Abstract: Researchers have identified elevated levels of a biomarker in the blood that persist for months in long-term patients with COVID who experience neuropsychiatric symptoms.
Source: UCSF
In a new study on long-term COVID published March 13, 2022, in the Annals of Neurology, UC San Francisco researchers identified biomarkers present at high levels that may persist for many months in the blood of study participants who they had COVID for a long time with neuropsychiatric symptoms.
The results are promising for the development of laboratory tests to assess the long-term risks of COVID and to evaluate new therapies to deal with a form of COVID that has sometimes been thought of as a subjective syndrome that is difficult to describe and measure.
“For much of the first year of the pandemic, many people with long-term COVID were told that what they were experiencing was not even valid,” said Michael Peluso, MD, associate professor of medicine at UCSF and first author of the study.
“Now, we are beginning to identify objective biological measures that correlate with what people are telling us about their long-term symptoms of COVID.”
Long COVID-19 is characterized by continuous or new symptoms such as fatigue, shortness of breath, cognitive impairment, heart rhythm abnormalities, sleep disorders, and muscle and joint pain, which may persist for months after acute virus infection. SARS-CoV2.
Researchers estimate that between 10% and 30% of those infected with the SARS-CoV-2 virus experience long-term symptoms of COVID (although this seems to be less likely among vaccinated people). As many as 23 million people in the United States may already have chronic health problems caused by an infection, according to a recent report from the U.S. Government Accountability Office.
Long COVID-19 can even affect people who initially experienced only a mild illness and perhaps even those who were asymptomatic despite testing positive for the infection.
Viral proteins remain in brain cells
To conduct the study, physicians surveyed 46 previously infected patients with about 32 long-term physical symptoms of COVID, as well as mental health symptoms such as memory loss, irritability, agitation, depression, anxiety, post-traumatic stress, and loss. specific sensory.
In addition, laboratory researchers analyzed blood plasma samples from 12 control subjects never infected without neuropsychiatric symptoms to compare.
All study participants were patients in the COVID-19 study of the long-term impact of the new coronavirus infection (LIINC) in San Francisco, and were enrolled from March 2020 to February 2021, after giving positive for infection.
The original intention of the study was to follow patients over time to monitor natural immunity following COVID infection, but when it became clear that patients on return visits continued to experience symptoms many weeks after infection, understanding of these long symptoms of COVID became an important focus of the study.
New findings are based on a single time point, but patients continue to be monitored for changes in symptoms and immunological and other potential biomarkers.
Blind to patient identity and symptom status, the team used a technique based on blood plasma samples, developed by the corresponding author, Edward Goetzl, MD, professor emeritus of medicine at UCSF, to measure viral and patient proteins derived from neurons.
The researchers first isolated sacs full of proteins, called exosomes, released into the blood by all types of cells, and then selected only those exosomes derived from neurons and support cells known as astrocytes. Goetzl sees this approach as an indirect measure that reflects the disruption that occurs in brain cells after SARS-CoV-2 infection.
The analysis found much higher mean levels of two measured SARS-CoV-2 viral proteins (the nucleocapsid protein and the ear protein) in blood plasma samples collected six to 12 weeks after the diagnosis of COVID-infected patients. who had neuropsychiatric symptoms in comparison. to samples of those who had COVID for a long time, but who had no neuropsychiatric symptoms.
The levels of these neuronal exosome proteins in long-term COVID patients without neuropsychiatric disease were still higher than the levels of patients without long-term COVID.
Goetzl said that SARS-CoV-2, like many other viruses, targets structures called mitochondria within the cells it invades. The virus is likely to interfere with normal mitochondrial tasks, he said, which include providing the cell with a useful form of energy and contributing to the immune system’s ability to respond to infection.
Long COVID-19 is characterized by continuous or new symptoms such as fatigue, shortness of breath, cognitive impairment, heart rhythm abnormalities, sleep disorders, and muscle and joint pain, which may persist for months after acute virus infection. SARS-CoV2. The image is in the public domain
According to Goetzl, the researchers measured significant differences in the levels of various mitochondrial proteins among long-term patients with COVID with and without neuropsychiatric symptoms, pointing to alterations in mitochondrial function within neurons.
“I think most scientists who have raised this may say that virus particles are very unlikely to remain infectious at this stage, but these viral proteins that are in the cell can still do bad things.” , said Goetzl. She is optimistic about the development of small molecule drugs that can enter infected cells and destroy specific viral proteins.
Advancing towards diagnosis and treatment
See also
Peluso said many researchers attribute chronic symptoms in long-term COVID primarily to prolonged or altered immune responses. Initial acute infection can cause long-term maladaptive changes in the immune system.
The continued presence of viral proteins within the body can lead to chronic inflammatory responses. The presence of certain viral molecules can also trigger autoimmune responses in which the immune system attacks the body’s own tissues.
“By identifying biomarkers like these, we will be able to more accurately diagnose long-term COVID and identify effective treatments through well-designed clinical trials,” Peluso said. “With this study, we have taken an important step towards this goal.”
On this news of long research on VOCID and mental health
Author: Jeffrey NorrisSource: UCSFContact: Jeffrey Norris – UCSFIIimage: Image is in the public domain
Original search: open access. “SARS-CoV-2 and Mitochondrial Proteins in Neural-Derived Exosomes of COVID-19” by Michael J. Peluso et al. Annals of Neurology
Summary
SARS-CoV-2 and mitochondrial proteins in exosomes derived from COVID-19 neurols
Goal
Because SARS-CoV-2 is known to invade the mitochondria of neuronal cells, a plasma system was used to quantify central nervous system proteins in living humans to investigate the neuropathogenic mechanisms of long COVID-19.
Methods
SARS-CoV-2 proteins and mitochondrial proteins (MPs) in extracellular vesicles derived from enriched plasma neurons (NDEV) and EVs derived from astrocytes (ADEV) were quantified in acute COVID-19 resolved without post-sequelae. acute SARS-CoV-2. (PASC), PASC without neuropsychiatric manifestations (NP), PASC with NP and healthy controls.
Results
Mean NDEV and ADEV levels of SARS-CoV-2 S1 and nucleocapsid (N) proteins were higher in all PASC subgroups than controls, but only N levels were higher in PASC than with no NP. The mean levels of NDEV normalized with the CD81 exosome marker of subunit 6 of complex I of the respiratory chain MP and subunit 10 of complex III and neuroprotective MPs Humanin and the mitochondrial open reading frame of 12S rRNA-c ( MOTS-c) were significantly reduced in PASC with NP but not in PASC without NP in relation to controls. NDEV levels of the MPs strain-dependent selective channel 1 protein (VDAC1) and N-methyl-D-aspartate receptor 1 (NMDAR1) were reduced in PASC without and with NP, while the of the calcium channel MPs mitochondrial calcium uniporter (MCU), sodium / calcium exchanger (NCLX) and the leucine zipper EF containing transmembrane protein 1 (LETM1) were only reduced in PASC with NP. MCU and NCLX ADV levels were only increased in PASC without and with NP.
Interpretation
Abnormal NDEV and ADEV levels of SARS-CoV-2 N and S1 and MP proteins correlate with NP and may be biomarkers for long-term COVID therapeutic trials and prognosis. ANN NEUROL 2022; 91: 772–781