Researchers Identify Viral Suspects and Co-infections Fueling Long COVID

Viral Suspects and Epstein-Barr Reactivation

The review brings together existing scientific findings and expert opinions to highlight pathogens that may act alongside SARS-CoV-2 to trigger chronic illness. According to Maria Laura Gennaro, a microbiologist at the Rutgers New Jersey Medical School who chaired the Microbiology Task Force for the National Institutes of Health’s Researching COVID to Enhance Recovery initiative, co-infections represent an aspect of long COVID that receives relatively little attention.

One of the strongest lines of evidence centers on the Epstein-Barr virus, or EBV, which causes mononucleosis. Roughly 95 percent of adults carry EBV in a latent form that usually remains dormant until an immune challenge disrupts it. According to early research cited in the review, two-thirds of people with long COVID showed markers of recent EBV activity, with higher antibody levels corresponding to a greater burden of symptoms. Subsequent studies have linked this viral reactivation to hallmark features of long COVID such as severe fatigue and cognitive difficulties.

Tuberculosis and Immunity Theft Concerns

Researchers are also examining tuberculosis, or TB, as a contributing factor. About one-quarter of the global population carries latent TB, and evidence indicates that COVID-19 may deplete the specific immune cells responsible for containing the bacterium. This reduction raises the risk of TB reactivation, while active TB can simultaneously worsen initial COVID-19 outcomes.

The review emphasizes that timing dictates how these pathogens interact with the coronavirus. Infections occurring prior to COVID-19 can weaken baseline immune defenses, while those acquired during the initial illness may intensify tissue damage. Pathogens arising after recovery can exploit lingering immune dysfunction left behind by the coronavirus. According to the authors, 44 countries have documented tenfold increases in at least 13 infectious diseases compared to pre-pandemic baselines. This trend aligns with the concept of immunity theft, which suggests an episode of acute COVID-19 leaves individuals more susceptible to subsequent infections.

Scientific Uncertainty and Future Research Needs

If co-infections actively drive long COVID, existing medical therapies could potentially be repurposed to treat patients. Standard antibiotics and antivirals might target these underlying pathogens, opening the door for clinical trials to test whether clearing secondary infections alleviates long COVID symptoms.

However, the researchers caution that the proposed connection remains entirely preliminary and unproven. No causal relationship has been officially established between any specific co-infection and long COVID. Everyone has heard it a million times, but it bears repeating: Correlation doesn’t equal causation, Gennaro said according to the published review coverage. Establishing causality will require large-scale epidemiological studies and dedicated animal research, though investigators note that the current lack of reliable animal models for long COVID continues to complicate those efforts.