 Trump and Hydroxychloroquine As I wrote before, it is unfortunate that the president of the United States has endorsed the use of hydroxychloroquine against COVID-19, because this has politicized everything having to do with the perception of this drug by the public. When scientists or non-scientists think about hydroxychloroquine, they should be thinking about it as “a drug” that we are researching to find out whether it’s beneficial against COVID-19. Unfortunately, as I warned before, this is becoming more and more difficult. Now hydroxychloroquine is “the president’s drug”. In the current social mindset if you think hydroxychloroquine works, then some people believe you are for the president and for promoting and using a worthless drug, and if you think hydroxychloroquine doesn’t work, some people believe you are against the president and against saving thousands of lives using a drug that has been proven to work. Any statement about the drug is viewed through these warped lenses. In my exchanges on Twitter, I often encounter individuals who promote many erroneous or ambiguous claims about hydroxychloroquine. I have stated, for example, that we can’t rely on the opinions and experiences of doctors and patients to establish whether the drug works. We need clinical trials. I try to explain that doctors, patients, and all human beings in general including scientists are prone to biases that arise through no fault of their own, and that is why we have procedures such as blind protocols and placebos to guard against these biases. However, my comment is invariably interpreted to mean that I am questioning the qualifications of hundreds of doctors, and the trustworthiness of thousands of patients, because I want to discredit positive results for hydroxychloroquine.
I have also tried to explain that not all clinical trials are well-designed. Just because some trials found that hydroxychloroquine works, that doesn’t mean it works. Just because some trials found that hydroxychloroquine doesn’t work, that doesn’t mean it doesn’t. Scientists have to evaluate the quality of the trials. All clinical trials have limitations, which we have to take into account before we make a decision. The results of one well-designed clinical trial can trump hundreds of poorly designed trials. However, my comments regarding the hydroxychloroquine clinical trials are invariably interpreted to mean that I am trying to discredit the studies that favor the drug because of ulterior motives. As I have stated before, I am a hydroxychloroquine skeptic, but my skepticism towards the drug is not rooted in a desire to shoot it down just because the president promoted it. My skepticism is based on well-designed published studies, soon to be published studies, and reviews that indicate that hydroxychloroquine as a single agent or combined with antibiotics is not effective to treat patients sick with COVID-19 or as a prophylactic to prevent patients from being infected with COVID-19 or at least ameliorating their disease. Below are some of these studies: Reviews Efficacy of Chloroquine or Hydroxychloroquine in COVID-19 Patients: A Systematic Review and Meta-Analysis Update I. A systematic review on the efficacy and safety of chloroquine/hydroxychloroquine for COVID-19 Studies A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19 Effect of Hydroxychloroquine in Hospitalized Patients with COVID-19: Preliminary results from a multi-centre, randomized, controlled trial A Cluster-Randomized Trial of Hydroxychloroquine as Prevention of Covid-19 Transmission and Disease Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19 Hydroxychloroquine for Early Treatment of Adults with Mild Covid-19: A Randomized-Controlled Trial Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19 Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial In addition to the above, the hydroxychloroquine trials at the World Health Organization (Solidarity trial) and the NIH (Orchid trial) were halted when independent reviewers of the data concluded that hydroxychloroquine offered no benefits (these trials have not yet been published).. Early on in the pandemic, the