BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: COVID-19 (Page 1 of 4)

Novel Nanobody Treatment Could be Used to Treat Animals Infected with SARS-CoV-2

As we have learned in AP Biology class, the spike protein, or S protein, is located on the surface of SARS-CoV-2 is linked to transmissibility and cell entry. Located on the S protein is the receptor-binding domain (RBD) which is a key factor that allows the virus to dock to body receptors and invade host cells. Effective antibody therapeutics target S proteins.

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Due to their small size and ability to penetrate into lung tissue, nanobodies have been speculated to be an excellent source for novel COVID-19 antibody therapeutics. A recent study measured these proposed capabilities for potential usage as a treatment. The proposed therapeutics would be used in veterinary medicine and aim to directly prevent SARS-CoV-2 pseudoviruses from compromising host cells.

The researchers screened and sequenced specific nanobodies, then, they were produced and amplified. The study validated the speculation by observing the carefully selected nanobodies bind to the SARS-CoV-2 S protein and RBD protein simultaneously. 85% of pseudoviruses were observed to be inhibited in a solution with 100mg of nanobody concentration.

What makes nanobodies even more attractive for usage in veterinary medicine is that its inexpensive to produce and can be made in large amounts. Given these beneficial qualities of nanobodies, they seem to be a plausible and favorable COVID-19 treatment.

The Promise of Messenger RNA Therapy

A recent article about messenger RNA therapy outlines the evolution of messenger RNA therapy and how it has gone from an idea to a globally used treatment in just the past seventeen years. Recently, messenger RNA therapies such as the Pfizer-BioNTech and Moderna COVID-19 vaccines have been used by hundreds of millions of people around the world. 

The author Drew Weissman, a vaccine research professor at the University of Pennsylvania, and his colleague Katalin Karikó created mRNA molecules back in 2005 that would not cause harm when injected into animal tissue. Then in 2017, Weissman and Norbert Pardi found that this mRNA creation could be brought into human cells through a fatlike nanoparticle without harm, and that bringing this modified mRNA in protect mRNA from being broken down by the body and resulted in the immune system generating antibodies and more effectively neutralize the invading virus. Vaccines-09-00065-g001This mRNA fatlike nanoparticle is known as mRNA-LNP (pictured to the left). mRNA is able to enter cells without harm because it is carried in by this liquid nanoparticle which is known for its role in transportation. The Pfizer-BioNTech and Moderna COVID-19 vaccines use this mRNA-LNP, and in clinical trials have shown to successfully prevent over 90% of treated people from contracting COVID-19.

The positive results from many trials and studies of the Pfizer-BioNTech and Moderna COVID-19 vaccines have provided a lot of information on the success of mRNA-LNP. It has been found that mRNA-LNP is much more effective and quicker than other approaches to COVID-19 treatments such as growing vaccines in laboratory cell cultures. 

41541 2020 159 Fig1 HTMLMessenger RNA therapy works by making cells create proteins that induce a reaction from the immune system in response to invading viruses (pictured to the right). This reaction in response to invading viruses is called the humoral response, where cytotoxic T cells are made to release proteins that destroy infected cells. The humoral response also trains the immune system to respond to and attack that virus in the future by creating memory B cells to recognize it, which is called a secondary immune response.  This method of instructing cells to create these proteins yields a greater quantity at a time that conventional protein and monoclonal antibody therapies. 

The success of messenger RNA therapy in COVID-19 vaccines has inspired the further research and use of this method for other viruses, as well as cancers, food, allergies, and autoimmune diseases, and many clinical trials are underway. Messenger RNA therapy could be a much more time and cost efficient alternative for a lot of conditions and treatments. More research still needs to be done, and there are many improvements that could be made (such as smaller doses of or a better supply chain for the vaccine), but overall messenger RNA therapy is very promising for treatments of the future.

Could Sharks be the Solution to Ineffective SARS-CoV-2 Antibody Treatments?

Sharks are often associated with gruesome stories of attacks and horror. However, lead researcher at the University of Wisconsin-Madison School of Medicine and Public Health, Dr. Aaron LeBeau believes sharks deserve to be recognized in a more positive light– due to their potential for creating advanced neutralizing antibodies (NAb) therapeutics for treating SARS-CoV-2.

Ginglymostoma cirratum bluffs

Neutralizing antibodies have demonstrated efficacy in treating SARS-CoV-2 in previous trials. In the recent past, the FDA authorized two NAb therapeutics for emergency use for SARS-CoV-2. However, the effectiveness of these two treatments has been complicated by the development of new variants with highly mutated target antigens. These naturally occurring mutations in the target antigen result in insufficient neutralization of the virus when using those current therapeutics derived from classical human antibodies. 

This is news for concern as genome sequencing exposed the virus to create two single-letter mutations each month

As we learned in our AP Biology class, mutations to proteins such as SARS-CoV-2 antigens occur within the amino acid chains in the protein’s primary structure. These changes in chemicals could alter the kinds of covalent or ionic bonds in the protein’s tertiary structure. This, of course, changes the antigen’s three-dimensional shape. This is why the original NAbs have experienced diminished performance as new variants emerged. The antibodies from the treatments simply could no longer recognize the virus’ new antigen structure.

Therefore, there is a dire need for the development of new, more specialized NAbs, that can recognize the newly mutated epitopes that are currently incompatible with current neutralizing antibody therapeutics.

