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Article ; Online: TIM-3 signaling contributes to the suppressive capacity of Tregs from people with HIV on antiretroviral therapy.

Nieves-Rosado, Hector M / Jacobs, Jana L / Naqvi, Asma / Mellors, John W / Macatangay, Bernard J C / Kane, Lawrence P

2023 Volume 114, Issue 4, Page(s) 368–372

Abstract: TIM-3 expression is increased on peripheral regulatory T cells (Tregs) of virally suppressed persons with HIV-1 on antiretroviral therapy (PWH-ART). However, the relevance of TIM-3 expression in this setting is unclear. We used flow cytometry to evaluate ...

Abstract	TIM-3 expression is increased on peripheral regulatory T cells (Tregs) of virally suppressed persons with HIV-1 on antiretroviral therapy (PWH-ART). However, the relevance of TIM-3 expression in this setting is unclear. We used flow cytometry to evaluate the suppressive phenotype and signaling pathways in peripheral TIM-3- vs TIM-3+ Tregs in PWH-ART. TIM-3+ Tregs showed increased expression of IL-10 compared with persons without HIV-1. In addition, TIM-3+ Tregs displayed elevated signaling and activation, relative to TIM-3- Tregs from the same PWH-ART. Dramatically, TIM-3 blockade restrained the in vitro suppressive capacity of peripheral Tregs. Therefore, our data demonstrate not only that TIM-3 expression by Tregs is associated with an immunosuppressive response among PWH-ART, but also that TIM-3 contributes directly to the enhanced suppressive activity of Tregs in this setting.
MeSH term(s)	Humans ; Hepatitis A Virus Cellular Receptor 2/metabolism ; T-Lymphocytes, Regulatory/metabolism ; HIV Infections/drug therapy ; HIV Infections/metabolism
Chemical Substances	Hepatitis A Virus Cellular Receptor 2
Language	English
Publishing date	2023-06-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	605722-6
ISSN	1938-3673 ; 0741-5400
ISSN (online)	1938-3673
ISSN	0741-5400
DOI	10.1093/jleuko/qiad068
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Article ; Online: Subphenotypes of self-reported symptoms and outcomes in long COVID: a prospective cohort study with latent class analysis.

BMJ open

2024 Volume 14, Issue 3, Page(s) e077869

Abstract: Objective: To characterise subphenotypes of self-reported symptoms and outcomes (SRSOs) in postacute sequelae of COVID-19 (PASC).: Design: Prospective, observational cohort study of subjects with PASC.: Setting: Academic tertiary centre from five ... ...

Abstract	Objective: To characterise subphenotypes of self-reported symptoms and outcomes (SRSOs) in postacute sequelae of COVID-19 (PASC). Design: Prospective, observational cohort study of subjects with PASC. Setting: Academic tertiary centre from five clinical referral sources. Participants: Adults with COVID-19 ≥20 days before enrolment and presence of any new self-reported symptoms following COVID-19. Exposures: We collected data on clinical variables and SRSOs via structured telephone interviews and performed standardised assessments with validated clinical numerical scales to capture psychological symptoms, neurocognitive functioning and cardiopulmonary function. We collected saliva and stool samples for quantification of SARS-CoV-2 RNA via quantitative PCR. Outcomes measures: Description of PASC SRSOs burden and duration, derivation of distinct PASC subphenotypes via latent class analysis (LCA) and relationship with viral load. Results: We analysed baseline data for 214 individuals with a study visit at a median of 197.5 days after COVID-19 diagnosis. Participants reported ever having a median of 9/16 symptoms (IQR 6-11) after acute COVID-19, with muscle-aches, dyspnoea and headache being the most common. Fatigue, cognitive impairment and dyspnoea were experienced for a longer time. Participants had a lower burden of active symptoms (median 3 (1-6)) than those ever experienced (p<0.001). Unsupervised LCA of symptoms revealed three clinically active PASC subphenotypes: a high burden constitutional symptoms (21.9%), a persistent loss/change of smell and taste (20.6%) and a minimal residual symptoms subphenotype (57.5%). Subphenotype assignments were strongly associated with self-assessments of global health, recovery and PASC impact on employment (p<0.001) as well as referral source for enrolment. Viral persistence (5.6% saliva and 1% stool samples positive) did not explain SRSOs or subphenotypes. Conclusions: We identified three distinct PASC subphenotypes. We highlight that although most symptoms progressively resolve, specific PASC subpopulations are impacted by either high burden of constitutional symptoms or persistent olfactory/gustatory dysfunction, requiring prospective identification and targeted preventive or therapeutic interventions.
MeSH term(s)	Adult ; Humans ; Post-Acute COVID-19 Syndrome ; COVID-19/epidemiology ; Prospective Studies ; Self Report ; COVID-19 Testing ; Latent Class Analysis ; RNA, Viral ; SARS-CoV-2 ; Disease Progression ; Dyspnea
Chemical Substances	RNA, Viral
Language	English
Publishing date	2024-03-14
Publishing country	England
Document type	Observational Study ; Journal Article
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2023-077869
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Article: Plasma SARS-CoV-2 RNA levels as a biomarker of lower respiratory tract SARS-CoV-2 infection in critically ill patients with COVID-19.

