Infectious Disease

Paxlovid may not reduce risk for long COVID, study shows

January 16, 2024

2 min read

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Key takeaways:

  • Rates of long COVID were similar between groups of people who received Paxlovid and those who do not.
  • COVID-19 rebound is not linked to an overall risk for long COVID.

Paxlovid did not reduce the risk for long COVID among vaccinated, nonhospitalized people who received it within a month of their first SARS-CoV-2 infection, a study showed.

The FDA approved Paxlovid in May 2023 for adults at risk for severe COVID-19, making it the first oral antiviral to gain full approval to treat the disease, although it was available under an emergency use authorization for more than a year before that.

COVID home test_AdobeStock

Rebound does not increase risk for long COVID, according to a study. Image: Adobe Stock

In the new study, researchers at the University of California, San Francisco (UCSF) found that the risk for long COVID was relatively similar between people treated with Paxlovid and people who had not received the antiviral medication, which contains the protease inhibitor nirmatrelvir and a low dose of ritonavir.

In the study, roughly one-quarter of people treated with Paxlovid experienced COVID-19 rebound, which is similar to previous findings, but the study did not show an association between rebound symptoms and long COVID.

“We were surprised,” Matthew S. Durstenfeld, MD, MAS, a cardiologist and assistant professor of medicine at the UCSF, told Healio. “We expected that Paxlovid would prevent long COVID and that those who experienced rebound would be more likely to later develop long COVID.”

The researchers reviewed data on more than 100,000 people from an online cohort study and identified 4,684 participants for the new analysis who were vaccinated, not hospitalized and not pregnant and who reported their first positive SARS-CoV-2 infection between March 2022 and August 2022, after Paxlovid became available.

In December 2022, they asked participants to complete a follow-up survey with questions about long COVID, COVID rebound symptoms and how long they continued to test positive.

Among the 4,684 participants, 353 were treated with Paxlovid and responded to the survey, and 1,258 people not treated with Paxlovid also responded to the survey. Among the 1,611 total survey respondents, median age was 55 years and 66% were female.

According to the study, roughly 16% of patients treated with Paxlovid experienced long COVID compared with 14% of patients not treated with Paxlovid (OR = 1.15; 95% CI, 0.80–1.64).

Among people whose COVID-19 symptoms improved during Paxlovid treatment, 21% reported rebound symptoms. In the rebound group, 10.8% later reported long COVID symptoms compared with 8.3% of people who did not rebound (OR = 1.34; 95% CI, 0.74–2.41.)

Additionally, 25.7% of participants repeatedly tested negative for SARS-CoV-2 after Paxlovid treatment. Overall, 26.1% of participants reported either rebound symptoms or a positive COVID-19 test, according to the study.

Durstenfeld said it was reassuring that rebound did not appear to portend an increased risk for long COVID.

“The COVID-19 pandemic is not over, and there are no proven treatments for long COVID,” Durstenfeld said. “Prescribing Paxlovid does not eliminate the risk for long COVID, even for vaccinated people in the omicron era. Therefore, masks, indoor purification and physical distancing are still relevant prevention strategies.”

References:

Perspective

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Ziyad Al-Aly, MD)

Ziyad Al-Aly, MD

This is an interesting observational (but small) study that relies on self-reported use of Paxlovid and self-reported long COVID. The study is interesting, but important caveats should be noted to help contextualize the results.

Only a third of study participants responded to the long COVID survey. People who opt to take Paxlovid may be generally sicker than people who do not and may also be more aware of long COVID (eg, brain fog and post-exertional malaise). All these biases may have led to underestimation of the effectiveness of Paxlovid in reducing the risk of long COVID.

Ziyad Al-Aly, MD

Chief of research and development

VA St. Louis Health Care System

Disclosures: Al-Aly reports no relevant financial disclosures.

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Sources/Disclosures

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Disclosures:
Durstenfeld reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

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