Dr. Aaron LeBeau believes that key findings for creating more efficient NAb treatments could be derived from the likes of nurse sharks! Within the immune systems of sharks, antibody-like proteins called Variable New Antigen Receptors (VNARs) were found to be highly effective at neutralizing coronaviruses, according to his recent publication in the Nature Communications journal.

Due to the small and highly specialized structure, VNARs are able to access and bind to epitopes that human antibodies normally couldn’t. This superior ability allows VNARs to reach deep into pockets and grooves within the target antigen, allowing for a better fit and neutralization. Dr. LeBeau’s research team concluded that their data suggests that VNARs would be effective therapeutic agents against emerging SARS-CoV-2 mutants, such as the Delta and Omnicron variants. 

With the help from researchers from the University of Minnesota and the Scottish biotech company, Elasmogen, the team hopes to develop the shark antibodies for therapeutic use within 10 years.

Do you think this is promising news? How do you feel about using shark “antibodies” in place of our own for serious cases of SARS-CoV-2? Assuming it’s safe, effective, and accessible to you, would you accept this treatment if you contracted a serious case of SARS-CoV-2? Please leave your thoughts in the comments.

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.

Omicron’s Effect on the Vaccinated by Vaccination Status

As the world continues to be stricken by the seemingly everlasting wave of strains of Sars-Cov-2, the vaccine began to give people hope as it was extremely effective against the original disease as well as all the other strains up until now. With sudden jump in corona cases, researchers have discovered that there is a new virus that is soon to take over as the most prevalent virus in the world. It’s been named Omicron but the question that is on a lot of people’s mind is if this new strain will be hindered by the vaccine or will it continue on its rampage across the world.

Study Participant Receives NIAID-GSK Candidate Ebola Vaccine (3)

Studies show that the answer is dependent on vaccination status. Omicron has accounted for “90% of COVID cases in areas like the Midwest” states Doctor Rochelle Walensky. The article later goes on to state that the booster vaccination shot ” increased by 25-fold people’s levels of virus-fighting antibodies.” Ultimately the amount of vulnerability you have to this new strain is directly tied to how many vaccination shot you have. But why do we even need a booster shot if the first two doses should have been enough? Well to answer this question we first need to look at how the initial two doses work. The CDC states that “Vaccines work by stimulating your immune system to produce antibodies, exactly like it would if you were exposed to the disease.”  As we learned in our AP Biology class, by giving you a small amount of sars-cov-2, the dendritic cell is able to enlist the help of plasma B cells and memory B cells by sending out T helper cells. This is known as theHumorale Immunantwort humoral response and is what gives you the ability to fight off breakthrough infections as well as help hinder the symptoms of sars-cov-2. It is able to suppress symptoms as well as prevent reinfections because once your body has fought off a little bit of the virus with the antibodies created by B helper cells your body is able to make a copy of how to deal with it in your B memory cells. The memory B cells are what give you your immunity to the virus. However over time they do run out as you were only given a small amount of the virus so this is where the booster comes into affect. The booster shot is designed so that your body is able to continue to get stimulated by the virus so that you B plasma and helper cells are able to keep memorizing and keep fighting off small (in the case of the vaccine) or big (in the case of an actual infection) Covid cases. There may continue to be more booster that you must take in order to keep your immunity, and no its not because the chip is running out of battery or they want to keep injecting you, but its due to the fact that your body simply can’t remember such a small amount of the virus for very long and if you don’t get the booster you are 25x more likely to contract Omicron than those who have all three. Ultimately the vaccine is still effective against Omicron, however Omicrons ability to be more infectious than any other variant before it is why it was able to take over the world so quickly. That being said there is a very real possibility that there will be a Omicron centered booster shot that will be significantly more effective than the past three shots against this devastating variant. Feel free to let me know how you feel about Omicron, a special new booster, or about how that Vaccine works down below.

 

Will Shark Antibodies Help Create an End to the COVID-19 Pandemic?

A recent study shows that shark antibodies, known as VNARs, haven proven to be effective in halting the infection of WIV1-CoV in human cells. WIV1-CoV is a type of coronavirus, currently only circulating in bats, where SARS-CoV-2 likely originated from. The study has shown that while this method of COVID-19 prevention is not ready to be put to use yet, it can be used in future SARS outbreaks. 

The anti-SARS-CoV-2 VNARs, unlike human antibodies, are very small and are able to fit in tiny nooks where human antibodies can not fit. The VNARs have the ability to bind to the infectious coronavirus proteins and block their ability to connect with and infect human cells. These shark antibodies were tested against SARS-CoV-2 and a different version of this virus that is unable to replicate in cells, known as a pseudotype. After testing a pool of billions of possible VNARs, three effective candidates were identified. 

Tiburón azul (Prionace glauca), canal Fayal-Pico, islas Azores, Portugal, 2020-07-27, DD 28

The most effective VNAR is called 3B4. The 3B4 VNAR attaches itself to a small groove on the spike protein of the SARS-CoV-2 virus; this process effectively blocked the SARS-CoV-2 spike protein from binding to the human cell. This process is very similar to the actions of a competitive inhibitor. As we learned in AP Biology,  a competitive inhibitor is when a compound, similar to the substrate, competes for the same active site.

