Gut Microbiota and Mitochondria: Health and Pathophysiological Aspects of Long COVID

Abstract

The current understanding of long COVID (LC) is still limited. This review highlights key findings regarding the role of gut microbiota, mitochondria, and the main pathophysiological aspects of LC revealed by clinical studies, related to the complex interplay between infection, intestinal dysbiosis, dysfunctional mitochondria, and systemic inflammation generated in a vicious circle, reflecting the molecular and cellular processes from the “leaky gut” to the “leaky electron transport chain (ETC)” into a quantum leap. The heterogeneity of LC has hindered progress in deciphering all the pathophysiological mechanisms, and therefore, the approach must be multidisciplinary, with a special focus not only on symptomatic management but also on addressing the underlying health problems of the patients. It is imperative to further assess and validate the effects of COVID-19 and LC on the gut microbiome and their relationship to infections with other viral agents or pathogens. Further studies are needed to better understand LC and expand the interdisciplinary points of view that are required to accurately diagnose and effectively treat this heterogeneous condition. Given the ability of SARS-CoV-2 to induce autoimmunity in susceptible patients, they should be monitored for symptoms of autoimmune disease after contracting the viral infection. One question remains open, namely, whether the various vaccines developed to end the pandemic will also induce autoimmunity. Recent data highlighted in this review have revealed that the persistence of SARS-CoV-2 and dysfunctional mitochondria in organs such as the heart and, to a lesser extent, the kidneys, liver, and lymph nodes, long after the organism has been able to clear the virus from the lungs, could be an explanation for LC.

Modulatory role of Faecalibacterium on insulin resistance and coagulation in patients with post-viral long haulers depending on adiposity

“…In fact, one of the species lost in COVID-19 associated dysbiosis is Faecalibacterium prausnitzii (from Faecalibacterium genus), which has been shown to have a role in the inhibition of the production of pro-inflammatory cytokines. 34 , 35 , 36 On the other hand, D-dimer, a fibrin degradation product, serves as a biomarker of ongoing fibrinolysis and thrombotic activity. Elevated D-dimer levels observed in patients with post-viral long hauler with higher BMI may reflect a hypercoagulable state and increased thrombotic risk associated with adiposity and chronic inflammation.…”