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

Žarković, Neven; Jakovčević, Antonia; Mataić, Ana; Jaganjac, Morana; Vuković, Tea; Waeg, Georg; Žarković, Kamelija

doi:10.3390/cells11030444

Cited by 22 publications

(29 citation statements)

References 55 publications

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“…As demonstrated by the analysis conducted so far, "COVID-19 Is Not Comparable to H1N1 Influenza" [56] (Table 2, Ref. [1,[11][12][13][14][15][16][17][18][19][20][21][22][23][24][26][27][28][31][32][33][34][35][36][37][38][39][40][41][42][47][48][49][50][51][52][53][54][55]57]) and histopathological findings play a key role in understanding the pathophysiological mechanisms of diseases and, thus possible therapeutic approaches.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, a study on post-mortem preparations would seem to confirm the role of oxidative stress in the pathogenesis of lethal forms of COVID-19, demonstrated by an abundant immunohistochemical expression of the lipid peroxidation product: 4-hydroxynonenal (4-HNE). The origin of 4-HNE would be vascular stress similar to sepsis and the organs most affected were the lungs with diffuse alveolar damage and the brain with edema and reactive astrocytosis [57]. A recent study attempted to define a unifying theory of the two souls of SARS-CoV-2 infection [65].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

COVID-19 and H1N1-09: A Systematic Review of Two Pandemics with a Focus on the Lung at Autopsy

Bertozzi¹,

Ferrara²,

Maiese³

et al. 2022

Front. Biosci. (Landmark Ed)

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Background:The purpose of this manuscript is to provide a comparative overview of the two global pandemics: the first on June 11th 2009 due to influenza A H1N1 (H1N1-09); the second and current pandemic caused by coronavirus 2019 (COVID-19) on March 11th 2020, focusing on how autopsy can contribute to the definition of cellular pathology, to clinical pathology and, more generally, to public health. Methods: A systematic literature search selection was conducted on PubMed database on June 5, 2021, with this search strategy: (COVID-19) AND (H1N1 influenza) showing 101 results. The following inclusion criteria were selected: English language; published in a scholarly peer-reviewed journal; full-length articles were further elected. To further refine the research was to focus on the type of manuscript: review, systematic review, and meta-analysis. A critical appraisal of the collected studies was conducted, analyzing titles and abstracts, excluding the following topics: treatment, public health measures and perception of the general population or healthcare personnel about their quality of life. According to these procedures, 54 eligible studies were included in the present review. Results: Histopathological findings play a key role in understanding the pathophysiological mechanisms of diseases and, thus possible therapeutic approaches. The evidence on the thrombo-inflammatory mechanism underlying COVID-19 is growing to a much greater magnitude than the diffuse alveolar damage in common with H1N1-09; our study appears to be in line with these results. The prevailing scientific thinking to explain the morbidity and mortality of COVID-19 patients is that it elicits an exuberant immune reaction characterized by dysregulated cytokine production, known as a "cytokine storm". Conclusions: The histological and immunohistochemical pattern demonstrated similarities and differences between the infectious manifestations of the two pathogens, which justify empirical therapeutic approaches, in the first phase of the COVID-19 pandemic. Therefore, the previous pandemic should have taught us to promote a culture of clinical and forensic autopsies in order to provide timely evidence from integration among autopsy and clinical data for early adopting adequate therapies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

COVID-19 and H1N1-09: A Systematic Review of Two Pandemics with a Focus on the Lung at Autopsy

Bertozzi¹,

Ferrara²,

Maiese³

et al. 2022

Front. Biosci. (Landmark Ed)

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“…Under physiological conditions, Nrf2 functions in the cytoplasm in the form of a complex with its inhibitor, the protein Keap1, which directs Nrf2 to ubiquitination-dependent degradation [30]. On the other hand, under oxidative conditions resulting from viral replication, an indicator of which can be observed, an increased level of the lipid peroxidation product -4HNE in the plasma of the same patients with COVID-19 [31] may lead to modifications, by ROS or electrophilic compounds, of the critical sulfhydryl groups of the cysteine of Keap1, the consequence of which is the dissociation of the Nrf2-Keap1 complex and the migration of Nrf2 to the nucleus, where it binds to a DNA sequence known as an antioxidant response element (ARE), in the promoter regions of target genes coding mainly antioxidant enzymes [32], thus increasing the transcription of these genes. The Nrf2 gene also contains the ARE sequence in its promoter [33], enhancing its expression in the positive feedback loop.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, one of the inhibitors of the NFκB-IκB complex is major bioactive product of PUFA peroxidation 4-HNE, the level of which increases under oxidative stress [48,49] and was found to be associated with systemic vascular stress in COVID-19 patients, in particular in those who passed away [31,51]. However, it is known that NFκB is essential for maintaining immune homeostasis and preventing autoimmunity caused by COVID-19 [46].…”

