Altered Mitochondrial Respiration in Peripheral Blood Mononuclear Cells of Post-Acute Sequelae of SARS-CoV-2 Infection

Authors: Sahera Dirajlal-Fargo, David P Maison, Jared C Durieux, Anastasia Andrukhiv, Nicholas Funderburg, Kate Ailstock, Mariana Gerschenson, Grace A Mccomsey

Published in: Mitochondrion, 75 (2024) 101849

Date: February 2024

Study Overview: This research investigates the mitochondrial function in peripheral blood mononuclear cells (PBMCs) in individuals with post-acute sequelae of SARS-CoV-2 (PASC), commonly known as Long COVID. The study compares mitochondrial respiration in three groups: those without a history of COVID-19, those who had COVID-19 but fully recovered, and those with PASC.

Key Findings:

  1. Mitochondrial Respiration:
    • PBMCs from PASC patients showed higher mitochondrial basal respiration, ATP-linked respiration, maximal respiration, spare respiration capacity, and non-mitochondrial respiration.
    • Increases in these mitochondrial respiration metrics were associated with higher odds of having PASC.
  2. Patient Characteristics:
    • The study included 59 participants: 19 without COVID-19 history, 20 who recovered from COVID-19, and 20 with PASC.
    • Among those with PASC, a higher proportion were female, with the highest average body mass index (BMI).
  3. Symptoms and Pathology:
    • PASC patients frequently reported fatigue, post-exertional malaise, pain, anxiety, depression, stress, trauma-related symptoms, and dizziness.
  4. Blood Count Comparisons:
    • No significant differences in blood counts (monocytes, lymphocytes, neutrophils, white blood cells) were observed among the three groups.
  5. Inflammation and Activation Markers:
    • The study did not find significant differences in inflammation, gut permeability, and monocyte activation markers among the groups.
  6. Discussion and Implications:
    • The findings suggest that the energetic needs of PASC PBMCs are higher than in those who recovered from COVID-19 or never had it.
    • Mitochondrial dysfunction, previously observed in acute SARS-CoV-2 infection, may persist in PASC.
    • The results indicate potential mechanisms for PASC, including ongoing inflammation and immune dysregulation, possibly linked to monocyte activity and residual viral reservoirs in hematopoietic stem cells.
  7. Limitations:
    • The study is cross-sectional, preventing assessment of longitudinal changes in mitochondrial respiration.
    • The study acknowledges potential residual confounding factors.
  8. Conclusion:
    • Altered cellular bioenergetics in PASC, characterized by increased oxygen consumption and ATP-linked respiration, might be crucial in understanding the condition.
    • The study opens avenues for future research and potential treatments targeting mitochondrial dysfunction in PASC.

Funding and Conflicts of Interest:

  • Funded by the Clinical and Translational Science Collaborative of Cleveland, National Center for Advancing Translational Sciences, and NIH.
  • One author disclosed potential conflicts of interest due to associations with various pharmaceutical companies.

This summary provides a comprehensive overview of the study, highlighting its significant findings, methodology, and implications. Remember, for personalized advice or interpretation, it’s essential to consult healthcare professionals. ​

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