Most patients with COVID-19 are recovering from their acute infection within two weeks, but some virus fragments may take time to clear from the body. A new studyone of the largest involving people hospitalized with COVID-19, shows that some patients may continue to carry these viral residues for weeks or even months after their primary symptoms have disappeared.
The study suggests that when the genetic material of the virus, called RNA, persists in the body for more than fourteen days, patients may face more serious consequences, suffer from delirium, stay in hospital longer and have a higher risk of dying from COVID-19 compared to those who cleared the virus faster. Virus persistence may also play a role in long COVIDs, that is, when symptoms can last for months. According to estimates, in the United States alone, between 7.7 and 23 million peopleare today affected by the long COVID.
In the absence of immunity from vaccination or previous infection, SARS-CoV-2, the virus that causes COVID-19, reproduces and spreads throughout the body and is excreted through the nose, mouth and digestive system. But for most people infected, levels of virus in the body reach their maximum between three and six days after contamination, and the immune system eliminates the pathogen within ten days. In fgeneral, the virus shed after this period is no longer contagious.
Even taking into account the severity of the disease, and whether the patients required intubation or had underlying medical comorbidities, “there is something to indicate that patients who continue to be positive on PCR tests suffer more from the disease” , declares Ayush Batraa neurologist at Northwestern University Feinberg School of Medicine, who led the new study.
Batra’s study shows patients who shed virus for longer during acute infection are at risk of more severe consequences from COVID-19, says Timothy Henrich, a virologist and immunologist at the University of California, San Francisco, who was not involved in the new study. But this one does not seek to know if this persistent virus is directly responsible for the long COVID.
“Many major hypotheses exist as to the cause of long COVID, and in particular viral persistence. It may be that several processes come into play, perhaps to different degrees in the same person, ”explains Linda Genga doctor at Stanford Health Care who co-runs a recently opened specialty clinic to treat people with long COVID.
VIRUS PERSISTENCE CAUSES MORE SEVERE COVID-19
Batra and his team began studying persistent coronavirus infections after observing that some patients returning to hospital still tested positive for the virus four or five weeks after the infection was initially diagnosed.
For their new study, the team analyzed 2,518 patients hospitalized in the Northwestern Medicine healthcare system between March and August 2020. They focused on PCR testing, which is considered as the absolute reference since they detect the genetic material of the virus, and are therefore very sensitive and less likely to give false negatives.
The team found that 42% of patients continued to have a positive PCR test two weeks or more after the initial diagnosis. After more than 90 days, 12% of people who were still shedding virus were still positive; one person even tested positive 269 days after the initial infection.
Viral persistence has already been observed in previous smaller studies. Researchers have shown that even patients without obvious symptoms of COVID-19 carried SARS-CoV-2 for some monthseven plus. In some immunocompromised patients, the virus can not be eliminated for one year. In the framework of of a trial on chronic infection by COVID-19 at Stanford, 4% of patients continued to excrete viral RNA in the stool seven months after diagnosis. However, Batra’s study shows that more patients take longer to clear the virus than previously thought.
“Persistent shedding of RNA would mean that there is still a reservoir of virus somewhere in the body,” explains Michael VanElzakkera neuroscientist affiliated with Massachusetts General Hospital, Harvard Medical School, and Tufts University. Such reservoirs would allow the virus to persist over a long period and could thus trigger an abnormal reaction of the immune system, which could be the cause of long COVID.
“Some patients, for various reasons, are not able to eliminate this reservoir, or their immune system reacts abnormally, resulting in persistent symptoms that are called long COVID,” says Batra.
Yet many scientists don’t think enough evidence exists to link viral RNA persistence to long COVID.
SLEEPING VIRUSES
The list of body tissues in which SARS-CoV-2 hides long after initial infection is growing. Studies have identified the virus, or its genetic material, in patient intestines four months after the initial infection, and inside the lung from a donor who died more than 100 days after recovering from COVID-19. A study that has not yet been approved has also detected virus in appendix and breast tissues respectively 175 and 462 days after infections. Finally, a study from the United States National Institutes of Health, which has not yet been approved, has detected persistence of SARS-CoV-2 RNA at low levels in several tissues for more than seven months, even though it was undetectable in the blood.
“It is not surprising to find viruses encountered in life” that survive in body tissues, says Kei Sato, a virologist at the University of Tokyo. Indeed, Sato’s work has shown that humans frequently accumulate viruses such as Epstein-Barr virus, or varicella-zoster virus (which causes chickenpox) and many herpesviruses under dormant forms. These persistent viruses are usually present at low levels, so only extensive genetic sequencing can identify them.
This shows how complicated it is to prove or disprove the association between persistent SARS-CoV-2 and long COVID. Shingles, for example, occurs decades after a chickenpox infectionwhen the latent virus is reactivated due to immune stress.
Likewise, the persistence of SARS-CoV-2 could lead to long-term health problems. According to Henrich, when the virus is implanted in deep tissues, it can tip the immune system into an uncontrolled inflammatory reaction. Such a state is “probably evidence that the virus is able to persist, and perhaps even settle into some kind of precarious truce with the body,” VanElzakker says.
Nevertheless, extensive studies will be needed to link a persistent virus to a long COVID. “We still don’t know enough to draw firm conclusions about either of the currently proposed mechanisms, but active research is being conducted to answer these questions,” says Geng.
REMOVE PERSISTENT VIRUS TO CURE LONG COVID?
The groups of Geng and of Henrich both reported preliminary case studies showing improvement in long COVID symptoms when patients were treated with the antiviral Paxlovid against Pfizer’s COVID-19. Paxlovid prevents the virus from replicating, which is why some experts believe it can eliminate any lingering virus. But both the author and author urge caution and not assume too quickly that Paxlovid will be safe enough, effective, or even enough to be a reliable cure for long COVID.
“There are a few interesting hypotheses about how Paxlovid might be useful in the treatment of long COVID, but we would need more research and clinical trials before drawing any conclusions,” Geng says.
The United States Food and Drug Administration cautioned against misuse Paxlovid, which is not approved for the treatment of long COVID. The organization gave an emergency use authorization for Paxlovid to treat mild to moderate COVID-19 in people at risk of severe disease, twice daily for five days soon after a positive test.
“It would be important to think about the optimal duration of treatment [du Paxlovid] to ensure long-term and sustainable results,” says Geng.
President Joe Biden has asked his Secretary of Health and Human Services to create a national action plan on COVID-19and the National Institutes of Health launched a multi-year study called RECOVER to understand, prevent and treat the long-term health effects of COVID-19.
In the meantime, vaccines not only continue to protect against serious disease, but emerging evidence indicates that they can also prevent many symptoms of long COVID. A new study compared 1.5 million unvaccinated patients with COVID-19 to 25,225 vaccinated patients with infections despite being vaccinated. She found that vaccines significantly reduced the risk of developing symptoms of COVID long twenty-eight days after an infection. The protective effect of vaccination was even greater ninety days after infection.
“While the majority of people don’t develop long COVID, it’s a real risk, and COVID doesn’t stop after the first ten days of infection,” Henrich says. “For those who don’t take COVID seriously enough, it can really change their lives. »