Viral Persistance in Long Covid

One of the theories of Long Covid (LC) is viral persistence. This is when the SARS-CoV-2 virus, or particles of it, remain in the body long after recovery from the initial acute infection.

This first came to light with the discovery of local infection in the gut lining cells by Neureth et al - covered in my post "The Gut Microbiome and SARS-CoV-2". This was even in cases with negative PCR tests.

Then there was the preprint "SARS-CoV-2 infection and persistence throughout the human body and brain" where replicating SAR-CoV-2 virus was found in the eyes, nerves, heart and brain up to 230 days after infection. Read more in my post Persistent SARS-CoV-2 Infection in the Body and Brain .

Lee et al earlier this year released "Residual SARS-CoV-2 viral antigens detected in GI and hepatic tissues from five recovered patients with COVID-19". Here they reported the persistence of residual viral antigens for up to 180 days in gut and liver tissues of COVID-19 patients recovering from an acute Covid-19 infection.

In their new preprint "Persistence of residual SARS-CoV-2 viral antigen and RNA in tissues of patients with Long COVID-19" they have focused on the presence of such antigens in tissues from LC patients.

"We believe this is the first study to detect viral RNA and/or antigen in the tissues of patients with Long COVID, up to 426 days after the onset of COVID-19 symptoms".

They obtained samples of the appendix, skin, and breast in two patients who exhibited LC symptoms 175-426 days after a positive diagnosis of COVID-19. Using multiplex immunohistochemistry, they detected SARS-CoV-2 nucleocapsid protein in the appendix and breast supporting the persistence of residual viral particles in these tissues for more than a year after infection. They did not find any in the skin.

Figure 1 A,B = appendix, different stains C,D = breast , different stains. SARS-CoV-2 nucleocapsid protein shows up as green. CD68 are white blood cells.

Interestingly, in the breast, viral nucleocapsid protein was present only in the tumour-adjacent area, but not in the tumour itself - see below:

Figure 2 D Arrows = Virus outside of breast cells

They were also able to detect viral RNA in the appendix and breast tissue. This is suggestive of ongoing viral replication.

Having established the presence of residual virus within the tissues of the LC patients, the team then aimed to assess its significance for those with LC.

The gastrointestinal tract is a major viral shedding route, with high ACE2 receptor expression and residual viral RNA and/or antigen detectable throughout its tissues and bodily fluids. Thus the team concluded that, with the growing evidence of the viral persistence, the gastrointestinal tract might serve as a SARS-CoV-2 reservoir among recovering and Long COVID patients.

Overall, they reported on persistent SARS-CoV-2 lingering within tissues of patients with LC. These antigens found were potentially in the state of active replication.

To validate the teams findings future studies should recruit a larger cohort of patients from different populations and geographical regions.

What does all this growing evidence mean for long haulers?

Essentially researchers are proving time and time again that COVID-19 can be found hiding in the body somewhere.

There are other viruses are known to linger in parts of the body for months or even years, creating a "viral reservoir" in places where the immune system is not as likely to discover and destroy them. Examples include the Varicella virus which comes back as shingles, or Epstein Barr virus which can reactivate causing chronic symptoms or Multiple Sclerosis, or the Herpes virus causing cold sores.

And the evidence was already there. Scientists found evidence of the virus that causes Ebola in tissue and body fluids long after the initial infection. Some Ebola survivors suffer from chronic symptoms, and they appear to have waxing and waning immune responses against the virus, as if they were still infected. Recent research even suggests an outbreak of Ebola in West Africa originated with someone who was infected years earlier and had harbored the virus.

This theory of viral persistence would also explain why some people with long COVID start to feel better after receiving the COVID vaccines, because the shot would essentially boost their immune response against the lingering virus.

I do wonder when we will see a trial of Long Covid sufferers being given antivirals?


Persistence of residual SARS-CoV-2 viral antigen and RNA in tissues of patients with long COVID-19

SARS-CoV-2 infection and persistence throughout the human body and brain

Residual SARS-CoV-2 viral antigens detected in GI and hepatic tissues from five recovered patients with COVID-19

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