The long COVID could be caused by the virus lingering in the body. Here’s what the science says

While most people survive and recover from COVID, for some people the symptoms can persist for months or years. When symptoms last for more than 12 weeks, the condition is known as long COVID.

Long COVID encompasses up to 200 different symptoms. To determine evidence-based treatments for these symptoms, we need to understand the causes. One factor that may be associated with long COVID is that the virus has not cleared completely from the body after the initial infection.

We know from other viruses that viral fragments can remain in different tissues for months or even years. This could be the case with SARS-CoV-2, the virus that causes COVID. Here’s what the science says so far.

Other viruses hide in the body

Herpes viruses (such as Epstein-Barr virus, which causes glandular fever), as well as HIV (human immunodeficiency virus) can exist in a “latency state” for life. This means that the virus hides in the cells and remains dormant.

HIV, in particular, can lie dormant in infected cells throughout the body. Even though it is inactive, it can still promote immune activation and inflammation.

Other viruses such as Zika, measles And Ebola have been found in the tissues of infected people months or years after the initial infection. This viral persistence can cause chronic disease.

Several studies have shown that COVID can also reactivate the Epstein-Barr virus, which has remained in the body in a latent state. Research shows that it has been related to fatigue and problems with thinking and reasoning people with long-term COVID.

How do we know that COVID stays in the body?

Several studies have identified SARS-CoV-2 genetic sequences (RNA) as well as SARS-CoV-2 proteins in tissue and stool (poop) samples months after infection.

These studies include several autopsy reports that found viral RNA and proteins in a variety of tissues of people who died up to seven months after infection. SARS-CoV-2 RNA was detected in at least half of the heart, lymph, eye, nerve, brain and lung tissue samples tested.

In those who survived, viral RNA was found four months after infection in intestinal tissue obtained by colonoscopy, when a thin tube is used to remove tissue from the large intestine. These patients had asymptomatic COVID and were PCR negative from nose and throat swabs at four months.

A 2022 study found SARS-CoV-2 in the stools of about half of participants during the first week after infection. At four months, there was no virus present in the respiratory tract but 12.7% of stool samples were RNA positive. Another 3.8% of faecal samples remained positive for RNA at seven months.

Initial studies have not consistently suggested a strong relationship between long-term SARS-CoV-2 detection and long COVID symptoms.

But more recently, the presence of SARS-CoV-2 RNA (or protein translated from RNA) in the blood and the intestinal tissue turned out increase the probability to develop long symptoms of COVID.

What impact might the delay in clearing the virus have on people with long COVID?

Delayed clearance of SARS-CoV-2 particles in different parts of the body could drive disease through several potential processes:

1) Inflammation. Continuous immune stimulation by viral proteins causes inflammation, tires our immune system, and alters the functioning of our immune cells over time.

We have shown previously immune dysfunction and inflammation persist for up to eight months in people with long COVID who initially had mild to moderate disease.

2) Activation of other dormant viruses. The continued immune response to persistent SARS-CoV-2 can cause reactivation of latent viruses.

Antibodies reactive to Epstein-Barr virus are elevated in people with long COVID suggesting Epstein-Barr virus reactivationprobably by activating the immune system.

It has recently been shown that other latent viruses, such as human endogenous retroviruses (HERV, ancient viruses that are now part of our DNA, like a genetic fossil), reactivate after infection. HERV proteins have been detected in blood cells and tissues of COVID patients.

These proteins could potentially lead to inflammatory processes in long COVIDs.

3) Antibodies made by fighting SARS-CoV-2 could become “self” reactive. These auto-antibodies (antibodies produced by our immune system that mistakenly target and attack our own body’s tissues or organs) can cross-react with host receptors or proteins and drive autoimmune disease.

It is important to note that recent studies have shown that the appearance of new autoimmune diseases (such as type 1 diabetes, inflammatory bowel disease and psoriasis) is significantly associated with infection with SARS-CoV-2 and a link between autoimmunity and long COVID is plausible.

This suggests that COVID not only has immediate health effects, but could also potentially trigger long-term changes in the immune system.

While the studies mentioned above provide initial evidence for the persistence of SARS-CoV-2 long after initial infection, further studies are needed to show a convincing link between the persisting virus and long COVID. This should include examination of viral RNA and proteins in blood and tissues in people who have had COVID for a long time, regardless of disease severity. And that must involve well-developed cohort studies that follow large groups of people internationally.

Several trials are in progress to assess whether treating long COVIDs with antivirals such as Paxlovid can reduce viral antigens and improve symptoms, although this remains experimental.