Section: Discussionmentioning

confidence: 99%

Alterations of the Antioxidant and Inflammatory Response of the Peripheral Blood Granulocytes to SARS-CoV-2 Infection in the Deceased COVID-19 Patients

Žarković¹,

Biernacki²,

Wójcik³

et al. 2022

Preprint

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It is assumed that upon SARS-CoV-2 infection granulocytes can undergo potentially destructive oxidative burst. Therefore, the aim of this study was to evaluate some parameters of redox and inflammatory signaling in granulocytes of recovered and of deceased COVID-19 pa-tients. Granulocytes were isolated from the blood of 32 COVID-19 patients on admission to the hospital (16 survived and 16 died within a week). The levels of proteins (immunoassay), eico-sanoids (UPLC-MS) and antioxidants activity (spectrophotometry) were examined. Enhanced activation of Nrf2 and NFκB and the levels of heme oxygenase and proinflammatory cytokines where found in granulocytes of all COVID-19 patients, while Cu,Zn-SOD and Mn-SOD activities were decreased, especially in deceased patients. Moreover, in patients who died increased levels of pro-inflammatory eicosanoids (PGE2 and TXB2) and decreased of anti-inflammatory (15d-PGJ2 and 5-HETE) were observed. However TXB2 was decreased, and IL-2 and IL-10 levels were in-creased in survivors, if compared both to healthy subjects and deceased patients, who did not change their cytokine generation. Therefore, it seems that by triggering transcription factors granulocytes activate redox signaling, leading to the production of pro-inflammatory eicosanoids, while reducing cellular antioxidant capacity via SOD, they express altered response to COVID-19, which might result in the onset of the vicious cycle of systemic oxidative stress in deceased patients.

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“…Not only that, the levels of pulmonary 4-HNE were upregulated in patients with COPD (18). In addition, the autopsy report revealed that 4-HNE is more highly expressed in the lungs and kidneys of patients with COVID-19 (27,28).…”

Section: The Predictive Powers For Severity and Deathmentioning

confidence: 93%

Serum Level of 4-Hydroxynonenal in Community-Acquired Pneumonia: A Potential Biomarker for Severity and Prognosis

et al. 2022

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BackgroundFour-hydroxynonenal (4-HNE) exerts a central role in the pathophysiological process of pulmonary diseases. The aim of this project was to evaluate the correlations between serum 4-HNE with severity and prognosis in patients with community-acquired pneumonia (CAP) by a prospective cohort study.Materials and MethodsA total of 239 patients with CAP and healthy volunteers were recruited. Fasting blood was collected. Serum 4-HNE was measured with ELISA. Clinical characteristics and demographic information were obtained. The relationships between serum 4-HNE and clinical characteristics were evaluated through the Spearman or Pearson correlation coefficient. The associations of serum 4-HNE with severity and prognosis were estimated through logistic regression analysis.ResultsOn admission, serum 4-HNE was upregulated in patients with CAP compared with healthy volunteers. Serum 4-HNE was gradually increased in line with CAP scores. Additionally, elderly patients with CAP were more prone to suffer from 4-HNE elevation. Moreover, serum 4-HNE was positively correlated with CAP severity scores. Meanwhile, the poor prognostic outcomes were tracked among patients with CAP. Higher serum 4-HNE on admission increased the risks of mechanical ventilation, vasoactive agent usage, and death in patients with CAP during hospitalization. The predictive powers for severity and death were increased in serum 4-HNE compared with CAP severity scores and inflammatory cytokines.ConclusionSerum 4-HNE on admission is positively correlated with the severity and poor prognosis among patients with CAP, indicating that 4-HNE participates in the pathophysiology of CAP. Serum 4-HNE may be used as an earlier biomarker for diagnosis and prognosis in patients with CAP.

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

Cited by 22 publications

References 55 publications

COVID-19 and H1N1-09: A Systematic Review of Two Pandemics with a Focus on the Lung at Autopsy

COVID-19 and H1N1-09: A Systematic Review of Two Pandemics with a Focus on the Lung at Autopsy

Alterations of the Antioxidant and Inflammatory Response of the Peripheral Blood Granulocytes to SARS-CoV-2 Infection in the Deceased COVID-19 Patients

Serum Level of 4-Hydroxynonenal in Community-Acquired Pneumonia: A Potential Biomarker for Severity and Prognosis

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