These shark VNARs are so important to the research against future and current coronavirus outbreaks because it is effective against all variants of this virus. As stated earlier, these antibodies stop the infection of  WIV1-CoV in human cells; because it halts the infection of the virus where COVID-19 likely originated from, it will be effective to all COVID-19 variants. Additionally, with more research these different antibodies can be used together if proven to be more effective. The shark antibodies are cheaper and easier to manufacture compared to human antibodies. While this method of protection against COVID-19 has yet to be tested on humans, with more research this could be the new way that humans protect themselves against all SARS-CoV viruses to come. What do you think?

 

 

Optimus Prime, Megatron, Proteins? The New Transformer Vaccine Candidate!

Amid the global outbreak of COVID-19, with no end in sight after nearly two years, the future wellbeing of humans is in danger. Coughs, fevers, and shortness of breath have lent way to millions of deaths across the globe. As thousands of researchers relentlessly work to find solutions to this virus, multiple vaccine candidates have emerged. Specifically, in the United States, millions of Americans have received doses of the Pfizer-BioNTech, Moderna, and Johnson & Johnson’s Janssen vaccines. However, scientists at Scripps Research recently recognized a new, self-assembling COVID-19 vaccine as a potentially more efficient and effective way to fight this worldwide battle.

 

Primarily, it is critical to understand how vaccines function as they help protect the immune system. The COVID-19 vaccines currently in effect are mRNA-based; in other words, the messenger RNA signals one’s body to produce a harmless viral protein that resembles the structure of a spike protein. The body, with the help of T-Helper cells, recognizes this structure as a foreign invader as B cells bind to and identify the antigen. The T-Helper cells will then signal these B cells to form B-Plasma cells and B-Memory cells. When getting the vaccine, the B-Memory cells are especially important as they prevent reinfection. This is a process known as adaptive immunity. Here, in the event of future infection with the spike-protein COVID-19, the memory cells would help carry out the same response more quickly and efficiently. Essentially, this process acts as the body’s training in case of any future infections.

 

While the Scripps Research COVID-19 vaccine would evoke a similar immune response to that described above, it differs from other candidates in how it assembles in the human body; this new vaccine would be comprised of proteins that are able to self-assemble. On their own, these nanoparticle proteins would transform into a sphere protein structure surrounded by smaller proteins, mimicking the coronavirus’s shape. Here, the self-assembled spike proteins are more sturdy and stable than in an mRNA-produced structure. Thus, it more accurately prepares the body for future infection with COVID-19. In fact, multiple tests found that mice who were given the experimental vaccine were able to fight off not only SARS-CoV-2 but also SARS-CoV1 along with the alpha, beta and gamma variants.

 

Nonetheless, influencing the public to get a newer vaccine instead of the well-trusted vaccines already in production requires proof of the candidate’s benefits. Primarily, as mentioned, early results find that this new candidate would perform well with many different strains of COVID-19. Additionally, researchers assert that this vaccine would be relatively simple to produce on a mass scale. Lastly, scientists found that this vaccine may well be more protective and long-lasting than current vaccine candidates. Although the process of vaccine approval is lengthy and often difficult, I am hopeful for the future of the Scripps Research vaccine if it is put into production. Moreover, I believe that such experimentation with self-assembling nanoparticle proteins transcends the current pandemic. The benefits of this field present a wide array of opportunities, and I look forward to seeing what its future may hold.

 

What do you think? Are these transformer-like self-assembling particles a gateway to the future of medicine or an unnecessary distraction from effective treatments already in circulation?

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?

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The Key to SARS-CoV-2 Survival

Can your chance of surviving SARS-Cov-2 be predicted? It sure can be due to recently combined research efforts by ISB, Fred Hutchinson Cancer Research Center, Stanford University, Swedish Medical Center St. John’s Cancer Institute at Saint John’s Health Center, the University of Washington, the Howard Hughes Medical Institute. It comes from studying your immune system and a special part of your endocrine system, your metabolism

The researchers sampled the blood of nearly 200 COVID-19 patients. They took two draws per patient during the first week after being diagnosed with SARS-CoV-2 infection, totaling 374 blood samples. The researchers then analyzed their plasma and single immune cells. The analysis included 1,387 genes involved in metabolic pathways and 1,050 plasma metabolites. 

“We analyzed thousands of biological markers linked to metabolic pathways that underlie the immune system and found some clues as to what immune-metabolic changes may be pivotal in severe disease,” says researcher and graduate student from Fred Hutchinson Cancer Research Center, Jihoon Lee. Well, what were these clues? The clue is the link between how certain metabolic changes regulate how immune cells react when it comes to disease severity and predicting patient survival. Basically, increased COVID-19 severity leads to increased immune-related activity. 

Image drawn by author

With these new discoveries, researchers used single-cell sequencing to further investigate. They found that each major immune cell type has a distinct metabolic signature. “We have found metabolic reprogramming that is highly specific to individual immune cell classes (e.g. “killer” CD8+ T cells, “helper” CD4+ T cells, antibody-secreting B cells, etc.) and even cell subtypes, and the complex metabolic reprogramming of the immune system is associated with the plasma global metabolome and are predictive of disease severity and even patient death,”  says Dr. Yapeng Su, a research scientist at Institute for Systems Biology.

Despite the need for more advanced single-cell multi-omic analysis, this research has proven to be very successful. It provides significant insights for developing more effective treatments against COVID-19. What do you think about this research being used for predicting survivability for other diseases to come? 

