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Article ; Online: Cytokine Storm.

Mudd, Philip A / Crawford, Jeremy C / Thomas, Paul G

2021 Volume 384, Issue 16, Page(s) e59

MeSH term(s)	COVID-19 ; Cytokine Release Syndrome ; Cytokines ; Humans
Chemical Substances	Cytokines
Language	English
Publishing date	2021-05-07
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMc2036236
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Article ; Online: Prolonged adaptive immune activation in COVID-19: implications for maintenance of long-term immunity?

Mudd, Philip A / Remy, Kenneth E

The Journal of clinical investigation

2020 Volume 131, Issue 1

Abstract: Ongoing observational clinical research has prioritized understanding the human immune response to SARS-CoV-2 during the coronavirus disease 2019 (COVID-19) pandemic. Several recent studies suggest that immune dysregulation with early and prolonged ... ...

Abstract	Ongoing observational clinical research has prioritized understanding the human immune response to SARS-CoV-2 during the coronavirus disease 2019 (COVID-19) pandemic. Several recent studies suggest that immune dysregulation with early and prolonged adaptive immune system activation can result in cellular exhaustion. In this issue of the JCI, Files et al. compared cellular immune phenotypes during the first two months of COVID-19 in hospitalized and less severe, non-hospitalized patients. The authors utilized flow cytometry to analyze circulating peripheral blood mononuclear cells. Both patient cohorts maintained B and T cell phenotypes consistent with activation and cellular exhaustion throughout the first two months of infection. Additionally, follow-up samples from the non-hospitalized patient cohort showed that activation markers and cellular exhaustion increased over time. These findings illustrate the persistent nature of the adaptive immune system changes that have been noted in COVID-19 and suggest longer term effects that may shape the maintenance of immunity to SARS-CoV-2.
MeSH term(s)	Adaptive Immunity ; B-Lymphocytes/immunology ; B-Lymphocytes/pathology ; COVID-19/immunology ; COVID-19/pathology ; Female ; Humans ; Male ; SARS-CoV-2/immunology ; T-Lymphocytes/immunology ; T-Lymphocytes/pathology
Keywords	covid19
Language	English
Publishing date	2020-10-01
Publishing country	United States
Document type	Journal Article ; Observational Study ; Research Support, N.I.H., Extramural
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI143928
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Article ; Online: Emergency medicine residency pathways for MD/PhD trainees: A national cross-sectional study of physician-scientist training programs.

Cyndari, Karen / White, Libby / Mudd, Philip A / Vakkalanka, J Priyanka / Krispin, Sydney / Wallace, Kelli / Schagrin, Megan / Mohr, Nicholas

AEM education and training

2024 Volume 8, Issue 2, Page(s) e10960

Abstract: Background: Combined clinical and research training is common in residency programs outside emergency medicine (EM), and these pathways are particularly valuable for combined MD/PhD graduates planning to pursue a career as a physician-scientist. However, ...

Abstract	Background: Combined clinical and research training is common in residency programs outside emergency medicine (EM), and these pathways are particularly valuable for combined MD/PhD graduates planning to pursue a career as a physician-scientist. However, EM departments may not know what resources to provide these trainees during residency to create research-focused, productive, future faculty, and trainees may not know which programs support their goal of becoming a physician-scientist in EM. The objective of this study was to describe research training and resources available to MD/PhD graduates in EM residency training with a focus on dedicated research pathways. Methods: This study was a cross-sectional inventory conducted through an electronic survey of EM residency program directors. We sought to identify dedicated MD/PhD research training pathways, with a focus on both resources and training priorities. Descriptive statistics were used to summarize survey responses. Results: We collected 192 survey responses (69.6% response rate). Among respondents, 41 programs (21.4%) offered a research pathway/track, 52 (27.4%) offered a research fellowship, 22 (11.5%) offered both a residency research pathway/track and a research fellowship, and two (1.0%) offered a dedicated EM physician-scientist training pathway. Most programs considered research a priority and were enthusiastic about interviewing applicants planning a research career, but recruitment of physician-scientist applicants was not generally prioritized. Conclusions: Some EM residency programs offer combined clinical and mentored research training for prospective physician-scientists, and nearly all residency programs considered research important. Future work will focus on improving the EM physician-scientist pipeline by optimizing pathways available to trainees during residency and fellowship.
Language	English
Publishing date	2024-03-21
Publishing country	United States
Document type	Journal Article
ISSN	2472-5390
ISSN (online)	2472-5390
DOI	10.1002/aet2.10960
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Article ; Online: 142 A Community Mini-Grant Program

Ashley G. Hall / Philip A. Kern / Mudd-Martin

Journal of Clinical and Translational Science, Vol 6, Pp 12-

Community Leaders and Academic Partners Work Together to Improve Health in Appalachian Kentucky

2022 Volume 12

Abstract: OBJECTIVES/GOALS: Through the Community Mini-Grant program, the University of Kentucky Center for Clinical and Translational Science Community Engagement and Research Core (CERC) provides a unique funding mechanism designed to empower community response ... ...

