Journal News

Finding a way to combat long COVID

Recent study reveals neurodegenerative biomarkers after COVID-19, gives clues for monitoring and potential treatment
Marissa Locke Rottinghaus
April 5, 2023

A new study has identified potential neurological biomarkers of long COVID-19 in nonhuman primates that may help physicians diagnose, monitor and treat this condition.

Over 65 million people worldwide have developed long COVID after being infected with SARS-CoV-2, and cases are only becoming more common. Long COVID symptoms can last weeks, months or years. Even more perplexing is the fact that symptoms can vary widely between individuals and consist of any combination of fatigue, fever, chest pain, trouble breathing, neurological symptoms such as “brain fog,” and many more. Long COVID puts a gigantic burden on the U.S. healthcare system, and some doctors doubt the condition exists, leaving some patients unable to find care.

A team of researchers at Tulane University is trying to shed light on this condition and find tools to manage it. They published their work in the journal Molecular & Cellular Proteomics.

According to the Centers for Disease Control and Prevention, symptoms of long COVID are more often found in people who had severe COVID-19 illness, but even people who didn't know they'd been infected can experience them.

“Our primary goal was to better understand the inside of the brain after COVID infection,” said Jia Fan, an assistant professor of biochemistry and molecular biology who oversaw the study. “This understanding could provide a potential target to use in the clinic for long COVID evaluation and monitoring. We also thought this study may give us some clues to find a potential treatment strategy for long COVID in patients.”

However, because long COVID can vary drastically between individuals, studying this disorder has been difficult for scientists and clinicians alike.

“There's a very limited understanding of the neuropathogenesis of long COVID,” Fan said. “It is almost impossible to get any brain tissue or samples of any kind from patients that have mild symptoms or no long COVID symptoms because there is no reason for invasive procedures.”

Therefore, the group turned to a nonhuman primate model of long COVID. They used two different types of nonhuman primates, the rhesus macaque and the African green monkey, to mimic the genetic differences seen in humans.

Figure 1 in the paper "Cerebrospinal fluid protein markers indicate neuro-damage in SARS-CoV-2-infected non-human primates" provides an overview of the study design, non-human primate cohorts and proteomic workflow.

“Macaques are bred in captivity,” Sudipa Maity, a postdoctoral fellow at Tulane and lead author of the study, said. “So, they are born, fed and live their entire life in the research center. They also have very similar genetic backgrounds. On the contrary, the African green monkeys live in the wild and are brought to the center around one year before the study. Therefore, the individual genetic variations are larger in the African green monkey than the rhesus macaque.”

The team found that certain proteins associated with neurodegenerative disorders, such as Parkinson's disease, were elevated in the brain, cerebrospinal fluid and blood after SARS-CoV-2 infection even in nonhuman primates that showed mild or no symptoms. Maity explained that these elevated proteins indicate that the immune systems of the monkeys remained activated even after infection.

“Our findings suggest that the major neurological complications are arising due to the body's natural immune defenses,” Maity said. “The immune system has a very important and significant impact on the neurological complications of COVID.”

The next steps of the project involve validating the biomarkers the team identified in human samples such as blood, said Fan.

“It is currently hard to score the severity of (long COVID) patient symptoms because they are based on self-reports,” Fan said. “If we can find a group of proteins in the blood associated with long COVID, this is a less invasive way to easily evaluate the severity of the long COVID patients. We hope what we started can provide a clue to find a potential treatment to better the long COVID patient experience.”

Figure 6 in the paper shows potential interactions between innate immunity and hemostasis in the brain and plasma. Proteins enriched in blood and brain that play a role in innate immune system (green), hemostasis (red) or both (blue). Proteins in bold were found associated with the pathways linked to neurological disorders.

Enjoy reading ASBMB Today?

Become a member to receive the print edition monthly and the digital edition weekly.

Learn more
Marissa Locke Rottinghaus

Marissa Locke Rottinghaus is the science and policy communications specialist for the ASBMB.

Related articles

From the journals: March 2019
John Arnst, Courtney Chandler, Isha Dey & Catherine Goodman
From the journals: February 2019
Gelareh (Abulwerdi) Vinueza, Kerri Beth Boggs & Sasha Mushegian

Get the latest from ASBMB Today

Enter your email address, and we’ll send you a weekly email with recent articles, interviews and more.

Latest in Science

Science highlights or most popular articles

'CoA as the central core'

'CoA as the central core'

June 2, 2023

ASBMB meeting on CoA and its derivatives will take place in Wisconsin in August and will feature sessions on metabolism, intracellular cross talk, proteostasis, autophagy and technological advances in mass spectrometry.

Study uncovers a unique, efficient method of copper delivery in cells

Study uncovers a unique, efficient method of copper delivery in cells

May 28, 2023

Discovery will help in treating Menkes disease, other copper deficiency disorders.

As microbiome science forges ahead, will some be left behind?

As microbiome science forges ahead, will some be left behind?

May 27, 2023

The FDA’s approval of the first fecal microbiota treatment was a watershed moment — and also a wakeup call.

Cystic fibrosis: current understanding and prospects
Health Observance

Cystic fibrosis: current understanding and prospects

May 26, 2023

In observance of National Cystic Fibrosis Awareness Month, we talked with researcher Neil Bradbury.

A great escape — how SARS-CoV-2 evades our defenses
Journal News

A great escape — how SARS-CoV-2 evades our defenses

May 25, 2023

Preliminary evidence shows that SARS-CoV-2 uses molecular mimicry, in which one of its proteins acts like a protein in our immune system.

John H. Exton: A cell signaling pioneer

John H. Exton: A cell signaling pioneer

May 24, 2023

Colleagues recall a distinguished member of the Vanderbilt University faculty for six decades who had been an ASBMB member since 1970.