How The Covid-19 Virus Persists in the Body for Months

Reason 3: Hiding in the saliva to evade the immune system. And what it means for immunity.

Virus clearance differs between individuals. It is also one reason why some recover from infections more quickly than others. And the word recovery can be tricky, referring to either disappearance of clinical symptoms or virus elements, or both. So, this article will focus on virus clearance (i.e., being tested negative) rather than recovery.

Persistent Infection

Published studies report that positive diagnosis status for SARS-CoV-2, the causative agent of Covid-19, can last for months, despite being symptomless. This is a persistent infection, which is by no means novel.

“Persistent infections are characterized as those in which the virus is not cleared but remains in specific cells of infected individuals,” the Medical Microbiology textbook defined. “Persistent infections may involve stages of both silent and productive infection without rapidly killing or even producing excessive damage to host cells.

Viruses cause most cases of persistent infections. Examples include herpes simplex virus, HIV, measles virus, Epstein-bar virus, hepatitis B virus, etc. Inferring from them, scientists agree that no sole mechanism underpins how persistent infection works. The same applies to SARS-CoV-2 as well, and scientists have theorized at least five mechanisms to date.

Mechanism 1: Coexistence

In a China study printed in May, they documented a 47-year-old woman with mild Covid-19 symptoms. She no longer had symptoms after 2–3 weeks but retained a positive RT-PCR diagnosis status for over two months. The hospital quarantined her, for the precaution that symptomless people could still transmit the virus.

The fact that her symptoms did not relapse means that her immune system is not in a pro-inflammatory mode to stop the virus replication. In other words, the virus seems to be well-controlled by the immune system.

“The immune system of the patient and SARS-CoV-2 may have reached a state of balanced coexistence,” the study noted. “And the patient remains as an asymptomatic virus carrier without any clinical symptoms and imaging manifestations.”

Mechanism 2: Low Antibody Production

A study in Portugal, published in June, did diagnostic RT-PCR tests on 210 people, of whom 116 patients (55.2%) had two consecutive negative tests after ~25 days. The remaining 94 patients (44.8%) took a week longer to clear the virus than the other patients.

Why? The study authors then found that those with slower virus clearance had milder symptoms and lower antibody levels. An ineffective antibody immune response could, thus, lead to persistent SARS-CoV-2 infection.

Mechanism 3: Immune Evasion

An April study in China reported a 44-year-old man, free of medical comorbidities, who recovered after 11 days and tested negative on RT-PCR. But three days after clinical remission, a positive SARS-CoV-2 test reappeared in his throat swab and saliva, which then persisted for over a month. Antiviral therapy and traditional Chinese medicine failed to clear the virus.

Three days are too short for the incubation period of SARS-CoV-2 — i.e., a mean of 5–6 days — to establish a new infection. “Thus, we deduced that the reappearance of the viral RNA was a recrudescence, rather than a new infection.” The patient also produced antibodies against the virus, indicating that the immune responses cannot clear the virus.

Why? The authors believe that SARS-CoV-2 is evading the immune system by residing in an immune-privileged site — i.e., the saliva. “Particularly, an extremely high level of viral RNA was detected in saliva,” they discovered.

Immune-privileged sites are tissues that can tolerate foreign entities without eliciting an inflammatory response. The previous SARS-CoV is also capable of infecting the salivary gland. And cytomegalovirus can exploit the salivary gland to establish a persistent infection.

As follows, SARS-CoV-2 hiding in the saliva could be swallowed and re-enter the respiratory and digestive tracts. The host would then be tested positive for Covid-19 again. The virus-containing saliva also bears consequences as a hidden source of contagious droplets, the Chinese cautioned.

A review in the Journal of Dental Research, titled “Salivary Glands: Potential Reservoirs for COVID-19 Asymptomatic Infection,” also raised the issue of saliva as a hidden source of SARS-CoV-2. Salivary glands have much higher ACE2 expression than the lungs, their bioinformatics data revealed. And a cohort study found 91.7% of patients harbour live and infectious SARS-CoV-2 in their saliva. “This suggests that Covid-19 transmitted by asymptomatic infection may originate from infected saliva,” the review said.

Mechanism 4: Reactivation or Reinfection

There have been many cases in which discharged patients returned to the hospital with milder symptoms and positive Covid-19 status, which I detailed here. Current science agrees that it is more likely for Covid-19 to reactivate than reinfect. Reactivation means the same initial virus is replicating again (after lying dormant for a while), whereas reinfection means a new, different source of infection.

For example, a Switzerland study concludes: “Reinfection appears unlikely since Covid-19 infection rates were low in the region of our hospital and the trend of new infections declining at the time the patients were treated.”

“Few researchers think that this is actually a case of reinfection or an issue of accuracy in test kits,” Hwang Seung-sik, a professor of epidemiology at Seoul National University, agreed. “Many are looking at this more as a virus reactivation.” This is rather good news as reinfection would mean that the body‘s immunity cannot prevent a second infection, complicating vaccine design.

But this is not to say reinfection is not possible. If a different variant is sufficiently different to elicit a distinct immune response, then reinfection could happen, the professor added, which is no longer a persistent infection. Because persistent infection means that the initial virus is not completely cleared and, thus, persists in the host. Only persistent SARS-CoV-2 infection can reactivate.

Mechanism 5: Intermittent Viral Shedding

Another probable scenario is intermittent viral shedding, as a June study suggested, which would explain re-tested positive individuals who are symptomless and not contagious. But biological mechanisms for intermittent viral shedding are rather obscure in the literature. If the body sheds the virus periodically, the initial replicating virus (that later sheds) should be detected by the RT-PCR diagnostic test.

The Good and Bad of Covid-19 Persistence

A positive result from the RT-PCR test does not ascertain if one is contagious or not. The detected genetic material could just be non-infectious remnants or leftovers following clinical recovery.

Although such viral remnants could still trigger an immune response and, depending on the degree, could lead to post-viral repercussions. The Atlantic, for instance, reported that a few people had relapsing Covid-19 symptoms for months. Researchers think that this could be myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), a disease involving chronic symptoms such as fatigue, sleep and concentration problems, pain, and dizziness.

In contrast, other researchers think the virus remnants might help induce long-term immunity. A small subset of cells that the immune system can’t afford to destroy — such as neurons with weak regenerative capacity — could still retain the virus genetic material and transcribe it into proteins. These remnant viral proteins might keep the immune system alert, explained Diane E. Griffin, a distinguished professor at the John Hopkins Bloomberg School of Public Health. Persistent measles virus genes in the body, for example, might share a similar mechanism in inducing life-long immunity.

These diverse immune responses of how people deal with Covid-19 make vaccine design difficult. “The same viral particle won’t have the same effect in every person,” remarked Santosh Vardhana, an oncologist at Memorial Sloan Kettering Cancer Center in New York who is currently researching on Covid-19 immunology. That is also the reason why most vaccines do not confer universal immunity, he added.