequently peaking same week as first positive PCR test. These expanding TCR CDR3s were enriched for sequences functionally annotated specific. Epitopes recognized by highly conserved between...
Abstract Blood transcriptional biomarkers of acute viral infections typically reflect type 1 interferon (IFN) signalling, but it is not known whether there are biological differences in their regulation that can be leveraged for distinct translational applications. We use high frequency sampling the SARS-CoV-2 human challenge model to show induction IFN-stimulated gene (ISG) expression with different temporal and cellular profiles. MX1 correlates a rapid transient wave ISG across all cell...
Summary Evaluation of host-response blood transcriptional signatures viral infection have so far failed to test whether these biomarkers reflect different biological processes that may be leveraged for distinct translational applications. We addressed this question in the SARS-CoV-2 human challenge model. found differential time profiles interferon (IFN) stimulated responses represented by measurement single genes. MX1 transcripts correlated with a rapid and transient wave type 1 IFN genes...
Abstract Studies of adaptive immunity to SARS-CoV-2 include characterisation lethal, severe and mild cases 1-8 . Understanding how long lasts in people who have had or asymptomatic infection is crucial. Healthcare worker (HCW) cohorts exposed infected by during the early stages pandemic are an invaluable resource study this question 9-14 The UK COVIDsortium a longitudinal, London hospital HCW cohort, followed from time lockdown 9,10 ; weekly PCR, serology symptom diaries allowed capture...
Download This Paper Open PDF in Browser Add to My Library Share: Permalink Using these links will ensure access this page indefinitely Copy URL DOI
Abstract We hypothesised that host-response biomarkers of viral infections may contribute to early identification SARS-CoV-2 infected individuals, critical breaking chains transmission. identified 20 candidate blood transcriptomic signatures infection by systematic review and evaluated their ability detect infection, compared the gold-standard virus PCR tests, among a prospective cohort 400 hospital staff subjected weekly testing when fit attend work. The transcriptional had limited overlap,...
Abstract The correlates of natural protective immunity to SARS-CoV-2 in the majority who experience asymptomatic infection or non-severe disease are not fully characterised, and remain important as new variants emerge. We addressed this question using blood transcriptomics, multiparameter flow cytometry T cell receptor (TCR) sequencing spanning time incident infection. identified a type 1 interferon (IFN) response common other acute respiratory viruses, proliferation that discriminated from...
Abstract We analyzed the dynamics of earliest T cell response to SARS-COV-2. A wave TCRs strongly but transiently expand during infection, frequently peaking same week as first positive PCR test. These expanding TCR CDR3s were enriched for sequences functionally annotated SARS-COV-2 specific. Most epitopes recognized by highly conserved between strains, not with circulating human coronaviruses. Many also present at high precursor frequency in pre-pandemic repertoires. similar set early...
Reasons for the spectrum of severity active tuberculosis (TB) disease are incompletely understood. We sought to identify master regulators host immune responses that determine in pulmonary TB. performed molecular profiling human vivo discover associations with extent radiographic TB a patient cohort. then undertook mechanistic studies test causality observed using zebrafish larval Mycobacterium marinum infection model. Transcriptional recall tuberculin skin (TST) challenge, surrogate lung,...
Abstract The tuberculin skin test (TST) is a cutaneous delayed hypersensitivity reaction to antigen from Mycobacterium tuberculosis (Mtb). We provide the first single cell sequencing characterisation of human TST reaction, based on suction blisters induced at site day 2 in 31 individuals. Integrated RNA and TCR showed immune response be dominated by T cells, with smaller populations NK cells myeloid cells. comprised CD4, CD8, gamma/delta 50% all identified as cytotoxic 14% regulatory....
ABSTRACT Background We have previously reported detection of genomic DNA Mycobacterium tuberculosis (Mtb) in peripheral blood mononuclear cells (PBMC) asymptomatic adults with recent household exposure to an index case infectious pulmonary (TB). It is not known whether this phenomenon indicates quiescent Mtb infection or incipient TB disease. Methods did a cross-sectional study nested prospective component, utilizing samples collected from studied cohort contacts recruited Ethiopia detect...
We analyzed the dynamics of earliest T cell response to SARS-COV-2. A wave TCRs strongly but transiently expand during infection, frequently peaking same week as first positive PCR test. These expanding TCR CDR3s were enriched for sequences functionally annotated SARS-COV-2 specific. Most epitopes recognized by highly conserved between strains, not with circulating human coronaviruses. Many also present at high precursor frequency in pre-pandemic repertoires. similar set early specific...