narrative was put forward that patients with Lupus who were taking hydroxychloroquine were less affected, or did not develop COVID-19 with the same severity. But this is not true. Lupus patients on hydroxychloroquine get COVID-19 at rates and severity comparable to Lupus patients not taking hydroxychloroquine. Baseline use of hydroxychloroquine in systemic lupus erythematosus does not preclude SARS-CoV-2 infection and severe COVID-19 Finally, there are also studies with animals that have shown no effects of hydroxychloroquine. Hydroxychloroquine Proves Ineffective in Hamsters and Macaques Infected with SARS-CoV-2 Hydroxychloroquine use against SARS-CoV-2 infection in non-human primates Back in 2005, some observations on the effectiveness of chloroquine were made in an experiment performed in culture on a cell line derived from the kidneys of an African Green Monkey (Vero E6 cells). The results of this experiment have been used nowadays to try to discredit Dr. Fauci. In the article that I quoted above on testing hydroxychloroquine on non-human primates, the authors tested hydroxychloroquine on Vero E6 cells and found that it has an antiviral effect. Then they tried the drug on a model of reconstituted human airway epithelium developed from primary nasal or bronchial cells (a more relevant model) and they found that hydroxychloroquine has no antiviral effect, whereas previously the authors had found that remdesivir did have an antiviral effect in this model. Based on some of the above evidence the FDA revoked its emergency use authorization of hydroxychloroquine. Like I have said many times, all studies have limitations, and it’s healthy to discuss the strengths and weaknesses of studies. But in their comments, many of the apologists of hydroxychloroquine go beyond this, as they infer a nefarious intent behind the limitations of the studies, which they assume to have been introduced into the study protocol on purpose to make hydroxychloroquine (and the president) look bad. If these people have very good evidence that this is the case, then they should present it, otherwise engaging in this innuendo is unwarranted, disrespectful, and unacceptable. Even though I am skeptical of hydroxychloroquine, I don’t want to be right, I want to save lives. If well-designed clinical trials prove that hydroxychloroquine works, then it works, and we HAVE to accept it works; no excuses. However, if well-designed clinical trials prove that hydroxychloroquine doesn’t work, then it doesn’t work, and we HAVE to accept it doesn’t work; no excuses. Whether the president promoted the drug or whether the results of the studies agree with your politics is irrelevant. This is what science is, or at least should be about. Hydroxychloroquine should just be “another drug” being evaluated for COVID-19 by scientists having the best interests of the patients in mind. Hydroxychloroquine should not be “the president’s drug”. Making it the president’s drug fans the biases and prevents a rational appraisal of whether it works or not. Note: after I published this, it was pointed out to me that hydroxychloroquine may work when combined with zinc. I have acknowledged that to establish this we need to wait for the results of several clinical trials that are ongoing. However, the subject of this post is the original claim that was made for hydroxychloroquine: that it works as a single agent or combined with antibiotics. Sure, we will move on to zinc, but first can we agree that the evidence from the best studies indicates that hydroxychloroquine as a single agent or combined with antibiotics DOES NOT work against COVID-19? The photo of President Trump from Whitehouse.gov is in the public domain. This photo was merged with an image of hydroxychloroquine by Fvasconcellos also in the public domain.
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 With all the anxiety and uncertainty around us, I think it is again time to bring some levity to my blog. A while back I posted some terrible science jokes and puns that people seemed to like, so here I present you with more terrible science jokes and puns along with explanations of why they are funny.
