The Power of Paxlovid

"The underuse of Covid treatments is leading to many needless deaths.

A worrisome pattern has emerged with Paxlovid and other drugs that reduce the severity of Covid: Many people who would benefit most are not receiving the treatments, likely causing hundreds of unnecessary deaths every day in the U.S.

There seem to be two main explanations for the drugs’ underuse. The first is that the public discussion of them has tended to focus on caveats and concerns, rather than on the overwhelming evidence that they reduce the risk of hospitalization and death. The second explanation is that many Americans, especially Republicans, still do not take Covid seriously.

Today’s newsletter will dig into both issues.

“A large chunk of deaths are preventable right now with Paxlovid alone,” Dr. Ashish Jha, the White House Covid response coordinator, told me. He predicted that if every American 50 and above with Covid received a course of either Paxlovid or a treatment known as monoclonal antibodies, daily deaths might fall to about 50 per day, from about 400 per day in recent months.

Dr. Rebecca Wang, an infectious disease specialist at Dartmouth Hitchcock Medical Center, has said: “Never really in recent history for a respiratory virus can I think of an anti-viral medication being as effective, demonstrated in scientific literature, as what Paxlovid has shown.”

Dr. Robert Wachter, the chair of the medicine department at the University of California, San Francisco, told me that he thought the underuse of Paxlovid was already associated with thousands of preventable deaths in the U.S. “The public doesn’t seem to understand that the evidence around hospitalization and deaths is really powerful,” Wachter said.

Bad-news bias

By now, you have surely heard about the downsides and shortcomings of Paxlovid.

The drug can produce a metallic taste in the mouth. (One member of my family described it as among the worst tastes she had ever experienced.) Some research has also found that the drug might not cause a statistically significant reduction in hospitalization among younger adults. Most prominently, people who take Paxlovid can endure “rebound” Covid — as both President Biden and Jill Biden did — in which symptoms return after the five-day course of pills has ended.

All of this is true. It also does not change the big picture. Covid is a deadly virus, especially for older people, and Paxlovid reduces Covid’s severity. It does so by inhibiting the virus’s replication inside the human body, the same process that has made H.I.V. treatments so effective.

With Paxlovid, both randomized trials and data from electronic health records have pointed to its effectiveness. Some research finds an effect across all age groups, while other research finds one only among older patients. But that is not surprising. The Covid death rate for people under 50 is already so close to zero that reducing it in a statistically significant way is difficult.

“I think almost everybody benefits from Paxlovid,” Jha said. “For some people, the benefit is tiny. For others, the benefit is massive.” (People who can’t take Paxlovid because it interacts dangerously with another drug they’re taking can usually take monoclonal antibodies.)

A recent analysis of about 568,000 patients by Epic Research found that 0.016 percent of Covid patients over 50 who received Paxlovid died. The death rate for patients who did not get the drug was more than four times higher, or 0.070 percent. And yet the Epic data showed that only about 25 percent of patients eligible to receive Paxlovid actually did, even though the drug is widely available and free for patients.

Perhaps the most shocking statistic about Paxlovid’s underuse — and Jha used the word “shocking” when describing it to me — is that a smaller share of 80-year-olds with Covid in the U.S. is now receiving the drug than 45-year-olds with Covid, according to data he has seen. Many doctors are evidently worried about side effects or rebound cases among their more vulnerable patients.

Even in rebound cases, however, symptoms tend to be milder than they would have been without Paxlovid. After Dr. Anthony Fauci, another White House adviser, who’s 81, contracted Covid in June and then took Paxlovid, he experienced a rebound — and also believed that the drug kept him out of the hospital.

“Medicine is about weighing costs and benefits,” Wachter said. “The recommendation should be clear and unambiguous for people at high risk: The benefits of the drug outweigh the downsides.”

Red Covid

When I last wrote about “red Covid” — the concentration of Covid deaths in conservative communities because of vaccine skepticism — almost eight months ago, I explained why the partisan gap could eventually shrink: Republican communities might have built up more natural immunity through previous infections, and treatments like Paxlovid were becoming more widely available.

This spring and summer, the gap did narrow somewhat. But it has begun growing again in the past two months, according to an analysis by my colleague Ashley Wu.

One possible explanation is that Paxlovid takeup rates appear to be lower in Republican areas, even though they are the very places where the drug could do the most good, because of lower vaccination rates. Government data shows that of the 20 states with the least Paxlovid use between late August and late September (per 100 diagnosed cases of Covid), 18 were won by Donald Trump in 2020.

The shunning of Paxlovid seems to be part of a pattern in which Republican voters have wrongly dismissed Covid as little different from the flu. That mistake has had tragic consequences. A new study by three Yale University researchers found that the wide partisan gap in Covid deaths remained even after controlling for other factors, like age.

Solutions

Jha told me that the Biden administration was committed to increasing the use of Paxlovid and monoclonal antibodies nationwide. “We are going to go after this problem hard,” he said. “We have got to fix it, and we’ve got to fix it in weeks.”

What might make a difference?

Persuading more doctors of Paxlovid’s benefits would probably have the biggest impact. Wachter thinks that accelerating research about rebound Covid — including whether a longer course of Paxlovid would help — could also increase use, given the fear around the issue. He added that he was surprised that government, academic and private researchers had still not learned more about what causes a rebound and how to prevent it.

In coming months, this newsletter will follow up and see whether this country can do a better job of using a widely available treatment to save lives."