Monocytic mitochondrial dysfunction and impaired monocytic bioenergetic profile in patients with heart failure symptoms in post-COVID syndrome

Abstract

Abstract Introduction/Purpose Approximately 35% of COVD-19 patients have persistent symptoms similar to congestive heart failure. The so called post-Covid syndrome, which includes symptoms such as dyspnea and angina pectoris, is presumably associated to cellular metabolism and oxidative stress, yet whether mitochondrial function is impaired in post-COVID patients is still unclear. We thus investigated the mitochondrial function in monocytes of symptomatic post-COVID patients compared to matched controls. Methods Patients with persisting cardiac symptoms in their daily activities and diagnosed with post-COVID syndrome (n=14) were recruited and matched with unaffected controls (n=10) for age, sex and cardiovascular risk factors. Structural heart disease was excluded through cardiac work-up (echocardiography, functional stress testing and when necessary coronary angiography). Primary monocytes were isolated using negative selection method. The bioenergetic status of the monocytes was assessed using the Agilent Seahorse XF Cell Mito Stress Test without and after modulation of reactive oxygen species (ROS) by buthionine sulfoximine (BSO). Results CD14++ monocytes isolated from post-COVID patients showed non-significantly increased basal proton leak (p=0.57), reduced maximal respiration, and reserved respiratory capacity (p=0.19) compared to controls. Induction of additional oxidative stress by ROS modulation revealed a significantly impaired bioenergetic profile of monocytes in terms of reduction of basal respiration (3-fold, p=0.0005), maximal respiration (4-fold, p=0.004) and spare respiratory capacity (5-fold, p=0.008). Conclusions We demonstrated an impaired bioenergetic profile of CD14++ monocytic mitochondria in patients suffering from heart failure symptoms following COVID-19 infection. Whether the findings provide a novel biomarker for measuring systemic oxidative stress conditions or whether there is a direct link between symptoms of post-COVID disease and monocytic function needs to be addressed in further studies.