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Identification of pre-infection markers and differential plasma protein expression following SARS-CoV-2 infection in people living with HIV
BACKGROUND: Mechanisms 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. METHODS: We leveraged data from the...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10037041/ https://www.ncbi.nlm.nih.gov/pubmed/36966617 http://dx.doi.org/10.1016/j.ebiom.2023.104538 |
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author | Kolossváry, Márton deFilippi, Chris McCallum, Sara Fitch, Kathleen V. Diggs, Marissa R. Fulda, Evelynne S. Ribaudo, Heather J. Fichtenbaum, Carl J. Aberg, Judith A. Malvestutto, Carlos D. Currier, Judith S. Casado, Jose L. Gutiérrez, Félix Sereti, Irini Douglas, Pamela S. Zanni, Markella V. Grinspoon, Steven K. |
author_facet | Kolossváry, Márton deFilippi, Chris McCallum, Sara Fitch, Kathleen V. Diggs, Marissa R. Fulda, Evelynne S. Ribaudo, Heather J. Fichtenbaum, Carl J. Aberg, Judith A. Malvestutto, Carlos D. Currier, Judith S. Casado, Jose L. Gutiérrez, Félix Sereti, Irini Douglas, Pamela S. Zanni, Markella V. Grinspoon, Steven K. |
author_sort | Kolossváry, Márton |
collection | PubMed |
description | BACKGROUND: Mechanisms 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. METHODS: We 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. FINDINGS: We 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. INTERPRETATION: We 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. FUNDING: This study is supported through 10.13039/100000002NIH grants U01HL123336, U01HL123336-06 and 3U01HL12336-06S3, to the clinical coordinating center, and U01HL123339, to the data coordinating center as well as funding from 10.13039/100011027Kowa Pharmaceuticals, 10.13039/100005564Gilead Sciences, and a grant award through 10.13039/100010877ViiV Healthcare. The 10.13039/100000060NIAID supported this study through grants UM1 AI068636, which supports the 10.13039/100006392AIDS Clinical Trials Group (ACTG) Leadership and Operations Center, and UM1 AI106701, which supports the ACTG Laboratory Center. This work was also supported by 10.13039/100000060NIAID through grant K24AI157882 to MZ. The work of IS was supported by the intramural research program of NIAID/10.13039/100000002NIH. |
format | Online Article Text |
id | pubmed-10037041 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-100370412023-03-24 Identification of pre-infection markers and differential plasma protein expression following SARS-CoV-2 infection in people living with HIV Kolossváry, Márton deFilippi, Chris McCallum, Sara Fitch, Kathleen V. Diggs, Marissa R. Fulda, Evelynne S. Ribaudo, Heather J. Fichtenbaum, Carl J. Aberg, Judith A. Malvestutto, Carlos D. Currier, Judith S. Casado, Jose L. Gutiérrez, Félix Sereti, Irini Douglas, Pamela S. Zanni, Markella V. Grinspoon, Steven K. eBioMedicine Articles BACKGROUND: Mechanisms 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. METHODS: We 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. FINDINGS: We 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. INTERPRETATION: We 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. FUNDING: This study is supported through 10.13039/100000002NIH grants U01HL123336, U01HL123336-06 and 3U01HL12336-06S3, to the clinical coordinating center, and U01HL123339, to the data coordinating center as well as funding from 10.13039/100011027Kowa Pharmaceuticals, 10.13039/100005564Gilead Sciences, and a grant award through 10.13039/100010877ViiV Healthcare. The 10.13039/100000060NIAID supported this study through grants UM1 AI068636, which supports the 10.13039/100006392AIDS Clinical Trials Group (ACTG) Leadership and Operations Center, and UM1 AI106701, which supports the ACTG Laboratory Center. This work was also supported by 10.13039/100000060NIAID through grant K24AI157882 to MZ. The work of IS was supported by the intramural research program of NIAID/10.13039/100000002NIH. Elsevier 2023-03-24 /pmc/articles/PMC10037041/ /pubmed/36966617 http://dx.doi.org/10.1016/j.ebiom.2023.104538 Text en © 2023 The Author(s) |
spellingShingle | Articles Kolossváry, Márton deFilippi, Chris McCallum, Sara Fitch, Kathleen V. Diggs, Marissa R. Fulda, Evelynne S. Ribaudo, Heather J. Fichtenbaum, Carl J. Aberg, Judith A. Malvestutto, Carlos D. Currier, Judith S. Casado, Jose L. Gutiérrez, Félix Sereti, Irini Douglas, Pamela S. Zanni, Markella V. Grinspoon, Steven K. Identification of pre-infection markers and differential plasma protein expression following SARS-CoV-2 infection in people living with HIV |
title | Identification of pre-infection markers and differential plasma protein expression following SARS-CoV-2 infection in people living with HIV |
title_full | Identification of pre-infection markers and differential plasma protein expression following SARS-CoV-2 infection in people living with HIV |
title_fullStr | Identification of pre-infection markers and differential plasma protein expression following SARS-CoV-2 infection in people living with HIV |
title_full_unstemmed | Identification of pre-infection markers and differential plasma protein expression following SARS-CoV-2 infection in people living with HIV |
title_short | Identification of pre-infection markers and differential plasma protein expression following SARS-CoV-2 infection in people living with HIV |
title_sort | identification of pre-infection markers and differential plasma protein expression following sars-cov-2 infection in people living with hiv |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10037041/ https://www.ncbi.nlm.nih.gov/pubmed/36966617 http://dx.doi.org/10.1016/j.ebiom.2023.104538 |
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