You may have recently heard on the news about what is called the “restoration of Paxlovid”. This has happened to several high-profile individuals, including Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, and President Joe Biden.
The term may sound ominous, but Paxlovid’s rebound doesn’t seem dangerous, and it certainly isn’t a reason to skip a potentially life-saving antiviral treatment. Here’s what you need to know about restoring Paxlovid, especially if you have a weakened immune system.
Reinfection with COVID-19 vs Reinfection with COVID
First, let’s get one thing clear: having a relapse of COVID-19 is not the same as getting infected with COVID-19 a second time.
The U.S. Centers for Disease Control and Prevention (CDC) characterizes the COVID-19 rebound as a recurrence of symptoms or a new positive test for the virus after a negative result. This is reported to occur shortly after initial recovery.
In case of relapse, it is the same virus that causes symptoms or a positive test. It just hasn’t completely cleansed your body yet.
“It’s not clear why this happens — and it happens even in people who aren’t on antiviral therapy,” says infectious disease physician Amesh A. Adalya, MD, senior scientist at the Johns Hopkins Center for Health Security.
COVID-19 relapse is different from COVID-19 reinfection, in which someone destroys the virus and then becomes infected again (often months later). In this case, another strain of COVID-19 is causing the infection.
Cases of relapse after treatment with Paxlovid
Paxlovid treatment includes two different drugs packaged together: nirmatrelvir (two tablets) and ritonavir (one tablet). Nirmatrelvir stops the replication of the SARS-CoV-2 protein, and ritonavir interferes with the metabolism of nirmatrelvir in the liver and helps it stay in the body longer.
When you are prescribed Paxlovid, you will be asked to take three tablets twice a day for five days. (Learn more about how Paxlovid works.)
There are many more questions about Paxlovide and rebound cases. Ironically, the patients completed the five-day course and tested negative, but a few days later they tested positive and developed symptoms of COVID-19 again. (If you have a relapse of COVID-19, you are still contagious, and it is important to isolate to avoid infecting others.)
Experts suggest that Paxlovid may not completely rid the body of the virus in some people. Some pockets of viable virus may still exist and multiply after treatment is stopped. Meanwhile, since Paxlovid is administered shortly after the onset of symptoms, the body may not have the opportunity to develop an immune response during this time.
“For some people, these five days of treatment may not be enough to get rid of all the virus,” says Jeffrey D. Klausner, MD, MPH, Clinical Professor of Medicine, Population and Public Health Sciences at the Keck School of Medicine. University of Southern California. “A small amount of virus remains, below the detection limit of the test. Over time, this small amount of virus can increase in the absence of Paxlovid, leading to a new positive test result.”
In a study published in June 2022 in the journal Clinical infectious diseases, The investigators studied a cohort of 483 high-risk patients treated with Paxlovid. In four patients (0.8 percent), symptoms returned. These relapse symptoms were generally mild and all resolved without additional therapy directed at COVID-19.
One in four Paxlovid rebound patients had comorbidities known to complicate recovery from COVID-19.
Among the patients were:
- A 75-year-old man with coronary artery disease who developed cough and muscle pain 19 days after treatment.
- A 40-year-old obese woman with hypertension and kidney disease who felt tired and had a sore throat six days after treatment.
- A 69-year-old man with hypertension and obesity who developed a runny nose and cough 10 days after therapy.
- A 70-year-old man with prostate cancer, obesity, hypertension, and a history of high cholesterol who developed sinus congestion 10 days after treatment.
All four patients were fully vaccinated with three doses of the mRNA vaccine more than 90 days prior to exposure to COVID-19.
The one percent rebound rate in this study matches the results of the Pfizer clinical trial, but the study authors suspect that the actual rate may be higher. Based on discussions lead author Aditya Shah, MBBS, has since had with other doctors and patients, he believes “the actual rate could be as high as 5 to 10 percent,” he said. Scientific American.
