Researchers discovered that individuals experiencing a variety of long COVID symptoms are twice as likely to have SARS-CoV-2 proteins present in their bloodstream compared to those who do not exhibit long COVID symptoms.
Brigham researchers discovered that individuals experiencing a variety of long COVID symptoms are twice as likely to have SARS-CoV-2 proteins present in their bloodstream compared to those who do not exhibit long COVID symptoms.
A new study from Brigham and Women’s Hospital suggests that ongoing infection may account for why some individuals continue to suffer from long COVID symptoms. The research indicates chronic infection in 43% of participants with symptoms affecting the heart, lungs, musculoskeletal system, or nervous system. These findings are detailed in the journal Clinical Microbiology and Infection.
Lead author Zoe Swank, PhD, a postdoctoral fellow at Brigham and Women’s Hospital, stated, “Identifying people with ongoing viral symptoms due to viral reservoirs in their bodies might allow us to use antivirals to help alleviate these symptoms.”
The study examined 1,569 blood samples from 706 individuals, including 392 participants from the NIH-supported Researching COVID to Enhance Recovery (RECOVER) Initiative, all of whom had previously tested positive for COVID-19. Researchers employed a highly sensitive test to identify both complete and partial proteins from the SARS-CoV-2 virus and analyzed the long COVID symptoms of the participants using data from their medical records or surveys completed simultaneously with the blood sample collection.
Those who reported ongoing symptoms affecting multiple bodily systems, including the heart, lungs, and musculoskeletal areas, were found to be roughly twice as likely to have detectable SARS-CoV-2 proteins in their blood compared to those without long COVID symptoms. The team utilized Simoa, an ultra-sensitive test capable of detecting singular molecules, to successfully identify the spike protein and other SARS-CoV-2 components. Common long COVID symptoms reported included fatigue, cognitive difficulties, muscular pain, joint pain, back pain, headaches, sleep issues, and loss of smell or taste, as well as gastrointestinal problems.
Notably, 43% of those with long COVID symptoms impacting three major systems — cardiopulmonary, musculoskeletal, and neurological — tested positive for viral proteins within 1 to 14 months following their positive COVID tests, while only 21% of those who reported no long COVID symptoms showed the same positive SARS-CoV-2 biomarker results during that timeframe.
This data points to the possibility that persistent infection could account for some, but not all, of the symptoms experienced by long COVID patients. This suggests that testing and treatment strategies could benefit those who might respond well to antiviral medications.
A Condition with More Than One Cause
The study brings forth questions about why over half of patients with diverse long COVID symptoms tested negative for persistent viral proteins.
“This finding indicates that there are likely multiple causes of long COVID,” explained David Walt, PhD, a Pathology professor at Brigham and Women’s Hospital and Principal Investigator of the study. “For instance, the virus could potentially damage the immune system, leading to ongoing immune dysfunction after the virus is cleared.”
To further explore whether ongoing infection is responsible for some patients’ long COVID symptoms, Swank, Walt, and their team are conducting follow-up studies. They are analyzing blood samples and symptom information from a broader patient population, including individuals of varying ages and those with weakened immune systems, to determine if certain individuals have a higher likelihood of harboring the persistent virus.
“We still have much to learn about how this virus impacts individuals,” said David C. Goff, M.D., Ph.D., senior scientific program director for the RECOVER Observational Consortium Steering Committee and director of Cardiovascular Sciences at the National Heart, Lung, and Blood Institute (NHLBI), a part of NIH. “Such studies are vital for better understanding the mechanisms of long COVID, which will assist in pinpointing suitable treatment targets.”
Goff noted that these findings also bolster ongoing research into antiviral treatment options.
The blood test for SARS-CoV-2 developed by researchers at Brigham and Women’s Hospital is also being used in a national study known as RECOVER-VITAL. This study is assessing whether antiviral medication aids in the recovery of patients from long COVID. The RECOVER-VITAL trial will evaluate the blood of participants before and after antiviral treatment to see if the treatment can clear persistent viral proteins from the bloodstream.
The concept of a virus lingering in the body and causing continued symptoms long after infection isn’t exclusive to COVID. “Other viruses have been linked to similar post-acute syndromes,” noted Swank. She highlighted that animal studies have detected Ebola and Zika proteins in tissues after infection, which have also been connected to long-term health issues.
Authorship: Besides Swank and Walt, authors from Mass General Brigham 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 contributors 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, and M. Juliana McElrath.
Conflict of Interest: Michael J. Peluso has reported receiving consulting fees from Gilead Sciences and AstraZeneca, as well as research support from Aerium Therapeutics, all unrelated to the submitted work. Steven G. Deeks has consulted for Enanta Pharmaceuticals and Pfizer and received research support from Aerium Therapeutics not related to this work. Jonathan Z. Li has consulted for AbbVie and obtained research funding from Merck. David Walt holds financial interest in Quanterix Corporation, a firm developing an ultra-sensitive digital immunoassay platform, is an inventor of Simoa technology, and is a board member of the company.
Funding: The research was funded by the National Institutes of Health (NIH) and Barbara and Amos Hostetter.
