Cargando…

Post-mortem Findings of Inflammatory Cells and the Association of 4-Hydroxynonenal with Systemic Vascular and Oxidative Stress in Lethal COVID-19 †

A recent comparison of clinical and inflammatory parameters, together with biomarkers of oxidative stress, in patients who died from aggressive COVID-19 and survivors suggested that the lipid peroxidation product 4-hydroxynonenal (4-HNE) might be detrimental in lethal SARS-CoV-2 infection. The curre...

Descripción completa

Detalles Bibliográficos
Autores principales: Zarkovic, Neven, Jakovcevic, Antonia, Mataic, Ana, Jaganjac, Morana, Vukovic, Tea, Waeg, Georg, Zarkovic, Kamelija
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8834180/
https://www.ncbi.nlm.nih.gov/pubmed/35159254
http://dx.doi.org/10.3390/cells11030444
_version_ 1784649121745862656
author Zarkovic, Neven
Jakovcevic, Antonia
Mataic, Ana
Jaganjac, Morana
Vukovic, Tea
Waeg, Georg
Zarkovic, Kamelija
author_facet Zarkovic, Neven
Jakovcevic, Antonia
Mataic, Ana
Jaganjac, Morana
Vukovic, Tea
Waeg, Georg
Zarkovic, Kamelija
author_sort Zarkovic, Neven
collection PubMed
description A recent comparison of clinical and inflammatory parameters, together with biomarkers of oxidative stress, in patients who died from aggressive COVID-19 and survivors suggested that the lipid peroxidation product 4-hydroxynonenal (4-HNE) might be detrimental in lethal SARS-CoV-2 infection. The current study further explores the involvement of inflammatory cells, systemic vascular stress, and 4-HNE in lethal COVID-19 using specific immunohistochemical analyses of the inflammatory cells within the vital organs obtained by autopsy of nine patients who died from aggressive SAR-CoV-2 infection. Besides 4-HNE, myeloperoxidase (MPO) and mitochondrial superoxide dismutase (SOD2) were analyzed alongside standard leukocyte biomarkers (CDs). All the immunohistochemical slides were simultaneously prepared for each analyzed biomarker. The results revealed abundant 4-HNE in the vital organs, but the primary origin of 4-HNE was sepsis-like vascular stress, not an oxidative burst of the inflammatory cells. In particular, inflammatory cells were often negative for 4-HNE, while blood vessels were always very strongly immunopositive, as was edematous tissue even in the absence of inflammatory cells. The most affected organs were the lungs with diffuse alveolar damage and the brain with edema and reactive astrocytes, whereas despite acute tubular necrosis, 4-HNE was not abundant in the kidneys, which had prominent SOD2. Although SOD2 in most cases gave strong immunohistochemical positivity similar to 4-HNE, unlike 4-HNE, it was always limited to the cells, as was MPO. Due to their differential expressions in blood vessels, inflammatory cells, and the kidneys, we think that SOD2 could, together with 4-HNE, be a potential link between a malfunctioning immune system, oxidative stress, and vascular stress in lethal COVID-19.
format Online
Article
Text
id pubmed-8834180
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-88341802022-02-12 Post-mortem Findings of Inflammatory Cells and the Association of 4-Hydroxynonenal with Systemic Vascular and Oxidative Stress in Lethal COVID-19 † Zarkovic, Neven Jakovcevic, Antonia Mataic, Ana Jaganjac, Morana Vukovic, Tea Waeg, Georg Zarkovic, Kamelija Cells Article A recent comparison of clinical and inflammatory parameters, together with biomarkers of oxidative stress, in patients who died from aggressive COVID-19 and survivors suggested that the lipid peroxidation product 4-hydroxynonenal (4-HNE) might be detrimental in lethal SARS-CoV-2 infection. The current study further explores the involvement of inflammatory cells, systemic vascular stress, and 4-HNE in lethal COVID-19 using specific immunohistochemical analyses of the inflammatory cells within the vital