Could Viral Persistence Explain Long Covid?

In December 2020, the National Institutes of Health received $1 billion to fund Long Covid research and treatment. After two years, distinct patient subgroups are emerging to drive research directions. The myriad, overlapping symptoms of Long Covid can be broken out into three major groups:

  • Cardiovascular - shortness of breath, tachycardia, abnormal blood pressure, and blood clots
  • Neurocognitive - brain fog, vertigo, memory issues, headaches, neuropathy
  • Fatigue - post-exertional malaise, insomnia, fatigue

Each symptom cluster is deserving of its own investigation for possible causes and treatments. However, an increasing number of researchers are wondering if a root cause might be behind the 25+ symptoms associated with Long Covid - viral persistence.

What is viral persistence?

Viral persistence means the body’s immune response was unable to fully kill off the virus and some amount of virus remains in the body, potentially wreaking havoc. These viral reservoirs may exist in tissues other than the respiratory tract and would not be picked up by an antigen or PCR test. Viral persistence could be driving a chronic inflammatory immune response that leads to the most common Long Covid symptoms. Classic symptoms of systemic inflammation include fatigue, brain fog, and shortness of breath, all symptoms experienced by many Long Covid patients. This might also be why Long Covid patients tend to respond well, at least temporarily, to steroids and anti-histamines, drugs known to reduce inflammation and calm the immune system.

The presence of microclots may be another clue. Researchers Resia Pretorius and Douglas Kell discovered that both acute Covid patients and Long Covid patients have unusual microclots in their blood compared to healthy controls. Microclots block the smallest blood vessels and interfere with oxygenation of surrounding tissues. ****Given these microclots are not found in recovered Covid patients without Long Covid, viral persistence could be driving the continued formation of microclots in the bloodstream.

What makes viral persistence a promising theory?

There is precedence for viral persistence. Viruses known to persist in the body after acute infection include Chickenpox, Epstein-Barr Virus (EBV), and HIV. Chronic viruses may only occasionally reactivate and cause symptoms, for example shingles in the case of chickenpox. Chronic viral infections can also lead to secondary symptom sets, which is well-documented in HIV-AIDS patients.

If you’re still having symptoms, you might still have an infection.

Seems simple, right? The difficulty comes from trying to test for viral persistence. The best evidence so far comes from autopsy-based studies where the virus has been found in various organ systems for upwards of 8 months after infection. A study in Nature found evidence of viral persistence in the gastrointestinal tracts of “rebound” patients, meaning patients who left the hospital testing negative but returned shortly after with a new positive test. Seventy-one percent of those patients were found to have actively replicating virus in stool samples. Despite the research, we do not yet have a diagnostic test to identify persistent infection in tissues other than the nasal passageways.

Who is researching viral persistence?

The Long Covid Research Initiative, a project by PolyBio led by Dr. Amy Proal, is focused on diagnosing viral persistence. ****Their methods include tissue biopsy to identify Covid and its proteins, autopsy and imaging studies to find deep tissue viral reservoirs, and identifying blood biomarkers of viral presence.

But Long Covid patients can’t wait. Acting on initial warning signs of viral persistence, the US National Institutes of Health will begin testing longer courses of the anti-viral Paxlovid for Long Covid starting in early 2023. If successful, this treatment could be rolled out to the public relatively quickly, as the drug is already approved by the FDA for use against acute Covid.

Until more treatments are available, Long Covid patients can trial at-home protocols to address viral persistence. Protocols to try include fasting to kill off infected cells, taking supplements shown to have antiviral properties, and boosting the innate immune system through probiotics.

Eureka will track your symptoms to help you test effectively, and use your data to share insights with other patients. All interventions should be done under supervision of a trained medical professional.

Additional reading

Here are some great resources to learn more about viral persistence:

What can you do about it?

While research is still ongoing, there are some treatments that, in theory, can target viral persistence, and have been showing promise in the community.

Fasting for Autophagy

Autophagy is the natural cycle of cellular die off and regrowth. Think of it like the body’s recycling system. Malfunctioning parts of cells are cleaned out and repurposed, and old cells in favor of new ones in a process known as cellular senescence.

Autophagy is thought to help with viral persistence by getting rid of cells that may be harboring viral reservoirs. It naturally occurs in the body on a daily basis, especially during sleep. Autophagy increases the longer the body goes without food. To induce additional autophagy, some people practice fasting. While long fasts can be difficult and is not advisable for severe Long Covid patients, time-restricted eating, also known as “intermittent fasting,” can induce similar benefits to multi-day fasts with less risk.

Learn more at Eureka's Fasting for Autophagy Plan page.


Long Covid patients should consider ways to support a healthy gut microbiome with both pre- and probiotics. One specific probiotic, LP299v, has been shown to help with post-Covid symptoms. Lactobacillus Plantarum 299v controls inflammation and improves vascular function in patients with Long Covid. Study participants showed improvement after 6 weeks of daily supplementation.

Learn more at Eureka's Probiotics Plan page.