Does Paxlovid Prevent Long COVID? Experts Aren’t Sure
Key takeaways:
Paxlovid (nirmatrelvir / ritonavir) is an oral medication that can treat mild to moderate COVID-19 in people at high risk for developing severe symptoms.
Research is conflicting whether Paxlovid can lower the risk of developing long COVID. Some studies suggest it may help prevent it, while others say it doesn’t significantly help. More studies are needed to determine Paxlovid’s role in preventing long COVID.
Paxlovid is fairly well tolerated, typically only causing mild side effects. But it has many drug interactions, some of which can prevent you from being able to take it.
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Table of contents
Many health experts consider Paxlovid (nirmatrelvir / ritonavir) to be one of the most influential medications to be approved by the FDA in the recent past. This 5-day course of oral tablets can help lower the risk of hospitalization and death due to COVID-19 for people at high risk of developing severe illness.
We know that Paxlovid works well for an initial COVID infection. But how about when it comes to long COVID? Can Paxlovid lower the risk of developing long-term complications from the illness? Unfortunately, the answer’s not clear cut.
How does Paxlovid treat COVID?
Paxlovid is a combination of two antiviral medications: nirmatrelvir and ritonavir.
Nirmatrelvir does the brunt of the work when it comes to treating COVID. It stops the COVID virus from multiplying and spreading to other cells in the body. This gives your body’s immune system time to catch up and start killing the virus.
Ritonavir acts like a sidekick. It helps nirmatrelvir stick around in the body longer and at higher levels. This helps it fight COVID better.
Does Paxlovid prevent long COVID?
The evidence is conflicting about whether Paxlovid can help prevent long COVID. Some studies say yes, while others say no.
One study of over 35,000 people found that taking Paxlovid lowered the risk of developing long COVID by 26%. The people in the study had at least one risk factor for developing post-COVID complications, such as being over 60 years old, a history of diabetes, or a weakened immune system. All study participants who took Paxlovid started it within 5 days of first developing symptoms of or testing positive for COVID.
But another study of over 4,600 people found that Paxlovid didn’t significantly reduce the risk of developing long COVID. This study included people with and without risk factors for developing long COVID. But participants weren’t required to start Paxlovid within 5 days of first feeling symptoms. They could take part in the study as long as they took the medication within 30 days.
With conflicting findings, it is unclear whether Paxlovid can help prevent long COVID. However, both studies have limitations that we should keep in mind:
Neither study is a randomized controlled trial (the best type of study for determining cause and effect). This makes it hard to say if there’s a definite link between Paxlovid and preventing long COVID.
The first study only focused on people with existing risk factors for developing long COVID. This makes it hard to apply the results to a broader population, since not everyone has risk factors.
The second study didn’t require participants to take Paxlovid as it is recommended by the manufacturer and healthcare experts. We know the medication is most effective when started within 5 days of developing symptoms. This makes it difficult to interpret the study’s results, since not everyone took Paxlovid appropriately.
More studies are needed to fully determine Paxlovid’s role in preventing long COVID. Ideally, these studies should be better designed to determine cause and effect and be more applicable to the general population.
Paxlovid is still a first-choice COVID treatment for certain people. This is because it can help lower the risk of hospitalization and death due to COVID for those at high risk for severe illness. So it’s still well worth taking for many people, regardless of whether or not it can help prevent long COVID.
Who is Paxlovid recommended for?
Paxlovid is FDA approved for adults with mild to moderate COVID symptoms who are at high risk of developing severe illness. It’s also authorized for high-risk adolescents ages 12 years and older who weigh at least 88 lbs (40 kg).
You may have a higher risk of developing severe COVID if you:
Are 50 years of age or older
Have a weakened immune system
Take medications that weaken the immune system, such as prednisone
Have certain health conditions, such as chronic kidney disease, diabetes, or asthma
Are considered overweight or obese
Are pregnant or gave birth within the past 6 weeks (42 days)
Have a history of smoking or currently smoke
You should start taking Paxlovid within 5 days of first developing symptoms or getting a positive test. But keep in mind that a positive test isn’t required to qualify for the medication. Your healthcare provider or pharmacist can determine if you likely have COVID based on your symptoms and any recent exposures.