Abstract	OBJECTIVES/GOALS: Through the Community Mini-Grant program, the University of Kentucky Center for Clinical and Translational Science Community Engagement and Research Core (CERC) provides a unique funding mechanism designed to empower community response by supporting local solutions to complex health issues facing central Appalachian Kentucky communities. METHODS/STUDY POPULATION: Four $2500 grants are awarded annually to Appalachian organizations to implement evidence-based programs responsive to community-identified priority health needs. The CERC also supports program implementation and evaluation by facilitating collaborations between the organizations, community practitioners, and academic researchers. RESULTS/ANTICIPATED RESULTS: Since inception, grants have been awarded to 20 community organizations in 14 Appalachian counties. Health issues addressed have ranged from Alzheimers disease, cancer treatment and prevention, obesity, healthy lifestyle, and chronic disease management and prevention. Evidence-based programs have focused on improving health outcomes among older adults, caregivers, youth, children, women and infants, and families. Program outcomes have included immediate health benefits and long-term benefits resulting from community adoption of and ongoing financial support for programs. As example, results of an evidence-based educational program to improve diabetic foot assessment among clinicians in a large Appalachian healthcare network resulted in establishment of a traveling podiatrist program. DISCUSSION/SIGNIFICANCE: Community mini-grant recipients have successfully implemented projects that address the most significant health disparities in the region. Also of benefit are expanded partnerships that are foundational to the creation of new academic-community collaborations to address the challenging health issues of Appalachian populations in Kentucky.
Keywords	Medicine ; R
Subject code	360
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	Cambridge University Press
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Prolonged adaptive immune activation in COVID-19: implications for maintenance of long-term immunity?

Mudd, Philip A / Remy, Kenneth E

J. clin. invest

Abstract: Ongoing observational clinical research has prioritized understanding the human immune response to the SARS-CoV-2 during the COVID-19 pandemic. Several recent studies suggest that immune dysregulation with early and prolonged adaptive immune system ... ...

Abstract	Ongoing observational clinical research has prioritized understanding the human immune response to the SARS-CoV-2 during the COVID-19 pandemic. Several recent studies suggest that immune dysregulation with early and prolonged adaptive immune system activation can result in cellular exhaustion. In this issue of the JCI, Files et al. compared cellular immune phenotypes during the first two months of COVID-19 in hospitalized and less severe, non-hospitalized patients. The authors utilized flow cytometry to analyze circulating peripheral blood mononuclear cells. Both patient-cohorts maintained B and T cell phenotypes consistent with activation and cellular exhaustion throughout the first two months of infection. Additionally, follow-up samples from the non-hospitalized patient cohort showed that activation markers and cellular exhaustion increased over time. These findings illustrate the persistent nature of the adaptive immune system changes that have been noted in COVID-19 and suggest longer-term effects that may shape the maintenance of immunity to SARS-CoV-2.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #890007
Database	COVID19

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Article: Assessment of antibodies in the upper and lower human respiratory tract at steady state and after respiratory viral infection.

Koutsakos, Marios / Turner, Jackson S / Guillamet, M Cristina Vazquez / Reynolds, Daniel / Lei, Tingting / Byers, Derek E / Ellebedy, Ali H / Mudd, Philip A

Clinical & translational immunology

2023 Volume 12, Issue 8, Page(s) e1460

Abstract: Objectives: There is an increasing appreciation for the need to study mucosal antibody responses in humans. Our aim was to determine the utility of different types of samples from the human respiratory tract, specifically nasopharyngeal (NP) swabs ... ...

