BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: PAXLOVID

Pockets Galore! Pockets of COVID-19 Antigens are Stuck in the Body and are Causing Long COVID

Do you know someone who has long COVID? It turns out that they may have pockets of SARS-CoV-2 hiding in their body! 

Researchers at University of Colorado’s Anschutz Medical Campus have found in a recent study that patients who suffer from long-term COVID symptoms (called PASC) have 100x more SARS-CoV-2 specific T cells than those who have recovered fully from the virus.  This discovery suggests that the virus itself lingers in the body, not that symptoms continue even after the virus has left.  

This evidence will allow doctors and researchers to shift the mentality surrounding treatment of PASC, as prevPaxlovidiously the only option was to treat exclusively the symptoms.  The shift has led them to antiviral medications (such as Paxlovid) and vaccines, both of which use adaptive immunity to their advantage.  The study found that the body’s natural adaptive immune response focused on systemic inflammation, pulmonary symptoms and reduced lung function because of the high levels of T-cells in the body.  The T-cells are very important in the primary stages of the infection because they help identify and destroy infected cells, however after controlling the infection, it creates longer symptoms, along with continued shortness of breath and lung damage.

About 20-30% of patients infected with COVID developed PASC.  Over the course of over 500 million COVID infections, healthcare systems are pressed to support 150 million patients with lasting symptoms, so a solution is a priority for physicians.  The upcoming solutions’ primary goal is to clear the virus from the body entirely so that T-cell levels decrease back to a normal level.  

In addition to identifying the higher levels of T-cells, the researchers found that the higher the level of SARS-CoV-2 specific T-cells there were in the body, the higher the inflammation levels there were in the body, showing that the T-cells play a role in creating lasting inflammation associated with PASC.  

The next step for the researchers is to continue to do research on the differences in lung cells between people with PASC and people who have not had COVID.  They claim that this research is vital because the “kitchen sink symptomatic treatments have not solved the problem” (Palmer).  

Is The Virus That Has Turned Our World Upside Down Able To Be Solved With a Pill?

The scientific method of developing a hypothesis, testing the hypothesis, collecting the data and presenting the data to other scientists has led the world to many of its greatest scientific accomplishments. As we face greater and greater scientific problems each year, it is necessary to continue this method to find the best treatments for the world’s diseases. Covid-19 and its variants will continue to be at the top of the world’s problems since we see that vaccines don’t stop the spread of the disease and we just don’t know what new variants will do. To solve this, scientists are working hard to create new drug solutions to treat this deadly virus once a patient has been infected. The most recent being the Merck and Pfizer’s pills: Molnupiravir and Paxlovid. Both of these drugs are to be ingested soon after noticing symptoms. Both have shown promising results, but if we want this pandemic to be over with so we can get back to normal, we need assurances that these pills work now and for the coming variants.

Pfizer tested their antiviral combination Paxlovid pill and found that their pill works with an astonishing 89% decrease in hospitalization given in a 3 day symptom onset. When given within 5 days it was slightly less, yet still an improvement from our current numbers. Their research found three of the 389 people with Covid-19 (.08%) were hospitalized, compared to a 27 out of 385 (7%) in the placebo group. The pill is a protease inhibitor, just like the ones used to help stop the spread of HIV. It stops the action of protease, which halts the ability of the virus to replicate. Paxlovid uses a decades-old HIV drug, called ritonavir, that accelerates the protease inhibitor. With this data, the FDA approved Paxlovid just before Christmas.

Pfizer (2021)

Merck partnered with Ridgeback Therapeutics to produce their molnupiravir pill. It is a nucleoside analog, meaning it is an artificial building block of RNA, this introduces errors into the DNA of the Covid virus so it can’t replicate. The early trial stages gave a 48% reduction of the chances of hospitalization or death. The trial stopped once these results were revealed in hopes that it would be distributed to the public early. It was approved by the FDA one day after the Pfizer drug, but can’t be used in kids because of side effects. The effective success rate of the drug later dropped to 30%, so much lower than the Pfizer drug. After staying at a 30% success rate, there were more problems that arose. Due to it being a nucleoside analog, it was shown to be able to potentially harm human RNA in pregnant women. There were animal tests completed that showed both growth problems which would make it impossible to give the pill to pregnant women, children, or adolescents. Lindsay Baden, an infectious disease doctor who was apart of the FDA’s advisory committee said the drug might be helpful for “the right patient population, the right virus at the right time.” Ridgeback and Merck recently decided to let developing, poor countries make molnupiravir so that the drug can help countries that can’t usually afford expensive medicine we buy in the USA.

