A5089835252- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Respiratory viral infections research
- Long-Term Effects of COVID-19
- Immune Cell Function and Interaction
- Asthma and respiratory diseases
- Neonatal Respiratory Health Research
- Inhalation and Respiratory Drug Delivery
- Fungal Infections and Studies
- Viral Infections and Immunology Research
- Fungal and yeast genetics research
- Plant Pathogens and Fungal Diseases
- IL-33, ST2, and ILC Pathways
- PARP inhibition in cancer therapy
- COVID-19 Impact on Reproduction
- Skin Protection and Aging
- Immune responses and vaccinations
- Viral gastroenteritis research and epidemiology
- CRISPR and Genetic Engineering
- Competency Development and Evaluation
- interferon and immune responses
- Inflammation biomarkers and pathways
- Single-cell and spatial transcriptomics
- Research in Social Sciences
- Plant-Microbe Interactions and Immunity
Gilead Sciences (United States)
2022-2024
University of California, San Francisco
2019-2024
United States Department of Veterans Affairs
2024
SUNY Upstate Medical University
2024
Mental Illness Research, Education and Clinical Centers
2024
Syracuse VA Medical Center
2024
Institute of Public Health
2021-2023
Advanced ENT and Allergy
2022
Cardiovascular Institute Hospital
2022
Universidad Católica de Santa Fe
2022
Although infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has pleiotropic and systemic effects in some individuals1-3, many others experience milder symptoms. Here, to gain a more comprehensive understanding of the distinction between mild phenotypes pathology disease 2019 (COVID-19) its origins, we performed whole-blood-preserving single-cell analysis protocol integrate contributions from all major immune cell types blood-including neutrophils, monocytes,...
Genetic variation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence and rapid spread multiple variants throughout pandemic, which Omicron is currently predominant variant circulating worldwide. SARS-CoV-2 concern/variants interest (VOC/VOI) have evidence increased viral transmission, disease severity, or decreased effectiveness vaccines neutralizing antibodies. Remdesivir (RDV [VEKLURY]) a nucleoside analog prodrug first FDA-approved antiviral...
Asthma is associated with chronic changes in the airway epithelium, a key target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Many epithelial changes, including goblet cell metaplasia, are driven by type cytokine IL-13, but effects IL-13 on SARS-CoV-2 infection unknown. We found that stimulation differentiated human bronchial cells (HBECs) cultured at air–liquid interface reduced viral RNA recovered from SARS-CoV-2–infected and decreased double-stranded RNA, marker...
Rationale: Autopsy and biomarker studies suggest that endotheliopathy contributes to coronavirus disease (COVID-19)-associated acute respiratory distress syndrome. However, the effects of COVID-19 on lung endothelium are not well defined. We hypothesized is caused by circulating host factors direct endothelial infection severe syndrome 2 (SARS-CoV-2). Objectives: aimed determine SARS-CoV-2 or sera from patients with permeability inflammatory activation microvascular cells. Methods: Human...
Remdesivir 1 is an phosphoramidate prodrug that releases the monophosphate of nucleoside GS-441524 (2) into lung cells, thereby forming bioactive triphosphate 2-NTP. 2-NTP, analog ATP, inhibits SARS-CoV-2 RNA-dependent RNA polymerase replication and transcription viral RNA. Strong clinical results for have prompted interest in oral approaches to generate Here, we describe discovery a 5′-isobutyryl ester 2 (GS-5245, Obeldesivir, 3) has low cellular cytotoxicity 3–7-fold improved delivery...
The impact of the COVID-19 public health social measures (PHSM) on behaviours is poorly understood. We aimed to identify factors associated with changes in alcohol and tobacco consumption during strictest period PHSM 'lockdown'.
Abstract Background Remdesivir is approved for treatment of coronavirus disease 2019 (COVID-19) in nonhospitalized and hospitalized adult pediatric patients. Here we present severe acute respiratory syndrome 2 (SARS-CoV-2) resistance analyses from the phase 3 ACTT-1 randomized placebo-controlled trial conducted participants with COVID-19. Methods Swab samples were collected at baseline longitudinally through day 29. SARS-CoV-2 genomes sequenced using next-generation sequencing. Phenotypic...
Abstract As SARS-CoV-2 continues to spread worldwide, tractable primary airway cell models that recapitulate the cell-intrinsic response arising viral variants are needed. Here we describe an adult stem cell-derived human organoid model overexpressing ACE2 receptor (ACE2-OE) supports robust replication while maintaining 3D architecture and cellular diversity of epithelium. ACE2-OE organoids were infected with subjected single-cell RNA-sequencing. Interferon-lambda was upregulated in cells...
In the PINETREE study, early remdesivir treatment reduced risk of coronavirus disease 2019 (COVID-19)-related hospitalizations or all-cause death versus placebo by 87% day 28 in high-risk, non-hospitalized patients. Here we report results assessment heterogeneity effect (HTE) outpatient remdesivir, focusing on time from symptom onset and number baseline factors (RFs).PINETREE was a double-blind, placebo-controlled trial patients with COVID-19 who were randomized within 7 days had ≥ 1 RF for...