Jacobs, Jana L / Naqvi, Asma / Shah, Faraaz A / Boltz, Valerie F / Kearney, Mary F / McVerry, Bryan J / Ray, Prabir / Schaefer, Caitlin / Fitzpatrick, Meghan / Methé, Barbara / Lee, Janet / Morris, Alison / Mellors, John W / Kitsios, Georgios D / Bain, William

medRxiv : the preprint server for health sciences

2022

Abstract: Plasma SARS-CoV-2 viral RNA (vRNA) levels are predictive of COVID-19 outcomes in hospitalized patients, but whether plasma vRNA reflects lower respiratory tract (LRT) vRNA levels is unclear. We compared plasma and LRT vRNA levels in simultaneously ... ...

Abstract	Plasma SARS-CoV-2 viral RNA (vRNA) levels are predictive of COVID-19 outcomes in hospitalized patients, but whether plasma vRNA reflects lower respiratory tract (LRT) vRNA levels is unclear. We compared plasma and LRT vRNA levels in simultaneously collected longitudinal samples from mechanically-ventilated patients with COVID-19. LRT and plasma vRNA levels were strongly correlated at first sampling (r=0.83, p<10
Language	English
Publishing date	2022-01-11
Publishing country	United States
Document type	Preprint
DOI	10.1101/2022.01.10.22269018
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Article ; Online: Plasma SARS-CoV-2 RNA Levels as a Biomarker of Lower Respiratory Tract SARS-CoV-2 Infection in Critically Ill Patients With COVID-19.

Jacobs, Jana L / Naqvi, Asma / Shah, Faraaz A / Boltz, Valerie F / Kearney, Mary F / McVerry, Bryan J / Ray, Prabir / Schaefer, Caitlin / Fitzpatrick, Meghan / Methé, Barbara / Lee, Janet S / Morris, Alison / Mellors, John W / Kitsios, Georgios D / Bain, William

The Journal of infectious diseases

2022 Volume 226, Issue 12, Page(s) 2089–2094

Abstract	Plasma SARS-CoV-2 viral RNA (vRNA) levels are predictive of COVID-19 outcomes in hospitalized patients, but whether plasma vRNA reflects lower respiratory tract (LRT) vRNA levels is unclear. We compared plasma and LRT vRNA levels in serially collected samples from mechanically ventilated patients with COVID-19. LRT and plasma vRNA levels were strongly correlated at first sampling (n = 33, r = 0.83, P < 10-9) and then declined in parallel in available serial samples except in nonsurvivors who exhibited delayed vRNA clearance in LRT samples. Plasma vRNA measurement may offer a practical surrogate of LRT vRNA burden in critically ill patients, especially early after ICU admission.
MeSH term(s)	Humans ; SARS-CoV-2 ; COVID-19/diagnosis ; RNA, Viral ; Critical Illness ; Biomarkers ; Respiratory System
Chemical Substances	RNA, Viral ; Biomarkers
Language	English
Publishing date	2022-04-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiac157
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Article ; Online: Impact of antiretroviral therapy during acute or early HIV infection on virologic and immunologic outcomes: results from a multinational clinical trial.

Crowell, Trevor A / Ritz, Justin / Zheng, Lu / Naqvi, Asma / Cyktor, Joshua C / Puleo, Joseph / Clagett, Brian / Lama, Javier R / Kanyama, Cecilia / Little, Susan J / Cohn, Susan E / Riddler, Sharon A / Collier, Ann C / Heath, Sonya L / Tantivitayakul, Pornphen / Grinsztejn, Beatriz / Arduino, Roberto C / Rooney, James F / van Zyl, Gert U /

Coombs, Robert W / Fox, Lawrence / Ananworanich, Jintanat / Eron, Joseph J / Sieg, Scott F / Mellors, John W / Daar, Eric S

AIDS (London, England)

2024

Abstract: Objective: To assess how antiretroviral therapy (ART) initiation during acute or early HIV infection (AEHI) affects the viral reservoir and host immune responses.: Design: Single-arm trial of ART initiation during AEHI at 30 sites in the Americas, ... ...

