What Have Government Restrictions Accomplished with COVID-19?

Cumulative COVID-19 cases (left) and deaths (right) per million in Sweden and Denmark
(click for a larger view)

In a previous post, I compared COVID-19 cases and deaths in Sweden and Denmark. As I said then, it’s because they are very similar countries in the same basic region of the world, but they have remarkably different responses to the disease. Sweden has avoided lockdowns and tried to target their social restrictions, while Denmark has followed the practices of most other countries, strongly limiting what their citizens can do during the pandemic. While no comparison of two different countries is conclusive, I think the results are very interesting. The data come from the European Centre for Disease Prevention and Control, and while it may very well be a biased source of data, at least it is equally biased for both countries.

The graph on the left shows the cumulative COVID-19 cases per million. That means each day on the graph shows the total cases that were reported by that date, divided by the population in millions. Initially, Denmark had more cases (probably because initially they were testing more), but as you can see, Sweden quickly surpassed Denmark in cases per million, and the difference between the two countries has continued to grow. Since the death rate of COVID-19 is low (but higher than most infectious respiratory diseases), many people (including myself) think that death rate is a better indicator of the severity of the pandemic. Thus, the graph on the right shows the cumulative deaths per million. Notice that Sweden has more than 5 times the deaths per million as Denmark.

If the comparison between these two countries is legitimate, then, government restrictions did reduce the number of COVID-19 deaths per million in Denmark. However, there are those who suggest that this might be okay, since Sweden will reach herd immunity faster than Denmark. In the long term, then, Sweden will have fewer COVID-19 deaths because the spread of the disease will stop sooner.

Based on my evaluation of the data, I don’t think Sweden is significantly closer to herd immunity than Denmark. Take a look at the graph below, which records cases per day per million. Rather than adding all the cases reported by a given date (as is done in the graph on the left above), this shows the daily reports of COVID-19 cases per million.

If Sweden were closer to herd immunity than Denmark, the recent cases per million per day in Sweden should be lower than the cases per million per day in Denmark. However, they are not. For most of August, Sweden and Denmark have roughly equivalent cases per million per day. That tells me the disease is spreading roughly the same in the two countries right now, but Sweden has lost five times the people (per capita) as Denmark. As a result, my analysis indicates that Denmark’s restrictions kept a lot of people from dying of COVID-19, and that will continue to be the case in the long run.

Now please understand that this analysis considers only deaths from COVID-19. We know that government restrictions have also caused deaths. There are those who say that the government restrictions will cause more deaths than the ones that were saved from COVID-19. Others say that overall, the restrictions have saved lives. I think the data are insufficient to make that determination, but I do agree that most countries are ignoring the devastating death toll caused by the restrictions themselves. Nevertheless, I think the data are now clear that Sweden’s strategy has not accomplished what the country had hoped it would.

Another Possible COVID-19 Treatment

The three components of blood (click for credit)
So far, there are no widely-accepted treatments for COVID-19. Hydroxychloroquine, often mixed with other things like azithromycin, was initially thought to be promising, but the data so far are inconclusive. While there are some indications that it is effective (and some physicians are convinced it works very well), the controlled studies that have been done so far see no significant benefit to its use. The antiviral drug remdesivir shows some promise, as does the corticosteroid drug dexamethasone. However, there are not enough data yet to make a firm decision on either of them.

Yesterday, President Trump held a press conference to announce a new possible treatment: convalescent plasma. Based on an analysis of several different studies, it seems to be the best candidate yet (in my non-medical-doctor opinion). I say this because of the kinds of studies that have been done. First, there have been three randomized clinical trials. This means patients were assigned to either get the treatment or not get the treatment based on random chance. The group that got the treatment was compared to the group that didn’t (called the control group). In the three studies, the death rate in the treatment group was half that of the control group. There were also five matched-control studies, where the treated patients were compared to a control group specifically selected to closely match them. The results of those studies were similar to those of the randomized clinical trials. There were also four case-series studies, where patients were given the treatment and their progress was tracked. While that kind of study has practical uses for physicians, its ability to determine the effectiveness of a treatment is extremely limited. However, the case-series studies seem to support the other two kinds of studies. All of the studies were done on patients with severe or life-threatening cases of COVID-19.

