[Long COVID - neurological or somatoform disease?]

Post-COVID condition (also known as long COVID) is a syndrome characterized by persistent symptoms following a suspected or confirmed SARS-CoV-2 infection, lasting for at least two months and are not attributable to other conditions. The most common symptoms include fatigue, diffuse pain, post-exertional malaise and “brain fog” (impairment of memory and concentration). The pathomechanism of long COVID is the subject of ongoing, intensive research. Our purpose was to review the literature on the pathomechanism of long COVID.

We reviewed original and review articles in Hungarian and English on the pathomechanism of long COVID, published between January 2019 and June 2024, in the PubMed and Google Scholar databases.

Potential underlying causes of the symptoms are outlined in three main theories. 1) The concept of “long COVID as a distinct neurological disease” suggests that direct viral neuroinvasion, apoptosis, and demyelination processes are responsible for the symptoms. 2) The theory of “long COVID as a systemic disease with neurological symptoms” is based on the virus induced, prolonged cytokine and chemokine release, as well as the reactivation of latent viral infections. 3) According to the concept of “long COVID as a somatoform disorder”, the disease results from abnormal activation of the proinflammatory cytokine network leading to central nervous system sensitization, a well-known psychoneuroimmunological mechanism. Our study highlighted significant overlaps between long COVID and conditions such as chronic fatigue syndrome/myalgic encephalomyelitis, a group of symptoms not defined as a distinct mental disorder in DSM-5, but commonly referred to as Gulf War syndrome, chronic Lyme disease and somatic symptom disorder.

The pathomechanism of long COVID, which presents with a wide range of nonspecific symptoms, remains unknown, and no reproducible disease-specific biomarker has been identified to date. Clarifying the etiology of the disease is crucial for determining adequate and effective therapeutic methods.