Understanding COVID-19 progression with longitudinal peripheral blood mononuclear cell proteomics, 2023, Leite et al.

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Understanding COVID-19 progression with longitudinal peripheral blood mononuclear cell proteomics: Changes in the cellular proteome over time
Giuseppe Gianini Figueirêdo Leite; Milena Karina Colo Brunialti; Paula M. Peçanha-Pietrobom; Paulo R. Abrão Ferreira; Jaquelina Sonoe Ota-Arakaki; Edecio Cunha-Neto; Bianca Lima Ferreira; Graziella E. Ronsein; Alexandre Keiji Tashima; Reinaldo Salomão

The clinical presentation of COVID-19 is highly variable, and understanding the underlying biological processes is crucial.

This study utilized a proteomic analysis to investigate dysregulated processes in the peripheral blood mononuclear cells of patients with COVID-19 compared to healthy volunteers. Samples were collected at different stages of the disease, including hospital admission, after 7 days of hospitalization, and 30 days after discharge.

Metabolic pathway alterations and increased abundance of neutrophil-related proteins were observed in patients. Patients progressing to critical illness had significantly low-abundance proteins in the pentose phosphate and glycolysis pathways compared with those presenting clinical recovery. Important biological processes, such as fatty acid concentration and glucose metabolism disorder, remained altered even after 30 days of hospital discharge. Temporal proteomic changes revealed distinct pathways in critically ill and non-critically ill patients.

Our study emphasizes the significance of longitudinal cellular proteomic studies in identifying disease progression-related pathways and persistent protein changes post-hospitalization.


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Broad dysregulation of proteins related to metabolic machinery may represent either an antiviral response or viral-mediated disruption of host transcripts and translation. Previous omics studies have reported altered metabolic pathways during SARS-CoV-2 infection. These results are consistent with those of our study, which showed a switch from OXPHOS to glycolysis at D0 and D7 with a ‘‘truncated’’ TCA cycle, similar to that observed in the Warburg effect, in which it supports defense against bacterial and viral infection. These cellular metabolic changes drive an important cellular immune response. For example, a switch to glycolysis is related to the sufficient generation of adenosine triphosphate (ATP) and biosynthetic intermediates to perform their specific effect functions, 32,33 including phagocytosis and antimicrobial response, which are predicted to be increased in this study.

Metabolic pathways, such as those related to fatty acid metabolism, OXPHOS, glucose metabolism disorder, and insulin resistance, remained altered during the hospital stay (D0 and D7 samples) and even after hospital discharge (CS30 samples) compared with HVs. Proteins involved in the TCA cycle (MDH2 and OGDH) and mitochondrial electron transport chain and ATP synthesis (NDUFA4, NDUFAB1, NDUFS1, ATP5IF1, and ATP5ME) were found in low-abundance 30 days after discharge. This finding is consistent with previous reports on post-acute sequelae of COVID-19 or long COVID-19 showing a chronic and self-perpetuating metabolically imbalanced non-resolving condition defined by mitochondrial dysfunction, in which ROS drive inflammation and a switch to glycolysis.