Long-COVID: Advances in Diagnostics, Biomarkers and Innovative Therapies

Abstract

Introduction: Long COVID is a medical condition that affects individuals who have had COVID-19 and whose symptoms persist beyond three months after the acute phase. The World Health Organization (WHO) defines it as a multisystem syndrome that affects systems such as the respiratory, cardiovascular, neurological, and gastrointestinal systems, and significantly affects quality of life. The most common symptoms include extreme fatigue, shortness of breath, cognitive disorders, sleep disturbances, and muscle pain.

State of the art: Although the exact mechanisms are not fully understood, several possible causes have been identified, such as viral persistence, chronic inflammation, and mitochondrial dysfunction. Immune imbalance is a central factor, as an exacerbated immune system response generates a persistent inflammatory state. Overproduction of cytokines, such as interleukin-6 (IL-6), along with autoimmune processes, contribute to prolonged tissue damage. Furthermore, patients with comorbidities, a history of severe illness, or lack of vaccination are at higher risk of developing Long COVID. The microbiota also plays a relevant role. Its alteration (dysbiosis) could amplify systemic inflammation and neurological symptoms. Recent research explores microbiota modulation through probiotics as a possible therapeutic strategy. However, clinical studies are in their initial stages. In parallel, some antivirals and immunomodulators are being evaluated, although there is still no standardized treatment. Despite these limitations, vaccination has proven effective in reducing the incidence of Long-COVID, as well as the severity of its manifestations. Currently, multiple international studies seek to identify risk factors, diagnostic biomarkers, and new therapeutic options.

Discussion: Long-COVID represents a major health challenge that requires coordinated responses.

Conclusion: A review of the pathogenetic mechanisms, immunological implications, and potential therapeutic strategies highlights the need for a multidisciplinary approach that integrates basic, clinical, and epidemiological research. Only through this approach will it be possible to move toward more accurate diagnoses and effective treatments that improve the quality of life of affected patients.