Abstract	Objectives: There is an increasing appreciation for the need to study mucosal antibody responses in humans. Our aim was to determine the utility of different types of samples from the human respiratory tract, specifically nasopharyngeal (NP) swabs obtained for diagnostic purposes and bronchoalveolar lavage (BAL) obtained in outpatient and inpatient settings. Methods: We analysed antibody levels in plasma and NP swabs from 67 individuals with acute influenza as well as plasma and BAL from individuals undergoing bronchoscopy, including five control subjects as well as seven moderately and seven severely ill subjects with a respiratory viral infection. Levels of α2-macroglobulin were determined in BAL and plasma to assess plasma exudation. Results: IgG and IgA were readily detectable in BAL and NP swabs, albeit at different ratios, while IgM levels were low. The total amount of antibody recovered from NP swabs varied greatly between study participants. Accordingly, the levels of influenza HA-specific antibodies varied, and individuals with lower amounts of total Ig in NP swabs had undetectable levels of HA-specific Ig. Similarly, the total amount of antibody recovered from BAL varied between study participants. However, severely ill patients showed evidence of increased plasma exudation, which may confound analysis of their BAL samples for mucosal antibodies. Conclusion: Nasopharyngeal swabs collected for diagnostic purposes may have utility in assessing antibodies from the human nasal mucosa, but variability in sampling should be accounted for. BAL samples can be utilised to study antibodies from the lower respiratory tract, but the possibility of plasma exudation should be excluded.
Language	English
Publishing date	2023-08-08
Publishing country	Australia
Document type	Journal Article
ZDB-ID	2694482-0
ISSN	2050-0068
ISSN	2050-0068
DOI	10.1002/cti2.1460
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The nasopharyngeal and salivary microbiomes in COVID-19 patients with and without asthma.

Kim, Josh G / Zhang, Ai / Rauseo, Adriana M / Goss, Charles W / Mudd, Philip A / O'Halloran, Jane A / Wang, Leyao

Allergy

2022 Volume 77, Issue 12, Page(s) 3676–3679

MeSH term(s)	Humans ; COVID-19 ; Nasopharynx ; Microbiota ; Asthma/diagnosis ; Saliva
Language	English
Publishing date	2022-07-23
Publishing country	Denmark
Document type	Letter ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	391933-x
ISSN	1398-9995 ; 0105-4538
ISSN (online)	1398-9995
ISSN	0105-4538
DOI	10.1111/all.15438
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Article ; Online: Quantitative SARS-CoV-2 RT-PCR and Bronchoalveolar Cytokine Concentrations Redefine the COVID-19 Phenotypes in Critically Ill Patients.

Vazquez Guillamet, M Cristina / Vazquez Guillamet, Rodrigo / Rjob, Ashraf / Reynolds, Daniel / Parikh, Bijal / Despotovic, Vladimir / Byers, Derek E / Ellebedy, Ali H / Kollef, Marin H / Mudd, Philip A

Journal of intensive care medicine

2024 , Page(s) 8850666231217707

Abstract: Rationale: Recent studies suggest that both hypo- and hyperinflammatory acute respiratory distress syndrome (ARDS) phenotypes characterize severe COVID-19-related pneumonia. The role of lung Severe Acute Respiratory Syndrome - Coronavirus 2 (SARS-CoV-2) ...

Abstract	Rationale: Recent studies suggest that both hypo- and hyperinflammatory acute respiratory distress syndrome (ARDS) phenotypes characterize severe COVID-19-related pneumonia. The role of lung Severe Acute Respiratory Syndrome - Coronavirus 2 (SARS-CoV-2) viral load in contributing to these phenotypes remains unknown. Objectives: To redefine COVID-19 ARDS phenotypes when considering quantitative SARS-CoV-2 RT-PCR in the bronchoalveolar lavage of intubated patients. To compare the relevance of deep respiratory samples versus plasma in linking the immune response and the quantitative viral loads. Methods: Eligible subjects were adults diagnosed with COVID-19 ARDS who required mechanical ventilation and underwent bronchoscopy. We recorded the immune response in the bronchoalveolar lavage and plasma and the quantitative SARS-CoV-2 RT-PCR in the bronchoalveolar lavage. Hierarchical clustering on principal components was applied separately on the 2 compartments' datasets. Baseline characteristics were compared between clusters. Measurements and results: Twenty subjects were enrolled between August 2020 and March 2021. Subjects underwent bronchoscopy on average 3.6 days after intubation. All subjects were treated with dexamethasone prior to bronchoscopy, 11 of 20 (55.6%) received remdesivir and 1 of 20 (5%) received tocilizumab. Adding viral load information to the classic 2-cluster model of ARDS revealed a new cluster characterized by hypoinflammatory responses and high viral load in 23.1% of the cohort. Hyperinflammatory ARDS was noted in 15.4% of subjects. Bronchoalveolar lavage clusters were more stable compared to plasma. Conclusions: We identified a unique group of critically ill subjects with COVID-19 ARDS who exhibit hypoinflammatory responses but high viral loads in the lower airways. These clusters may warrant different treatment approaches to improve clinical outcomes.
Language	English
Publishing date	2024-04-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	632828-3
ISSN	1525-1489 ; 0885-0666
ISSN (online)	1525-1489
ISSN	0885-0666
DOI	10.1177/08850666231217707
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Article ; Online: The salivary and nasopharyngeal microbiomes are associated with SARS-CoV-2 infection and disease severity.