Taken all together, then, the treatment looks very promising. However, I do have to say that each study was very small, so even when all the patients were analyzed, the total number was only 804. Phase three clinical trials that determine whether or not a drug should be widely used typically involve a few thousand patients. Thus, this is still a limited data set. Also, many of the studies (as well as the analysis linked above) are not peer-reviewed. As a result, there could be major flaws that have not been noticed. A recent analysis (once again not peer reviewed) of more than 35,000 patients seems to support the small studies, but since it has no control group, it cannot be used to draw any real conclusions. Nevertheless, the FDA has approved emergency use of the treatment, and it is asking those who have recovered from the disease to help in determining whether or not it is truly effective.

How can someone who has recovered from COVID-19 help determine the effectiveness of the treatment? To understand that, you need to learn a bit about the wonderful mixture that is running through your circulatory system.

Continue reading “Another Possible COVID-19 Treatment”

Another Exciting Development in COVID-19 Prevention

AeroNabs could be delivered as a nasal spray. (click for credit)
Scientists are pursuing several different strategies to protect people from the virus that causes COVID-19, and a recent paper that hasn’t been peer reviewed reports on a strategy I haven’t seen before. It makes use of the fact that the virus starts the infection process by employing specific chemicals called spike proteins to bind to an enzyme (ACE2) in human cells. The idea is simple: Block the virus’s ability to bind to that enzyme, and it will be unable to start the infection process. But how can that be accomplished? In the paper, the researchers report on making a small molecule, called a nanobody, that binds to the spike proteins on the virus. Once the nanobody binds to them, the spike proteins can no longer bind to the ACE2 enzyme.

First found in alpacas, nanobodies are like antibodies, but they are smaller, simpler molecules. Because of that, they are easy to make and manipulate. Essentially, scientists can build a small gene that produces the nanobody, insert it into certain microorganisms, and let the microorganisms churn out the nanobodies. As a result, there have been many, many different kinds of nanobodies produced over the years. The researchers searched a database that contained more than two billion nanobody genes, and they found 21 that should be able to bind to the virus’s spike proteins in some way. They put those genes into yeast, extracted the nanobodies that were produced, and studied them.

Based on their analysis, they found the three most promising candidates and tested them against the virus itself. One of the nanobodies was particularly effective, so they focused on it. They mutated the gene multiple times to make slight changes to the nanobody and tested the result against the virus. They then produced a gene that could take the three most effective nanobodies and chain them together. The result was a chemical that basically shut down the virus’s ability to infect human cells.

Continue reading “Another Exciting Development in COVID-19 Prevention”

Why Are Children Less Susceptible to COVID-19?

Children make up less than 2% of all identified COVID-19 cases. This is unusual, since they make up 20-30% of influenza cases. Why is COVID-19 so much rarer in children? A study from the Icahn School of Medicine at Mount Sinai Hospital in New York might have found the answer. Cells found in the nose, lungs, veins, and other parts of the body sometimes have an enzyme called ACE2 in their membranes. The enzyme is important, because it can participate in a process that lowers blood pressure when necessary. Studies show that the virus which causes COVID-19 (SARS-CoV-2) attacks cells by attaching to that enzyme.

The researchers examined nasal tissue from people between the ages of 4 and 60. The tissue collection had already been done between 2015 and 2018 for a research study on asthma. The researchers specifically looked at how much the gene that makes ACE2 was expressed. The more the gene is expressed, the more ACE2 is made. They found that the youngest children expressed the gene the least, older children expressed it more, young adults even more, and older adults even more. Thus, the younger you are, the fewer ACE2 proteins in the cells that line your nasal cavity, so the fewer places the virus has from which to attack. As a result, the less likely you are to be infected.

Because of the nature of the original study for which the tissue was collected, nearly half of the people from whom the tissue came had asthma. Also, they didn’t have tissue from anyone over 60 years of age. Thus, the sample is not truly representative of the nation as a whole. Nevertheless, the results are very intriguing, and they seem to explain why this respiratory virus affects children differently from most common respiratory viruses.