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Who shouldn’t take Paxlovid?
Paxlovid isn’t right for everyone. If you have a severe allergy to any ingredient in the medication, you shouldn’t take it. People with severe kidney or liver disease should also avoid it.
Paxlovid has a number of interactions to consider, as well. In some cases, you may need to take a different COVID treatment to avoid issues. Or your provider may have you temporarily stop your medication while you’re taking Paxlovid, if it’s appropriate.
Examples of severe Paxlovid interactions include:
Heart rhythm medications, such as amiodarone (Pacerone)
Some antipsychotics, such as lurasidone (Latuda)
Colchicine (Colcrys)
Alfuzosin (Uroxatral)
Certain migraine medications, such as eletriptan (Relpax)
These aren’t the only medications that interact with Paxlovid. It’s a good idea to share a complete medication list with your healthcare provider and pharmacist. This can help your healthcare team discover and manage or avoid potential interactions.
What are the risks of taking Paxlovid?
Paxlovid is generally well tolerated. But it does have some side effects to know about. Common Paxlovid side effects include:
A bad taste in the mouth (“Paxlovid mouth”)
Diarrhea
Headache
Temporary increase in blood pressure
Ritonavir, one of the components in Paxlovid, is known to cause liver damage. This serious side effect wasn’t seen in Paxlovid’s clinical trials. But the manufacturer warns about the possibility based on ritonavir’s risks.
Contact your healthcare provider right away if you develop symptoms of liver damage while taking Paxlovid. These include stomach pain or swelling, dark-colored urine, or yellowing of the skin or eyes (jaundice).
Does Paxlovid cause rebound COVID?
No. Paxlovid doesn’t cause rebound COVID (a return of symptoms).
Everyone’s immune system fights the COVID virus a little differently. For some people, this causes initial symptom improvement, followed by symptom worsening a few days later. This is common and is not a side effect of Paxlovid. In fact, rebound symptoms can happen even if you receive no COVID treatment at all.
In an interview with GoodRx Health, Christina Madison, PharmD, the founder and CEO of The Public Health Pharmacist, discussed COVID rebound and why it happens.
“COVID-19 rebound symptoms have occurred in both treated and untreated individuals,” said Madison. “The rebound effects that have been experienced by [people] who have taken Paxlovid seem to be based on how the body’s immune system responds to the infection, the ability of the medication to get to affected tissues, and viral reservoirs — and [it] is not considered a side effect of the medication.”
The bottom line
Paxlovid (nirmatrelvir / ritonavir) is an oral COVID-19 treatment. Research is conflicting about whether Paxlovid can help lower the risk of developing long COVID. More studies are needed to provide a conclusive, accurate answer. For Paxlovid to be most effective, you should start it within 5 days of first feeling symptoms or having a positive COVID test result.
Paxlovid is recommended for adults with mild to moderate COVID symptoms who have a high risk of developing severe illness. It’s also recommended for high-risk adolescents ages 12 and older who weigh at least 88 lbs. Paxlovid is generally well tolerated, but has a number of drug interactions to consider before taking it.
Why trust our experts?
References
Centers for Disease Control and Prevention. (2023). Factors that affect your risk of getting very sick from COVID-19.
Centers for Disease Control and Prevention. (2023). People with certain medical conditions.
Durstenfeld, M. S., et al. (2024). Association of nirmatrelvir for acute SARS-CoV-2 infection with subsequent Long COVID symptoms in an observational cohort study. Journal of Medical Virology.
National Institutes of Health. (2023). What is long COVID?
NIH COVID-19 Treatment Guidelines. (2023). Therapeutic management of nonhospitalized adults with COVID-19.
Pfizer Laboratories Div Pfizer Inc. (2023). Paxlovid- nirmatrelvir and ritonavir [package insert].
U.S. Food and Drug Administration. (2022). Coronavirus (COVID-19) Update: FDA authorizes pharmacists to prescribe Paxlovid with certain limitations.
Wong. K. W. H., et al. (2023). Risk of acute liver injury following the nirmatrelvir/ritonavir use. Liver International.
Xie, Y., et al. (2023). Association of treatment with nirmatrelvir and the risk of post–COVID-19 condition. Journal of the American Medical Association Internal Medicine.
