Persistent coronavirus can trigger COVID-19 symptoms
Persistent coronavirus can trigger COVID-19 symptoms

Persistent coronavirus can trigger COVID-19 symptoms

Most COVID-19 patients recover from their acute infection within two weeks, but parts of the virus do not always disappear from patients’ bodies immediately. Now a new one study, one of the largest focusing on inpatient COVID-19 patients, shows that some patients harbor these viral residues for weeks to months after the disappearance of their primary COVID-19 symptoms.

The study suggests that when the genetic material of the virus, called RNA, stays in the body for more than 14 days, patients may have worse disease outcomes, experience delirium, stay longer in hospital and have a higher risk of dying from COVID-19 compared with those who removed the virus quickly. The persistence of the virus can also play a role in prolonged COVID, the debilitating series of symptoms that can last for several months. Estimates suggest between 7.7 and 23 million people in the United States alone is now affected by prolonged COVID.

Without immunity to vaccination or a previous infection, SARS-CoV-2 – the virus that causes COVID-19 –replicates and spreads throughout the body and excreted through the nose, mouth and intestines. But for most infected people, virus levels in the body peak between three and six days after the initial infection, and the immune system cleans the pathogen within 10 days. That virus excretion after this period is generally not contagious.

Even after taking into account the severity of the disease, whether the patients were intubated or had underlying medical comorbidities, “there is something here that signals that patients who are persistently PCR-positive have poorer outcomes,” says Ayush Batraa neurologist at Northwestern University Feinberg School of Medicine who led the new study.

Batra’s study shows that patients who had prolonged outcomes during an acute infection risk more severe outcomes of COVID-19, says Timothy Henrich, a virologist and immunologist at the University of California, San Francisco, who was not involved in the new research. However, the study does not investigate whether this persistent virus is directly responsible for long-term COVID.

“There are several leading hypotheses out there about the cause of long-term COVID, including viral persistence, and it may be that there are several pathways at play, perhaps to some degree in a person,” says Linda Genga physician at Stanford Health Care who co-authored a newly opened post-acute COVID-19 syndrome clinic for the treatment of long-term COVID patients.

Persistent viruses cause worse COVID-19 results

Batra and his team began studying persistent coronavirus infections after observing that some patients returning to the hospital still tested positive for the virus four or five weeks after being diagnosed with the first infection.

For their new study, the team analyzed 2,518 COVID-19 patients admitted to the Northwestern Medicine Healthcare system between March and August 2020. They focused on PCR tests, which are considered the gold standardbecause such tests detect genetic material from the virus and therefore are very sensitive and less likely to return false negatives.

The team found that 42 percent of patients continued to test PCR-positive two weeks or longer after their initial diagnosis. After more than 90 days, 12 percent of the perennial crops still tested positive; one person tested positive 269 days after the initial infection.

Viral persistence has been noted before in previous smaller studies. Researchers showed that even patients without obvious COVID-19 symptoms housed SARS-CoV-2 for a period of time couple of months and Besides. In some immunocompromised patients, virus can not be cleared for a year. Four percent of COVID-19 patients in one trials of chronic COVID-19 infection at Stanford continued with secrete viral RNA in feces seven months after diagnosis. However, Batra’s study illustrates that a larger number of patients are taking longer to remove the virus than previously thought.

“Sustained RNA release would mean that there is still a reservoir of virus somewhere in the body,” says Michael VanElzakker, a neuroscientist affiliated with Massachusetts General Hospital, Harvard Medical School and Tufts University. Such reservoirs are thought to allow the virus to continue over a long period of time and may cause the immune system to have aberrant effects, perhaps causing prolonged COVID.

“Some patients, for various reasons, are unable to clear this reservoir, or their immune system reacts in some abnormal way, resulting in these persistent symptoms that have been termed prolonged COVID,” says Batra.

Yet many scientists do not believe that there is sufficient evidence yet to link the persistence of viral RNA with long-lasting COVID.

Sleeping virus

The list of human tissues where SARS-CoV-2 hides long after the first infection is growing. Studies have identified the virus, or genetic material from it, in patients’ intestines four months after the first infection, and inside the lung of a deceased donor more than one hundred days after recovery from COVID-19. A study that has not yet been peer reviewed also discovered the virus in appendix and breast tissue 175 and 462 days after coronavirus infections, respectively. And research from the US National Institutes of Health, which is also not peer reviewed yet detected SARS-CoV-2 RNA that persists at low levels across multiple tissues for more than seven months, even when it could not be detected in the blood.

“It is not surprising to find viruses that have been encountered over the course of a lifetime” that survive in human tissues, says Kei Sato, a virologist at the University of Tokyo. In fact, Sato’s work has shown that humans often accumulate viruses such as Epstein-Barr virus, varicella zoster virus (which causes chickenpox) and many herpes viruses in resting forms. These persistent viruses are typically present at low levels so that only extensive genetic sequencing can identify them.

This highlights how complicated it is to prove or disprove the link between persistent SARS-CoV-2 and long-lasting COVID. Shingles, e.g. occurs decades after a chickenpox infectionwhen the latent virus is reactivated under immune stress.

Likewise, lingering SARS-CoV-2 can cause long-term health problems. Henrich believes that when the virus is seen in deep tissues, it can potentially cause the immune system to switch to a dysregulated inflammatory condition. Such a condition is “probably evidence that the virus is capable of continuing and perhaps coming down into some sort of restless ceasefire with the body,” VanElzakker says.

Still, linking any long-term virus with long-term COVID will require extensive research. “We still do not know enough to draw strong conclusions about any of the current proposed mechanisms, but research is actively underway to answer these questions,” Geng said.

Remediation of persistent virus can cure long-lasting COVID

Both Geng and Henrich’s groups have reported preliminary case studies showing a improvement of prolonged COVID symptoms after patients were treated with Pfizer’s COVID-19 oral antiviral Paxlovid. Paxlovid prevents the virus from replicating, which is why some experts believe it can remove any long-lasting virus. However, both authors call for caution before assuming that Paxlovid will be safe, effective or adequate and thus a reliable cure for long-term COVID.

“There are some interesting hypotheses about how Paxlovid may be useful in the treatment of long-term COVID, but we need further studies and clinical trials before we can reach any conclusions,” says Geng.

It has the US Food and Drug Administration warned against off-label use of Paxlovid, which is not approved for long-term COVID treatment. The agency has given Paxlovid one emergency use permit for the treatment of mild to moderate COVID-19 in those at risk of developing serious illness, twice daily for five days shortly after a positive test.

“It would be important to consider the optimal duration of treatment [of Paxlovid] to ensure long-term and lasting results, ”says Geng.

President Joe Biden has chaired the Secretary of Health and Human Services to draw up a national action plan for long-term COVIDand the NIH has launched a multi-year study called RETURN to understand, prevent and treat long-term health effects related to COVID-19.

Meanwhile, vaccines not only continue to protect against serious illness, but there are also signs that they can prevent many long-term COVID symptoms. A new one study compared 1.5 million unvaccinated COVID-19 patients with 25,225 vaccinated patients with breakthrough infections, and it found that vaccines significantly reduced the risk of developing long-term COVID symptoms 28 days after an infection. The protective effect of vaccination became even greater 90 days after infection.

“Although a majority of people do not develop long-term COVID, it is certainly a risk and COVID does not stop after the first 10 days after becoming infected,” says Henrich. “For those who do not take COVID seriously, it can be landmark.”


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