Please DO NOT Get Your COVID-19 Information from Social Media!

So far, I have written three articles about how horrible social media is as a source of scientific information (see here, here, and here). Facebook might be a great way to find out what your friends are eating, but it is one of the worst places you can go to learn about science, especially the COVID-19 pandemic. That’s because lots of people (left, right, and center) have decided to politicize the pandemic, and the unscrupulous among them have transformed science from its true nature (a very imperfect mode of inquiry) into a weapon. Unfortunately, many people don’t recognize weaponized science, and as a result, they tend to share things that fit their political views, regardless of whether or not they are accurate.

Consider, for example, the statement shown above. I have seen it on my Facebook feed at least a dozen times. While the statement is factually accurate, it supports a false narrative. Yes, there have been roughly 4 million cases of COVID-19 in the U.S. so far, and there were estimated to be 60 million cases of H1N1 during the 2009 pandemic. So the H1N1 pandemic of 2009 was “worse” than the COVID-19 pandemic today. Therefore, all the precautions we are taking against COVID-19 (shutting down schools, wearing masks, etc.) are just a result of politicians trying to use the current pandemic to their advantage. Of course, that’s simply not true. The reason we are taking precautions against COVID-19 is that it is significantly more deadly than H1N1. Out of the estimated 60 million cases of H1N1 in 2009, there were only about 12,500 deaths. Out of the roughly 4 million cases of COVID-19, there have been almost 150,000 deaths. Since 15 times fewer cases have produced more than 10 times as many deaths, it is easy to understand why we are taking more precautions against this virus!

Just to give you one more example, yesterday I saw this statement on my Facebook feed:

The COVID-19 death rate without a vaccine is lower than the flu death rate with a vaccine.

As far as I can tell, there is no way you can massage the data to make that statement even factually correct. For the 2018-2019 flu season, there were estimated to be more than 35.5 million cases and 34,200 deaths. Once again, for the current COVID-19 pandemic, there have been roughly 9 times fewer cases, but about 5 times as many deaths.

Now please understand that I am certain the number of COVID-19 deaths are being overreported. But they aren’t being overreported to the point where you can conceivably compare this current pandemic with the H1N1 pandemic of 2009 or the seasonal flu. In the same way, I know that politicians are using this pandemic to their advantage, but that doesn’t mean it isn’t real and isn’t serious.

So when it comes to getting information about the pandemic, choose your sources wisely, and do not include social media on the list!

A Very Promising Possibility for COVID-19 Treatment

A person using an inhaler, which is the way the drug in the study is delivered (click for credit)

There are several drug treatments that are currently being investigated for COVID-19. However, of all the studies I have seen so far, this one looks the most promising. In the study, UK-based Synairgen chose 101 hospital patients and randomly assigned them to get a placebo or a chemical called “interferon beta,” a protein that has antiviral properties and is naturally produced by the human body. Both the placebo and the protein were administered through inhalers so that they ended up in the lungs. Over the roughly two-month study, patients getting the protein were 79% less likely to develop severe symptoms that required a ventilator. Also, while three of the patients who received the placebo died, none of those who received the protein died.

The study seems well designed. For example, patient ages were very similar. The placebo group’s average age was 56.5 years, while the protein group’s average age was 57.8 years. The difference is very small, but note that it favors the placebo group. In other words, since the patients getting the placebo were younger, they were automatically a bit less at risk than the protein group. In addition, the average amount of time the patients exhibited COVID-19 symptoms before getting the treatment was very similar, 9.8 days for the placebo group and 9.6 days for the protein group.

I do, however, see two potential problems. First, the number of patients in the study is small. As a result, they made a lot of other interesting observations, but they couldn’t determine whether those observations were the result of the protein or random chance. For example, the patients who received the protein were roughly twice as likely to recover within the two-month period than the ones who did not receive the protein. However, because the number of patients is so small, mathematics tells us it is possible that this result is caused by chance and not by a difference between the placebo and the protein.

