It is becoming harder to avoid infection, and reinfection, from the coronavirus with each variant that emerges. Omicron offshoots like the latest one, the XBB.1.5 subvariant, are better at dodging antibodies. But COVID cases also seem to be growing milder, either because new variants are less likely to go deep into the lungs or because most people have been vaccinated, exposed or both.
Which raises the question: Do mild cases of COVID warrant treatment with an antiviral medication like Paxlovid?
In many cases, they do. Paxlovid is known to reduce the severity of illness and even lower the risk of developing long-term symptoms such as chronic fatigue, muscle pain, kidney disease, heart disease, blood clotting problems and neurocognitive impairments. Research has shown that it can offer these benefits for both vaccinated and unvaccinated people, those who are experiencing their first infection and those who have had a reinfection.
Paxlovid’s ability to lower the odds of hospitalization and death is well documented. Studies conducted before the drug was authorized in December 2021 showed that Paxlovid reduced these severe outcomes by up to 89% in unvaccinated people. While data from last year was slightly less impressive in vaccinated people, Paxlovid still decreased the odds of hospitalization and death by about 57%.
Paxlovid stops the coronavirus from replicating in cells. Scientists hypothesize that by reducing the viral load in the body quickly, Paxlovid hinders many problems linked to severe outcomes and long-lasting symptoms, like damage to blood vessels, widespread inflammation and overactivation of the immune system.
In a study published online in November and currently undergoing peer review, researchers found that among patients in the Veterans Health Administration system who had at least one risk factor qualifying them for antiviral treatment, those who took Paxlovid within five days of testing positive were 26% less likely to develop long COVID symptoms. Yet only about 15% of patients eligible for the drug took it. Other studies have suggested an even lower uptake.
Many experts agree that more people should be taking Paxlovid and that the treatment should be considered even for mild cases of COVID-19.
“A drug that you don’t take surely can’t prevent long COVID or reduce your likelihood of serious illness, hospitalization or death,” said Michael Osterholm, a public health researcher and the director of the Center for Infectious Disease Research and Policy at the University of Minnesota.
“The threshold for giving Paxlovid should be lower and more people should be getting it, because it’s really not harmful,” said Dr. Peter Chin-Hong, an infectious disease specialist at the University of California, San Francisco.
All adults older than 65 are eligible for the drug, as are adults and children 12 years and older who weigh at least 88 pounds and have one or more risk factors for severe COVID. People in these categories should talk to their doctor about taking Paxlovid if they test positive. The antiviral treatment is only given if a prescription can be filled within the first five days of symptom onset. In particular, studies show that adults older than 65 benefit the most from taking Paxlovid. Their age puts them at higher risk for poor outcomes regardless of whether they have other medical conditions, Chin-Hong said.
The evidence is less clear on whether Paxlovid is worth taking for people younger than 65 who are not immunocompromised and do not have medical conditions like cancer, chronic lung disease, diabetes or many others.
“It is a personal decision between the person who’s affected and their provider whether to take Paxlovid or not,” said Dr. Ziyad Al-Aly, a clinical public health researcher at Washington University in St. Louis and chief of research at the Veterans Affairs St. Louis Healthcare System. When a younger colleague recently had COVID, for instance, Al-Aly, who led the November study on long COVID, recommended that the person take the antiviral because it might still provide some of the same benefit against long-term symptoms.
Many doctors aren’t prescribing Paxlovid. And patients who do have access to the drug are refusing it.
“It is really baffling,” Al-Aly said. “But that’s what’s happening in the U.S.: Paxlovid is being remarkably underutilized.”
The treatment, which has been available for more than a year and is provided free by the federal government, has been plagued with public relations problems from the beginning.
For the first few months after it received emergency use authorization from the Food and Drug Administration, Paxlovid supplies were hard to find. Then, patients who took the drug began reporting a bitter or metallic taste that stuck with them throughout the treatment. Several high-profile cases of Paxlovid rebound, or the recurrence of COVID symptoms, also led to the speculation that this unwanted side effect was fairly common.
“There have now been several studies, and there’s such good information that there’s very little difference in the rate of rebounds among those who take Paxlovid and those who don’t. Yet that myth continues,” Osterholm said.
Who should get the antiviral treatment has also remained a source of confusion for both patients and health care providers, Osterholm said. Because the drug is provided under an emergency use authorization by the FDA, doctors don’t typically prescribe it outside the stated eligibility criteria. (Prescribers tend to be more flexible with a fully approved drug. Some approved medicines can be prescribed or refilled early if you are going on vacation, for instance, but many people traveling abroad, including Osterholm, have found it difficult to get hold of Paxlovid in advance.)
Another source of confusion is interactions that Paxlovid can have with many drugs, including statins, beta blockers, blood thinners, antipsychotic medicines, seizure medicines, certain migraine medicines and hormonal birth control. It is likely that the long list of potential interactions puts many people off. But a doctor can help patients take Paxlovid safely and avoid side effects in several cases, Osterholm said. For example, patients can stop taking statins while on Paxlovid, he said, and that is “not going to have a material impact on your health.”
Several experts said they knew of cases in which primary care providers dissuaded patients from taking Paxlovid because the doctor thought that the patient either did not qualify or did not need the treatment. Many may be under the false impression that you can take Paxlovid only if you have severe disease, Chin-Hong said, when, in fact, the drug is for anyone at risk of such disease.
In July, the FDA revised Paxlovid’s emergency use authorization so that pharmacists could prescribe the drug. But that has not had a significant impact on Paxlovid use, Chin-Hong said.
The problem is about to become much worse, Chin-Hong said. The U.S. government bought millions of Paxlovid pills at about $530 per course, a discount that drugmaker Pfizer gave it for purchasing in bulk. But government support for the medication is expected to run out in the middle of this year. When the drug enters the private insurance market, Pfizer could increase the price, making it inaccessible for the people at highest risk of severe COVID and the least able to afford treatment: seniors and the uninsured.
To improve access and uptake of the drug, Chin-Hong said, “we’re going to need systemic changes.”
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