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

Autor: Neven Zarkovic, Antonia Jakovcevic, Ana Mataic, Morana Jaganjac, Tea Vukovic, Georg Waeg, Kamelija Zarkovic
Rok vydání: 2022
Předmět:
COVID-19 / metabolism
Male
COVID-19 / virology
Pandemics / prevention & control
QH301-705.5
T-Lymphocytes
4-hydroxynonenal (4-HNE)
SARS-CoV-2 virus
T-Lymphocytes / virology
Aldehydes / metabolism
reactive oxygen species (ROS)
SARS-CoV-2 / physiology
COVID-19 / epidemiology
Biomarkers / metabolism
Macrophages
Alveolar
Clinical Medical Sciences
Humans
Biology (General)
Child
Pandemics
Biology
Aged
Respiratory Burst
Macrophages
Alveolar / pathology
Aldehydes
SARS-CoV-2
Superoxide Dismutase
Macrophages
Alveolar / metabolism
COVID-19
Reactive Oxygen Species / metabolism
General Medicine
Middle Aged
oxidative stress
vascular stress
lipid peroxidation
superoxide dismutase (SOD)
granulocytes
sepsis
Oxidative Stress
Macrophages
Alveolar / virology
Superoxide Dismutase / metabolism
Female
Autopsy
Lipid Peroxidation
Reactive Oxygen Species
T-Lymphocytes / metabolism
Biomarkers
T-Lymphocytes / pathology
Zdroj: Cells, Vol 11, Iss 444, p 444 (2022)
Cells
Cells; Volume 11; Issue 3; Pages: 444
ISSN: 2073-4409
Popis: 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.
Databáze: OpenAIRE
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