Viral Load is Associated with Mitochondrial Dysfunction and Altered Monocyte Phenotype in Acute Severe SARS-CoV-2 Infection

Romão, Pedro R T; Teixeira, Paula Costa; Schipper, Lucas de Lima; Silva, Igor da; Filho, Paulo Santana; Júnior, Luiz Carlos Rodrigues; Peres, Alessandra; Fonseca, Simone Gonçalves; Monteiro, Marta Chagas; Lira, Fábio Santos; Frade, Marco Andrey Cipriani; Comerlato, Juliana; Comerlato, Carolina Baldisserotto; Sant’Anna, Fernando Hayashi; Bessel, Marina; Abreu, Celina Monteiro; Wendland, Eliana; Dorneles, Gilson Pires

doi:10.2139/ssrn.3999042

Cited by 3 publications

(5 citation statements)

References 10 publications

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“…By using the MiNA plugin, we verified that infected HBMECs had increased mitochondrial footprint, as an estimation of overall TOMM20 pixel signal. Recent reports have also shown an effect of SARS-CoV-2 and COVID-19 on mitochondrial biology: monocytes isolated from COVID-19 patients display reduced mitochondrial membrane potential and SARS-CoV-2 viral load was positively correlated with generation of ROS (Romão et al, 2022). Importantly, endothelial cells exposed to SARS-CoV-2 Spike1 protein showed decreased tubular and increased fragmented mitochondrial networks in vitro , which was accompanied by a decrease in oxygen consumption rate and increase extracellular acidification rate (Lei et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 infection of human brain microvascular endothelial cells leads to inflammatory activation through NF-κB non-canonical pathway and mitochondrial remodeling

Torices

Motta

Rosa

et al. 2022

Preprint

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Neurological effects of COVID-19 and long-COVID-19 as well as neuroinvasion by SARS-CoV-2 still pose several questions and are of both clinical and scientific relevance. We described the cellular and molecular effects of the human brain microvascular endothelial cells (HBMECs) in vitro infection by SARS-CoV-2 to understand the underlying mechanisms of viral transmigration through the Blood-Brain Barrier. Despite the low to non- productive viral replication, SARS-CoV-2-infected cultures displayed increased apoptotic cell death and tight junction protein expression and immunolocalization. Transcriptomic profiling of infected cultures revealed endothelial activation via NF-κB non-canonical pathway, including RELB overexpression, and mitochondrial dysfunction. Additionally, SARS-CoV-2 led to altered secretion of key angiogenic factors and to significant changes in mitochondrial dynamics, with increased mitofusin-2 expression and increased mitochondrial networks. Endothelial activation and remodeling can further contribute to neuroinflammatory processes and lead to further BBB permeability in COVID-19.

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Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 infection of human brain microvascular endothelial cells leads to inflammatory activation through NF-κB non-canonical pathway and mitochondrial remodeling

Torices

Motta

Rosa

et al. 2022

Preprint

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“…In this sense, excessive levels of ROS from neutrophils have been implicated in a cascade of biological events that drive pathological host response in COVID‐19, including tissue damage, thrombosis and red blood cell dysfunction 29 . Furthermore, oxidative stress induced by neutrophils predict COVID‐19‐associated mortality, 30 and increased mitochondrial ROS production and impaired MMP in CD14+ monocytes were observed in severe COVID‐19 patients who presented higher SARS‐CoV‐2 viral load 9 . The imbalance in redox state of innate immune cells leads to the activation of intracellular inflammatory pathways, mainly inflammasome, contributing to the COVID‐19 hyperinflammation in severe cases 31 .…”

Section: Discussionmentioning

confidence: 99%

“…29 Furthermore, oxidative stress induced by neutrophils predict COVID-19-associated mortality, 30 and increased mitochondrial ROS production and impaired MMP in CD14+ monocytes were observed in severe COVID-19 patients who presented higher SARS-CoV-2 viral load. 9 The imbalance in redox state of innate immune cells leads to the activation of intracellular inflammatory pathways, mainly inflammasome, contributing to the COVID-19 hyperinflammation in severe cases. 31 In fact, several pro-oxidant genes were The first phase of the SARS-CoV-2 infection is the viral replication and the innate immune response, followed by symptoms manifestation and higher levels of cytokines.…”

