An antiviral drug approved for high-risk COVID patients may also benefit those with long COVID, according to the findings of a small case series that need to be confirmed with future rigorous studies.
In December, the Food and Drug Administration (FDA) granted Paxlovid an emergency use authorization (EUA) for patients who had tested positive for the coronavirus and were 65-plus, or had underlying conditions like obesity, diabetes or cancer. In a clinical trial, the drug was found to reduce the risk of death and hospitalization by 89%. A combination of two generic antivirals, nirmatrelvir and ritonavir, Paxlovid is taken in pill form for five days and must be initiated within five days of the onset of symptoms, according to the conditions of the EUA.
In a case series posted on May 3, 2022, on the preprint server Research Square that has not been peer-reviewed or published in a journal, researchers from UC San Francisco followed three patients in their 40s, who had been enrolled in the LIINC study. They had tested positive for COVID and later struggled with debilitating symptoms, consistent with long COVID, which is believed to affect about one in three people infected with SARS-CoV-2.
In two of the three patients, Paxlovid was taken weeks after the start of symptoms, contrary to its indications. One patient was prescribed the antiviral after re-exposure to the virus, more than seven weeks after symptom onset, and his health improved until he felt almost back to normal. A second patient took Paxlovid approximately three weeks after symptom onset and was less fatigued the day after completing therapy, although she continued to experience shortness of breath and muscle pain.
The key aspect of this case is that longer courses of Paxlovid may be needed, and giving it too early might not be optimal.
Researchers speculate the symptoms may arise from the immune system’s ongoing reaction to the virus that remains in the body after the acute phase of the infection is over.
“Data from other studies shows that SARS-CoV-2 might linger for months,” said first author Michael J. Peluso, MD, an assistant professor of medicine and infectious disease specialist at UCSF and Zuckerberg San Francisco General Hospital. “A recent study shows persistent shedding of virus from the gastrointestinal tract for up to seven months in some people. This doesn’t mean the virus is infectious, but there might be pieces of the virus, or viral activity, that could be stimulating the immune system.”
It seems that Paxlovid may benefit patients with long COVID,” said Peluso, “but there is no way to access the drug unless a doctor is willing to break the rules, which we are not advocating.” Its safety is also unknown, he said.
Early Treatment May Fail to Prevent Rebound Symptoms
A third patient started Paxlovid within 24 hours of symptoms onset, in accordance with the EUA conditions. His symptoms improved, but then rebounded four days after he completed the therapy, with fever, runny nose, cough and chest pain. During this period, he had worn a fitness device that recorded his heartbeat, temperature and respiratory rate, all of which were elevated. Approximately two weeks later, he developed brain fog, chest soreness, fatigue and post-exertion malaise, symptoms that are consistent with long COVID.
“The key aspect of this case is that longer courses of Paxlovid may be needed, and giving it too early might not be optimal,” Peluso said, adding that there is no safety data yet to support extended use of the drug.
While these three cases represent anecdotal data, or are “hypothesis-generating,” meaning they only provide scientists with clues as to what might be going on biologically, the case underscores the importance of studies, said Peluso.
“Only by doing rigorous studies will we get answers,” he said. “There is a critical need for this, given the large number of people who have had COVID, a significant subset of whom have long COVID.”
Authors: Senior author is Steven G. Deeks, MD, of UCSF and Zuckerberg San Francisco General Hospital. Co-authors are Khamal Anglin, MPH, Matthew S. Durstenfeld, MD, Jeffrey N. Martin, MD, J. Daniel Kelly, MD, Priscilla Y. Hsue, MD, and Timothy J. Henrich, MD, all of Zuckerberg San Francisco General Hospital and/or UCSF.
Funding: National Institute of Allergy and Infectious Diseases (NIH/NIAID 3R01AI141003-03S1).
The authors report no conflicts of interest.