A team of microbiologists suggests that infections occurring alongside SARS-CoV-2 may contribute to some cases of long COVID, potentially by reactivating latent pathogens such as Epstein–Barr virus or altering the course of tuberculosis. Their perspective, published in eLife, stresses that this remains a hypothesis and calls for large studies and better animal models to test whether these co-infections help drive persistent symptoms like fatigue and brain fog.
Long COVID continues to puzzle scientists, with estimates suggesting that hundreds of millions of people worldwide have experienced lingering problems ranging from breathlessness and fatigue to cognitive complaints, according to Rutgers University and other research groups.
A new perspective article in eLife, authored by 17 experts including researchers from Rutgers Health, argues that additional infections occurring before, during, or after COVID-19 may contribute to these long-term effects.
The paper, chaired by Maria Laura Gennaro of Rutgers New Jersey Medical School, proposes that SARS-CoV-2 can disrupt the immune system in ways that might allow latent or concurrent pathogens to play a role in post-acute sequelae of SARS-CoV-2 (PASC), often called long COVID.
One of the strongest lines of circumstantial evidence centers on Epstein–Barr virus (EBV), the virus that causes mononucleosis. Roughly 95 percent of adults worldwide carry EBV in a latent form that typically remains silent until an immune challenge triggers its reactivation, according to studies cited in the eLife perspective and related reviews. (sciencedaily.com)
In an early study highlighted by the eLife authors, about two-thirds of people with long COVID showed markers of recent EBV activity, and those with more symptoms had higher antibody levels. Later work similarly linked serological evidence of recent EBV reactivation with hallmark features of long COVID, including fatigue and cognitive difficulties. (elifesciences.org)
Tuberculosis (TB) is another pathogen receiving attention in the review. Roughly one-quarter of the global population is estimated to carry latent TB infection, a figure widely cited in public health literature. The eLife perspective notes evidence that COVID-19 may reduce the immune cells that normally contain TB and that TB itself can worsen COVID outcomes, raising the possibility of a bidirectional relationship between the two diseases. (sciencedaily.com)
The authors emphasize that timing and causality remain unclear. They outline scenarios in which pre-existing infections could weaken immunity before a person contracts COVID-19, or in which pathogens might take advantage of lingering immune dysfunction after acute infection, but they stress that these ideas have not yet been proven.
The Rutgers summary of the eLife article describes long COVID as having affected up to an estimated 400 million people globally and notes that the condition can involve multiple organ systems, including the brain, heart, lungs, and digestive tract. It also underscores that there are still no proven, broadly effective treatments because the underlying mechanisms remain uncertain. (sciencedaily.com)
Separate analyses of global surveillance data, conducted by Airfinity and reported with Bloomberg News, have found that more than 40 countries or territories have reported at least one infectious disease resurgence that is 10-fold or more above pre-pandemic baselines, with at least 13 infectious diseases showing a post-pandemic surge. These findings suggest that the pandemic period has coincided with increased vulnerability to a range of pathogens, although the analyses attribute this pattern mainly to factors such as disrupted vaccination, waning population immunity, and climate change rather than specifically to long COVID. (globenewswire.com)
"This is an aspect of long COVID that is not talked about a lot," said Gennaro, a microbiologist at Rutgers New Jersey Medical School who chaired the Microbiology Task Force for the U.S. National Institutes of Health's Researching COVID to Enhance Recovery (RECOVER) initiative, a large-scale long COVID study. (sciencedaily.com)
The researchers argue that, if co-infections are shown to meaningfully contribute to long COVID in some patients, existing tools such as targeted antivirals or antibiotics might eventually be repurposed as part of treatment strategies. However, they caution that this possibility is speculative at present and must not be assumed in clinical practice without rigorous testing.
"Everyone has heard it a million times, but it bears repeating: Correlation doesn't equal causation," Gennaro said, according to Rutgers. She noted that confirming any causal links between specific co-infections and long COVID will require large epidemiological studies and animal experiments, a task complicated by the current lack of reliable animal models for long COVID. (sciencedaily.com)
For now, the eLife perspective primarily serves as a call to broaden the search for answers. Its authors hope that systematically investigating co-infections and latent pathogen reactivation will shed light on why some people continue to experience debilitating symptoms long after their initial coronavirus infection — and whether looking beyond SARS-CoV-2 itself will be key to understanding and treating long COVID. (sciencedaily.com)
