Hargun K. Khanna
- COVID-19 Clinical Research Studies
- SARS-CoV-2 and COVID-19 Research
- Long-Term Effects of COVID-19
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- vaccines and immunoinformatics approaches
- COVID-19 Impact on Reproduction
- Extracellular vesicles in disease
- Diabetes and associated disorders
- Respiratory Support and Mechanisms
- SARS-CoV-2 detection and testing
- Viral Infections and Outbreaks Research
- Immune cells in cancer
- Sepsis Diagnosis and Treatment
- Immunotherapy and Immune Responses
- Immune responses and vaccinations
Massachusetts General Hospital
2020-2022
Harvard University
2021
Understanding humoral responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for improving diagnostics, therapeutics, and vaccines. Deep serological profiling of 232 disease 2019 (COVID-19) patients 190 pre–COVID-19 era controls using VirScan revealed more than 800 epitopes in the SARS-CoV-2 proteome, including 10 likely recognized by neutralizing antibodies. Preexisting antibodies ORF1, whereas only COVID-19 patient primarily spike protein nucleoprotein. A...
Mechanisms underlying severe coronavirus disease 2019 (COVID-19) remain poorly understood. We analyze several thousand plasma proteins longitudinally in 306 COVID-19 patients and 78 symptomatic controls, uncovering immune non-immune linked to COVID-19. Deconvolution of our proteome data using published scRNA-seq datasets reveals contributions from circulating tissue cells. Sixteen percent display reduced inflammation yet comparably poor outcomes. Comparison who died severely ill survivors...
The hallmark of severe COVID-19 is an uncontrolled inflammatory response, resulting from poorly understood immunological dysfunction. We hypothesized that perturbations in FoxP3+ T regulatory cells (Treg), key enforcers immune homeostasis, contribute to pathology. Cytometric and transcriptomic profiling revealed a distinct Treg phenotype patients, with increase proportions intracellular levels the lineage-defining transcription factor FoxP3, correlating poor outcomes. These Tregs showed...
T cell-mediated immunity plays an important role in controlling SARS-CoV-2 infection, but the repertoire of naturally processed and presented viral epitopes on class I human leukocyte antigen (HLA-I) remains uncharacterized. Here, we report first HLA-I immunopeptidome two cell lines at different times post infection using mass spectrometry. We found peptides derived not only from canonical open reading frames (ORFs) also internal out-of-frame ORFs spike nucleocapsid captured by current...
BACKGROUND. SARS-CoV-2 plasma viremia has been associated with severe disease and death in COVID-19 small-scale cohort studies. The mechanisms behind this association remain elusive.
Rationale: Alveolar and endothelial injury may be differentially associated with coronavirus disease (COVID-19) severity over time. Objectives: To describe alveolar dynamics associations COVID-19 severity, cardiorenovascular injury, outcomes. Methods: This single-center observational study enrolled patients requiring respiratory support at emergency department presentation. More than 40 markers of (including receptor for advanced glycation endproducts [RAGE]), angiopoietin-2), renin, kidney...
Preexisting cross-coronavirus immunity influences the early development of SARS-CoV-2 humoral after COVID-19.
Mechanisms of neutrophil involvement in severe coronavirus disease 2019 (COVID-19) remain incompletely understood. Here, we collect longitudinal blood samples from 306 hospitalized COVID-19+ patients and 86 controls perform bulk RNA sequencing enriched neutrophils, plasma proteomics, high-throughput antibody profiling to investigate relationships between states severity. We identify dynamic switches six distinct subtypes. At days 3 7 post-hospitalization, with display a granulocytic...
Summary COVID-19 has caused over 1 million deaths globally, yet the cellular mechanisms underlying severe disease remain poorly understood. By analyzing several thousand plasma proteins in 306 patients and 78 symptomatic controls serial timepoints using two complementary approaches, we uncover host immune non-immune not previously linked to this disease. Integration of proteomics with nine published scRNAseq datasets shows that SARS-CoV-2 infection upregulates monocyte/macrophage,...
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) plasma viremia has been associated with severe disease and death in coronavirus 2019 (COVID-19) small-scale cohort studies. The mechanisms behind this association remain elusive. We evaluated the relationship between SARS-CoV-2 viremia, outcome, inflammatory proteomic profiles a of COVID-19 emergency department participants. viral load was measured using qRT-PCR based platform. Proteomic data were generated Proximity Extension...
Multiple studies have identified an association between neutrophils and COVID-19 disease severity; however, the mechanistic basis of this remains incompletely understood. Here we collected 781 longitudinal blood samples from 306 hospitalized + patients, 78 âˆ' acute respiratory distress syndrome 8 healthy controls, performed bulk RNA-sequencing enriched neutrophils, plasma proteomics, cfDNA measurements high throughput antibody profiling assays to investigate relationship neutrophil states...
Multiple studies have identified an association between neutrophils and COVID-19 disease severity; however, the mechanistic basis of this remains incompletely understood. Here we collected 781 longitudinal blood samples from 306 hospitalized + patients, 78 - acute respiratory distress syndrome 8 healthy controls, performed bulk RNA-sequencing enriched neutrophils, plasma proteomics, cfDNA measurements high throughput antibody profiling assays to investigate relationship neutrophil states...