A man got cooled to absolute zero. He's 0K now. The so called “absolute zero” (the temperature at which molecular motion ceases) is reached at -459.67°F and is measured in units called Kelvins symbolized by a “K”. Absolute zero is reached at zero Kelvins or “0K” (zero degrees Kelvin), which is used as a pun for “OK” as in “all right”. A scientist started reading a book about Helium, and he just couldn't put it down. Helium is a gas which is lighter than air, so it rises. Q: What is a cation afraid of? A: A dogion! A cation is an atom that has lost an electron and thus has acquired a positive charge. The joke is a play on words with the animal, “cat”, and its traditional nemesis, the dog. The nerd says, “My girlfriend is like the square root of -100, a solid 10, but also imaginary.” An imaginary number is a number that is multiplied by the square root of -1, which is symbolized as “i”. The square root of -100 is 10 multiplied by “i”, in other words, “10i” (ten, but also imaginary). The elements oxygen, hydrogen, sulfur, sodium, and phosphorous walk into a bar. The bartender sees them and rolling his eyes says, “Oh, snap!” The chemical symbols for these elements are: oxygen (O), hydrogen (H), sulfur (S), sodium (Na), and phosphorous (P). The old professor had studied endothermic reactions way before they were cool. Endothermic reactions are chemical reactions that take up a net amount of heat from the environment. The joke exploits the play on words of “cool” as in low temperature and “cool” as trendy. The name's Bond, Ionic Bond. Taken, not shared The joke is a play on words on some James Bond quotes. One is providing his name (The name’s Bond, James Bond), and the other is ordering a martini “shaken, not stirred”. The joke is based on the fact that when two atoms are bound by an ionic bond (as opposed to a covalent bond), they don’t share electrons; rather one atom takes an electron and acquires a negative charge while the atom that loses the electron acquires a positive charge. There is an argument at the scientists’ bar. Newton threateningly says to Einstein, “I don’t think you understand the gravity of this situation”. Einstein smiling cheekily replies, “Oh, I believe I’m relatively aware of it.” Darwin steps between them and says, Hey, guys, don’t let this evolve into a fight.” Newton formulated the law of universal gravitation, Einstein the theory of relativity, and Darwin the theory of evolution. Despite the joke, Newton (1642-1726), Einstein (1879-1955), and Darwin (1809-1882) were not contemporaries (Darwin died when Einstein was 3 years old). If you are a student struggling with calculus, just remember that Isaac Newton also struggled with calculus…when he invented it. Gee, thanks. After many years of effort, Einstein developed a theory about space, and it was about time too. Einstein’s theory was about both space and time, which were merged into a single entity called “spacetime”. Here the play on words is made with the phrase “it was about time too” as in promptness. The doctoral student turned in the first draft of his thesis on Darwin’s theory of evolution. His professor said it would be decent with modification. Darwin defined evolution as “descent with modification”. A newlywed couple visiting Yellowstone National Park engages in a game to see which of them can get closer to a wild buffalo. The question is: who wins? The answer is: Darwin. Darwin’s stated mechanism for evolution, natural selection, is a process by which those organisms that are fit, survive and have progeny. The implication of the joke is that if you do something stupid that gets you killed you will not be able to pass your genes to the next generation (you will be selected against). Despite their popularity, antibiotics will never go viral. Antibiotics are not useful for viral infections, but the word “viral” is used as in when a meme spreads in social media. When life gives you mold, make penicillin. This is a play on word on the phrase, “When life gives you lemons, make lemonade.” It is an allusion to the accidental discovery by Alexander Fleming that certain molds secrete a substance with antibacterial properties. This substance is penicillin, the first antibiotic. In 1945 Fleming was corecipient of the Nobel Prize for the discovery of penicillin. A chemist and a biologist go hunting, and a statistician tags along with them. They find a deer and the chemist and the biologist shoot it at the same time. The biologist’s shot misses the deer by a foot to the left. The chemist’s shot misses the deer by a foot to the right. The statistician yells, “We got him!” The average of both shots is, of course, smack in the middle of the deer. A medical student hit another student in the head with a human bone during anatomy class. It was humerus. Humerus, the bone vs, humorous, the funny situation. Are you a carbon sample? I’m asking because I would love to date you. This is a play on words on dating as in determining the age of something and dating the social interaction. Gregor Mendel received the Nobel Peas Prize. Gregor Mendel is considered the father of genetics due to his ground-breaking work in figuring out the laws of inheritance by breeding peas. He died in 1886. The first Nobel Prizes were awarded in 1901. One of the Nobel prizes is the Nobel Peace Prize. The thymocyte wailed in despair, “Oh my God, I can’t do this alone! Please, is there anyone out there who