Comment Covid patients treated with Paxlovid, the oral antiviral that has been shown to be highly effective in preventing hospitalization and death in elderly and at-risk people, appeared less likely to suffer from several key symptoms associated with long-term covid, according to a new study. The report, which is based on databases from the Department of Veterans Affairs, looked at more than 9,000 people who received Paxlovid, along with a control group of nearly 50,000 people who tested positive but did not take the drug. It showed about a 25 percent reduction in 10 of the 12 symptoms studied, including the common complaints of prolonged fatigue and brain fog. The results held true whether people had been vaccinated or previously infected. “This study is very important,” said Akiko Iwasaki, a professor of immunobiology and molecular, cellular and developmental biology at Yale University. “It has public health implications that are quite relevant today.” Although vaccines have reduced the risk of hospitalization and death from SARS-CoV-2 infection, researchers remain concerned about the individual sufferer and population-wide threats from long-term Covid. Data released this summer from the Centers for Disease Control and Prevention’s Household Pulse Survey suggests that nearly 15 percent of adults have long had Covid, developing symptoms that last three or more months after contracting the virus. The CDC recently refined the online survey to assess how much of an impact these symptoms have on travelers’ ability to carry out daily activities. Ziyad Al-Aly, head of research and development at VA St. Louis Health Care System and lead author of the new report, said it shows the importance of introducing an antiviral to reduce the severity of acute illness. It also lends credence to the idea that long-lasting Covid symptoms may be due, at least in part, to persistence of the virus, in which the virus is not fully cleared from infected individuals. “Suppressing viral load can reduce the problem of viral persistence,” said Al-Aly, a clinical epidemiologist at Washington University in St. Louis. The new study, funded by the VA, was released online as a preprint, meaning it has not yet been peer-reviewed as is standard protocol for academic journals. Publishing preprints has become more common in the urgent atmosphere of the pandemic, often leading to a form of near-instant online peer review. Several prominent virologists came online quickly and positively. The pandemic is rewriting the rules of science. But at what cost? Eric Topol, a professor of molecular medicine and executive vice president of Scripps Research, tweeted that the report is “an important advance” and discussed the findings in an online post that underscores the urgent need to develop treatments for what is now widely recognized as a mass. – power off state. “We have no treatment that has been validated to treat Long Covid,” Topol wrote. “Rigorous, randomized, definitive clinical trials are long overdue.” Plans are in place to measure the impact of the Pfizer drug (nirmatrelvir and ritonavir) next year as part of the National Institutes of Health’s $1.15 billion RECOVER program, the agency recently announced. 1,700 adults will participate in the clinical trial. Results are not expected until 2024. Some researchers said it would be useful to have access to data from Pfizer’s placebo-controlled clinical trials evaluating the antiviral’s impact on acute Covid in thousands of volunteers. “We could do a long-term follow-up to determine whether both groups have the same or different rates of persistent symptoms,” said David Putrino, director of rehabilitation innovation at Mount Sinai Health System in New York. Pfizer said the company is “working with several institutions to initiate studies evaluating Paxlovid for potential use in the treatment of long-term Covid.” In its 2022 financial guidance, the company reported Paxlovid revenue of $22 billion. Clinicians have been stymied in developing specific treatments for long-term covid largely because the mechanism – or mechanisms – behind the vast variety of reported symptoms has not been identified. Leading theories include viral persistence, microthrombi development, and acute inflammation, which other studies have shown can cause long-term damage. Iwasaki speculates that using Paxlovid to stop the virus from replicating may not only prevent the persistence of the virus but other mechanisms as well, containing the virus in the upper respiratory tract before it migrates to other organs. “The virus is the trigger for all the other cases,” Iwasaki said. “Cut it out as quickly as possible and some of this could be avoided.” He said he thinks there may be advantages to taking Paxlovid as soon as possible after diagnosis. The new study has inherent limitations. The people enrolled were eligible to receive the drug under the emergency use authorization issued last year by the Food and Drug Administration, which applies to anyone 12 years of age or older who is at risk of serious disease, including those 65 and older. As a result, the study did not include previously healthy young people, who represent the majority of patients who visit many long-term coronavirus clinics, according to Benjamin Abramoff, director of clinical assessment and recovery after COVID-19 at Penn Medicine. There are no data to show whether these previously healthy young people will reap the same benefits as people at risk of serious illness. Putrino cautioned that the study’s promising results may be related to the antiviral’s ability to reduce the severity of acute illness that can lead to lingering complications such as lung fibrosis from pneumonia, pericarditis from inflammation and what’s known as post-infection syndrome. ICU symptoms he usually sees. “Many, many others with long covid had mild/non-hospitalized acute illness but went on to develop this debilitating, syndromic, long-term ME/CFS type coronavirus,” Putrino said, referring to chronic fatigue syndrome. As a retrospective study rather than a randomized controlled trial, there may also be underlying differences not accounted for in the study between those who received Paxlovid and the control group, including greater engagement with their doctors, Abramoff said. “The study provides more evidence for the importance of prospective controlled studies to examine Paxlovid as a long-term coronavirus prevention agent in the broader population,” Abramoff said. Al-Aly, the lead author, said the study also highlighted for him the remarkable underuse of an effective treatment, with 85 percent of people eligible to be prescribed the antiviral not taking it. “Is it because it wasn’t offered to them or they had concerns?” asked. In the short time since the study was released online, Al-Aly said he has seen ordinary readers jump to the wrong conclusions. “We are not saying any and all people should take Paxlovid,” Al-Aly said. “At this point, we don’t know. People need to understand that.”