Abstract	Objective: To assess how antiretroviral therapy (ART) initiation during acute or early HIV infection (AEHI) affects the viral reservoir and host immune responses. Design: Single-arm trial of ART initiation during AEHI at 30 sites in the Americas, Africa, and Asia. Methods: HIV DNA was measured at week 48 of ART in 5 million CD4+ T cells by sensitive qPCR assays targeting HIV gag and pol. Peripheral blood mononuclear cells were stimulated with potential HIV T cell epitope peptide pools consisting of env, gag, nef, and pol peptides and stained for expression of CD3, CD4, CD8, and intracellular cytokines/chemokines. Results: From 2017 to 2019, 188 participants initiated ART during Fiebig stages I (n = 6), II (n = 43), III (n = 56), IV (n = 23), and V (n = 60). Median age was 27 years (interquartile range 23-38), 27 (14%) participants were female, and 180 (97%) cisgender. Among 154 virally suppressed participants at week 48, 100% had detectable HIV gag or pol DNA. Participants treated during Fiebig I had the lowest HIV DNA levels (P < 0.001). Week 48 HIV DNA mostly did not correlate with concurrent CD4+ or CD8+ T cell HIV-specific immune responses (rho range -0.11 to +0.19, all P > 0.025). At week 48, the magnitude, but not polyfunctionality, of HIV-specific T cell responses was moderately reduced among participants who initiated ART earliest. Conclusion: Earlier ART initiation during AEHI reduced but did not eliminate the persistence of HIV-infected cells in blood. These findings explain the rapid viral rebound observed after ART cessation in early-treated individuals with undetectable HIV DNA by less sensitive methods.
Language	English
Publishing date	2024-03-14
Publishing country	England
Document type	Journal Article
ZDB-ID	639076-6
ISSN	1473-5571 ; 0269-9370 ; 1350-2840
ISSN (online)	1473-5571
ISSN	0269-9370 ; 1350-2840
DOI	10.1097/QAD.0000000000003881
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Article ; Online: Noninvasive diagnosis of secondary infections in COVID-19 by sequencing of plasma microbial cell-free DNA.

iScience

2023 Volume 26, Issue 11, Page(s) 108093

Abstract: Secondary infection (SI) diagnosis in severe COVID-19 remains challenging. We correlated metagenomic sequencing of plasma microbial cell-free DNA (mcfDNA-Seq) with clinical SI assessment, immune response, and outcomes. We classified 42 COVID-19 ... ...

Abstract	Secondary infection (SI) diagnosis in severe COVID-19 remains challenging. We correlated metagenomic sequencing of plasma microbial cell-free DNA (mcfDNA-Seq) with clinical SI assessment, immune response, and outcomes. We classified 42 COVID-19 inpatients as microbiologically confirmed-SI (Micro-SI, n = 8), clinically diagnosed-SI (Clinical-SI, n = 13, i.e., empiric antimicrobials), or no-clinical-suspicion-for-SI (No-Suspected-SI, n = 21). McfDNA-Seq was successful in 73% of samples. McfDNA detection was higher in Micro-SI (94%) compared to Clinical-SI (57%, p = 0.03), and unexpectedly high in No-Suspected-SI (83%), similar to Micro-SI. We detected culture-concordant mcfDNA species in 81% of Micro-SI samples. McfDNA correlated with LRT 16S rRNA bacterial burden (r = 0.74, p = 0.02), and biomarkers (white blood cell count, IL-6, IL-8, SPD, all p < 0.05). McfDNA levels were predictive of worse 90-day survival (hazard ratio 1.30 [1.02-1.64] for each log
Language	English
Publishing date	2023-10-11
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.108093
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Article: Rapid Emergence of Potentially Transmissible Severe Acute Respiratory Syndrome Coronavirus 2 With Resistance to Combination Monoclonal Antibody Therapy.

Open forum infectious diseases

2023 Volume 10, Issue 5, Page(s) ofad278

Abstract: Prolonged coronavirus disease 2019 may generate new viral variants. We report an immunocompromised patient treated with monoclonal antibodies who experienced rebound of viral RNA and emergence of an antibody-resistant (>1000-fold) variant containing 5 ... ...