Not 1, But 2: The Antiviral Pills That Could Change The Game For Covid-19

Right on time. As cases begin to rise again due to the omicron variant of SARS-CoV-2, the race for treatments against the virus becomes more urgent. Well, celebration is in order, for both Merck and Ridgeback Biotherapeutics and Pfizer have developed antiviral drugs in the form of a pill to fight the virus. 

Molnupiravir, the drug created by Merck and Ridgeback Biotherapeutics, and Paxlovid, Pfizer’s antiviral pill, are both pills that can be taken at home when one identifies early signs of Covid in themselves. For Merck, the latest data reads that their pill cut the rate of hospitalization or death by 30%. On the other hand, Paxlovid’s trial displayed reduced death and hospitalization rates of 89%, as long as the pill was consumed within 3 days of symptoms. 

Both effective medications and exciting progress, these two contrasting antiviral pills work in two distinct ways to stop viral replication. As we learned in AP Bio, viral replication is what occurs when a virus escapes the innate immunity responses, or the 1st line of defense, and enters the nasal epithelium, replicating in nasal passages and tissue fluids. This is what makes immunity responses to viruses often a long process, and is why we have to take sick days to allow time for our B and T cells to destroy the many invading pathogens and infected cells, respectively. A nucleoside analogue, Molnupiravir disguises as one of the aspects of RNA that makes up SARS-CoV-2. Normally, once inside the cells the virus would use a polymerase enzyme to assemble all the pieces of RNA into new copies of viral RNA, ultimately replicating itself. However, with the Molnupiravir drug’s deception, the virus creates new versions of itself with defective genetic materials, making it noninfectious. In juxtaposition, Paxlovid has a similar process of HIV treatments in that it is a protease inhibitor. After replicating its RNA, SARS-CoV-2 makes a large polyprotein containing all of the virus’s parts. But to function properly, this polyprotein must be broken into many small pieces by the enzyme protease. What Paxlovid does is it blocks that enzyme from its function, preventing the necessary production of small virus particles. Again like protease inhibitors for HIV, though, the Pfizer drug requires a second drug called ritonavir to make it last longer (like a booster).

COVID-19 Virus

Because both of these antiviral pills target the immune response in a general, nonspecific way (the replication process), they can work similarly against many different coronaviruses found in animals such as ​​bats, pigs, people, and mice. This is not only reason to believe these pills will probably be effective against other variants such as omicron, but it also means this scientific progress plays a role in fighting future pandemics, as well as the current one. 

While it is easy to get caught in the incessant loop of bad news concerning the pandemic, especially lately, I recommend balancing that awareness of threats with the acknowledgement of the improvements and steps forward, for everyday scientists are hard at work fighting this pandemic. In a similar lens, our work in AP Bio with beginning to understand immunology and how viruses work is our baseline in becoming the future of medicine, doctors, and scientists!

A New Way Of Detecting the COVID-19 Virus

In a study conceived by Mayo Clinic investigators it was found that Artificial Intelligence may offer a new way of detecting if a person has contracted Covid-19. Researchers found that the Covid-19 virus creates small electrical changes in the heart that Artificial Intelligence (AI) can detect and be used for a new form of a rapid, reliable test. Since Covid-19 has a 10-14 day incubation period, symptoms take long periods of time to show up. Once patients do show symptoms it is hard to access a reliable Covid test with fast results. An Artificial Intelligence enhanced EKG is a rapid and cost effective alternative for Covid testing.

Covid - 19 virus

This study was done on a racially diverse population of volunteers from 14 different countries. Patients selected had previous EKG data from when they were diagnosed with Covid-19. This data was compared with the EKG data of patients not infected by Covid-19. AI was then trained to detect the subtle changes in the heart by more than 26,000 EKG’s and tested on 7,800 EKG’s that were not previously used. The prevalence of Covid-19 was about 33% and the accuracy of the negative predictive value of the AI was about 99.2%.

For any form of Covid test, accuracy is the most important value. The study shows the consistency of biological signals in the EKG and the Covid-19 infection. To confirm that Artificial Intelligence will be a helpful factor in our fight against the pandemic, this study needs to be tested on asymptomatic people.

In AP biology class this year, my class has learned about sending signals between cells. A heartbeat happens when the SA node (pacemaker of the heart) sends out an electrical impulse.The upper chambers of the heart contract and the AV node sends an impulse into the ventricles.The lower heart chambers then contract and the cycle starts over again.

Is A Vaccine Update On Its Way?

On December 11, 2020, the Pfizer-BioNTech COVID-19 vaccine was approved for its first public use. Since that day, there have been multiple variants of the virus, varying in their mutations from the original strain. One of these strains, in particular, is the Omicron variant. This variant is a new strain of COVID-19 and was first identified on November 24, 2021, in Botswana. With the emergence of this new unknown variant, in addition to all of the past variants, has the time come for an updated vaccine that is tailored specifically to the variants? This question is explored in the Bloomberg article Third Pfizer-BioNTech Dose Is Ket To Fight Omicron’s Spread

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After researching the Omicron variant in relation to two doses of the COVID-19 vaccine, there was seen to be a 25% reduction in antibodies capable of fighting the virus. However, after a third dose of the vaccine, increased antibody levels close to that of those made for the original COVID-19 strain. With this information in mind, Pfizer stated that an Omicron-specific vaccine may be required. This new vaccine is projected to be ready for the public by March of 2022. The company also stated that their vaccine would change from a two-dose to a three-dose vaccine with the third shot being for Omicron. The third shot would be administered about three months after the first two doses have been given.

