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Ein Ruf nach besserer Diagnose und Behandlung

von NFI Redaktion

In a recent review published in the journal Nature Reviews Microbiology, a group of authors summarized the recent advances in understanding the mechanisms, effects, and research needs of Long-Coronavirus Disease (COVID) for improved diagnosis and treatment.

Review: Long COVID: key insights, mechanisms, and recommendations

Review: Long COVID: key insights, mechanisms, and recommendations


Long-COVID, affecting over 65 million people worldwide, manifests with diverse systemic symptoms independent of the severity of the initial infection. This condition leads to various health problems like cardiovascular diseases and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), resulting in profound disabilities and impacts on the workforce. Pathogenesis theories include the persistent presence of viruses and dysregulation of the immune system; however, effective treatments have not been established. Research has identified risk factors such as gender and socioeconomic status, although many patients had no pre-existing conditions. The similarity of Long-COVID to other post-viral syndromes underscores the urgent need for research on its mechanisms, risk factors, and treatments to improve patient outcomes.

Immunological and Virological Discoveries in Long COVID

Long COVID triggers significant immune changes, particularly post-mild COVID, characterized by T-cell exhaustion, decreased effector memory, CD4+, and CD8+ T-cells, elevated Programmed Death-1 (PD1) expression, and activated innate immune responses. The lack of naive T and B cells, along with persistently high Type I and III interferon levels, suggests ongoing immune weakness. Altered immune cell balance, including increased non-classical monocytes, reduced dendritic cells, and low cortisol levels, highlights a distinct immune profile in Long-COVID.

Research indicates autoimmunity in Long-COVID, highlighted by increased autoantibodies against key receptors like Angiotensin-Converting Enzyme 2 (ACE2). Viral reactivations, especially Epstein-Barr Virus (EBV) and Human Herpesvirus 6 (HHV-6), play a significant role and impact mitochondrial function and energy metabolism. The disease’s progression is initially associated with inadequate immune responses, including a weak antibody and T-cell response. Signs of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) persistence in multiple body tissues suggest a potential mechanism for the longevity of Long COVID symptoms.

Systemic Effects and Organ Damage

SARS-CoV-2 causes extensive organ damage beyond the respiratory system, affecting the circulatory system through endothelial dysfunction and increased thrombosis risk. Long-term changes in blood properties and vascular density contribute to the increased prevalence of cardiovascular diseases post-COVID, highlighting the systemic and lasting effects of the virus.

Neurological Impacts

Long-COVID leads to neurological and cognitive issues like memory loss and cognitive impairments, with effects comparable to significant aging. Possible underlying mechanisms like neuroinflammation and neuronal damage link these symptoms to an Alzheimer-like pathology, indicating severe implications on the brain.

ME/CFS and Related Conditions

There is notable overlap between Long-COVID and ME/CFS, with many patients meeting the criteria for the latter. This relationship underscores commonalities like immune changes and mitochondrial dysfunction, with Dysautonomia often occurring simultaneously, suggesting shared pathophysiological mechanisms.

Reproductive and Respiratory Issues

The effects of Long-COVID on reproduction require targeted research on gender-specific impacts, while persistent respiratory symptoms suggest lasting lung damage. These aspects highlight the broad spectrum of the disease’s impact.

Gastrointestinal Symptoms and Chronicity

Ongoing gastrointestinal issues and altered gut microbiota in Long-COVID patients underscore the systemic nature of the illness. The differing occurrence and duration of symptoms among individual patients emphasize the complexity of the disease and the challenge of predicting individual outcomes.

Diagnostic Progress and Challenges

Diagnostic approaches for Long-COVID are evolving, with existing techniques like tilt-table tests and Magnetic Resonance Imaging (MRI) often inadequately detecting the condition. New diagnostic methods, including microclot imaging, corneal microscopy, and novel Electrocardiogram (EKG) markers, offer hope for more accurate identification. Research on biomarkers and unconventional methods like odor detection by dogs signifies innovative avenues being explored to enhance Long COVID diagnosis.

Treatment Landscape and Future Directions

Current treatment strategies for Long-COVID primarily focus on symptoms, with some successes using methods adopted from ME/CFS management. Innovations like low-dose naltrexone and anticoagulant therapies show promise, while experimental treatments like Paxlovid and probiotics are beginning to demonstrate potential benefits. However, the need for robust clinical trials to establish effective treatments remains crucial, underscoring the early stage of Long-COVID care and the importance of ongoing research.

Vaccine Impact and the Role of Variants

The impact of vaccination on Long-COVID varies, showing both minimal and reduced risk. Variants and vaccine doses can impact the likelihood of long-term COVID-19 infection, with early studies indicating variant-dependent risks and vaccine effectiveness. Reinfections, especially multiple ones, could increase the risk of Long-COVID, emphasizing the importance of continuous research and monitoring.

Diagnosis of Long-COVID: Obstacles and Solutions

The diagnostic challenges of the early pandemic, such as limited availability of PCR tests and high false-negative rates, led to widespread underdiagnosis, particularly affecting non-hospitalized individuals. Compounded by unreliable antibody tests, especially in certain groups like women, children, and those with mild infections, these issues significantly hindered Long-COVID research and patient care. Misclassification and study exclusions have blurred our understanding of the disease. A comprehensive approach that incorporates insights from ME/CFS and Dysautonomia is crucial for improving Long-COVID research. Emphasizing clinical trials, diverse participant involvement, engagement with patient communities, and updated health education will enhance patient outcomes and advance our knowledge of Long-COVID.

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