Evidence mapPaperPMID 36966617Full record

ArticleEBioMedicine2023

Identification of pre-infection markers and differential plasma protein expression following SARS-CoV-2 infection in people living with HIV.

Márton Kolossváry, Chris deFilippi, Sara McCallum, Kathleen V Fitch, Marissa R Diggs, Evelynne S Fulda, Heather J Ribaudo, Carl J Fichtenbaum, Judith A Aberg, Carlos D Malvestutto and 7 more

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in EBioMedicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT02344290. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
1.0field-weighted citation impact, top 27% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02344290 phase3completed

Randomized Trial to Prevent Vascular Events in HIV - REPRIEVE

Ran2015Enrolled7,769Registered outcomes37Posted comparisons40ConditionsCardiovascular Diseases, HIVArmsPitavastatin, Placebo
Open the trial in the graph
3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 12 institutions in 2 countries.

Márton KolossváryMetabolism Unit, Massachusetts General Hospital, Boston, MA, 02114, USA; Cardiovascular Imaging Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Chris deFilippiInova Heart and Vascular Institute, Falls Church, VA, 22042, USA.
Sara McCallumMetabolism Unit, Massachusetts General Hospital, Boston, MA, 02114, USA.
Kathleen V FitchMetabolism Unit, Massachusetts General Hospital, Boston, MA, 02114, USA.
Marissa R DiggsMetabolism Unit, Massachusetts General Hospital, Boston, MA, 02114, USA.
Evelynne S FuldaMetabolism Unit, Massachusetts General Hospital, Boston, MA, 02114, USA.
Heather J RibaudoCenter for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Carl J FichtenbaumDivision of Infectious Diseases, Department of Medicine, University of Cincinnati, Cincinnati, OH, USA.
Judith A AbergDivision of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Carlos D MalvestuttoDivision of Infectious Diseases, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
Judith S CurrierDivision of Infectious Diseases, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
Jose L CasadoDivision of Infectious Diseases, Ramon y Cajal Health Research Institute (IRyCIS), University Hospital Ramon y Cajal, Madrid, Spain.
Félix GutiérrezDivision of Infectious Diseases, Hospital General Universitario de Elche and University Miguel Hernández, Alicante, Spain; CIBERINFEC, Instituto de Salud Carlos III, Madrid, Spain.
Irini SeretiLaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Pamela S DouglasDuke Clinical Research Institute, Duke University School of Medicine, Durham, NC, 27708, USA.
Markella V ZanniMetabolism Unit, Massachusetts General Hospital, Boston, MA, 02114, USA.
Steven K GrinspoonMetabolism Unit, Massachusetts General Hospital, Boston, MA, 02114, USA. Electronic address: sgrinspoon@mgh.harvard.edu.
Massachusetts General Hospital · USAlaska Heart and Vascular Institute · USCancer Research And Biostatistics · USDuke University · USHarvard University · USIcahn School of Medicine at Mount Sinai · USInstituto Cajal · ESNational Institutes of Health · USThe Ohio State University Wexner Medical Center · USUniversitat de Miguel Hernández d'Elx · ESUniversity of California, Los Angeles · USUniversity of Cincinnati · US

