Most COVID-19 patients recover from their acute infectionwithin two weeks, but parts of the virus do not always disappear from the patient's body immediately. now a new oneStudy, one of the largest, focused on hospitalized patients with COVID-19, showsthat some patients harbor this residual virus for weeks or months after their primary symptoms of COVID-19 have resolved.
The study suggests that when the virus's genetic material, called RNA, remains in the body for more than 14 days, patients experience worse disease outcomes, experience delirium, stay longer in hospital and are at increased risk of dying from COVID. 19 compared to those who cleared the virus quickly. The persistence of the virus may also play a role in long-term COVID, the series of debilitating symptoms that can last for months.
Without immunity from a vaccine or previous infection, SARS-CoV-2, the virus that causes COVID-19,replicated and disseminatedthrough the body and is eliminated through the nose, mouth, and intestines. But for most people who are infectedVirus levels in the body peak three to six days after the initial infection., and the immune system eliminates the pathogen in 10 days. HeVirus shedding after this timeit is generally not contagious.
Even after accounting for disease severity, whether patients were intubated or had underlying medical comorbidities, "there is something here to suggest that patients who are persistently PCR positive have worse outcomes," he says.Ayush Batra, a neurologist at Northwestern University Feinberg School of Medicine who led the new study.
Batra's study shows that patients who had prolonged shedding during an acute infection are at risk of more severe consequences from COVID-19, he 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 examine whether this stubborn virus is directly responsible for the long duration of COVID.
"There are several leading hypotheses about the cause of prolonged COVID, including the persistence of the virus, and it may be that multiple pathways are at play, perhaps to different degrees in each individual," he says.cute gene, a Stanford Health Care physician who co-directs a newly opened post-acute COVID-19 syndrome clinic to treat patients with long-term COVID-19 disease.
Persistent virus causes worse COVID-19 outcomes
Batra and his team began investigating ongoing coronavirus infections after noticing that some patients who returned to the hospital were still testing positive for the virus four to five weeks after the initial infection was diagnosed.
For their new study, the team analyzed 2,518 COVID-19 patients hospitalized at the Northwestern Medicine healthcare system between March and August 2020. They focused on PCR testing.is considered the gold standard, as such tests detect genetic material from the virus and are therefore highly sensitive and less likely to give false negative results.
The team found that 42 percent of patients continued to test positive by PCR two weeks or more after their initial diagnosis. After more than 90 days, 12 percent of the lingering droppings still tested positive; one person tested positive 269 days after the original infection.
Viral persistence has been observed in earlier, smaller studies. The researchers showed that even patients without obvious symptoms of COVID-19 carried SARS-CoV-2 for aa few monthsYoutside. In some immunocompromised patients, the viruscannot be deleted for one year. Four percent of COVID-19 patients in aChronic COVID-19 Infection Study at Stanfordfurtherexcrete viral RNA in feces seven months laterDiagnosis. However, Batra's study shows that more patients are taking longer to clear the virus than previously thought.
"Persistent RNA shedding would mean that there is still a virus reservoir somewhere in the body," he says.Michael Van Elzakker, a neuroscientist affiliated with Massachusetts General Hospital, Harvard Medical School, and Tufts University. SimilarReservoirs are thought to allow the virus to persistover a long period of time and could cause the immune system to act abnormally, possibly leading to prolonged COVID.
"Some patients are unable to clear this reservoir for various reasons, or their immune system responds abnormally, resulting in these persistent symptoms called long-term COVID," Batra says.
Still, many scientists believe that there is not yet enough evidence to link persistent viral RNA to long-term COVID.
Hidden viruses
The list of human tissues in which SARS-CoV-2 lurks long after initial infection is growing. Studies have identified the virus or its genetic materialintestines of patientsfour months after initial infection andinside the lungsfrom a deceased donor more than one hundred days after recovering from COVID-19. A study that has not yet been peer-reviewed also detected the virus in theAppendix and breast tissue175 and 462 days after coronavirus infections. And research from the US National Institutes of Health, which has not yet been peer-reviewedSARS-CoV-2 RNA detected that persists at low levelsacross multiple tissues for more than seven months, even if undetectable in blood.
"It's not surprising to find viruses that you encounter throughout your life" surviving in human tissue, he says.kei sato, virologist at the University of Tokyo. In fact, Sato's work has shown that people commonly hoard viruses such as the Epstein-Barr virus, the varicella-zoster virus (which causes chickenpox), and many herpes viruses.latent forms.These persistent viruses are often present in low concentrations and can therefore only be identified by extensive genetic sequencing.
This shows how complicated it is to prove or disprove the link between persistent SARS-CoV-2 and long-term COVID. shingles for exampleoccurs decades after chickenpox infection, when the latent virus is reactivated during immunological stress.
Likewise, prolonged SARS-CoV-2 could cause long-term health problems. Henrich believes that if the virus is seeded into deep tissue, it can cause the immune system to build up in adysregulated inflammatory state. Such a condition is "probably evidence that the virus is able to survive and perhaps enter into some sort of uncomfortable truce with the body," says VanElzakker.
However, linking an ongoing virus to prolonged COVID requires extensive studies. "We still don't know enough to draw meaningful conclusions about the currently proposed mechanisms, but research is underway to answer these questions," says Geng.
Removing persistent viruses could cure COVID for a long time
BothGengYhenrich's groups preliminary case studies have been reported showing aLong-term improvement in COVID-19 symptoms after patients were treated with Pfizer's oral antiviral drug for COVID-19, Paxlovid. Paxlovid prevents the virus from replicating, so some experts believe that it can kill any remaining virus. However, both authors recommend caution before assuming that Paxlovid will be safe, effective, or sufficient, and therefore a reliable cure for long-term COVID.
"There are some interesting hypotheses about how Paxlovid could be useful in the treatment of long-term COVID, but we need more research and clinical trials before we can draw any conclusions," says Geng.
US Food and Drug Administration HatWarned against off-label uses of Paxlovid, which is not approved for the long-term treatment of COVID. The agency gave Paxlovid oneEmergency authorization to treat mild to moderate COVID-19 in people at risk of developing severe illness, twice daily for five days shortly after testing positive.
"It would be important to consider the optimal duration of [Paxlovid] treatment to ensure sustainable long-term results," says Geng.
Meanwhile, vaccines not only continue to protect against serious disease, but there is evidence that they can prevent many long-standing COVID symptoms. new oneThe study compared 1.5 million unvaccinated COVID-19 patients with 25,225 vaccinated patients with breakthrough infections, and vaccines were found to significantly reduce the risk of developing prolonged COVID symptoms 28 days after infection. The protective effect of vaccination became even greater 90 days after infection.
"Although most people don't develop COVID long-term, it's certainly a risk, and COVID doesn't stop after the first 10 days of infection," Henrich says. "For those who don't take COVID seriously, it can be life-changing."