Merck & Co

Although a lot of the world is desperate for a swift end to the virus that has changed our lives over the past 2 years, these studies have shown how difficult this virus is to prevent and treat. Paxlovid looks like the most usable and safe drug to take when it is compared to molnupiravir.

Understanding Merck’s Molnupiravir

Since the beginning of the pandemic, research of antiviral medicines and drugs have only become more specific with combating the Coronavirus. Merck’s new drug, Molnupiravir, was a result of pharmaceuticals amplifying research on Covid. The foreshadowing of this drug shows a bright future and an end to Covid-19 once and for all.

Merck applied for authorization first in October and many praised the new drug as a potential game-changer. Pfizer submitted their version of medication called Paxlovid in November. The Food and Drug Administration has provided emergency use authorizations for pills from both Merck and Pfizer while scientists continue to study the real-world effectiveness of both. Molnupiravir is administered as four 200 milligram capsules taken orally every 12 hours for five days, for a total of 40 capsules. It is not authorized for use for longer than five consecutive days where its use seems to be feasible to all users.

Molnupiravir works by introducing errors into the SARS-CoV-2 virus’ genetic code where it prevents the virus from further replicating. Dr. Shaw, a Yale Medicine infectious diseases specialist, explains when the drug enters your bloodstream, it blocks the ability of the SARS-CoV-2 virus to replicate, a Yale Medicine infectious diseases specialist, Dr. Shaw explains. The coronavirus uses RNA as its genetic material. The structure of Molnupiravir resembles the nucleosides (or chemical building blocks) used to make the virus’s RNA. The drug works by incorporating itself into the RNA as it’s being synthesized where it “results in many mutations, or changes in the RNA genetic code, introduced into the viral RNA,” says Dr. Shaw. “And when this RNA is translated into viral proteins, these proteins contain too many mutations for the virus to function.” If this disables replication and RNA’s ability to infect our cells, we will not be as sick from Covid no longer.

An early report showed the Merck drug cut the risk of hospitalization and death to 50% in patients who had mild-to-moderate cases. Results from the Molnupiravir clinical trial, conducted in the U.S. and other countries, suggested the drug would be effective against CDC “variants of concern,” including the Delta, Gamma, and Mu mutations. Scientists are still studying how well the drug works to treat Omicron and are optimistic since its application is the same with Omicron’s RNA.

While this is exciting news, the vaccine many researchers, scientist, and doctors say is still our first line of defense. Some are even concerned that the attention on Molnupiravir will “draw attention away from vaccination,” says Dr. Meyer. “Some people might say, ‘I’m not getting vaccinated because I’ll have access to these medications’—to this pill or to remdesivir or other treatments. But you can’t trade one for the other. If you haven’t done so already, the most important thing is still to get the vaccine.”

PAXLOVID: A Breath of Fresh Air?

Right now, it seems like the only defense against the evasiveness of COVID is the vaccine. However, there has been a new emergence that might help alleviate some worries. This is the PAXLOVID anti-viral drug. This new drug is given to people with high-risk cases of COVID a few days after they are infected. Though, before this pill is approved, it has to run through many trials, and it has to be confirmed by the FDA (Food and Drug Administration). The numbers that are coming out of the trials of the drug are nothing short of astonishing….

Pfizer made the announcement that within 3 days of infection, the PAXLOVID drug reduces the risk of hospitalization or death by 89%. The trials for the drug were over a substantial amount of time. The numbers that have been received as of now are that out of 607 people tested, only 6 were hospitalized and NONE died. These are very promising numbers for the drug, and it is a big step towards approval. To further boost PAXLOVID’s credibility, placebo, a “control” drug was tested alongside PAXLOVID. This control drug is a fake pill to make people believe it is doing good for them. This is called the placebo effect. In the end, the fantastic numbers produced by PAXLOVID against placebo proved that PAXLOVID is the way to go and that it is a successful drug that actually works. Now you may be wondering how does this “anti-viral drug” work to defend against COVID?