will assist me?” It was a Helpless T Cell. Immune cells originating in the bone marrow and reaching maturity in the thymus are called thymocytes or “T cells”. Some T cells differentiate into a type of cell called “Helper T cells” which have important roles in immunity. The one featured in the joke was obviously not up to par. I told a joke involving the elements, cobalt, radon, and yttrium. People thought it was corny. The chemical symbols for these elements are: cobalt (Co), radon (Rn), and yttrium (Y). OK, I'm out of Science jokes, maybe I should Zinc of a new one. Zinc/think, get it? Wait don’t go, I’ve got another joke. It’s on the tip of my tungsten. Tungsten/tongue, get it? To my knowledge these jokes and puns are not copyrighted. If you hold the copyright to any of these jokes or puns, please let me know and I will acknowledge it. Image by Perlenmuschel from Pixabay is free for commercial use and was modified.  CDC Cloth Mask Guidelines There is a lot of ignorance, misinformation, and conspiracy theories being spread about wearing masks during the COVID-19 pandemic, and I thought I would devote a post in my blog to set the record straight and provide references. Here I want to clarify that by “masks” I am referring to the regular loose fitting surgical or cloth masks that most people normally wear. For my post, I will describe the things people argue about masks and then reply to each one. When you buy the masks that many people use, it says on the box that they won’t protect the wearer from the coronavirus. Many doctors and scientists say that surgical or cloth masks worn by most people will not prevent them from getting the virus. This is an aspect of mask wearing that is not well understood by the general public and even by quite a few scientists, so I will try to explain. Masks got a bad rap back in 1918 when they were considered to have failed in controlling the spread of influenza, and a lot of this thinking still prevails in the scientific community today. However, it has been understood that the wearing of masks back then was often not performed adequately and was not coupled effectively with other measures. The type of masks most people wear will only provide limited protection from breathing in droplets (inward direction) emitted by unmasked people when they are talking, coughing, or sneezing within a short distance of the wearer (less than 6 feet). But that IS NOT the point of wearing these masks. The point of wearing these masks is to contribute to PROTECT OTHERS from the droplets emitted by the wearer when talking, coughing, or sneezing, in other words, to stop droplets in the outward direction (this is referred to as “source control”). There is abundant evidence that these masks can do this, not perfectly, but fairly well (1, 2, 3, 4, 5, 6, 7). You can find some fun demonstrations of the effectiveness of masks here, here, and here. Additionally, taking into account that we now know that many individuals with COVID-19 can transmit the virus even while they are presymptomatic or asymptomatic, mask wearing by the public is even more important to protect others. However, if others do not wear a mask in your presence, this defeats the purpose of wearing masks. The point of wearing a mask is to minimize the chance that the wearer will contaminate others. Nevertheless, it must be emphasized that the intention is for masks to be worn in addition to social distancing, hand washing, and avoiding or minimizing your exposure to crowded places. Doing ALL these greatly decreases your probability of catching the virus. The virus is tiny, it will not be stopped by face masks with large fabric holes like the ones most people wear. Wearing a cloth mask to stop the virus is like putting up a chain link fence to stop mosquitoes.
Yes it will be stopped, because viral particles are expelled forming part of liquid droplets, and the majority of these droplets are hundreds to thousands of times larger than the virus. The mask stops or deflects a significant proportion of these droplets. Cloth masks will trap all the germs like bacteria, viruses, and fungi you expel and then you will breathe them back in and this is bad for your health. That is kind of the point of wearing masks: to trap the germs! This is why you should wash cloth masks after you use them. You put on clean clothes before you begin your day, right? Well, also put on a clean mask. How hard is that? Wearing a mask will trap carbon dioxide and you will breathe back all that carbon dioxide which will decrease your oxygen levels and harm you. This has been demonstrated by performing carbon dioxide measurements inside the masks while people are wearing them. If you (wrongly) argue that it is impossible to trap the COVID-19 virus with a cloth mask because it is so small, then you can’t argue at the same time that the mask will trap carbon dioxide. Carbon dioxide is a gas. A molecule of carbon dioxide is hundreds of times smaller than the COVID-19 virus and tens of thousands of times smaller than the liquid droplets which contain the virus. The social media notion that masks trap carbon dioxide arose as a result of a video posted by a person who used a measuring device improperly and obtained bogus measurements. This notion is inaccurate as the space between the mask and the face is very small and makes a negligible contribution to the dead volume of the lungs. With each inhalation