Funding

AIDS Clinical Trials Group for Research on Therapeutics for HIV and Related InfectionsUM1AI068636 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 to 2025
$229.0M
Statistical and Data Management Center (SDMC), AIDS Clinical Trials Group (ACTG)UM1AI068634 · NIAID · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · 2021 to 2025
$81.6M
University of North Carolina Global HIV Prevention and Treatment Clinical Trials UnitUM1AI069423 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 to 2025
$23.6M
Boston HIV CTUUM1AI069412 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · 2021 to 2025
$22.8M
Case Clinical Trials UnitUM1AI069501 · NIAID · CASE WESTERN RESERVE UNIVERSITY · 2021 to 2025
$13.2M
Pitt-Ohio State Clinical Trials UnitUM1AI069494 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 to 2025
$13.1M
UNC Center for AIDS Research Core F BiostatisticsP30AI050410 · UNIV OF NORTH CAROLINA CHAPEL HILL · 2001 to 2025
$10.9M
Botswana-Harvard T.H. Chan School of Public Health AIDS Initiative Partnership CTUUM1AI069456 · NIAID · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · 2021 to 2025
$9.9M
1/2 REPRIEVE Extension for Trial CompletionUG3HL164285 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · 2023 to 2025
$9.5M
2/2 REPRIEVE Extension for Trial CompletionU24HL164284 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · 2023 to 2025
$1.7M
Immunopathogenic Mechanisms of Human Immunodeficiency Virus (HIV) DiseaseZIAAI001121 · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2025 to 2025
$1.5M
Consequences of Persistent Immune Activation among ART-treated Women with HIVK24AI157882 · MASSACHUSETTS GENERAL HOSPITAL · 2025 to 2025
$182k
NHLBI NIH HHS U01 HL123336NHLBI NIH HHS U01 HL123339NHLBI NIH HHS U24 HL164284NHLBI NIH HHS UG3 HL164285NIAID NIH HHS K24 AI157882NIAID NIH HHS P30 AI050410NIAID NIH HHS UM1 AI068634NIAID NIH HHS UM1 AI068636NIAID NIH HHS UM1 AI069412NIAID NIH HHS UM1 AI069423NIAID NIH HHS UM1 AI069456NIAID NIH HHS UM1 AI069494NIAID NIH HHS UM1 AI069501
6 · The paper itself

Abstract

backgroundMechanisms contributing to COVID-19 severity in people with HIV (PWH) are poorly understood. We evaluated temporal changes in plasma proteins following SARS-CoV-2 infection and identified pre-infection proteomic markers associated with future COVID-19.

methodsWe leveraged data from the global Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE). Antiretroviral therapy (ART)-treated PWH with clinical, antibody-confirmed COVID-19 as of September 2021 were matched on geographic region, age, and sample timing to antibody negative controls. For cases and controls, pre COVID-19 pandemic specimens were obtained prior to January 2020 to assess change over time and relationship to COVID-19 severity, using false-discovery adjusted mixed effects modeling.

findingsWe compared 257 unique plasma proteins in 94 COVID-19 antibody-confirmed clinical cases and 113 matched antibody-negative controls, excluding COVID-19 vaccinated participants (age 50 years, 73% male). 40% of cases were characterized as mild; 60% moderate to severe. Median time from COVID-19 infection to follow-up sampling was 4 months. Temporal patterns of protein changes differed based on COVID-19 disease severity. Among those experiencing moderate to severe disease vs. controls, NOS3 increased whereas ANG, CASP-8, CD5, GZMH, GZMB, ITGB2, and KLRD1 decreased. Higher pre-pandemic levels of granzymes A, B and H (GZMA, GZMB and GZMH) were associated with the future development of moderate-severe COVID-19 and were related to immune function.

interpretationWe identified temporal changes in proteins closely linked to inflammatory, immune, and fibrotic pathways which may relate to COVID-19-related morbidity among ART-treated PWH. Further we identified key granzyme proteins associated with future COVID-19 in PWH.

fundingThis study is supported through NIH grants U01HL123336, U01HL123336-06 and 3U01HL12336-06S3, to the clinical coordinating center, and U01HL123339, to the data coordinating center as well as funding from Kowa Pharmaceuticals, Gilead Sciences, and a grant award through ViiV Healthcare. The NIAID supported this study through grants UM1 AI068636, which supports the AIDS Clinical Trials Group (ACTG) Leadership and Operations Center, and UM1 AI106701, which supports the ACTG Laboratory Center. This work was also supported by NIAID through grant K24AI157882 to MZ. The work of IS was supported by the intramural research program of NIAID/NIH.

Indexed as

COVID-19Antibodies, ViralAnti-Retroviral AgentsBlood ProteinsFemaleHumansMaleMiddle AgedPandemicsProteomicsSARS-CoV-2Antibodies, ViralAnti-Retroviral AgentsBlood ProteinsCOVID-19GranzymeHuman immunodeficiency virusSARS-CoV-2

Identifiers

PMID36966617
PMCPMC10037041
OpenAlexW4360853507

What Socratic holds

Textmetadata
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.