Covid ‘rebound’ symptoms: Why are some tests positive again, like Joe Biden?

What is PaxLovid and how does it work?

Paxlovid is a combination treatment that uses two different antivirals: nirmatrelvir and ritonavir.

Nirmatelvir works by stopping the replication of the virus. It does this by inhibiting a viral enzyme called protease.

SARS-CoV-2, like many viruses, rely on proteases to “activate” them. Without the protease, the virus replication cycle cannot be completed and the virus cannot be activated.

So instead of “killing” the virus, it prevents new “active” virus particles from forming.

Ritonavir is a “boosting agent” that inhibits the metabolism of nirmatrelvir, which means it stays in your system for a longer period of time.

Ritonavir has been used in low doses to enhance the effectiveness of other protease antivirals in infections such as HIV.

Paxlovid treatment involves taking two nirmatrelvir 150mg tablets and one ritonavir 100mg tablet together, every 12 hours for five days.

Like all antivirals, it is important to start a course of Paxlovid as soon as possible after a diagnosis of COVID-19. This should happen within five days of the onset of symptoms, so it can reduce virus replication and therefore reduce the spread of the virus in the body.

How effective is this?

In one clinical trial, Paxlovid showed an 89% reduction in the risk of hospitalization and death. No deaths were recorded among those receiving treatment.

Compared to those in the study who did not receive the drug, Paxlovid treatment also reduced viral load when measured on the fifth day of the study.

So what is rebound?

Rebound occurs when a person has cured and “eliminated” the virus, meaning they test negative on a very sensitive PCR test and have no symptoms. Then a few days later, they test positive again or the symptoms come back.

Rebound is not specific to people who have taken Paxlovid – it can also happen to people who have COVID who have not received any drug treatment.

A study that is yet to be reviewed (independently verified) also found that patients’ symptoms and viral load may worsen after an initial period of improvement in some cases. While this is not true “rebound” suggests that the course of the transition may not be linear.

There are now increasing reports of a rebound effect in people who were treated with Paxclovid, including President Biden. Biden finished his five-day course of Paxlovid and tested negative for the virus. Three days later, he tested positive.

Why and how the rebound occurs is still not known exactly. What we do know is that Paxlovid prevents the virus from replicating in a person’s body. It does not kill the virus already there. For this we need the immunity of the body.

One theory is that a five-day course is not enough to suppress virus replication to allow the immune system to try and kill the virus.

Or perhaps the time the treatment starts affects how the immune system works.

Another theory is that the medicine is not being taken as prescribed. Research into the causes of Paxlovid rebound is ongoing.

A recent study of 11,000 people with relapse after PaxLovid, which has not yet been peer-reviewed (independently verified), found that after seven days of treatment, 3.53% of participants had positive PCR tests and 2.31% had There were signs of rebound. After 30 days, 5.40% tested positive and 5.87% had symptoms.

So just because you’ve received SARS-CoV-2 antiviral treatment, it doesn’t mean you’ve been “cured.”

How sick are ‘rebounders’?

While scientists and doctors are in the early stages of investigating PaxLovid rebound, early reports indicate that the rebound is mild. Symptoms that return are usually sniffles, sore throat, or cough.

There are very few reports of serious rebound cases requiring hospitalization and no reports of rebound resulting in death that I am aware of.

It’s important to remember that you can still be contagious if you still have symptoms. Guidelines across Australia make it clear that if your symptoms continue after your period of isolation, you need to take care not to spread the virus.

However, a person in relapse – even if they are symptom-free – may also be able to spread the virus.

So is Paxlovid doing what we need?

If your goal is to prevent serious illness, hospitalization, and death in people at high risk, Paxlovid is doing a great job.

However, if you’re looking to shorten the duration of your symptoms, Paxlovid might not be the miracle drug we expected.

(by Lara Herrero, Research Leader in Virology and Infectious Disease, Griffith University)

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