A groundbreaking discovery has shed light on the potential culprits behind the mysterious long-term effects of COVID-19. For those battling long COVID, the persistent symptoms of breathlessness, fatigue, and brain fog have been a puzzle. However, a team of renowned microbiologists believes they've uncovered a crucial piece of the puzzle.
The experts suggest that, for some individuals, long COVID symptoms might be triggered by additional infections that occur simultaneously with SARS-CoV-2. A comprehensive review published in eLife, led by 17 experts including researchers from Rutgers Health, highlights the role of co-infections acquired before or during COVID-19 in driving long-lasting symptoms.
Maria Laura Gennaro, a microbiologist at Rutgers New Jersey Medical School and chair of the Microbiology Task Force for the National Institutes of Health's Researching COVID to Enhance Recovery initiative, emphasizes the importance of this aspect, which has been largely overlooked.
The evidence is mounting that other pathogens could be key players in long COVID. With up to 400 million people worldwide affected, long COVID can range from mild disruptions to severe disabilities, impacting various organs and systems. Despite its widespread impact, no proven treatments exist due to the unclear underlying cause.
This new review brings together existing scientific knowledge and expert insights to draw attention to the idea that infections other than the coronavirus itself may be significant contributors. One of the strongest pieces of evidence points to the Epstein-Barr virus (EBV), the culprit behind mononucleosis. Approximately 95% of adults carry EBV in a latent form, which can become active when triggered by an immune challenge like COVID-19.
Early studies have shown that two-thirds of people with long COVID exhibit markers of recent EBV activity, and those with more severe symptoms have higher antibody levels. Subsequent research has also linked EBV reactivation to well-known long COVID symptoms, such as fatigue and cognitive difficulties.
Another pathogen under scrutiny is tuberculosis (TB), which affects about a quarter of the global population in a latent form. Evidence suggests that COVID-19 may reduce the immune cells that typically keep TB in check, increasing the risk of reactivation. The connection between the two diseases appears to be bidirectional, as TB can also worsen COVID-19 outcomes.
The researchers stress the importance of timing. Infections that occur before COVID-19 may weaken the immune system, while infections during the initial illness may exacerbate tissue damage. Infections that arise post-recovery could exploit the lingering immune dysfunction caused by COVID-19.
The authors also highlight the alarming rise in other infectious diseases, with 44 countries experiencing tenfold increases in at least 13 infectious diseases compared to pre-pandemic levels. One theory they discuss, known as "immunity theft," proposes that an acute episode of COVID-19 may leave individuals more susceptible to other infections.
If co-infections indeed contribute to long COVID, existing treatments could potentially offer relief. Antibiotics and antivirals could be repurposed to target specific underlying infections, and clinical trials could investigate whether treating these infections improves long COVID symptoms.
However, the researchers caution that their hypothesis is still preliminary. While the connections they outline are biologically plausible, they remain unproven. No causal relationship has been established between any co-infection and long COVID.
Gennaro emphasizes the importance of not jumping to conclusions, stating, "Correlation does not equal causation." She adds that verifying the hypothesis will require large-scale epidemiological studies and animal research, which is challenging due to the lack of reliable animal models for long COVID.
The authors hope that their findings will spur further investigation into the role of co-infections in long COVID. While the review does not provide immediate solutions, it highlights the need to look beyond the coronavirus alone for effective treatment strategies.