Section: Phagocytes Generates Higher Amounts Of Ros Through Changes I...mentioning

confidence: 99%

“…The immune innate response begins when the virus enters into the airways and it activates macrophages and dendritic cells that release inflammatory cytokines and produce reactive oxygen species (ROS). The viral replication and the multisystemic pro‐inflammatory environment contributes to the constant production of ROS, due to respiratory burst activity of immune cells (macrophages and neutrophils mainly), alterations in the activity of enzymes as NADPH oxidase, xanthine oxidase, and respiratory chain in the mitochondria 9,10 . In this scenario, the virus acts diminishing the antioxidant defense through the transcriptor factor nuclear factor erythroid 2 (NFE2)‐related factor 2 (Nrf2) inhibition, which is responsible for the increase of antioxidant enzymes activity.…”

Section: Introductionmentioning

confidence: 99%

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Systemic redox imbalance in severe COVID‐19 patients

Postiga

Teixeira

Neves

et al. 2022

Cell Biochemistry & Function

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The aim of this study was to evaluate the systemic redox state and inflammatory markers in intensive care unit (ICU) or non‐ICU severe COVID‐19 patients during the hospitalization period. Blood samples were collected at hospital admission (T1) (Controls and COVID‐19 patients), 5–7 days after admission (T2: 5–7 days after hospital admission), and at the discharge time from the hospital (T3: 0–72 h before leaving hospital or death) to analyze systemic oxidative stress markers and inflammatory variables. The reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) were analyzed in peripheral granulocytes and monocytes. THP‐1 human monocytic cell line was incubated with plasma from non‐ICU and ICU COVID‐19 patients and cell viability and apoptosis rate were analyzed. Higher total antioxidant capacity, protein oxidation, lipid peroxidation, and IL‐6 at hospital admission were identified in both non‐ICU and ICU COVID‐19 patients. ICU COVID‐19 patients presented increased C‐reactive protein, ROS levels, and protein oxidation over hospitalization period compared to non‐ICU patients, despite increased antioxidant status. Granulocytes and monocytes of non‐ICU and ICU COVID‐19 patients presented lower MMP and higher ROS production compared to the healthy controls, with the highest values found in ICU COVID‐19 group. Finally, the incubation of THP‐1 cells with plasma acquired from ICU COVID‐19 patients at T3 hospitalization period decreased cell viability and apoptosis rate. In conclusion, disturbance in redox state is a hallmark of severe COVID‐19 and is associated with cell damage and death.

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“…Evidence of mitochondrial dysfunction, altered mitochondrial morphology, and altered cellular metabolism with increased glycolysis has thus been reported in peripheral blood mononuclear cells obtained from patients with COVID-19. 12 , 13 , 14 , 15 Coenzyme Q10 (CoQ10) is a natural occurring, endogenously produced vitamin-like compound that plays a key role in cellular bioenergetics by serving as an electron transporter in the mitochondrial membrane and is essential to aerobic respiration. 16 , 17 Based on the multi-organ symptomatology of PCC and studies showing impaired cellular mitochondrial metabolism in patients infected with SARS-CoV-2, we hypothesized that the fatigue, dyspnea, neurological symptoms, and muscle symptoms in patients who develop PCC are caused by chronic mitochondrial dysfunction.…”

Section: Introductionmentioning

confidence: 99%

High-dose coenzyme Q10 therapy versus placebo in patients with post COVID-19 condition: a randomized, phase 2, crossover trial

Hansen

Mogensen

Agergaard

et al. 2023

The Lancet Regional Health - Europe

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Viral Load is Associated with Mitochondrial Dysfunction and Altered Monocyte Phenotype in Acute Severe SARS-CoV-2 Infection

Cited by 3 publications

References 10 publications

SARS-CoV-2 infection of human brain microvascular endothelial cells leads to inflammatory activation through NF-κB non-canonical pathway and mitochondrial remodeling

SARS-CoV-2 infection of human brain microvascular endothelial cells leads to inflammatory activation through NF-κB non-canonical pathway and mitochondrial remodeling

Systemic redox imbalance in severe COVID‐19 patients

High-dose coenzyme Q10 therapy versus placebo in patients with post COVID-19 condition: a randomized, phase 2, crossover trial

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