the gas in this space is replaced by gas from the outside. In any case, the appropriate measurement to perform is whether the oxygen levels in the blood decrease as a result of wearing a mask. A number of health care professionals have done this and posted the results on social media. Masks don’t decrease blood oxygen levels. In many Asian countries huge numbers of people have worn masks during the cold and flu season for decades without any such problem arising. The real purpose of a mask is to serve as a mind control device by a manipulative government that wants to roll back our freedoms and make us afraid and submissive. This is a conspiracy theory, and it is up to their proponents to present evidence that it is true. An alternative explanation is that our elected representatives are just following the best evidence and facts available as relayed to them by science. But the argument portraying masks as a mind control device can be made about virtually anything. Use of seat belts, stopping at traffic lights, following speed limits, using a cross walk to cross the street, and many other safety guidelines or laws can all be interpreted as things or designs dreamed up by the powers that be to control our lives and reduce us to sheep. If we accept this, then any government action that involves requesting a change in the behavior of the population can then be assigned a nefarious motive becoming part of a conspiracy. People have fought against masks before and now they are doing it again. We know to a certain extent why people are fighting face masks and promoting conspiracy theories about them even while coronavirus cases, hospitalizations, and deaths are on the rise. It is a combination of the anxiety and loss of control that a situation like COVID-19 produces, the politicization of the issue, and the distrust of government many individuals profess coupled with the erosion of the trust in science that has taken place in our society. However, as I’ve written before, reality can’t be compromised. The evidence so far indicates that masks, when coupled to social distancing and other measures, contribute to decrease the spread of COVID-19. It is our job as scientists to uphold these facts. Many people will not like this. However the point of science is not to win popularity contests but to discover and convey the truth. And we are going to keep on doing just that. The image from the Centers for Disease Control and Prevention is in the public domain. 7/3/2020 Fighting Coronavirus Misinformation and Conspiracy Theories: Fauci, Hydroxychloroquine, and Retracted ArticlesRead Now Dr. Anthony Fauci Oh dear, so much COVID-19 misinformation, and conspiracy theories, and so little time and space. Let’s get started. Dr. Anthony Fauci is receiving a lot of criticism from people, ranging from those who deny the severity of COVID-19 and think he misadvised the president, promoting the interests of political elites and the deep state, to those who think he is denying the efficacy of hydroxychloroquine and promoting the economic interests of pharmaceutical companies to the detriment of the interests of patients. These people question his character, and call him a liar, a fraud, a traitor, and a saboteur who should be fired. As it turns out, these insults are nothing compared to the insults levied against him when he was coordinating the nation’s response to the AIDS epidemic in the 1980s. The notorious firebrand AIDS activist Larry Kramer criticized Dr. Fauci for moving too slowly in finding a treatment for AIDS, and said he was evil and represented a callous government. Kramer called Fauci a pill-pushing tool of the medical establishment, an incompetent idiot, a disgrace, and a murderer who should be put in front of a firing squad. Kramer compared him to a Nazi and even insulted Fauci’s wife! So what did Dr. Fauci do? He talked to Kramer and other AIDS activists, he heard their concerns, he realized they had a point, and he pushed for changes in the way clinical trials were conducted speeding up the process, making it more flexible, and giving patients a greater voice. He reached out to those who insulted him and worked with them to change medicine for the better and make history. Eventually, Dr. Fauci and Kramer became good friends. Fauci helped Kramer get medical treatment for his health problems, and Kramer made Fauci a character in one of his award winning plays. So when critics say Dr. Fauci doesn’t care for patients or is beholden to special interests, I am skeptical of these claims. I think that history so far indicates that this is not who Dr. Fauci is. This is not to say that Fauci doesn’t make mistakes, but I certainly believe that he is acting in the best interest of the American people. But can’t people change? Sure, but as far as I’m concerned, the burden of proof is on the critics to produce exceptional evidence that there is a nefarious intent behind his actions.  Hydroxychloroquine Another conspiracy theory involving Dr. Fauci states that he has known for 15 years that chloroquine (a drug related to hydroxychloroquine) was effective in hindering the spread of a virus, SARS-CoV, which is 79% related to the COVID-19 virus (SARS-CoV-2), in primate cells in culture based on a study published back in 2005. So it is claimed that Fauci is lying when he says that there is no good evidence for the effectiveness of hydroxychloroquine against COVID-19.
