Effectiveness Questioned: Study Finds That Paxlovid Fails To Reduce Long COVID Risk

Researchers at UCSF have discovered an unexpectedly high rate of COVID rebound following treatment with Paxlovid.

A group of scientists from the University of California, San Francisco, discovered that Paxlovid (Nirmatrelvir-ritonavir) was ineffective in lowering the chances of vaccinated, non-hospitalized patients contracting long COVID during their initial infection with the virusA virus is a tiny infectious agent that is not considered a living organism. It consists of genetic material, either DNA or RNA, that is surrounded by a protein coat called a capsid. Some viruses also have an outer envelope made up of lipids that surrounds the capsid. Viruses can infect a wide range of organisms, including humans, animals, plants, and even bacteria. They rely on host cells to replicate and multiply, hijacking the cell's machinery to make copies of themselves. This process can cause damage to the host cell and lead to various diseases, ranging from mild to severe. Common viral infections include the flu, colds, HIV, and COVID-19. Vaccines and antiviral medications can help prevent and treat viral infections.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]” tabindex=”0″ role=”link”>virus. Additionally, they observed a greater frequency of acute symptom recurrence and test positivity for the virus than what had been earlier documented.

The study was recently published in the Journal of Medical Virology.

Paxlovid treatment for acute COVID-19First identified in 2019 in Wuhan, China, COVID-19, or Coronavirus disease 2019, (which was originally called "2019 novel coronavirus" or 2019-nCoV) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has spread globally, resulting in the 2019–22 coronavirus pandemic.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]” tabindex=”0″ role=”link”>COVID-19 has been shown to be effective for high-risk unvaccinated individuals. But the effect of the treatment on long COVID risk, including whether it protects vaccinated people from getting long COVID, has been less clear.

The research team selected a group of vaccinated people from the UCSF Covid-19 Citizen Science study who had reported their first positive test for COVID-19 between March and August of 2022 and who were not hospitalized. Some of these participants reported taking oral Paxlovid treatment during the acute phase of their COVID infection, while others did not. In December of 2022, they were invited to answer a follow-up survey with questions about long COVID, COVID rebound symptoms, and how long they continued to test positive.

Study Findings on Long COVID and Symptom Rebound

Researchers found the two groups were similar. About 16% of those treated with Paxlovid had long COVID symptoms compared to 14% of those who were not treated with the medication. Commonly reported symptoms included fatigue, shortness of breath, confusion, headache, and altered taste and smell. Those who took Paxlovid and then went on to develop long COVID reported as many long COVID symptoms as those who were not treated with Paxlovid. A small percentage of people developed severe long COVID, and those who had received Paxlovid were just as likely to have severe Long COVID symptoms as those who did not.

Among individuals who experienced symptomatic improvement during Paxlovid treatment, 21% reported rebound symptoms. And among those with rebound symptoms, 10.8% reported one or more Long COVID symptoms compared to 8.3% without rebound symptoms. For participants who repeated antigen testing after testing negative and completing treatment, 25.7% reported rebound test positivity. In total, 26.1% reported rebound symptoms or test positivity.

Conclusions and Observations

“We found a higher proportion with clinical rebound than previously reported but did not identify an effect of post-treatment rebound on long COVID symptoms,” said study first author Matthew Durstenfeld, MD, MAS, a cardiologist and UCSF assistant professor of Medicine. “Our finding that Paxlovid treatment during acute infection is not associated with lower odds of long COVID surprised us, but it is consistent with two other rigorously conducted studies finding no difference in post-COVID conditions between 4 and 6 months after infection.”

The authors note that the study may have been impacted by limitations arising from its observational nature with researchers relying on patient self-reporting of treatment and Long COVID symptoms.

Reference: “Association of nirmatrelvir for acute SARS-CoV-2Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the official name of the virus strain that causes coronavirus disease (COVID-19). Previous to this name being adopted, it was commonly referred to as the 2019 novel coronavirus (2019-nCoV), the Wuhan coronavirus, or the Wuhan virus.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]” tabindex=”0″ role=”link”>SARS-CoV-2 infection with subsequent Long COVID symptoms in an observational cohort study” by Matthew S. Durstenfeld, Michael J. Peluso, Feng Lin, Noah D. Peyser, Carmen Isasi, Thomas W. Carton, Timothy J. Henrich, Steven G. Deeks, Jeffrey E. Olgin, Mark J. Pletcher, Alexis L. Beatty, Gregory M. Marcus and Priscilla Y. Hsue, 04 January 2024, Journal of Medical Virology.
DOI: 10.1002/jmv.29333

This work (Eureka Research Platform) was supported by NIH/NIBIB 3U2CEB021881-05S1. The COVID-19 Citizen Science Study is supported by Patient-Centered Outcomes Research Institute (PCORI) contract COVID-2020C2-10761 and Bill and Melinda Gates Foundation contract INV-017206. Dr. Durstenfeld is supported by NIH/NHLBI grant K12HL143961.