Kim, Josh G / Zhang, Ai / Rauseo, Adriana M / Goss, Charles W / Mudd, Philip A / O'Halloran, Jane A / Wang, Leyao

Journal of medical virology

2022 Volume 95, Issue 2, Page(s) e28445

Abstract: Emerging evidence suggests the oral and upper respiratory microbiota may play important roles in modulating host immune responses to viral infection. As the host microbiome may be involved in the pathophysiology of coronavirus disease 2019 (COVID-19), we ...

Abstract	Emerging evidence suggests the oral and upper respiratory microbiota may play important roles in modulating host immune responses to viral infection. As the host microbiome may be involved in the pathophysiology of coronavirus disease 2019 (COVID-19), we investigated associations between the oral and nasopharyngeal microbiome and COVID-19 severity. We collected saliva (n = 78) and nasopharyngeal swab (n = 66) samples from a COVID-19 cohort and characterized the microbiomes using 16S ribosomal RNA gene sequencing. We also examined associations between the salivary and nasopharyngeal microbiome and age, COVID-19 symptoms, and blood cytokines. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection status, but not COVID-19 severity, was associated with community-level differences in the oral and nasopharyngeal microbiomes. Salivary and nasopharyngeal microbiome alpha diversity negatively correlated with age and were associated with fever and diarrhea. Oral Bifidobacterium, Lactobacillus, and Solobacterium were depleted in patients with severe COVID-19. Nasopharyngeal Paracoccus was depleted while nasopharyngeal Proteus, Cupravidus, and Lactobacillus were increased in patients with severe COVID-19. Further analysis revealed that the abundance of oral Bifidobacterium was negatively associated with plasma concentrations of known COVID-19 biomarkers interleukin 17F and monocyte chemoattractant protein-1. Our results suggest COVID-19 disease severity is associated with the relative abundance of certain bacterial taxa.
MeSH term(s)	Humans ; COVID-19 ; SARS-CoV-2 ; Microbiota ; Nasopharynx ; Patient Acuity
Language	English
Publishing date	2022-12-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	752392-0
ISSN	1096-9071 ; 0146-6615
ISSN (online)	1096-9071
ISSN	0146-6615
DOI	10.1002/jmv.28445
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Article: Immune phenotypes that predict COVID-19 severity.

Liechti, Thomas / Iftikhar, Yaser / Mangino, Massimo / Beddall, Margaret / Goss, Charles W / O'Halloran, Jane A / Mudd, Philip / Roederer, Mario

Research square

2022

Abstract: Severe COVID-19 causes profound immune perturbations, but pre-infection immune signatures contributing to severe COVID-19 remain unknown. Genome-wide association studies (GWAS) identified strong associations between severe disease and several chemokine ... ...

Abstract	Severe COVID-19 causes profound immune perturbations, but pre-infection immune signatures contributing to severe COVID-19 remain unknown. Genome-wide association studies (GWAS) identified strong associations between severe disease and several chemokine receptors and molecules from the type I interferon pathway. Here, we define immune signatures associated with severe COVID-19 using high-dimensional flow cytometry. We measured the peripheral immune system from individuals who recovered from mild, moderate, severe or critical COVID-19 and focused only on those immune signatures returning to steady-state. Individuals that suffered from severe COVID-19 showed reduced frequencies of T cell, MAIT cell and dendritic cell (DCs) subsets and altered chemokine receptor expression on several subsets, such as reduced levels of CCR1 and CCR2 on monocyte subsets. Furthermore, we found reduced frequencies of type I interferon-producing plasmacytoid DCs and altered IFNAR2 expression on several myeloid cells in individuals recovered from severe COVID-19. Thus, these data identify potential immune mechanisms contributing to severe COVID-19.
Language	English
Publishing date	2022-03-10
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-1378671/v1
Database	MEDical Literature Analysis and Retrieval System OnLINE

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