Lisa Jarvis

We Finally Have Some Paxlovid Covid Data. Now We Need More.

A new study that mined health records from the Department of Veterans Affairs hints that the drug Paxlovid might be useful in preventing long Covid.

Scientists have been urging the government and the drug’s manufacturer, Pfizer, to study the idea that lingering virus could be the culprit behind some people’s long-term symptoms, and finally having data is a welcome advance.

But these results, which have yet to be published in a peer-reviewed journal, merely suggest Paxlovid’s effectiveness rather than prove it. What the study truly points to is the desperate need to look more carefully at existing drugs that have the potential to prevent and treat long Covid, which has pulled an estimated 3.5 million people out of the workforce.

The VA study reviewed electronic health records of tens of thousands of veterans who had at least one risk factor for severe Covid and asked whether the use of Paxlovid reduced the number of people who ended up with long Covid. They found that taking the five-day antiviral regimen in the early days of an infection could indeed lower the risk of some symptoms by 26%. It helped lessen the burden of issues like blood-clotting, heart problems, muscle pain, brain fog, fatigue and shortness of breath. That result translated across people who were vaccinated, vaccinated and boosted, or who had never received a Covid shot.

But the patients in the database skewed heavily male, White and older (the average age was 65), which means the positive indications might not translate into the population that is most likely to present with long-term symptoms. A recent survey by the Census Bureau and the National Center for Health Statistics found, for example, that women and younger adults were disproportionately affected by long Covid.

Ziyad Al-Aly, director of the Clinical Epidemiology Center at the Veterans Affairs St. Louis Health Care System in Missouri, who led the study, stressed that the findings do not address whether Paxlovid can prevent long Covid in lower-risk individuals, namely people who are young and healthy. That’s a study that needs to be done, he said.

And even in the group captured in the data, that 26% reduction in long Covid should be viewed as more of a signal of an effect rather than concrete evidence.

The results are “very interesting, but more hypothesis-generating” than definitive, said Paul Sax, clinical director of the Infectious Disease Clinic at Brigham and Women’s Hospital in Boston. When digging into data captured from the real world rather than a formal study, results can be complicated by differences in the people who did and did not take the drug — factors such as lifestyle and health-care choices that might influence their outcomes regardless of the drug. Those differences can foster or magnify a signal that might not be seen in a trial where people are chosen randomly to receive the drug or not.

Sax suggests better, more reliable data could come from reviewing the people who took part in Pfizer’s clinical trials and ask whether those who received Paxlovid instead of a placebo had lower rates of long Covid. Unfortunately, no one seems to be pursuing that question.

Add it to the long list of questions that should be explored through careful study, yet, frustratingly, might never be answered. For example, could a longer course of Paxlovid confirm or even improve upon the signal of efficacy found in this study? Would younger people who don’t have risk factors benefit from taking the drug? Could any of the other antivirals that have received emergency authorization or even those that are still in development help prevent long Covid? And how often, if at all, is persistent virus the cause of people’s lingering symptoms?

One question that is finally being studied is whether Paxlovid can treat long Covid. The National Institutes of Health said last month that it would begin a study that will test whether a 15-day course can help patients who have a cluster of long-Covid symptoms.

The trial doesn’t start until January, and according to data on the government’s clinical trials registry, won’t deliver results until early 2024. That’s an awfully long time to ask people who have been suffering with symptoms to wait.

Moreover, the NIH study might not even provide clear answers. Only 1,700 people will be enrolled, a size some infectious disease specialists say isn’t sufficient to draw real conclusions. Al-Aly points out that to find that signal in the VA study, researchers had to look at data from nearly 60,000 people, with about 10,000 who received the drug. That’s because people’s symptoms are so varied and persistent virus is unlikely to be the only driver of long Covid. “You can’t get what we got here with a 2,000-person trial,” he said.

Running a huge trial is expensive, and Pfizer, which expects to bring in $22 billion in sales of Paxlovid this year, has so far shown little interest in pursuing one.

Since December 2021, more than 5.5 million doses have been prescribed in the US. So many opportunities have been missed to capture data on Paxlovid and long Covid. It’s past time to do the kind of studies that might not be perfect but could still yield enough data to conclude whether an existing treatment can help people get back to their normal lives.