organs obtained by autopsy of nine patients who died from aggressive SAR-CoV-2 infection. Besides 4-HNE, myeloperoxidase (MPO) and mitochondrial superoxide dismutase (SOD2) were analyzed alongside standard leukocyte biomarkers (CDs). All the immunohistochemical slides were simultaneously prepared for each analyzed biomarker. The results revealed abundant 4-HNE in the vital organs, but the primary origin of 4-HNE was sepsis-like vascular stress, not an oxidative burst of the inflammatory cells. In particular, inflammatory cells were often negative for 4-HNE, while blood vessels were always very strongly immunopositive, as was edematous tissue even in the absence of inflammatory cells. The most affected organs were the lungs with diffuse alveolar damage and the brain with edema and reactive astrocytes, whereas despite acute tubular necrosis, 4-HNE was not abundant in the kidneys, which had prominent SOD2. Although SOD2 in most cases gave strong immunohistochemical positivity similar to 4-HNE, unlike 4-HNE, it was always limited to the cells, as was MPO. Due to their differential expressions in blood vessels, inflammatory cells, and the kidneys, we think that SOD2 could, together with 4-HNE, be a potential link between a malfunctioning immune system, oxidative stress, and vascular stress in lethal COVID-19. MDPI 2022-01-27 /pmc/articles/PMC8834180/ /pubmed/35159254 http://dx.doi.org/10.3390/cells11030444 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zarkovic, Neven
Jakovcevic, Antonia
Mataic, Ana
Jaganjac, Morana
Vukovic, Tea
Waeg, Georg
Zarkovic, Kamelija
Post-mortem Findings of Inflammatory Cells and the Association of 4-Hydroxynonenal with Systemic Vascular and Oxidative Stress in Lethal COVID-19 †
title Post-mortem Findings of Inflammatory Cells and the Association of 4-Hydroxynonenal with Systemic Vascular and Oxidative Stress in Lethal COVID-19 †
title_full Post-mortem Findings of Inflammatory Cells and the Association of 4-Hydroxynonenal with Systemic Vascular and Oxidative Stress in Lethal COVID-19 †
title_fullStr Post-mortem Findings of Inflammatory Cells and the Association of 4-Hydroxynonenal with Systemic Vascular and Oxidative Stress in Lethal COVID-19 †
title_full_unstemmed Post-mortem Findings of Inflammatory Cells and the Association of 4-Hydroxynonenal with Systemic Vascular and Oxidative Stress in Lethal COVID-19 †
title_short Post-mortem Findings of Inflammatory Cells and the Association of 4-Hydroxynonenal with Systemic Vascular and Oxidative Stress in Lethal COVID-19 †
title_sort post-mortem findings of inflammatory cells and the association of 4-hydroxynonenal with systemic vascular and oxidative stress in lethal covid-19 †
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8834180/
https://www.ncbi.nlm.nih.gov/pubmed/35159254
http://dx.doi.org/10.3390/cells11030444
work_keys_str_mv AT zarkovicneven postmortemfindingsofinflammatorycellsandtheassociationof4hydroxynonenalwithsystemicvascularandoxidativestressinlethalcovid19
AT jakovcevicantonia postmortemfindingsofinflammatorycellsandtheassociationof4hydroxynonenalwithsystemicvascularandoxidativestressinlethalcovid19
AT mataicana postmortemfindingsofinflammatorycellsandtheassociationof4hydroxynonenalwithsystemicvascularandoxidativestressinlethalcovid19
AT jaganjacmorana postmortemfindingsofinflammatorycellsandtheassociationof4hydroxynonenalwithsystemicvascularandoxidativestressinlethalcovid19
AT vukovictea postmortemfindingsofinflammatorycellsandtheassociationof4hydroxynonenalwithsystemicvascularandoxidativestressinlethalcovid19
AT waeggeorg postmortemfindingsofinflammatorycellsandtheassociationof4hydroxynonenalwithsystemicvascularandoxidativestressinlethalcovid19
AT zarkovickamelija postmortemfindingsofinflammatorycellsandtheassociationof4hydroxynonenalwithsystemicvascularandoxidativestressinlethalcovid19