Remdesivir decreases the risk of SARS-CoV-2 infection progressing to severe disease in adults. This study evaluated remdesivir safety and pharmacokinetics infants children.
Phenotypic switching between 2 opposing cellular states is a fundamental aspect of biology, and fungi provide facile systems to analyze the interactions regulons that control this type switch. A long-standing mystery in fungal pathogens humans how thermally dimorphic switch their developmental form response temperature. These fungi, including subject study, Histoplasma capsulatum, are temperature-responsive organisms utilize unknown regulatory pathways couple cell shape associated attributes...
Remdesivir (RDV) is a broad-spectrum nucleotide analog prodrug approved for the treatment of COVID-19 in hospitalized and non-hospitalized patients with clinical benefit demonstrated multiple Phase 3 trials. Here we present SARS-CoV-2 resistance analyses from SIMPLE studies evaluating RDV participants severe or moderate disease. The enrolled radiologic evidence pneumonia room-air oxygen saturation ≤94% >94%, respectively. Virology sample collection was optional study protocols. Sequencing...
Pseudomonas aeruginosa is a ubiquitous opportunistic pathogen which relies on highly adaptable metabolism to achieve broad pathogenesis. In one example of this flexibility, catalyze the NADH:quinone oxidoreductase step respiratory chain, P . has three different enzymes: NUO, NQR and NDH2, all carry out same redox function but have energy conservation ion transport properties. order better understand roles these enzymes, we constructed two series mutants: (i) single deletion mutants, each...
Abstract SARS coronavirus-2 (SARS-CoV-2) is causing a global pandemic with large variation in COVID-19 disease spectrum. SARS-CoV-2 infection requires host receptor ACE2 on lung epithelium, but epithelial underpinnings of are largely unknown. We capitalized comprehensive organoid assays to report remarkable rates organoids from different subjects. Tropism highest for TUBA- and MUC5AC-positive cells, levels TUBA-, MUC5A-, or ACE2-positive cells do not predict rate. identify surface molecule...
Ancestral SARS coronavirus-2 (SARS-CoV-2) and variants of concern (VOC) caused a global pandemic with spectrum disease severity. The mechanistic explaining variations related to airway epithelium are relatively understudied. Here, we biobanked organoids (AO) by preserving stem cell function. We optimized viral infection H1N1/PR8 comprehensively characterized epithelial responses SARS-CoV-2 in phenotypically stable AO from 20 different subjects. discovered Tetraspanin-8 (TSPAN8) as...
Abstract Remdesivir 1 is an amidate prodrug that releases the monophosphate of nucleoside GS-441524 ( 2 ) into lung cells thereby forming bioactive triphosphate 2-NTP . , analog ATP, inhibits SARS-CoV-2 RNA-dependent RNA polymerase replication and transcription viral RNA. Strong clinical results for have prompted interest in oral approaches to generate Here we describe discovery a 5’-isobutyryl ester GS-5245, Obeldesivir, 3 has low cellular cytotoxicity three seven-fold improved delivery...
Abstract While SARS-CoV-2 infection has pleiotropic and systemic effects in some patients, many others experience milder symptoms. We sought a holistic understanding of the severe/mild distinction COVID-19 pathology, its origins. performed wholeblood preserving single-cell analysis protocol to integrate contributions from all major cell types including neutrophils, monocytes, platelets, lymphocytes contents serum. Patients with mild disease display coordinated pattern interferonstimulated...
Abstract In the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic1, considerable focus has been placed on a model of viral entry into host epithelial populations, with separate upon responding immune system dysfunction that exacerbates or causes disease. We developed precision-cut lung slice model2,3 to investigate very early host-viral pathogenesis and found SARS-CoV-2 had rapid specific tropism for myeloid populations in human lung. Infection alveolar macrophages was...
Abstract Background Remdesivir (RDV), a nucleotide analog prodrug that targets the viral RNA-dependent RNA polymerase Nsp12, is approved to treat COVID-19 in hospitalized and nonhospitalized patients. Obeldesivir (ODV), an oral mono-5’-isobutyryl ester metabolized into same active triphosphate as RDV, being evaluated Phase 3 clinical trials. The antiviral activity of RDV ODV against previous Omicron subvariants (BA.1 BQ.1.1) was maintained with respect ancestral WA1 strain. We assessed...
Asthma is associated with chronic changes in the airway epithelium, a key target of SARS-CoV-2. Many epithelial are driven by type 2 cytokine IL-13, but effects IL-13 on SARS-CoV-2 infection unknown. We sought to discover how and other cytokines affect expression genes encoding SARS-CoV-2-associated host proteins human bronchial cells (HBECs) determine whether stimulation alters susceptibility infection. used bulk single cell RNA-seq identify cytokine-induced gene HBECs. related these...