The other problem, of course, is that this study was performed and reported by the pharmaceutical company that wants to produce and sell the drug. Initially, of course, this makes sense. Studies cost money, so the company that wants to make and sell the drug should spend the money to do the studies. However, before the drug can be approved for general use, there will need to be a larger study with independent analysis. I eagerly await that kind of study.

Dr. Fauci, Americans Believe Science, but They Don’t Believe Many Scientists (For Very Good Reasons).

Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases (click for credit)
Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases and one of the lead members of the White House Coronavirus Task Force was recently on the US Department of Health and Human Services’ podcast, which is called “The Learning Curve.” It exists so people can hear from experts in the department, learning what those experts are doing and what they think you should know. Obviously, Dr. Fauci was on to discuss the COVID-19 pandemic.

While some of what he said on the podcast was valuable, he made one statement that shows he is completely out of touch with most people in the United States:

One of the problems we face in the United States is that unfortunately, there is a combination of an anti-science bias that people are — for reasons that sometimes are, you know, inconceivable and not understandable — they just don’t believe science and they don’t believe authority…

Now, of course, you can always find people who don’t believe science for a variety of reasons. In my experience, however, they are few and far between. The majority of people in the United States hold science in very high regard. For example, Scientific American recently conducted a poll that found 90% of the people they surveyed wanted science to have a significant influence on society. An additional 7% wanted science to have some influence, which leaves a mere 3% that wanted science to have no influence at all. This is consistent with what I see around the nation. Most people believe science, some are skeptical, and very few think it has no value.

If people in the United States believe science, why does Dr. Fauci think they don’t? Because he is confusing science with scientists. As a scientist myself, let me put this very bluntly: In general, you can trust science. However, you cannot trust many scientists. Why do I say this? The Scientific American article linked above gives one reason: Many scientists have values that conflict with the majority of people in the United States, and those values affect how they interpret the science they know. For example, when a scientist doesn’t recognize that this world is a product of design, he or she will be led to all sorts of false conclusions. When the scientist communicates those false conclusions as if they are absolute fact, many reasonable people end up distrusting him or her.

But the Scientific American article linked above misses the more important reason people don’t trust scientists. It’s because scientists regularly make statements that they claim are absolutely true, but eventually, those statements are shown to be false. I highlighted a recent example a year ago. Visitors to Glacier National Park were told that computer models indicated the glaciers they are admiring will be gone by 2020. Well, it’s 2020, and the glaciers are still at the park. So what did the scientists do? Did they admit to their mistake? No. They quietly removed the signs, hoping the mistake would go unnoticed. In this day and age, however, such things rarely do.

The nonsense about the glaciers isn’t an isolated example. Time and time again, scientists make pronouncements and even take action based on ideas that they claim are absolutely true, but end up being utterly false. It was thought for a long time that the human appendix was a useless remnant of evolution. This silly notion was believed by surgeons, so many would remove the appendix from a patient having abdominal surgery, even if the appendix was entirely healthy. We now know that the appendix is an important lymphatic organ, and people without an appendix are more likely to have difficulty recovering from certain intestinal diseases. Tonsils are another example. It was once common practice to remove inflamed tonsils rather than treat the inflammation with medicine, because tonsils were supposed to be a leftover vestige of evolution. People who were unfortunate enough to be treated by someone who believed such nonsense (me, for example) are much more likely to suffer from respiratory, allergic, and infectious diseases. The fact that scientists routinely make definitive statements which are later shown to be wrong is so well-known that it is the subject of comedy routines.

In the end, scientists have themselves to blame when it comes to people not believing their pronouncements. They have betrayed the public trust too many times, because they have forgotten that by its very nature, science is tentative. Thus, it cannot be used to make grand pronouncements of absolute truth. Scientists have to realize that they are not priests. They are people who have expertise, but that expertise is based on a method of inquiry which routinely produces false conclusions. Rather than making grand pronouncements about the “truth,” they should show people the evidence and explain how they interpret the evidence. If they don’t communicate science that way, the public has no choice but to distrust them.

Are Hydroxychloroquine and Azithromycin Effective Against COVID-19?

