Severe COVID‐19 correlates with lower mitochondrial cristae density in PBMCs and greater sitting time in humans

Abstract

An interaction between mitochondrial dynamics, physical activity levels, and COVID‐19 severity has been previously hypothesized. However, this has not been tested. We aimed to compare mitochondrial morphology and cristae density of PBMCs between subjects with non‐severe COVID‐19, subjects with severe COVID‐19, and healthy controls. Additionally, we compared the level of moderate‐vigorous physical activity (MVPA) and sitting time between groups. Blood samples were taken to obtain PBMCs. Mitochondrial dynamics were assessed by electron microscopy images and western blot of protein that regulate mitochondrial dynamics. The International Physical Activity Questionnaire (IPAQ; short version) was used to estimate the level of MVPA and the sitting time The patients who develop severe COVID‐19 (COVID‐19++) not present alterations of mitochondrial size neither mitochondrial density in comparison to non‐severe patients COVID‐19 (COVID‐19) and control subjects (CTRL). However, compared to CTRL, COVID‐19 and COVID‐19++ groups have lower mitochondrial cristae length, a higher proportion of abnormal mitochondrial cristae. The COVID‐19++ group has lower number (trend) and length of mitochondrial cristae in comparison to COVID‐19 group. COVID‐19, but not COVID‐19++ group had lower Opa 1, Mfn 2 and SDHB (Complex II) proteins than CTRL group. Besides, COVID‐19++ group has a higher time sitting. Our results show that low mitochondrial cristae density, potentially due to physical inactivity, is associated with COVID‐19 severity.

Regulation of mitochondrial morphology and cristae architecture by the TLR4 pathway in human skeletal muscle

“…However, it is not fully understood how mitochondrial cristae density or architecture is regulated. A potential regulator is inflammation, as we showed that COVID-19 patients with severe infection, characterized by higher systemic inflammation, had a lower mononuclear cell mitochondrial cristae density ( Castro-Sepulveda et al, 2022 ). Our study in human myotubes is the first to evaluate the effects of LPS on mitochondrial cristae architecture.…”

Effect of epicatechin consumption on the inflammatory pathway and mitochondria morphology in PBMC from a R350P desminopathy patient: A case report

“…PBMCs were separated under sterile conditions on Ficoll‐Histopaque 1077 (Sigma, Milan, Italy) gradients from ~10 mL of freshly drawn blood (see Castro‐Sepulveda et al., 2022 ) to obtain ~80% lymphocytes. PBMCs were frozen and stored at −80°C for Western blotting.…”

“…We showed that PBMCs from COVID‐19 patients with acute inflammation present altered mitochondria morphology and mitochondria cristae architecture (Castro‐Sepulveda et al., 2022 ). Mitochondria are dynamic organelles that play an important role in highly active tissues, including skeletal muscle.…”