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SARS-CoV-2 induces mitochondrial dysfunction and cell death by oxidative stress in leukocytes of COVID-19 patients
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  • Joel De la Cruz-Enriquez,
  • Emmanuel Rojas-Morales ,
  • Maria Gema Ruiz-Garcia,
  • Julio Tobon-Velasco,
  • Jose Jimenez
Joel De la Cruz-Enriquez
Centro Medico Nacional de Biologia Molecular
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Emmanuel Rojas-Morales
Centro Medico Nacional de Biologia Molecular
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Maria Gema Ruiz-Garcia
Centro Medico Nacional de Biologia Molecular
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Julio Tobon-Velasco
Centro Medico Nacional de Biologia Molecular
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Jose Jimenez
Centro Medico Nacional de Biologia Molecular
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Abstract

Background: From sepsis to COVID-19-induced multi-organ failure, inflammation and immune system activation play an important role. It has been argued that inflammation and over-activation of the immune system could be mediating a pro-oxidant microenvironment that can induce cytotoxic effects that potentiate tissue damage favoring organic deterioration. Aims: To investigate whether induction of oxidative stress by COVID-19 infection could inhibit mitochondrial function and cause cellular damage in leukocytes. Methods: We evaluated plasma levels of nitric oxide, hydrogen peroxide and protein carbonylation using spectrophotometry, in addition to evaluating mitochondrial function and cell death by fluorescence microscopy and leukocyte morphology, in COVID-19 patients at two time points: viremia and severe sepsis with multi-organ failure. Results: COVID-19 induces increased oxidative stress markers that activate cellular damage processes. In the viremia stage, was observe with an increase in peroxide (28.9%), nitric oxide (370.3%) and carbonylated proteins (61.8%), which was correlated with an increase in inhibition of mitochondrial function (66%), early apoptosis (212%) necrosis (405%), and leukocytes-reactivity. The severe sepsis stage with multi-organ failure also showed a further increase in levels of peroxide (46.4%) with a slight decrease in nitric oxide (216.2%) but with more carbonylated proteins (102%), regarding what was observe in viremia. This oxidative process was correlate with less inhibition of mitochondrial function (32.4%) and an increase in late apoptosis (463%), and morphology changes evidencing damage in the leukocytes. Conclusion: SARS-CoV-2 induced damage promotes levels of oxidative stress markers and mitochondrial dysfunction that potentiate morphological changes and cell death in leukocytes. These cellular effects could be integrating into the physiopathology of COVID- 19. These processes explain the rapid changes in the immune system, and that present an initial over-activation and early massive death due to SARS-CoV-2 infection, promoting endothelial-alveolar damage that would cause multi-organ failure.

Peer review status:UNDER REVIEW

07 Aug 2020Submitted to International Journal of Clinical Practice
08 Aug 2020Assigned to Editor
08 Aug 2020Submission Checks Completed
10 Aug 2020Reviewer(s) Assigned