SARS-CoV-2 induces mitochondrial dysfunction and cell death by oxidative
stress in leukocytes of COVID-19 patients
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.