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While the public is waiting for the third dose from Pfizer, Pfizer says that people should use their current vaccine for a third dose, as it would give further protection against the virus. Then, once the Omicron vaccine comes out in early 2022, people should get a dose of that vaccine as well. This new strategy of getting the vaccine is due to new research from multiple labs on the effectiveness of the vaccine on the Omicron variant. An original observation saw a 25 times drop in antibodies, but two other labs found that there is actually a 40 times reduction with this variant. Globally, South Africa found a 41 times drop in antibodies, and a 37 times drop from a German lab. With this research, Pfizer is beginning to look into an Omicron vaccine but must find that it heavily increases protection against the new variant, and if not it will keep the current vaccine in circulation. There is also speculation about a yearly booster for the vaccine, but there must be research conducted on that as well.

Can HCQ(Hydroxychloroquine) Prevent COVID-19 Infection and Help Recovery? The Research Says “No”

Have you ever wondered what chemicals and such are being used to treat and illness you have? HydroxychloroquineWell, for treatment of the COVID-19 vaccine, one of the chemicals used is hydroxychloroquine (HCQ), also known as Plaquenil. HCQ is a immunosuppressive drug and anti-parasite that can treat and prevent malaria, lupus, and arthritis.

HCQ was used as pre-exposure prophylaxis against COVID-19 infection in healthcare workers as a study. There were 1294 participants from ages 24-38 with 61% being women. 273 (21.1%) of the participants were healthcare workers but still 83 (6.4%) of them tested positive after duty. This showed that the use of HCQ had no effect on the prevention of the COVID-19 virus.

What made hydroxychloroquine an option used in preventing COVID-19 in the first place? Symptoms of coronavirus disease 2019 2.0There are typically four phases of a more severe version of COVID-19. The first phase would be the incubation period that has a median of 5.1 days. After that is the second phase which lasts around 5-10 days where flu-like symptoms arise. These include, fever, cough, muscle pain/soreness, fatigue, nausea, and diarrhea. Up until the second phase, the severity of the illness can be considered normal. After the second phase, there is normally a progression to a hyperinflammatory acute respiratory distress syndrome (ARDS). ARDS is a life-threatening lung injury that makes breathing difficult. As the second phase progresses onto the third phase, ARDS causes dyspnea, tachypnea, and sometimes hypoxemia making a person extremely out of breath and in need for hospital care. During this third phase, a person affected severely of COVID-19 will normally have high fevers with elevated inflammatory markers and progressive formation of organ failure. For some of these severe cases of COVID-19, effective treatments were desperately needed.

From data of previous epidemics, HCQ have been widely used around the world for Ebola, H7N9 influenza, and SARS virus infection. HCQ has been used to treat a number of auto-immune diseases by raising intracellular pH and affect endosomal activity. However, in the case of COVID-19, HCQ has no positive effect in preventing the coronavirus and may even cause more harm to our bodies.

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As an immunosuppressive drug, it made sense to give HCQ to patients with early onset of COVID-19 and as a pre-exposure prophylaxis. HCQ impacts cytokine production and suppresses antigen presentation. The medication was used in various ways: as an oral medication by itself to take before contracting COVID-19, taking it after contracting COVID-19, and combined therapy with azithromycin. None of these ways had a surprising result in preventing COVID-19 or with helping a person recover. It was then believed that the impact of cytokine production and suppression of antigen presentation may cause immunologic consequences resulting in the hampering of the innate and adaptive antiviral immune response, possible making it more dangerous with patients with COVID-19. It has been determined that HCQ is not suitable for the treatment of COVID-19.

The process of proving HCQ effectiveness in fighting COVID-19 can be related to AP Biology because of the way the medication works with the immune system. Hydroxychloroquine is a medication that can raise intracellular pH and affect endosomal activity. Acidity of cell pH and endosomes are topics that we learned first quarter. In relation to the second quarter, HCQ is a immunosuppressive drug known to impact cytokine production and antigen presentation. Cytokines and antigens are part of the innate and adaptive immune system that we learned about recently.

The COVID-19 Vaccine: How, What, and Why

We have all seen the news lately – COVID, COVID, and more COVID! Should people get the vaccine? What about the booster shot? Are vaccines more harmful than COVID-19? Will my child have birth-defects? This blog post will (hopefully) answer most of your questions and clear up a very confusing topic of discussion!

Discovery of monoclonal antibodies that inhibit new coronavirus(Wuhan virus)

First off, what are some potential effects of COVID-19? They include, but are certainly not limited to, shortness of breath, joint pain, chest pain, loss of taste, fever, organ damage, blood clots, blood vessel problems, memory loss, hearing loss tinnitus, anosmia, attention disorder, and the list goes on. So, our next question naturally is: what are the common effects of the COVID-19 Vaccine? On the arm that an individual receives the vaccine the symptoms include pain, redness, and swelling. Throughout the body, tiredness, a headache, muscle pain, chills, fever, and nausea can be experienced. To me, these effects seem much less severe than COVID-19’s!

