Most COVID-19 patients recover from their acute infection within two weeks, but some pieces of the virus may take time to clear from the body. A new study, one of the largest with 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 virus’s genetic material, called RNA, persists in the body for more than 14 days, patients may face more serious consequences, suffer from delirium, stay longer in the hospital and have a higher risk of dying from COVID. -19. 19 compared to those who cleared the virus faster. The persistence of the virus can also play a role in prolonged COVID, that is, when symptoms can last for months. It is estimated that between 7.7 and 23 million people in the United States alone are affected by Long COVID today.
In the absence of immunity from previous vaccination or infection, SARS-CoV-2, the virus that causes COVID-19, replicates and spreads throughout the body and is excreted through the nose, mouth, and digestive system. But for most infected people, virus levels in the body peak three to six days after infection, and the immune system clears the pathogen within ten days. In general, the virus excreted 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 suggest that patients who continue to test positive on PCR tests suffer more from the disease,” says Ayush Batra, a neurologist. . at Northwestern University Feinberg School of Medicine, who led the new study.
Batra’s study shows that patients who shed virus longer during an acute infection are at risk of more severe consequences from COVID-19, according to Timothy Henrich, a virologist and immunologist at the University of California, San Francisco, who did not participate in the study. the new studio. But this one does not seek to know if this persistent virus is directly responsible for the long COVID.
“There are many important hypotheses about the cause of prolonged COVID and, in particular, viral persistence. There can be multiple processes involved, perhaps to varying degrees in the same person,” says Linda Geng, a physician at Stanford Health Care, who co-directs a specialty clinic recently opened to treat people with prolonged COVID.
THE PERSISTENCE OF THE VIRUS CAUSES THE MOST SERIOUS CAUSE OF COVID-19
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 to five weeks after the infection was initially diagnosed.
For their new study, the team looked at 2,518 patients hospitalized in the Northwestern Medicine health care system between March and August 2020. They focused on PCR tests, which are considered the gold standard as they detect genetic material from the virus. and, therefore, they are 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 initial diagnosis. After more than 90 days, 12% of people who were still shedding the virus were still testing positive; one person even tested positive 269 days after initial infection.
Viral persistence has already been observed in earlier, smaller studies. The researchers showed that even patients without obvious symptoms of COVID-19 carried SARS-CoV-2 for a few months or even longer. In some immunocompromised patients, the virus may not be cleared for up to a year. In a chronic COVID-19 infection trial at Stanford, 4% of patients continued to excrete viral RNA in stool seven months after diagnosis. However, Batra’s study shows that more patients are taking longer than previously thought to clear the virus.
“Persistent RNA shedding would mean 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 would allow the virus to persist for a long period of time and thus could trigger an abnormal reaction from the immune system, which could be the cause of prolonged COVID.
“Some patients, for various reasons, are not able to clear this reservoir, or their immune system reacts abnormally, resulting in persistent symptoms that are called prolonged COVID,” says Batra.
Still, many scientists do not believe there is enough evidence to link viral RNA persistence to prolonged 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 the intestines of patients four months after initial infection and within the lung of a donor who died more than 100 days after recovering from COVID-19. A yet-to-be-approved study also detected the virus in appendix and breast tissue 175 and 462 days after infections, respectively. Finally, a study by the United States National Institutes of Health, which has not yet been approved, detected the persistence of SARS-CoV-2 RNA at low levels in various tissues for more than seven months, despite the fact that it was undetectable in the blood. .
“It’s not surprising to find viruses found during life” surviving in body tissues, says Kei Sato, a virologist at the University of Tokyo. In fact, 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 in latent 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 prolonged COVID. Shingles, for example, occurs decades after a chickenpox infection, when the latent virus reactivates due to immune stress.
Likewise, the persistence of SARS-CoV-2 could lead to long-term health problems. According to Henrich, when the virus implants itself in deep tissue, it can drive the immune system into an inflammatory reaction out of control. Such a state is “probably evidence that the virus can persist, and perhaps even establish a kind of uneasy truce with the body,” says VanElzakker.
However, in-depth studies will be needed to link a persistent virus with prolonged COVID. “We don’t yet know enough to draw strong conclusions about any of the currently proposed mechanisms, but active research is underway to answer these questions,” says Geng.
ELIMINATE THE PERSISTENT VIRUS TO CURE THE LONG COVID?
Both Geng’s and Henrich’s groups reported preliminary case studies showing improvement in long-term COVID symptoms when patients were treated with Pfizer’s antiviral drug Paxlovid for COVID-19. Paxlovid prevents the virus from replicating, so some experts believe it can kill any lingering viruses. But both author and author urge caution and not too quickly assume that Paxlovid will be safe enough, effective, or even sufficient to be a reliable cure for prolonged COVID.
“Some hypotheses are interesting regarding how Paxlovid might be useful in the treatment of prolonged COVID, but we would need more research and clinical trials before drawing any conclusions,” says Geng.
The US Food and Drug Administration has warned against off-label uses of Paxlovid, which is not approved for the treatment of long-term COVID. The agency authorized emergency use of Paxlovid to treat mild to moderate COVID-19 in people who are at risk of developing severe illness, twice a day for five days shortly after testing positive.
“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 directed his Secretary of Health and Human Services to create a national action plan on COVID-19, and the National Institutes of Health has launched a multi-year study called RECOVER to understand, prevent, and treat COVID-19. COVID-19. Long-term health effects related to COVID-19.
In the meantime, not only do vaccines continue to protect against serious illness, but emerging evidence indicates they can also prevent many symptoms of prolonged COVID. A new study compared 1.5 million unvaccinated COVID-19 patients with 25,225 vaccinated patients who had infections despite being vaccinated. It found that the vaccines significantly reduced the risk of developing COVID symptoms twenty-eight days after an infection. The protective effect of vaccination was even greater ninety days after infection.
“Even though most people don’t develop COVID for very long, it’s a real risk, and COVID doesn’t stop after the first 10 days of infection,” says Henrich. “For those who don’t take COVID seriously enough, it can really change their lives. »
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