Abstract	Prolonged coronavirus disease 2019 may generate new viral variants. We report an immunocompromised patient treated with monoclonal antibodies who experienced rebound of viral RNA and emergence of an antibody-resistant (>1000-fold) variant containing 5 mutations in the spike gene. The mutant virus was isolated from respiratory secretions, suggesting the potential for secondary transmission.
Language	English
Publishing date	2023-05-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	2757767-3
ISSN	2328-8957
ISSN	2328-8957
DOI	10.1093/ofid/ofad278
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Article ; Online: Tracking HIV-1-Infected Cell Clones Using Integration Site-Specific qPCR.

Brandt, Leah D / Guo, Shuang / Joseph, Kevin W / Jacobs, Jana L / Naqvi, Asma / Coffin, John M / Kearney, Mary F / Halvas, Elias K / Wu, Xiaolin / Hughes, Stephen H / Mellors, John W

Viruses

2021 Volume 13, Issue 7

Abstract: Efforts to cure HIV-1 infection require better quantification of the HIV-1 reservoir, particularly the clones of cells harboring replication-competent (intact) proviruses, ... ...

Abstract	Efforts to cure HIV-1 infection require better quantification of the HIV-1 reservoir, particularly the clones of cells harboring replication-competent (intact) proviruses, termed
MeSH term(s)	5'-Nucleotidase/genetics ; CD4-Positive T-Lymphocytes/virology ; Cell Line ; Glycoproteins/genetics ; HIV Infections/virology ; HIV-1/genetics ; HIV-1/physiology ; Humans ; Leukocytes, Mononuclear/virology ; Proviruses/genetics ; Proviruses/physiology ; Real-Time Polymerase Chain Reaction ; Viral Load ; Virus Integration
Chemical Substances	Glycoproteins ; 5'-Nucleotidase (EC 3.1.3.5) ; NT5C3A protein, human (EC 3.1.3.5)
Language	English
Publishing date	2021-06-25
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v13071235
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Article: Tracking HIV-1-Infected Cell Clones Using Integration Site-Specific qPCR

Brandt, Leah D. / Guo, Shuang / Joseph, Kevin W. / Jacobs, Jana L. / Naqvi, Asma / Coffin, John M. / Kearney, Mary F. / Halvas, Elias K. / Wu, Xiaolin / Hughes, Stephen H. / Mellors, John W.

Viruses. 2021 June 25, v. 13, no. 7

2021

Abstract: Efforts to cure HIV-1 infection require better quantification of the HIV-1 reservoir, particularly the clones of cells harboring replication-competent (intact) proviruses, termed repliclones. The digital droplet PCR assays commonly used to quantify ... ...

Abstract	Efforts to cure HIV-1 infection require better quantification of the HIV-1 reservoir, particularly the clones of cells harboring replication-competent (intact) proviruses, termed repliclones. The digital droplet PCR assays commonly used to quantify intact proviruses do not differentiate among specific repliclones, thus the dynamics of repliclones are not well defined. The major challenge in tracking repliclones is the relative rarity of the cells carrying specific intact proviruses. To date, detection and accurate quantification of repliclones requires in-depth integration site sequencing. Here, we describe a simplified workflow using integration site-specific qPCR (IS-qPCR) to determine the frequencies of the proviruses integrated in individual repliclones. We designed IS-qPCR to determine the frequencies of repliclones and clones of cells that carry defective proviruses in samples from three donors. Comparing the results of IS-qPCR with deep integration site sequencing data showed that the two methods yielded concordant estimates of clone frequencies (r = 0.838). IS-qPCR is a potentially valuable tool that can be applied to multiple samples and cell types over time to measure the dynamics of individual repliclones and the efficacy of treatments designed to eliminate them.
Keywords	HIV infections ; droplets ; proviruses
Language	English
Dates of publication	2021-0625
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v13071235
Database	NAL-Catalogue (AGRICOLA)

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Article: Fatty Acids Rich Extract From

Erukainure, Ochuko L / Ashraf, Nadia / Naqvi, Asma S / Zaruwa, Moses Z / Muhammad, Aliyu / Odusote, Adenike D / Elemo, Gloria N

Frontiers in pharmacology

2018 Volume 9, Page(s) 251

Abstract: Glioblastoma multiforme (GBM) is a malignant primary type of brain cancer with high proliferation and metastasis rates due to involvement of the microglial cell. It is resistant against available chemotherapy. Many strategic protocols have been developed ...

Abstract	Glioblastoma multiforme (GBM) is a malignant primary type of brain cancer with high proliferation and metastasis rates due to involvement of the microglial cell. It is resistant against available chemotherapy. Many strategic protocols have been developed but prognosis and patient life has not improved substantially. In this study, the anti-metastatic and antioxidant effect of fatty acids from
Language	English
Publishing date	2018-03-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2018.00251
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