Long-COVID: New Research Results and Possible Treatment Options

Research into causes progresses, brain stimulation methods discussed as treatment

There is an acute need for improved diagnostic methods and effective therapeutic approaches for Long COVID: According to the World Health Organization (WHO), around 36 million people in Europe are affected by the long-term effects of coronavirus infection. In the population-based cohort research available to date, experts estimate the incidence of Long COVID at around six to 15 percent (Global Burden of Disease Long COVID Collaborators 2022; Peter et al. 2022; Thompson et al. 2022). Around a third of those affected suffer from neuro-Covid.

Early in the pandemic, it was recognized that SARS-CoV-2 is not only a respiratory disease, but can also affect various other organ systems, including the central nervous system (CNS). The mechanisms by which the virus causes neurological problems are diverse and can include direct viral invasion, inflammatory responses, immune-mediated damage and blood clot formation.

Cognitive impairment: Recent research reveals surprising effects on the brain

Previous research from Wuhan already indicated an increased risk of dementia after severe COVID-19 infections 1. Recent findings by British scientists now suggest that there is a significant decline in cognitive function, especially in people over the age of 50.

A British research team, including Prof. Anne Corbett from the University of Exeter Medical School, an expert in the field of dementia and cognitive health in old age, has looked at the impact of the pandemic on the cognitive health of older people. Her research was based on data from the PROTECT study 2. The results have now been published in the scientific journal THE LANCET 3.

Drop in cognitive performance by 50 percent and increased risk of dementia

The data basis of the study consisted of a cognitive assessment in which around 3,000 British citizens aged between 50 and 90 took part over an extended period of time. These tests aimed to evaluate mental skills such as logical thinking, problem-solving ability and memory performance. The resulting findings were clear: “The Covid-19 pandemic has led to a significant impairment of cognitive function in older adults”, and the risk of dementia has also increased significantly during this period.

The ongoing deterioration in mental health among the over 50s in the UK during the Covid pandemic is a cause for concern. Compared to before the pandemic, there has been a 50 percent decline in cognitive performance, which is also associated with an increased risk of dementia.

US study: Blood biomarkers highlight immune disorders in long-COVID

Intensive research is being conducted worldwide to better understand the full extent and mechanisms of Long COVID and to provide effective treatments for affected patients. Now, American scientists have identified specific blood biomarkers in patients with Long COVID. This groundbreaking study reveals significant differences in immune and hormonal responses between Long COVID sufferers and unaffected individuals.

The US Centers for Disease Control and Prevention report that one in thirteen adults in the US (or 7.5%) have symptoms that persist three months after contracting COVID-19, including cognitive impairments such as “brain fog”, extreme fatigue, shortness of breath and chronic pain. The exact causes of these persistent symptoms are still unknown. The new study by the Icahn School of Medicine at Mount Sinai and the Yale School of Medicine provides new insights that could help explain these symptoms.

The research group studied a total of 271 patients from January 2021 to June 2022 at three locations: Mount Sinai-Union Square, Mount Sinai Union Square and the Yale School of Medicine. They categorized the participants into three groups: Individuals with no previous SARS-CoV-2 infection, those who had fully recovered from COVID-19, and patients with persistent long-COVID symptoms after confirmed infection (median duration of long-term symptoms was 12 months post-infection).

Algorithm identifies long-Covid sufferers with 96 percent accuracy

All subjects were asked to complete comprehensive questionnaires about their symptoms, medical history and quality of life. The researchers then took blood samples, identified biomarker differences and similarities among the participants and used machine learning to identify the biomarkers that were most effective in identifying patients affected by Long COVID through the algorithm.

The algorithm was able to distinguish people with and without long-COVID with 96 percent accuracy by identifying features that were conspicuous in the blood samples of the long-COVID group. Distinctive differences that set the Long COVID group apart from the control groups were related to immune system disorders and hormone imbalances.

These differences were reflected in biomarkers that indicated unusual T-cell activity, reactivation of various dormant viruses (including Epstein-Barr and other herpes viruses) and a significant reduction in cortisol levels.

There is no “cure-all” for Long COVID, as it is a disease that affects complex systems such as immune and hormone regulation. Such complex clinical pictures require multi-layered treatment approaches. Urgent and accelerated research is needed to understand long-COVID more deeply and to develop innovative, promising treatment options, according to the researchers in the study 4 published in NATURE on September 25, 2023.

Non-invasive brain stimulation procedures as promising treatment approaches

Non-invasive brain stimulation methods can also represent innovative, promising treatment options: The Swiss “Altea Long Covid Network”, an association of experts from various disciplines and supported by the Swiss Federal Department of Home Affairs FDHA, Federal Office of Public Health FOPH, summarizes how non-invasive brain stimulation methods are currently being investigated in clinical trials for the treatment of Long COVID patients with cognitive impairment.

The focus is on deep magnetic stimulation (TMS), transcranial direct current stimulation (tDCS) and transcranial pulse stimulation (TPS). The three technologies use different types of physical signals: deep magnetic stimulation (TMS) uses a magnetic field to stimulate the brain, transcranial pulse stimulation (TPS) uses low-energy shock waves that can be precisely targeted to all areas of the brain and transcranial direct current stimulation (tDCS) uses continuous direct current. The type of brain stimulation varies depending on the technique used.

According to the 2020 European guidelines, transcranial magnetic stimulation (TMS) has been shown to be effective in the treatment of neuropathic pain, post-stroke motor deficits and depression. It can also improve symptoms of fibromyalgia, Parkinson’s disease, aphasia following a stroke, multiple sclerosis and post-traumatic stress disorder.

Similarly to TMS and TPS, transcranial direct current stimulation (tDCS) has also been recognized as an effective treatment method for various neurological and psychiatric conditions.

Transcranial pulse stimulation (TPS) possible form of treatment for various indications

Transcranial pulse stimulation (TPS) has shown positive effects on cognition, memory and depressive symptoms in Alzheimer’s patients after just a short period of use. It is being researched as a potential treatment for a range of neurological conditions, including depression, Alzheimer’s disease, Parkinson’s disease, autism spectrum disorders and fatigue.

Several clinical trials are currently investigating the potential benefits for long-COVID patients with cognitive and neurological symptoms and fatigue.

Against this background, the Altea network believes that non-invasive brain stimulation procedures could represent a constructive approach in the treatment of neurological and psychiatric disorders. This is particularly true for patients who do not respond to conventional therapies 5.


1 https://jamanetwork.com/journals/jamaneurology/fullarticle/2789919
2 https://www.protectstudy.org.uk
3 https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568%2823%2900187-3
4 https://www.nature.com/articles/s41586-023-06651-y
5 https://altea-network.com/blog/132-non-invasive-brain-stimulation