Researchers at Brigham and Women’s Hospital discovered that individuals exhibiting a wide range of long COVID symptoms were twice as likely to have SARS-CoV-2 proteins in their blood compared to those without such symptoms.
A new study suggests that a persistent infection may be the cause of long COVID symptoms in some people. Conducted by Brigham and Women’s Hospital, a key institution within the Mass General Brigham healthcare system, the research identified signs of ongoing infection in 43 percent of participants who reported cardiopulmonary, musculoskeletal, or neurologic symptoms associated with long COVID. These findings were published today (October 9) in Clinical Microbiology and Infection.
“If we can identify a subset of people who have persistent viral symptoms because of a reservoir of virus in the body, we may be able to treat them with antivirals to alleviate their symptoms,” said lead author Zoe Swank, PhD, a postdoctoral research fellow in the Department of Pathology at Brigham and Women’s Hospital.
Advanced Detection Methods and Study Results
The study analyzed 1,569 blood samples collected from 706 people, including 392 participants from the National Institutes of Health-supported Researching COVID to Enhance Recovery (RECOVER) Initiative, who had previously tested positive for a COVID infection. With a highly sensitive test they developed, researchers looked for whole and partial proteins from the SARS-CoV-2 virus. They also analyzed data from the participants’ long COVID symptoms, using electronic medical chart information or surveys that were gathered at the same time as the blood samples were taken.
Compared to people who didn’t report long COVID symptoms, those who reported persisting symptoms affecting heart and lung, brain, and musculoskeletal systems many organ systems were approximately twice as likely to have SARS-CoV-2 proteins circulating in their blood. The research team was able to detect the spike protein and other components of the SARS-CoV-2 virus using Simoa, an ultrasensitive test for detecting single molecules. Commonly reported long COVID symptoms included fatigue, brain fog, muscle pain, joint pain, back pain, headache, sleep disturbance, loss of smell or taste, and gastrointestinal symptoms.
Specifically, 43% of those with long COVID symptoms affecting three major systems in the body, including cardiopulmonary, musculoskeletal, and neurologic systems, tested positive for viral proteins within 1 to 14 months of their positive COVID test. But only 21% of those who didn’t report any long COVID symptoms tested positive for the SARS-CoV-2 biomarkers in this same period.
It’s possible that a persistent infection explains some – but not all – of the long COVID sufferers’ symptoms. If this is the case, testing and treatment could aid in identifying patients who may benefit from treatments such as antiviral medications.
Multiple Causes of Long COVID
One of the questions raised by the study is why more than half of patients with wide-ranging long COVID symptoms tested negative for persistent viral proteins.
“This finding suggests there is likely more than one cause of long COVID,” said David Walt, PhD, a professor of Pathology at Brigham and Women’s Hospital and Principal Investigator on the study. “For example, another possible cause of long-COVID symptoms could be that the virus harms the immune system, causing immune dysfunction to continue after the virus is cleared.”
Ongoing Research and Future Directions
To better understand whether an ongoing infection is behind some people’s long COVID symptoms, Swank, Walt and other researchers are currently conducting follow-up studies. They’re analyzing blood samples and symptom data in larger groups of patients, including people of wide age ranges and those with compromised immune symptoms. This way, they can also see if some people are more likely to have persistent virus in the body.
“There is still a lot that we don’t know about how this virus affects people,” said David C. Goff, M.D., Ph.D., a senior scientific program director for the RECOVER Observational Consortium Steering Committee and director of the Division of Cardiovascular Sciences at the National Heart, Lung, and Blood Institute (NHLBI), part of NIH. “These types of studies are critical to help investigators better understand the mechanisms underlying long COVID — which will help bring us closer to identifying the right targets for treatment.”
Goff added that these results also support ongoing efforts to study antiviral treatments.
The SARS-CoV-2 blood test developed by Brigham and Women’s researchers is also currently being used in a national study, called RECOVER-VITAL, that is testing whether an antiviral drug helps patients recover from long COVID. The RECOVER-VITAL trial will test the patients’ blood before and after treatment with an antiviral to see if treatment eliminates persistent viral proteins in the blood.
Potential Viral Persistence in Other Diseases
The idea that a virus can stay in the body and cause ongoing symptoms months after an infection isn’t unique to COVID. “Other viruses are associated with similar post-acute syndromes,” said Swank. She noted animal studies have found Ebola and Zika proteins in tissues post-infection, and these viruses have also been associated with post-infection illness.
Reference: “Measurement of circulating viral antigens post-SARS-CoV-2 infection in a multicohort study” 9 October 2024, Clinical Microbiology and Infection.
DOI: 10.1016/j.cmi.2024.09.001
In addition to Swank and Walt, Mass General Brigham authors include Ella Borberg, Yulu Chen, Yasmeen Senussi, Sujata Chalise, Zachary Manickas-Hill, Xu G. Yu, Jonathan Z. Li, Galit Alter, and Elizabeth W. Karlson.
Additional researchers include Timothy J. Henrich, J. Daniel Kelly, Rebecca Hoh, Sarah A. Goldberg, Steven G. Deeks, Jeffrey N. Martin, Michael J. Peluso, Aarthi Talla, Xiaojun Li, Peter Skene, Thomas F. Bumol, Troy R. Torgerson, Julie L. Czartoski, M. Juliana McElrath.
Conflict of Interest: Michael J. Peluso reported consulting fees from Gilead Sciences and AstraZeneca, and Research support from Aerium Therapeutics, outside the submitted work. Steven G. Deeks reports consulting for Enanta Pharmaceuticals and Pfizer and research support from Aerium Therapeutics, outside the submitted work. Jonathan Z. Li has consulted for Abbvie and received research funding from Merck. David Walt has a financial interest in Quanterix Corporation, a company that develops an ultra-sensitive digital immunoassay platform. He is an inventor of the Simoa technology, a founder of the company, and also serves on its Board of Directors.
Funding: Funding for this work came from the National Institutes of Health (NIH) and Barbara and Amos Hostetter.