Digitally Assessed Long COVID Symptomatology Is Associated With Lymphocyte Mitochondrial Dysfunction and Altered...

Area of Science:

• Immunology
• Mitochondrial Biology
• Virology

Background:

• Postacute sequelae of SARS-CoV-2 infection (long COVID) is a complex condition with poorly understood pathology.
• Metabolic dysregulations are described in long COVID, but immune cell immunometabolic alterations remain unclear.

Purpose of the Study:

• To investigate immunometabolic alterations in circulating immune cells of long COVID patients.
• To correlate immune cell mitochondrial function and cytokine responses with long COVID symptom severity.

Main Methods:

• Clinical, immunologic, and mitochondrial analyses were performed on 27 long COVID patients and 27 healthy controls.
• Mitochondrial function (mass, membrane potential) in lymphocytes and monocytes was assessed.
• Cytokine production (IFN-γ, IFN-β, IL-10) after stimulation was measured using multiplex immunoassay.

Main Results:

• Long COVID patients reported significant symptom burden compared to their pre-infection state.
• Decreased mitochondrial membrane potential was observed in CD56bright natural killer cells (dizziness) and CD4+ lymphocytes (breathlessness).
• Impaired IFN-γ production post-LPS stimulation and reduced IFN-β/IL-10 responses post-R848 stimulation were associated with specific symptoms.

Conclusions:

• Symptom severity in long COVID is linked to mitochondrial dysfunction in immune cells.
• Altered cytokine responses in long COVID patients may serve as potential disease biomarkers.
• These findings highlight potential targets for future therapeutic strategies in long COVID management.