Long-term effects of COVID-19, often referred to as long COVID or post-COVID syndrome, represent one of the greatest medical challenges to emerge in recent years. Despite intensive research efforts, the causes, diagnostic criteria, and effective treatments remain only partially understood. Nevertheless, scientific research is increasingly providing important clues about potential disease mechanisms and therapeutic stategies.
Current state of research
The study Long/Post-Covid: An Interdisciplinary Challenge by Reisinger et al. (2025) offers a comprehensive overview of the current research landscape. Drawing on numerous studies, the authors highlight several key findings.
Symptoms are varied and nonspecific
Symptoms of post-COVID syndrome vary widely between individuals. Many patients report pronounced fatigue, often accompanied by post-exertional malaise (PEM), meaning a worsening of symptoms after physical or mental exertion. Cognitive impairments such as «brain fog», including difficulties with concentration, attention, and memory, are also frequently reported.
In addition, symptoms affecting the cardiovascular and respiratory systems are common, such as palpitations, chest pain and shortness of breath. Headaches, muscle pain and joint pain are also frequently observed. Many individuals experience sleep disturbances, elevated blood pressure, gastrointestinal complaints, and changes in their sense of smell or taste. This wide spectrum of symptoms underscores that long COVID is not a uniform condition.
There are many hypotheses, but no definitive answer yet
The underlying causes of long COVID remain unclear. Severals hypotheses are currently being investigated. These include dysregulation of the immune system, such as chronic inflammation or autoimmune responses, as well as the persistence of viral components or proteins in the body.
Other proposed mechanisms involve damage to blood vessels and impaired microcirculation (i.e. blood flow in the smallest vessels), changes in blood clotting with the formation of small blood clots (microthrombi), dysfunction of the autonomic nervous system (which controls heart rate, blood pressure, and digestion), and possible alterations in the gut microbiome.
Many of these mechanisms overlap with those in other post-infectious diseases, such as myalgic encephalomyelitis/chronic fatigue syndrome ME/CFS. This supports the view that long COVID may belong to a broader group of post-acute infection syndromes.
Overall, long COVID is a complex condition whose causes and mechanisms are not yet fully understood. While no targeted, causal therapy is currently available, research is steadily generating valuable insights into disease processes and potential therapeutic approaches.
Diagnostics: still largely a diagnosis by exclusion
A major challenge for those affected is the lack of specific diagnostic tests or validated biomarkers that can definitively identify long COVID. Diagnosis is therefore typically made by excluding other possible conditions, often requiring an interdisciplinary approach. This process can be lengthy and burdensome for the patients. Many remain undiagnosed for extended periods or report that their symptoms are not taken seriously, adding to the burden of the condition.
Therapy: symptom-oriented approaches
At present, treatment for long COVID largely focused on managing individual symptoms. No therapy currently exists that directly targets the underlying disease mechanisms. Treatment strategies typically include rehabilitation programs, pacing approaches to manage energy levels, respiratory and occupational therapy, as well as interventions for pain and sleep disturbances.
Various pharmacological treatments are used in clinical practice on a case-by-case basis, while new drug-based approaches, such as immunomodulatory therapies, are being investigated in clinical studies. For many patients, treatment involves a process of trial and error, careful monitoring, and patience.
Current research trends
Current scientific literature and international expert recommendations indicate several key areas of focus:
- Improved definition and classification of long COVID:
Efforts are underway to better categorize symptom patterns, enabling more precise diagnosis and inidividualized treatment strategies.
- Identification of objective biomarkers:
Researchers are searching for measurable indicators in blood or tissue that could facilitate diagnosis and distinguish long COVID from other conditions.
- Investigation of pathophysiological mechanisms:
This includes studying viral persistence, autoimmune reactions, vascular damage, and other biological pathways that may explain symptoms.
- Cognitive and neuropsychological effects:
Ongoing research into brain fog, memory impairment, and concentration difficulties aim to support the development of targeted treatment strategies.
- Therapeutic strategies beyond symptom management:
In addition to rehabilitation and pacing, experimental treatments that may directly influence disease mechanisms and improve quality of life are being explored.
What does this mean for those affected?
For patients, these developments mean that long COVID is increasingly recognized as a serious medical condition. Research is steadily advancing our understanding of its mechanisms and potential treatments. Although reliable diagnostic tools and targeted therapies are still in development, progress is being made step by step toward improved diagnosis, treatment options, and long-term support.