Dr. Fauci is a competent scientist, and he knows that cell culture is a very preliminary step when employed to look for effective drugs. He knows that the results obtained with this method may not hold in more complete models that better reflect the complexity of the full organism. For example, hydroxychloroquine did not have either a therapeutic or prophylactic effect in hamsters and monkeys infected with the COVID-19 virus. This agrees with the best human studies so far that indicate that hydroxychloroquine is not effective. Another conspiracy theory that is making the rounds concerns retracted articles published in the scientific journals, The Lancet, and the New England Journal of Medicine (NEJM). These two journals published studies where scientists examined a database of patients treated with hydroxychloroquine and concluded not only that hydroxychloroquine was not effective, but that it was also harmful to the patients. The results of these studies led to a temporary halt of several hydroxychloroquine trials taking place worldwide. However, when the studies were examined by scientists, numerous discrepancies in the data and problems in its analysis were detected. Letters signed by more than one hundred scientists were delivered to the Lancet and to the NEJM outlining these problems. The journals expressed concerns about these discrepancies, and the authors of the articles retracted them when they were not able to dispel these concerns with the company that provided them with the hydroxychloroquine dataset. The conspiracy argument alleges that the publication of these articles proves that there is a concerted campaign by the scientific establishment to discredit hydroxychloroquine at the expense of the lives of people who could benefit from it, just to embarrass president Trump for advocating the use of this drug. The conspiracy theory argues that this scandal demonstrates that scientists have lost all credibility. However, what this argument ignores is that it was scientists who detected these problems and alerted the journals, and the journals proceeded to raise concerns with the authors, and the authors acknowledged those concerns and retracted the articles when they could not address said concerns. That this happened is not a scandal. Scientists make mistakes all the time. In fact, that is the strength of science. The only reason that science can be right is because it can be wrong. In this case, error was detected, addressed, and removed. The scandal would have been if the problems with the articles had not been addressed and the articles had not been retracted. The fact that the opposite happened is an indication that science worked the way it should, and vindicates our confidence in the scientific process. Finally, another conspiracy theory involves the claim that countries that have embraced the use of hydroxychloroquine are doing better than countries that haven’t. Therefore, the unwarranted rejection of hydroxychloroquine by the health care systems of some countries has led to many preventable deaths. Those that espouse this conspiracy theory do not make any efforts to address other variables that could explain these differences. For example, there is the number of infected people that spread the disease initially in the country (more disease spreaders equals more infections and more problems with the health care system). There is the timing of the spread of the disease (earlier spread means less time to adapt). There is the constellation of drugs and procedures that are used to treat patients (how do you separate the effect of hydroxychloroquine from that of other drugs and/or procedures). There is the age and health of the population affected (younger healthier people are less susceptible). There is the strength and effectiveness of the mitigation measures employed (older sicker people could have been protected better in one country than in another another). There are differences in reporting what constitutes a COVID-19 death from one country to another. If these and other variables are not considered and controlled for, the claim does not go beyond a mere anecdote. The misinformation and conspiracy theories I’ve mentioned are but a fraction of all the bilge that’s out there, but what they all have in common is that they are part of an effort to disqualify mainstream science and scientists as they deal with COVID-19 and evaluate hydroxychloroquine and other drugs. The image of Dr. Fauci ny NIAID is used here under an Attribution 2.0 Generic (CC BY 2.0) license. The image of hydroxychloroquine by Fvasconcellos is in the public domain. |
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