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

An interaction between mitochondrial dynamics, physical activity levels, andCOVID-19 severity has been previously hypothesized. However, this has notbeen tested. We aimed to compare mitochondrial morphology and cristae den-sity of PBMCs between subjects with non- severe COVID- 19, subjects with se-vere COVID- 19, and healthy controls. Additionally, we compared the level ofmoderate-vigorous physical activity (MVPA) and sitting time between groups.Blood samples were taken to obtain PBMCs. Mitochondrial dynamics were as-sessed by electron microscopy images and western blot of protein that regulatemitochondrial dynamics. The International Physical Activity Questionnaire(IPAQ; short version) was used to estimate the level of MVPA and the sitting timeThe patients who develop severe COVID-19 (COVID-19++) not present altera-tions 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 mitochon-drial cristae length, a higher proportion of abnormal mitochondrial cristae. TheCOVID-19++ group has lower number (trend) and length of mitochondrial cris-tae in comparison to COVID- 19 group. COVID- 19, but not COVID- 19++ grouphad 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 lowmitochondrial cristae density, potentially due to physical inactivity, is associatedwith COVID-19 severity.