For some individuals, COVID-19 doesn’t end with a negative test. Even after recovering from the initial infection, lingering symptoms like fatigue, brain fog, and digestive issues can persist for weeks or even months—a condition often referred to as long COVID, or medically as post-acute sequelae of COVID-19 (PASC).

A recent study published in the journal Cell provides new insights into the possible risk factors associated with long COVID. While more research is needed to confirm these findings and develop treatments, scientists have identified four biological markers that may predict who is more likely to experience persistent symptoms.

What Is Long COVID?

According to the Centers for Disease Control and Prevention (CDC), long COVID refers to symptoms that linger four weeks or more after the initial COVID-19 infection. These symptoms vary but commonly include:

  • Shortness of breath

  • Chronic fatigue

  • Difficulty concentrating ("brain fog")

  • Headaches

  • Chest pain

  • Insomnia

  • Digestive issues like diarrhea

  • Skin rashes

Estimates on the prevalence of long COVID vary widely. One review published in JAMA Open Network suggested that more than half of people who recover from COVID-19 experience at least one persistent symptom six months post-infection.

Four Key Factors Linked to Long COVID

The Cell study examined two groups of people diagnosed with COVID-19, tracking their immune responses and symptom progression over time. Researchers found four biological markers that may predict the development of long COVID:

1. Autoantibodies

These are immune proteins that mistakenly attack the body’s own tissues—similar to those found in autoimmune diseases like lupus. The study showed that elevated levels of autoantibodies were strongly linked to ongoing symptoms.

2. Epstein-Barr Virus (EBV) Reactivation

EBV, which causes mononucleosis and remains dormant in the body, was detected in some participants shortly after their COVID-19 diagnosis. Its temporary reactivation may play a role in triggering or worsening long COVID symptoms.

3. Viral Load of SARS-CoV-2

Participants with higher levels of the virus’s genetic material in their blood during the acute phase of illness were more likely to develop long-term complications.

4. Pre-existing Type 2 Diabetes

People with type 2 diabetes were found to be at higher risk for long COVID, possibly due to immune system alterations associated with the disease.

Implications for People with Autoimmune Conditions

Experts suggest that individuals with autoimmune conditions may be more susceptible to long COVID. However, treatments they receive could potentially offer some protection. More targeted studies are needed to confirm this.

Why EBV Matters

Reactivation of EBV might be a signal that the body is under stress. While it doesn’t confirm active infection, its presence could reflect the immune system’s response to SARS-CoV-2.

Looking Ahead

Though the study doesn’t establish causation, identifying these markers is a step toward developing diagnostic tools and treatments. Larger, long-term studies like the NIH’s RECOVER Initiative aim to expand on these findings.

Final Thoughts

Long COVID remains a complex and evolving condition. This new research offers valuable clues, but further investigation is essential to fully understand and manage it. If you're experiencing persistent symptoms after COVID-19, consult your healthcare provider to explore options for care and symptom management.

Note: This information is current as of publication. For the latest updates, refer to trusted sources such as the CDC, WHO, and your local health authorities.