A rebound from Covid-19 after taking Paxlovid is not exactly the same as a rebound relationship. Although both can make you sick in different ways. A post-Paxlovid rebound may occur after you feel better after taking Paxlovid for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The rebound is when you experience a relapse of Covid-19 symptoms at some point after completing five days of taking the drug. And it seems like more and more people have been reporting such relapses.

For example, there is this pre-printed case report that was uploaded to research place on April 26, 2022 by a 71-year-old man who had been fully vaccinated and boosted against Covid-19. He started taking Paxlovid as soon as he tested positive for Covid-19, two days after being exposed to the virus. His Covid-19 symptoms essentially disappeared after two days of Paxlovid. But nine days after he first tested positive and four days after completing the five-day course of Paxlovid, his runny nose, sore throat and difficulty breathing returned, along with a renewed increase in his SARS-CoV-2 levels. Values. Viral genome sequencing showed that he was infected with the SARS-CoV-2 subvariant BA.1 Omicron during his initial symptoms and symptom recurrence. Of course, a pre-print isn’t the same as a peer-reviewed article, and anyone with opposable thumbs, a laptop, and internet access could theoretically upload a pre-print. But the case report authors (Kalpana Gupta, Judith Strymish, Gary Stack, and Michael Charness) are legitimate physicians from legitimate healthcare systems, the Connecticut VA and Boston Healthcare Systems.

Also, this certainly wasn’t the only report of such a recovery. For example, here’s what Tatiana Prowell, MD, associate professor of oncology at the Johns Hopkins School of Medicine, tweeted:

And Peter Hotez, MD, PhD, Dean of the National School of Tropical Medicine at Baylor Medical College, tweeted about his case of relapsing after Paxlovid:

As a reminder, Paxlovid received an Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration (FDA) on December 22, 2021 to treat people 12 years and older with mild to moderate Covid-19. These antivirals are designed to stop the SARS-CoV-2 from doing evil in your body, which is a non-technical way of saying it’s replicating itself in your cells. While Paxlovid doesn’t put tiny condoms on the viral spikes, it is actually the combination of two different antiviral tablets, nirmatrelvir and ritonavir, packaged together. The recommended dose of these antivirals is two 150 mg tablets of nirmatrelvir together with one 100 mg tablet of ritonavir twice a day for five days, provided you have normal kidney function.

Like Hall & Oates, these two drugs work together. Nirmatrelvir can block the action of an enzyme called MPROFESSIONAL, not to be confused with GoPro. MPROFESSIONAL cleaves two different viral polyproteins, which may not sound very sexy, but is an important step if SARS-CoV-2 wants to multiply. Meanwhile, ritonavir blocks cytochrome P450 (CYP) 3A4 enzymes in the liver that can break down nirmatrelvir, allowing nirmatrelvir to stay in your body longer.

And just like condoms, Paxlovid doesn’t work according to Reproduction has already taken place. That’s why it’s important to start taking Paxlovid as soon as you find out you’ve tested positive for Covid-19. If you wait more than five days after symptoms first appear, the virus may multiply too much for Paxlovid to make much of a difference. So there is a finite window, less than half a Scaramucci, in which taking Paxlovid helps.

than this NBC News Segment shows the FDA is currently investigating the reports of Covid-19 rebound cases:

So do those rebound cases mean Paxlovid isn’t doing its job? No, not necessarily. Just because the symptoms are returning doesn’t mean it wouldn’t have been worse without the medication. Also, it is not yet clear what percentage of people have experienced such relapses. Again, stories on Twitter and a pre-printed case report are not the same as peer-reviewed studies. While Pfizer’s clinical trial showed a possible rebound of Covid-19, which occurred in about 2% of patients who received Paxlovid, about 1.5% of those who received only placebo experienced similar relapses. Because these two percentages were not statistically significantly different, the conclusion from the clinical study was that these rebounds were not specific to Paxlovid. Of course, what happens or doesn’t happen in a clinical trial doesn’t necessarily mean the same is true in the real world.

So what’s going on, in the words of Marvin Gaye? One possibility is that it turns out that taking the drug for five days is not enough for everyone. The drug is designed to suppress viral replication long enough for your immune system to clear the virus from your body. It’s like rubbing deodorant on yourself until you’ve had a chance to take a proper shower. Remember that Paxlovid does not remove the virus from your body. It just keeps it from replicating itself. The time it takes for your immune system to perform this task of clearing viruses can vary depending on the amount of virus in your body and the status of your immune system. It could be that your immune system is not sufficiently armed before the five-day intake of the drug is completed. So, a question is whether the course of Paxlovid should be longer than five days.

Another possibility is that the Omicron variant is so different from previous versions of the virus that the drug may not be quite as effective. Keep in mind that Pfizer’s clinical trial took place last year when the Delta variant was dominant. Therefore, all results may be more delta specific.

A third possibility is that the virus has developed resistance to the antiviral drug. While resistance is not futile, it can reduce the effectiveness of the drug. Resistance is why antiviral flu drugs like Tamiflu may not be as effective against certain strains of flu. And since the Covid-19 coronavirus is replicating so extensively, resistance could very well develop. Every time SARS-CoV-2 replicates, it can be like a drunk person making photocopies of their butt. Errors can occur when the virus attempts to copy its genetic code, leaving offspring with mutations and therefore different genetic sequences. Some of these mutations can alter viral proteins enough to allow the virus to better evade the antiviral agent.

Many people taking the antiviral drug could then choose viruses with such resistance mutations because they are better able to survive. These resistant versions could then eventually become the dominant version of the virus. For this reason, antiviral drugs should not be overused.

Although there was no clear evidence of resistance development during the Pfizer Paxlovid clinical study, the study may not have lasted long enough to recognize this possibility. It will be important for health authorities to monitor the possible emergence of resistant strains of the virus and potentially limit the use of Paxlovid if such resistance is identified.

A fourth possibility is reinfection. Could some of the alleged relapses actually be people getting infected and then reinfecting them in a short period of time? I have cover for forbes a case where someone becomes infected with the Omicron variant within 20 days of contracting the Delta variant. However, it is not clear how common it can be for two separate infections to occur within such a short period of time.

So what should you do if you have a rebound case of Covid-19 after taking Paxlovid? Should You Take More of This Antiviral Drug? Well, right now, things are about as clear as Nutella soup. There is not enough evidence on what to do. And the EUA only covers taking the drug for five days.

Ultimately, more studies, more data, and more drug surveillance are needed. All of this is a reminder that while Paxlovid can be a very useful part of dealing with the pandemic, it is not a magic pill. Nothing in life is a magic fix, except for avocados or chocolate. Relying solely on a drug to “save you” if you should get Covid-19 could be like relying on finding a soul mate to save you from your current life. Do not think that the existence of Covid-19 treatments can allow you to forgo other Covid-19 precautions such as wearing a face mask and getting vaccinated against Covid-19. Remember that Covid-19 interventions are like Swiss cheese, not that you should start putting them on your ham sandwich. Rather, it means that each and every precaution or treatment has its specific gaps. And it all means that while the pandemic is still ongoing and the virus is circulating widely around you, you should always layer at least several Covid-19 precautions on top of each other. If you don’t follow other Covid-19 precautions and rely solely on getting Paxlovid when needed, the Covid-19 coronavirus could very well catch you rebounding.

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