COVID-19 immunizations begin

Now that we have covered effects, you are probably wondering what exactly the COVID-19 Vaccine does – will it make it impossible for me to get COVID-19? Will I have superpowers? Well, you may not get superpowers, but your cells will certainly have a new weapon, which we will discuss in the next paragraph! The COVID-19 Vaccine reduces “the risk of COVID-19, including severe illness by 90 percent or more among people who are fully vaccinated,” reduces the overall spread of disease, and can “also provide protection against COVID-19 infections without symptoms” (asymptomatic cases) (Covid-19 Vaccines Work).

So, how does the vaccine work? Many people think that all vaccines send a small part of the disease into us so our cells learn how to fight it at a smaller scale. However, this is not the case with the COVID-19 vaccine! As we learned in biology class, COVID-19 Vaccines are mRNA vaccines which use mRNA (genetic material that tells our cells to produce proteins) wrapped in a layer of fat to attach to cells. This bubble of fat wrapped mRNA enters a dendritic cell through phagocytosis. Once inside of the cell, the fat falls off the mRNA and the strand is read by ribosomes (a protein maker) in the cytoplasm. A dendritic cell is a special part of the immune system because it is able to display epitopes on MHC proteins on its surface.

Corona-Virus

After being made by the ribosomes, pieces of the viral surface protein are displayed on the surface of the dendritic cell (specifically the MHC protein), and the cell travels to lymph nodes to show this surface protein. At the lymph nodes, it shows the epitope to other cells of the immune system including T-Helper Cells. The T-Helper Cells see what they’re dealing with and create an individualized response which they relay to T-Killer cells that attack and kill virus-infected cells. This individualized response is also stored in T-Memory cells so that if you do end up getting COVID-19, your body will already know how to fight it! The T-Helper Cells additionally gather B-Plasma cells to make antibodies that will keep COVID-19 from ever entering your cells. T-Helper Cells are amazing! As you can see, the vaccine never enters your nucleus, so it cannot effect your DNA! No birth-defects are possible!

You are now equipped with so much information and able to disregard many common misconceptions about the COVID-19 vaccine! Additionally, you can make an educated decision about whether or not you should get the vaccine. I think yes! If you have any questions, please feel free to comment them and I will answer. Thanks for reading!

 

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. 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Omicron: The Latest Invader

As it has been for the past few years, COVID-19 is the talk of the town. However, just when things seemed to be dying down, a new variant made its way into our lives. It goes by the name “Omicron”.

Unlike the past two variants, Delta and Mu, Omicron presents a whole new dilemma in the fight against COVID-19. After Delta took the world by storm with significantly greater infection rates than Mu, seemingly nothing could get worse. However, over 30 mutations to the spike proteins of the virus now trumps Omicron above all other variants. Identified in South Africa on November 24, 2021, Omicron has already made its way to many other countries around the world, including the US.

The threat of Omicron derives from its ability to resist the effects of the antibodies of the vaccine due to the changes in the protein structures. As we learned in our AP Biology class recently, the vaccine works by stimulating the production of plasma B cells, which secrete antibodies to identify and neutralize the antigen of the COVID-19 virus by recognizing the spike proteins, as well as B memory cells that exist to prevent further infection of the virus. The many changes to the spike protein make the antibodies unable to properly detect and neutralize it, allowing for the virus to continue to spread throughout our bodies. Virologist Penny Moore warns of the reduced effects the vaccine will have against Omicron, as well as the exponentially faster infection rates that pose threat to the world.

6VSB spike protein SARS-CoV-2 monomer in homotrimer

A recent study from a South African virologist, Alex Sigal, isolates blood samples from 12 Omicron infected patients who have been vaccinated with the Pfizer vaccine. The study shows that the antibodies from the vaccine are nearly forty times less effective against Omicron than the other two variants. This uncovers that the vaccine may not be efficient enough to combat the new virus. Sigal’s experiment also found that people previously infected with the virus held stronger immunity to Omicron than those with the vaccination. This is due to the fact that natural B memory cells made are able to evolve for multiple months to help fight against COVID-19 while B memory cells from the vaccine only evolve for a few weeks. Though, the experiment was not done with enough patients to make a certain conclusion.

Although, there is a glimpse of hope to retain some immunity against Omicron using the booster shot. Pfizer-BioNtech research has indicated that the third dose of the vaccine can produce antibody levels against Omicron that closely resemble the antibody levels of only two shots against the prior variants. Scientists have begun to branch off from the traditional concept of stimulating production of plasma B-cells to create antibodies in hope to find a new way to trigger the immune system to adapt to new COVID-19 variants. Biologist Jesse Bloom suggests a deeper dive into the function of T-cells, particularly cytotoxic T-killer cells, and their ability to destroy cells already infected with the virus.

Omicron poses severe potential threats to the state of the world with its fast infection rate and immunity to the vaccine. The studies of the few infected patients with Omicron do not seem to promising, but not enough has been collected about Omicron to determine its true potential. The only thing we can do now is hope for the best!

 

 

How COVID-19 Antibodies Are Causing Long-Term Effects

The COVID-19 vaccine has been essential in flattening the curve of the pandemic, but there have been reports of various side effects derived from the vaccine. These side effects include allergic reactions, heart inflammation, and blood clotting. These symptoms have been commonly thought to be because of the patient’s immune system. But, this question as to why these immune responses to both the vaccines and responses to the virus itself have been possibly answered in a new article in The New England Journal of Medicine.

