Some suffer Covid-19 relapses after taking Pfizer antiviral
Having a rebound from Covid-19 after taking Paxlovid is not exactly the same as having a rebound relationship. Although both can make you sick in different ways. Post-Paxlovid rebound may occur after you feel better after taking Paxlovid for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Rebound occurs when at some point after completing the five-day course of the drug, you experience a relapse of Covid-19 symptoms. And it seems that more and more people are reporting such relapses.
For example, there is this pre-printed case report uploaded to Research Square April 26, 2022, of a 71-year-old man 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. Her Covid-19 symptoms essentially disappeared after two days of Paxlovid. Yet 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 his SARS-levels. CoV-2 rising. Sequencing of the viral genome showed that during his first symptoms and when his symptoms returned, he was infected with the BA.1 Omicron subvariant of SARS-CoV-2. Of course, a preprint is not the same as a peer-reviewed article, and anyone with opposable thumbs, a laptop, and internet access could conceivably download a pre-print. impression. But the authors of the case report (Kalpana Gupta, Judith Strymish, Gary Stack and Michael Charness) are legitimate doctors from legitimate health systems, VA Connecticut and Boston Healthcare Systems.
Plus, that certainly wasn’t the only report of such a rebound. For example, here’s what Tatiana Prowell, MD, associate professor of oncology at 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 post-Paxlovid relapse case:
As a reminder, Paxlovid received Emergency Use Authorization (EUA) on December 22, 2021 from the United States Food and Drug Administration (FDA) as a treatment for people aged 12 and over with mild to moderate Covid-19. These antivirals are supposed to stop SARS-CoV-2 from doing harm in your body, which is a non-technical way of saying from reproducing in your cells. Although Paxlovid does not put tiny preservatives on the virus 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 nirmatrelvir tablets with one 100 mg ritonavir tablet twice a day for five days, assuming you have normal kidney function.
Like Hall & Oates, these two drugs work together. Nirmatrelvir can block the action of an enzyme called MPRO, not to be confused with GoPro. MPRO cleaves two different viral polyproteins, which might not sound very sexy but is an important step when SARS-CoV-2 wants to reproduce. During this time, ritonavir inhibits cytochrome P450 (CYP) 3A4 enzymes in the liver that can break down nirmatrelvir and thus allow nirmatrelvir to stay in your body longer.
And just like condoms, Paxlovid doesn’t work after reproduction has already taken place. This is why it is important to take Paxlovid as soon as you find out you are positive for Covid-19. Waiting longer than five days after the first symptoms appear may allow the virus to reproduce too much for Paxlovid to make a big difference. So there is a finite window, less than half a Scaramucci, during which taking Paxlovid will help.
Do these rebound cases then mean that Paxlovid is not doing its job? No not necessarily. Just because the symptoms come back doesn’t mean things wouldn’t have been worse without the medication. Moreover, it is not yet known what percentage of people have experienced such relapses. Again, Twitter stories and a pre-printed case report are not the same as peer-reviewed studies. While The Pfizer clinical trial showed possible Covid-19 rebound occurring in approximately 2% of those who received Paxlovid, approximately 1.5% of those who received only the placebo also experienced similar relapses. Since these two percentages were not statistically significantly different from each other, the conclusion of the clinical trial was that these rebounds were not specific to Paxlovid. Of course, what does or doesn’t happen in a clinical trial doesn’t necessarily mean the exact same thing will apply in the real world.
So what is going on, in the words of Marvin Gaye? One possibility is that the five-day course of the drug may not be long enough for everyone. The drug is supposed to suppress viral replication long enough for your immune system to clear the virus from your body. It’s kind of like slathering on deodorant until you’ve had a chance to take a real shower. Remember that Paxlovid does not eliminate the virus from your body. It just stops it from replicating. The time it takes for your immune system to complete this task of eliminating the virus can vary depending on the amount of virus in your body and the state of your immune system. Your immune system may not have prepared sufficiently by the end of the five-day treatment.
Another possibility is that the Omicron variant is different enough from previous versions of the virus that the drug isn’t as effective. Remember that the Pfizer clinical trial took place last year when the Delta variant was dominant. Thus, all results may be more specific to Delta.
A third possibility is that the virus has developed resistance to the antiviral drug. Although resistance is not futile, it can reduce the effectiveness of the drug. Resistance is why flu antivirals such as Tamiflu may not be as effective against certain strains of flu. And with the Covid-19 coronavirus replicating so much, resistance could very well develop. Every time SARS-CoV-2 replicates, it can look like a drunk person making photocopies of their butt. Mistakes can occur when the virus tries to copy its genetic code, leaving resulting offspring with mutations and therefore different genetic sequences. Some of these mutations may alter viral proteins enough to allow the virus to better evade the antiviral.
Many people using the antiviral drug could then end up selecting 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. This is why antiviral drugs should not be overused.
Although there was no clear evidence of resistance developing during the Pfizer Paxlovid clinical trial, the trial may not have lasted long enough to see this possibility. It will be important for public health officials to monitor the possible emergence of resistant viral strains and potentially limit the use of Paxlovid if such resistance is discovered.
A fourth possibility is reinfection. Could some of the supposed relapse cases actually be people infected and then re-infected in a short time? I covered for Forbes one case of infection of a person with the Omicron variant within 20 days of infection with the Delta variant. But it’s unclear how common it can be to get two separate infections in such a short time.
Ultimately, more studies, more data, and more drug monitoring are needed. All of this reminds us that while Paxlovid can be a very useful element in dealing with the pandemic, it is not a magic pill. Nothing in life is a magic bullet with the possible exception of avocados or chocolate. Relying solely on medication to “save” you if you were to catch Covid-19 could be like relying on finding a soul mate to save you from your current life. Don’t think that the existence of Covid-19 treatments can cause you to forego other Covid-19 precautions such as wearing face masks 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 individual precaution or treatment has its specific set of holes. And the hole thing means you should always layer at least several interventions on top of each other as long as the pandemic continues and the virus circulates widely around you. If you don’t maintain other Covid-19 precautions and rely solely on getting Paxlovid when needed, the Covid-19 coronavirus could very well catch you on the rebound.