Expected as a game-changer, Paxlovid is increasingly emerging as a last resort – hanging increasingly shakily in the wall of anti-Covid funds. There are increasing reports from the USA of people who were initially helped by the corona drug and who became positive again. Who still benefits.

First celebrated, currently much discussed: Paxlovid. The drug saves lives, that much is clear about the anti-Covid drug. Especially if it is used in good time. Because it serves to protect those who are at high risk of a severe course of the corona virus. The Paxlovid tablets from the US pharmaceutical company Pfizer can be taken at home if prescribed by a doctor. They are designed to inhibit virus multiplication in the body.

In a recent study, real-world data shows that people also benefit from the omicron wave: among those over 65, it reduced the risk of death by 81 percent and the risk of hospitalization by 67 percent.

The analysis has so far appeared as a preprint, i.e. it has not yet been reviewed by peers. However, it also shows that younger adults did not benefit significantly when it came to preventing a severe course.

Reports are growing in the United States that people treated with Paxlovid have tested positive for Corona again within about five days. This is the so-called rebound effect. That is, the effect of the drug sometimes wears off too soon. Former Harvard professor Eric Feigl-Ding warned in May not to underestimate this effect.

Medics at the Centers for Disease Control and Prevention (CDC) also warned that Covid-19 could come back after Paxlovid.

The Covid-19 rebound is characterized by a recurrence of symptoms or a new positive virus test after a negative test.

Case reports have shown that some patients with a normal immune response who have completed five days of treatment with the anti-Covid drug and recovered can fall ill again two to eight days later. Among them were vaccinated and boosted.

The representatives of the CDC write that there is currently little data. However, there is much to indicate that the rebound effect after Paxlovid causes mild symptoms. There were no reports of serious illnesses, the summary said. In addition, there is nothing to indicate that additional treatment with Paxlovid or other medication is necessary if a Covid-19 rebound is suspected.

Nevertheless, physician Eric Topol said – especially in view of the real-world data mentioned: Even with the now known rebound problem, it shows that the drug “really was a just-in-time breakthrough”.

The rebound effects are therefore no reason to do without the anti-virus pill. Expected by many to be a miracle pill, doctors saw it early on as an “emergency nail”. The active ingredients nirmatrelvir/ritonavir are not compatible with many other medicines such as allergy medicines, heart medicines or cancer medicines. The list of contraindications (contraindications), such as liver failure, is long.

These could be reasons why it has not celebrated any notable triumphs in Germany so far. The Federal Ministry of Health has ordered the drug for one million patients. According to research by “Welt”, only 17,200 doses have been prescribed.

According to CDC recommendations, Paxlovid should still be used to treat mild to moderate early-stage Covid-19 in people at high risk of severe disease.

According to the Robert Koch Institute (RKI), the European conditional approval for the treatment of adults without complaints or with mild symptoms, who do not need additional oxygen supply and have an increased risk of developing a severe course of Covid 19, applies in Germany . Specifically, the RKI recommends use in unvaccinated/incompletely vaccinated patients with at least one risk factor for a severe course of Covid-19 and in those with a high probability of vaccination failure. If the risk profile is very high/complex, clinicians might consider Paxlovid even with full vaccination.

So far, experts have no clear explanation for the fact that the infection returns after such a short time. One hypothesis is that people simply become infected with different variants of Sars-CoV-2 in quick succession. Because the cases in the country are increasing and the virus is mutating quickly. The rapid change also supports the other thesis: because the virus mutates so quickly, it has developed a way to escape Paxlovid and become resistant to it.

David Ho, actually an HIV researcher, has analyzed his own infection and other cases with his laboratory in more detail. This was reported by Time magazine. Ho thinks another explanation is plausible. His small study showed that three of the infections in his report – including his – were rebounds from the first. In other words, there were no new strains or a new Paxlovid-resistant variant. Based on the genetic sequencing data, “we showed that the re-emerging virus is not resistant to the protease inhibitor [the active ingredient in Paxlovid] because there is no change in the protease sequence,” he said. “It’s not reinfection with another virus. The processes are identical.” According to Pfizer, their studies made something similar clear: the virus had not developed any resistance to the protease inhibitor drug.

Infectiologist Bernd Salzberger also speaks out in the “Welt” for a possible cause of the rebound effect in this direction: For some patients, one remedy is simply not enough to defeat the pathogen in the long term. In the case of HIV and hepatitis C, combinations of active ingredients have also proven to be necessary in order to sufficiently suppress the multiplication of the pathogens. The head of infectiology at the University Hospital Regensburg recently treated a patient who became positive again ten days after the Paxlovid therapy and also developed symptoms. It was a woman with a very weakened immune system.

Ralf Bartenschlager, Head of Molecular Virology at Heidelberg University Hospital and President of the German Society for Virology, provided another theory: “The immune response takes quite a long time before it is strong enough for the infection to be controlled.”

In this respect, arguments seem to strengthen that the Paxlovid treatment should last longer than five days. However, there are still no official recommendations on this. As much as physician Eric Topol appreciates the drug as one that can currently save lives. At the same time, he demands that more powerful anti-virus pills must be developed.