COVID-19 vaccines (2021) A

Various types of the COVID-19 Vaccine

 

William Murphy and Dan Longo, both Professors of Dermatology and Medicine respectively, believe that the Network Hypothesis by Niels Jerne contains insight as to why these side effects occur. In this hypothesis, Jerne details the process as to which the immune system regulates antibodies. This process is a cascade, in which the immune system launches antibody responses initially to an antigen. These antibodies can trigger an antibody response toward themselves, causing them to disappear over time. Anti-idiotype antibodies, also known as secondary antibodies, bind and deplete the initial antibody responses. They have the ability to act like the original antigen itself, which would initiate side effects to the person. 

SARS-CoV-2

SARS-CoV-2 spike protein, the protein responsible for binding to ACE2 Receptors

SARS-CoV-2, the virus that causes COVID-19, enters the body by binding its protein spikes to the ACE2 receptor, thus gaining entry into the cell. The immune system then reacts by producing antibodies for the virus, which neutralizes the effects of the virus. However, these antibodies can cause immune responses with the anti-idiotype antibodies. These secondary antibody responses clear the initial antibodies, which results in the depletion of the initial antibodies and a weakened efficiency for antibody production. 

 

Murphy states that “A fascinating aspect of the newly formed anti-idiotype antibodies is that some of their structures can be a mirror image of the original antigen and act like it is binding to the same receptors that the viral antigen binds. This binding can potentially lead to unwanted actions and pathology, particularly in the long term.” He and Longo also believe that these anti-idiotype antibodies can also target the same ACE2 receptors. 

 

In an article published by The Conversation, the ACE2 receptors play an important role in the immune response against SARS-CoV-2. The authors, Krishna Sriram, Paul Insel, and Rohit Loomba, write that the “SARS-CoV-2 virus binds to ACE2 – like a key being inserted into a lock – prior to entry and infection of cells. Hence, ACE2 acts as a cellular doorway – a receptor – for the virus that causes COVID-19.” Personally, this fact baffles me, since it’s truly both amazing and terrifying that non-living viruses are able to manipulate and finesse their way into infecting the host cells. 

 

Returning to the main article, the ACE2 receptors could be responsible for the long-lasting effects being reported to both the vaccine and the virus itself. These responses can also answer why these long-term effects can occur, even long after the infection has passed. 

 

These terms are apparent in our AP Biology classroom, specifically regarding the Immunity System. The immune response used to combat SARS-CoV-2 is Adaptive Immunity, which develops after exposure to pathogens including bacteria, viruses, toxins, or other foreign substances. Due to the complexity of SARS-CoV-2, Adaptive Immunity is used because it’s a specific but slower response to the virus. Both B Lymphocytes and T Lymphocytes are used in the response against COVID-19 but during different stages of the infection. When the virus first enters the body, the Immune System performs Humoral Response, in which B Cells bind to the antigen and secrete antibodies that are made by B-Plasma cells, and these antibodies are stored in the B-Memory Cells to prevent future infection. In the case that COVID-19 enters and infects a cell, the Cell-Mediated Response is used to kill off infected cells using T-Killer Cells and T-Memory Cells are created to prevent future infection.

How do you think this research will be implemented for the prevention of these long-term effects? Let me know in the comments below and stay safe!

An Antidepressant Is The Next “Weapon” Against COVID-19

Is the COVID-19 vaccine the only way to lower death rates and hospitalization rates? While more individuals are becoming vaccinated against COVID-19, researchers have looked at how a low-cost antidepressant prescription could potentially tackle the virus. Fluvoxamine (Luvox), an antidepressant medication, has the capacity to reduce hospitalization and morality rates after patients receive COVID-19 within a few days. Although fluvoxamine is licensed by the FDA for the treatment of obsessive-compulsive disorder (OCD) and other disorders such as depression, it is not approved for the treatment of COVID-19. In a study, conducted in Brazil, 1,500 newly diagnosed COVID-19 patients were assessed. 741 of the participants received a 100 mg pill of fluvoxamine twice a day for 10 days and the remaining 756 participants received a placebo twice a day. 16 percent of those who took the placebo twice a day got ill enough to necessitate a lengthy hospital stay compared to 11 percent of those who took fluvoxamine. Researchers discovered that participants who took at least 80% of the fluvoxamine administered to them had a two-thirds lower chance of hospitalization! Furthermore, there was only one fatality among individuals that took fluvoxamine, compared to 12 fatalities in the placebo group. According to The Lancet Global Health, this research has shown that the drug has reduced morality rates by roughly 91 percent. The antidepressant drug can be easily prescribed by doctors for COVID-19 using their clinical judgement.

Diagnostics-10-00453-g001

When the COVID-19 virus enters the body through the eyes, nose, or mouth and travels to the lungs, the immune system strives to protect itself from the invading pathogens by producing antibodies that, on occasion, eliminate invading infections. If the invading pathogen is unfamiliar to the body, B-memory cells will be unable to detect it, and B-plasma cells (antibody secreting cells) will be unable to manufacture antibodies, allowing the virus to enter the cell and flourish in the body.

