Study Suggests Paxlovid Made People More Susceptible to COVID-19 Reinfection

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A colorized scanning electron micrograph of cells (blue) infected with the Omicron strain of SARS-CoV-2 virus (yellow), isolated from a patient sample. Variants of the original COVID-19 virus evolved to better dodge vaccine protections and immune response. Credit: National Institute of Allergy and Infectious Diseases (NIAID)

Key points: 

  • A new study shows SARS-CoV-2 subvariants can spread more rapidly among those previously infected.
  • The data suggests Paxlovid therapy caused greater susceptibility to reinfection by dampening the natural development of antibodies.
  • Researchers say early antiviral treatment can prevent severe COVID-19, but there is still need for subsequent vaccination.

A new study by researchers at UC San Diego suggests Paxlovid therapy increased susceptibility to COVID-19 reinfection during the pandemic. The findings also explain why COVID-19 subvariants spread rapidly among people previously infected.

The researchers found that mutations in the spike protein of BA.4 and BA.5 allowed it to evade neutralizing antibodies generated by vaccination or by an earlier SARS-CoV-2 infection. They also determined that taking Paxlovid, an oral antiviral pill, dampened the natural development of antibodies, which left people with lower immune responses and a chance at reinfection.

"Our findings suggest that while early antiviral treatment can prevent severe COVID-19, it does not obviate the need for subsequent vaccination or boosters to promote protective immune responses,” said senior author Davey Smith, MD, chief of Infectious Diseases and Global Public Health at UC San Diego School of Medicine and an infectious disease specialist at UC San Diego Health.

Paxlovid was among the first drugs developed and tested to treat COVID-19, and quickly became a go-to medication, often prescribed when symptoms first appeared and intended to reduce the likelihood of severe disease, hospitalization or death. Subsequent research has shown that Paxlovid treatment among non-hospitalized, unvaccinated patients at high risk of progression to severe disease reduced the risk of hospitalization or death by 88%, and the risk of long COVID. But Paxlovid proved poor insurance against recurrence of COVID-19 or subsequent re-infection.

In June 2022, Smith and colleagues published data suggesting the so-called “Paxlovid rebound” was likely due to insufficient drug exposure. Then, in October 2022, they published a different study that documented the likelihood of COVID-19 symptoms recurring in untreated patients after initial symptoms had disappeared.  

“The findings highlight the importance of ongoing research and the need for continued efforts to understand the virus and develop effective treatments and vaccines,” said Smith. “The past is prologue, not because the virus is the same, but because it is constantly changing, so we must evolve as well to meet the threat and anticipate the next pandemic.”

 

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