Long COVID: emerging pathophysiological mechanisms

Area of Science:

• Neurology
• Immunology
• Internal Medicine

Background:

• Post-COVID conditions (long COVID) represent a complex, heterogeneous set of symptoms persisting over 28 days post-infection.
• These conditions significantly contribute to global morbidity and functional limitations, impacting millions worldwide.
• The underlying pathophysiology and effective treatments for long COVID remain largely undefined.

Purpose of the Study:

• To present a conceptual framework for evaluating the diverse symptoms associated with long COVID.
• To review the evidence supporting proposed pathophysiologic mechanisms driving long COVID.
• To discuss potential therapeutic strategies for long COVID based on mechanistic plausibility.

Main Methods:

• Literature review and synthesis of proposed pathophysiologic mechanisms for long COVID.
• Conceptual framework development for symptom evaluation in long COVID patients.
• Analysis of evidence linking proposed mechanisms to clinical manifestations.

Main Results:

• Multiple pathophysiologic pathways are implicated in long COVID, including neuroinflammation, endothelial dysfunction, and autonomic dysfunction.
• Patient presentations vary, with contributions from different mechanisms differing individually.
• No FDA-approved therapies currently exist for long COVID.

Conclusions:

• A comprehensive understanding of long COVID requires considering multiple, potentially overlapping pathophysiologic drivers.
• A structured evaluation framework is proposed to guide the assessment of long COVID symptoms.
• Mechanistically plausible therapies show promise, warranting further investigation for long COVID treatment.