Fluvoxamine

Fluvoxamine is a 2-aminoethyl oxime ether of aralkylketones. The antidepressant medication, if taken promptly after receiving COVID-19, may be an additional method of minimizing viral transmission and accompanying medical concerns. Fluvoxamine is easy to get and inexpensive to manufacture, particularly as a generic drug. COVID-19 treatments, in general, serve as both a cure for severe sickness and a treatment for the beginning of illness. Fluvoxamine, as an SSRI (selective serotonin reuptake inhibitor), attaches to a cell’s receptor that governs cellular stress response and the generation of cytokines, proteins that alert the body of a problem and lead to extreme inflammation. Nevertheless, fluvoxamine has been shown to minimize inflammation. When people get COVID-19, it’s theorized that the damaged cells produce a slew of cytokines that generate inflammation in the lungs, making it difficult to breathe. Patients would be able to breathe better and require fewer hospitalizations if fluvoxamine was taken to help decrease inflammation.

Fimmu-11-01648-g002

Who knew that an antidepressant that inhibits the serotonin reuptake pump at the presynaptic neuronal membrane might reduce inflammation and allow you to breathe? Because fluvoxamine works by boosting serotonin levels between nerve cells in the brain, it is impressive that the medicine might be used for purposes other than treating depression or OCD. The lingering question is whether someone with COVID-19 who has been taking these antidepressants for a previous disorder has an edge.

Vitamin D Points to Potential Life-saving Therapeutics for Severe Cases of SARS-CoV-2

A promising new joint study by Purdue University and the National Institutes of Health (NIH) suggests that active metabolites of vitamin D are linked to reducing lung inflammation after SARS-COV2 infection. And no, before you break out your vitamin D pills, the vitamins inside your capsules are quite different from the active metabolites studied. Because of this, these researchers are warning those infected with COVID-19 against taking excessive supplements of vitamin D in hopes of reducing lung inflammation.

The researchers identified an autocrine loop involving vitamin D which allows T-helper (Type 1) cells to activate and respond to the active metabolites of Vitamin D which represses the signaling protein, Interferon Gamma. Distinguishing features of Interferon Gamma is the central role it plays in promoting inflammation

Interferon Gamma

Structure of interferon gamma. The two chains are colored in red (chain A) and green (chain B).

Although interferon gamma sounds wildly unrecognizable at first, we have actually learned about these proteins more broadly in our AP Biology class. Interferon Gamma is actually a type of cytokine! Regarding this cytokine’s structure, the proteins that compose interferon gamma are dimerized (sounds familiar? This is because we have also previously learned about dimerization through the tyrosine kinase receptor pathway in class!). 

Along with the suppression of Interferon Gamma, Interleukin 10, a cytokine with potent anti-inflammatory properties, is amplified. This is significant because this cytokine prevents damage to the host and maintains normal tissue homeostasis by reducing inflammation.

IL10 Crystal Structure.rsh

Structure of interleukin 10 as published in the Protein Data Bank.

In the near future, these pathways could be exploited therapeutically to accelerate the shutdown program of hyper-inflammatory lung cells in patients with severe SARS-CoV-2 infections. But for now, before vitamin D is adopted to treat COVID-19, clinical trials are still needed. However, research findings like these are critical to creating effective treatment not just for those infected with SARS-CoV-2, but also other respiratory diseases as well.

What do you think about this new discovery? Do you think this could lead to scientific progress regarding the treatment of inflammation?

New Covid-19 Pill! Will it work?

Pill 2

In a study conducted by Tina Saey, she looked at Merck’s Covid- 19 pill Molnupiravir and how it is affecting hospitalization rates of Covid-19. Molnupiravir, “an antiviral drug that can be taken at home” is the first medicine that can be taken orally that is approved to help fight off Covid-19. The drug is typically administered to patients who have mild to moderate Covid within five days of their symptoms appearing. Molnupiravir has been tested several times and is now waiting on the FDA for formal approval. This new pill could be a game-changer, but will it really be as great as it seems?

Ms. Saey states that “finding an early treatment hasn’t been easy”, so when Molnupiravir came around experts praised its development. Initially, the pill showed great signs of preventing hospitalizations and death from Covid-19. The results were so promising, a 48% decrease in hospitalizations, that the trial ended early so that the pill might become available to the public faster. However, when all the data was collected and analyzed the reduction in hospitalization rate dropped to 30%. The unexplained decrease happened when participants in the placebo group were no longer experiencing severe symptoms. Due to the decrease in reported effectiveness, the FDA’s antimicrobial drugs advisory committee came to a split 13-10 decision on whether the drug should be available for emergency use. 

The main concern for authorizing Molnupiravir is that the pill could create even more dangerous versions of the Covid- 19 coronavirus. The drug works by making mutations in the RNA. This is when a change occurs that affects nucleic acids, the building blocks of RNA. A handful of these mutations could land in the spike protein. Spike proteins interact with the cell receptors located on the host cell; in terms of Covid-19 it helps the coronavirus break into cells. The spike protein could also burst into other proteins making the virus more transmittable. James Hildreth, an immunologist stated that, “the potential for this drug to drive some very challenging variants into the public is of major, major concern.” Although this is a possibility it seems unlikely because, after five days of usage, infectious viruses in participants taking Molnupiravir were no longer detectable. 

SARS-CoV-2 without background

Spike Protein

Overall, there is much promise but also notable concerns to the new drug Molnupiravir. I believe that this new medicine, even with its downsides, could save hundreds of thousands of lives. As Ms. Saey states, “a 30 percent reduction in hospitalizations and deaths is worth giving the drug temporary authorization.”

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