Cerebral blood flow alterations and host genetic association in individuals with long COVID: A transcriptomic-neuroimaging study, 2024, Yao Wang et al

Rapid précis —

• The current study investigated the potential host genetic mechanism underlying CBF alterations in individuals with and without long COVID after COVID-19 infection.

• Our study suggested that lower CBF is associated with persistent clinical symptoms

• study aimed to define the CBF differences between long COVID and healthy controls and to identify the corresponding genes using spatial correlation

• hypothesize that altered CBF patterns observed in individuals with long COVID are influenced by specific brain gene expression profiles

• prospectively recruited 50, more than one-month postrecovery

• 22 of these individuals (22/50) were identified as the long COVID-19 group on the basis that they experienced persistent, recurring, or new symptoms for more than four weeks

• Additionally, healthy volunteers with negative nucleic acid test results were recruited from the community before the outbreak (from October 2021 to June 2022, n = 30)

• mean age of the long COVID was 54.18 years

• Compared to HC group, lower CBF was found in both the long COVID and COVID-19

• lower CBF was associated with greater fatigue and poorer immediate memory performance

• No significant association was found between the neuropsychological score and altered CBF in the COVID-19 group.

• GO analysis revealed that long COVID-19-related CBF genes were strongly associated with the structure and function of mitochondria.

• Specifically, these genes were enriched in the cellular component terms mitochondrion, mitochondrial respiratory chain complex, and ribosome, and they played important roles in the molecular function of NADH dehydrogenase (ubiquinone) activity. Moreover, these genes were involved in other energy metabolism processes, including mitochondrial electron transport, the mitochondrial respiratory chain, aerobic respiration, and synapse organization.

• long COVID-19-related CBF genes did not show specific expression in any tissue or cell type.

• low CBF in the left frontal gyrus/superior temporal gyrus was associated with fatigue and poor immediate recall performance in the long COVID group.

• demonstrated that CBF alterations were linked to the expression of multiple host genes

• findings suggest that the expression of long COVID-19-related CBF genes may play an important role in long-term symptomatology,

• significant hypoperfusion in the left frontal cortex and temporal cortex in both long COVID and COVID-19 survivors, consistent with the findings of prior studies

• genes were enriched in cellular components related to mitochondria and were mainly involved in processes related to energy metabolism, such as mitochondrial respiratory chain assembly and aerobic respiration.

• Aberrant mitochondrial energy metabolism can trigger dysfunction in neurological systems, including inhibition of immune processes and widespread metabolic dysregulation.

 

b GO_Biological process

Mitochondrial electron transport
Neuron cell-cell adhesion
Mitochondrial electron transport, NADH to ubiquinone-Mitochondrial ATP synthesis coupled proton transport
Membrane fission
Synapse organization
Mitochondrial respiratory chain complex I assembly
Aerobic respiration
Mitochondrial translation-Cytoplasmic translation