The answer is not so simple. The primary goal for PAXLOVID, and any other anti-viral drug is to prevent the virus from replicating. As we learned in our biology class, the way a virus replicates itself is by entering the dendritic cell or macrophage, then it can actually copy RNA virus and take command of the cell, basically hijacking it. However, the anti-viral drug is made up of two clear components that instead of interfering with RNA copying enzyme, it blocks something else. The drug has the ability to inhibit Protease enzymes. Protease enzymes are mainly responsible for activating long strains of protein by cutting them down.

Altogether, PAXLOVID is a versatile, and very useful drug that we will likely be seeing and hearing more about in the near future. If you contracted COVID, would you be willing to take PAXLOVID?

Prozac pills

Paxlovid and Molnupiravir: Our First Steps Toward Covid-19 Treatment?

Currently, the new Covid-19 variant Omicron is taking the world by storm. Originating in South Africa as of late November, it was considered a variant of concern(VOC) by the WHO on November 26th and the first US case was identified on December 1st. While masks and current vaccination provide significant protection against Covid-19 strains, there is always a chance of breakthrough infections

In response, both Merck and Pfizer have developed novel antiviral pills in attempts to treat Covid-19 symptoms. It is known that cures for viral diseases do not exist, since viruses tend to mutate extremely fast. However, there exist novel drugs that promise to alleviate Covid-19 symptoms in the early stages of infection, like Pfizer’s Paxlovid and Merck’s molnupiravir. 

It is known that Covid-19 infects human cells by its outer spike proteins attaching to ACE2 receptors on the outside of the cell membrane. When in the cell, Covid-19 viral pathogens insert their viral RNA into our cytoplasmic ribosomes, which then codes for the creation of new viruses that then get excreted by the human cell. Merck’s molnupiravir consists of a five day treatment in which mutations to the viral RNA are introduced, since molnupiravir resembles viral nucleosides, causing irregular viral replication and, ultimately, an inability for the Covid-19 viral population to collectively survive in their human host. Pfizer’s Paxlovid pill, on the other hand, is administered in the early stages of Covid-19 infection to stop the progression of the disease and to prevent severe Covid-19 symptoms by inhibiting protease enzymes from functioning, which leads to the inability of virus proteins to become segmented and to spread, leading to dysfunctional Covid-19 viral pathogens and the ultimate death of Covid-19 viruses in the human host.Omicron

Fortunately, these two treatments are showing promising results in current clinical data trials. According to a Merck Sharp and Dohme (MSD) clinical study, 14.1% of placebo-treated patients were admitted to the hospital or had died of Covid-19, while only 7.3% of molnupiravir-treated patients were either hospitalized. In addition, at the end of the trial, 0 deaths were recorded in the monopiravir trial, while 8 deaths were reported among the placebo group. These results lead MSD scientists to deduce that the novel molnupiravir to reduce hospitalization or death by 50%. 

Pfizer’s Paxlovid, on the other hand, is especially promising in its clinical results. According to a recent Pfizer clinical data trial, 7% of the placebo group was hospitalized, and 7 died, while a staggering .8% of Paxlovid-treated Covid-19 patients were hospitalized, with 0 deaths by the end of the trial. These results lead Pfizer to state that “Paxlovid is 89% effective at patients in risk of serious illness,” as reported by Pfizer CEO Albert Bourla. 

In conclusion, although Covid-19 cannot have a fixed “cure,” outside of a vaccine of course, yet convenient, short-course antiviral pill treatments like Pfizer’s Paxlovid and Merck’s molnupiravir provide promising clinical trial results that show efficacy in reducing hospitalization and death rates due to Covid-19. While clinical data trials provide important markers of understanding Covid-19 treatment, it is still impossible to predict the practical applications of these pill treatments in the real world. Who will have access to these pill treatments? How will they get distributed? Will these treatments create global and regional socioeconomic disparities? In the eyes of these questions, our current vaccination protocols remain firm. While novel Covid-19 antiviral treatments are a huge step against Covid-19, the necessity for society to continue vaccination, as well as attempt to reach herd immunity levels, still holds utmost importance. 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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