Go to main contentGo to footer
- 29 July 2022

Long COVID: Discovered specific blood markers related to neuropsychiatric symptoms

A recent study has identified some specific biomarkers related to neuropsychiatric symptoms resulting from COVID-19 infection, providing an essential contribution to the diagnosis and treatment of Long COVID.

Read the results of the study!

What is Long COVID?

Long COVID is a syndrome characterized by persistent or newly emerging symptoms that can last for many months following acute SARS-CoV-2 infection. Some of the most common symptoms among Long COVID patients include:

  • Fatigue

  • Shortness of breath

  • Cognitive impairments

  • Heart rhythm abnormalities

  • Sleep disturbances

  • Muscle and joint pain

Researchers estimate that between 10% and 30% of people infected with the SARS-CoV-2 virus develop prolonged COVID symptoms ― a risk that appears to be less common among people who have been vaccinated. As of today, according to a recent report from the U.S. Government Accountability Office, up to 23 million people in the United States alone may already be afflicted with chronic health issues caused by the infection.

It might be assumed that Long COVID primarily affects those who experienced severe symptoms during the acute phase of the illness, but this is not the case. In fact, it is now known that Long COVID can also affect those who initially exhibited only mild symptoms during the course of the infection. Additionally, it is hypothesized that Long COVID can develop even in those who tested positive for the infection but remained asymptomatic during the illness.

Long COVIDA Revolutionary Discovery

In a new study published on March 13, 2022, in the Annals of Neurology journal, researchers from the University of California, San Francisco, have identified specific blood biomarkers that persist for many months in individuals affected by Long COVID, offering promising prospects for the diagnosis and treatment of this disorder.

«For much of the first year of the Pandemic, many people with Long COVID were told that what they were experiencing was not a matter of concern or related to COVID,» says Michael Peluso, MD, an assistant professor of medicine at UCSF, and the lead author of the study. «For some time now, we've been starting to identify objective biological measures that correlate with what people report about their Long COVID symptoms.»

Study Participants

To conduct the study, UCSF physicians interviewed 46 individuals previously infected, asking questions about 32 physical symptoms related to Long COVID, as well as mental symptoms such as memory loss, irritability, agitation, depression, anxiety, post-traumatic stress, and specific sensory losses.

Researchers also conducted laboratory analyses on blood plasma samples from 12 control subjects who had never been infected and showed no neuropsychiatric symptoms, in order to perform a comparison with the data collected during the research.

All study participants were part of the Long-term Impact of Infection with Novel Coronavirus (LIINC) COVID-19 study based in San Francisco. They were enrolled between March 2020 and February 2021 after testing positive for COVID-19.

The Discovery of Biomarkers

The original intent of the study was to follow patients over time to monitor natural immunity following COVID infection. However, when it became evident that patients continued to exhibit symptoms for many weeks after the infection, understanding these extended COVID symptoms became a primary research focus.

In a double-blind experiment in relation to patient identity and symptom status, the research team used a blood plasma-based technique developed by the corresponding author of the study, Edward Goetzl, MD, emeritus professor of medicine at UCSF. This technique aimed to measure the patient's neuronal-derived viral proteins.

Researchers first isolated vesicles filled with proteins, known as exosomes, released into the blood by various cell types. They then selectively isolated exosomes derived from neurons and supporting cells known as astrocytes. Dr. Goetzl regards this approach as a measure reflecting alterations in brain cells following SARS-CoV-2 infection.

The analysis revealed significantly higher average levels of two viral proteins from SARS-CoV-2 — the nucleocapsid protein and the spike protein — in blood plasma samples collected between 6 and 12 weeks after diagnosis in patients with neuropsychiatric symptoms compared to samples from individuals with a history of COVID but without neuropsychiatric symptoms. Furthermore, the levels of these proteins were higher in Long COVID patients without a prior neuropsychiatric condition compared to those with a neuropsychiatric disorder but without Long COVID, highlighting the specificity of these markers for neuropsychiatric symptoms related to Long COVID.

Dr. Goetzl stated that SARS-CoV-2, like many other viruses, targets structures called mitochondria within invaded cells. It is highly likely that the virus interferes with normal mitochondrial functions, including the supply of cellular energy and contributions to the immune system's ability to respond to infections. According to Dr. Goetzl, researchers measured significant differences in the levels of various mitochondrial proteins among Long COVID patients, both with and without neuropsychiatric symptoms, indicating alterations in mitochondrial function within neurons.

Although the new results are based on a single-time-point, patients continue to be monitored to assess changes in symptoms and immune and other biomarkers.

New Perspectives for Diagnosis and Treatment

«I believe that most scientists who have considered this issue could say that it is very unlikely that viral particles remain infectious at this stage, but these viral proteins that remain in the cell can still do other kinds of damage,» Dr. Goetzl concluded, remaining optimistic about the possibility of developing drugs capable of entering infected cells and destroying specific viral proteins.

Many researchers attribute chronic Long COVID symptoms primarily to prolonged or altered immune responses. Dr. Peluso stated, «The initial acute infection may trigger long-term and maladaptive changes in the immune system.»

The continued presence of viral proteins in the system could lead to chronic inflammatory responses. The presence of certain viral molecules could also trigger autoimmune responses, in which the immune system attacks the body's tissues.

Identifying biomarkers like these could be a significant step toward a more accurate diagnosis of Long COVID and the discovery of effective treatments through well-designed clinical studies. «With this study, we have taken an important step toward this goal,» Dr. Peluso concluded.

The results of the study appear promising for the development of laboratory tests to understand the risks associated with Long COVID and to evaluate new therapies for this subjective and challenging-to-measure syndrome.

Last News