Approximately 5–10% of individuals infected with COVID-19 experience lingering symptoms for three months or more, a condition known as long COVID.
Researchers have explored various biological mechanisms behind this phenomenon, but a perspective article in the Medical Journal of Australia argues that the virus’s ability to persist in the body could be a primary cause.
The Viral Persistence Hypothesis
Early in the pandemic, it became evident that SARS-CoV-2—or its remnants—could linger in various tissues and organs for extended periods, a concept termed “viral persistence.” While the presence of residual viral fragments is well-documented, it remains uncertain whether live virus continues to exist in some individuals and whether this contributes to long COVID.
This distinction is critical, as live virus can be targeted with specific antiviral treatments, unlike non-replicating viral fragments.
Source of New Variants
In immunocompromised individuals, persistent infections may lead to the emergence of new and significantly altered variants, such as JN.1.
Extended Symptoms in the General Population
Persistent viral presence could result in prolonged symptoms for many, suggesting long COVID might stem from an ongoing infection.
Evidence Supporting Viral Persistence
Although no single study definitively links viral persistence to long COVID, emerging research presents a strong case:
Prolonged Viral Shedding
A Nature study found individuals with mild COVID symptoms who shed viral RNA for extended periods were more likely to develop long COVID.
Viral RNA in Blood and Tissues
Research has detected replicating viral RNA and proteins in blood samples years after infection, suggesting the virus might persist in hidden reservoirs such as blood cells.
Viral Presence in Multiple Organs
Studies have identified viral RNA in various tissues and blood up to four months post-infection. Those with persistent RNA were at higher risk of developing long COVID, with the gastrointestinal tract identified as a potential viral reservoir.
RECOVER Initiative Findings
Recent findings from the RECOVER initiative further support the link between persistent viral presence and long COVID symptoms.
However, isolating live virus from bodily reservoirs remains a technical challenge, leaving definitive proof elusive.
Researchers and policymakers must prioritize:
Fast-Tracking Antiviral Trials
Trials of existing antivirals and unconventional therapies like metformin should be accelerated. Metformin offers potential dual benefits: its antiviral properties and its ability to address fatigue-related impairments.
Developing New Treatments
Investment in novel drug development and rapid clinical trial platforms is essential to translate scientific advancements into effective clinical solutions.
Raising Awareness and Prevention
Understanding viral persistence as a potential driver of long COVID can:
Increase public and medical awareness.
Emphasize the importance of minimizing reinfections, as each subsequent infection raises the risk of long COVID.
Reducing Long COVID Risk
To reduce exposure and lower long COVID risks, individuals should:
Ensure Clean Indoor Air: Open windows, improve airflow, and use air filters in enclosed spaces.
Use High-Quality Masks: Opt for well-fitting masks like N95s in crowded or poorly ventilated settings.
Test and Isolate When Positive: Seek treatment when eligible and take precautions to protect others.
Stay Updated on Vaccines: Booster doses reduce the risk of long COVID and related complications.
While advancements in treatment and potential cures are on the horizon, increased understanding of long COVID’s biological basis is vital. Greater awareness can encourage healthcare providers to take patients’ concerns seriously, enabling them to access existing treatments and services.