Relapse of COVID-19 may be more common in untreated people. To better understand the trajectories of the virus and symptoms of COVID-19, another group of researchers analyzed a population of 568 people. raw participants in the preprint study in August 2022 (meaning it has not yet been peer-reviewed). They found that 12 percent had a viral rebound. Those who had a viral rebound were older than those who did not recover – an average of 54 years versus 47 years, respectively.
Overall, there are many unresolved questions about whether new variants of COVID-19 play a big role in the recovery of the virus. Paxlovid tests, for example, were carried out even before the era of Omicron.
To truly understand how often Paxlovid rebound occurs, it is necessary to define a more uniform definition of “rebound” across different studies. For example, if “rebound” is sometimes only classified as a recurrence of symptoms, and other times is classified as multiple negative tests followed by multiple positive tests, this can skew the data on how often “rebound” occurs. Without more answers, it’s hard for experts to make recommendations on how Paxlovid’s rebound can be avoided.
“It’s not clear what’s going on, so there’s no concrete way to prevent it,” says Dr. Adalya. “There are studies with extended treatments underway.”
There have also been reports of a relapse of COVID-19 occurring with the antiviral drug Molnupiravir.
In a June 2022 preliminary study of 13,644 patients, researchers found that rates of COVID-19 recurrence at 7 and 30 days after treatment with molnupiravir were 5.86 percent and 8.59 percent for COVID-19 infection and 3. 75 percent and 8.21 percent. percent for symptoms of COVID-19.
More research is needed to determine the natural course of infection with Omicron, how it is affected by antivirals, and how COVID-19 rebound differs between antivirals.
How serious are cases of Paxlovid recurrence?
People who experience rebound still tend to have positive results. Paxlovid is designed to prevent serious illness, hospitalization, and death—and it continues to do so even when relapses occur.
“According to the available data, the Paxlovid rebound was not dangerous,” says Dr. Klausner. “There are no reported, confirmed cases of hospitalization or death by rebound. Typically, people have a mild recurrence of symptoms or positive test results within a few days and then get better.”
Of course, since you are still contagious during this period, it is important to isolate yourself.
“The CDC recommends five days of isolation from the onset of symptoms and an additional five days of mask wearing,” says Dr. Klausner. “While some experts advise continuing isolation until the rapid test is negative and remains negative, this is not practical for most people. The five-day rule is a good compromise between individual needs and public health risks.”
Could Paxlovid rebound affect antiviral administration?
Future research may help determine if Paxlovid needs to be infused longer to prevent rebound, but at this point, experts see no change to Paxlovid’s prescribing guidelines.
“It will depend on whether the cause is determined and studies with extended dosing show promising results,” says Dr. Adalya.
Physicians sometimes prescribe an additional course of Paxlovid if a rebound occurs, but there is no data to show that Paxlovid should be taken again (and this is not recommended). Others have changed the dosing schedule to eliminate potential rebound.
“Some doctors have extended treatment from five to eight days by asking patients to change the way they take their medications,” says Dr. Klausner. “Instead of twice a day for five days, they recommend taking the medicine twice a day for the first two days and then daily for the next six days for a total of eight days. However, this drug has not been studied or approved for use by the FDA.”
Physicians can do this because the US Food and Drug Administration (FDA) regulates the sale and marketing of drugs, but not the practice of medicine.
What you should know about Paxlovide
Paxlovid’s main goal is to prevent severe illness, and it continues to do so even in those who experience a relapse of COVID-19. Paxlovid is given to people at high risk and is a life-saving medication so you should take it if your doctor prescribes it for you.
“The rebound from Paxlovid is not something that affects the benefit an immunocompromised person gets from Paxlovid,” says Dr. Adalya. “It’s still very effective in preventing what it was designed to do, which is severe disease.”
Paxlovid remains recommended for the early treatment of mild to moderate COVID-19 in those at high risk of progression to severe disease, in line with CDC health guidance.
If you have been prescribed Paxlovid, stay in touch with your healthcare provider about your symptoms and COVID-19 test results.
“Immunocompromised patients should be in close contact with their doctor,” says Dr. Klausner. “Some immunocompromised patients may benefit from longer therapy, a different treatment schedule, and retesting to document the infection.”
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