Dr. Didier Raoult, French physician and microbiologist who thinks he has an effective treatment for COVID-19 (click for image source)
Two weeks ago I wrote about a possible treatment for COVID-19, the pandemic disease that is affecting most of our lives. It has been championed by French physician and microbiologist Dr. Didier Raoult. So far, he has written two papers about it (here and here). I was excited about his initial report, and I was hoping for a serious follow-up study. When I saw that he had written a second paper, I eagerly read it. Unfortunately, it wasn’t the serious study that I had hoped for. Nevertheless, it has gotten some media attention and seems to have influenced the FDA, so I decided to share my thoughts on it.

The results seem very exciting. He and his colleagues treated 80 patients with the malaria-fighting drug hydroxychloroquine and the antibiotic azithromycin. They note that they saw “clinical improvement” in 78 of them. One of the other two (an 86 year-old patient) died, and the other (a 74 year-old patient) was still in intensive care when the paper was written. While that sounds really good, there are a couple of “red flags” that make me hesitant to think that the treatment is as effective as it seems.

The first problem is that there is no control group. In a serious medical study, there needs to be a similar group of patents who do not receive the treatment. The treated group can be then measured against the untreated (control) group. Without that, it is very difficult to determine what the actual effect of the treatment is. Of course, I understand why there is no control group. Dr. Raoult wants to save lives. He thinks his treatment is effective, so he wants to give it to as many people as he can. He would have to “withhold” his life-saving treatment from some people so that he could have a control group, and that could lead to more deaths. I can understand why a physician would shudder at that idea.

However, the control group is important, because we really have no idea what would have happened to the 78 people who recovered had they not been given the treatment. While we still don’t know, the fatality rate of this disease is thought to be 1-2%. In 80 people, then, you would expect only one or two (0.8-1.6 to be precise) deaths, so this group of patients has the fatality outcome we expect had there been no treatment at all.

Now, of course, Dr. Raoult and his colleagues did more than just track whether or not the patients died. They tracked the amount of virus in each patient’s nasal cavity and found that the amount of virus dropped significantly for most of them. Once again, that sounds nice, but without a control group, we simply don’t know whether or not that was because of the treatment.

The second problem is the profile of patients who got the treatment. They mostly seemed to have a mild case of the disease. Only 15% had fever. Only 53% showed signs of lower respiratory tract infection. Worse, 5% showed no symptoms at all. Once again, it isn’t surprising that most of these patients recovered – most of them fit the profile of people who are expected to recover.

There is a third problem. A scientific study has been done in China with a control group. It is very small, and I can’t read it, since it is in Chinese. However, based on a Forbes article, the study had 30 patients. Half were given hydroxychloroquine, and half were not. That study showed no significant difference between the control group and the treatment group. Thus, if that study is correct, hydroxychloroquine is not an effective treatment for COVID-19.

Now, of course, that study didn’t include the antibiotic, so it’s possible that Dr. Raoult’s treatment is better than the treatment assessed by the study. It’s also possible that because of problems with the Chinese study’s design (small number of patients and no placebo, for example), the Chinese study is wrong. From a scientific point of view, then, we simply do not know whether or not Dr. Raoult’s treatment (or hydroxychloroquine by itself) is effective against COVID-19.

Nevertheless, the FDA has approved using hydroxychloroquine and other, similar drugs to treat COVID-19. This is probably a good plan, since the risks of using the drugs are low. However, until serious, controlled studies are done, we have no idea whether or not they are doing any good.

A Possible Treatment for COVID-19

A transmission electron microscope image of the coronavirus SARS-CoV-2. The spikes surrounding the virus make it look like a crown, which is where it gets its name. (click for credit)

While countries are scrambling to prevent the spread of COVID-19 (the disease caused by the new coronavirus), doctors are trying to find the best treatment for it. In three separate studies, a surprising candidate has been found: the anti-malarial drug chloroquine. In a letter that was published on February 19th, three Chinese scientists reported that more than 100 patients were given the drug. Based on the patients’ responses, they write:

…chloroquine phosphate is superior to the control treatment in inhibiting the exacerbation of pneumonia, improving lung imaging findings, promoting a virusnegative conversion, and shortening the disease course…

The authors also report that there were no adverse side effects noted in the patients.

A report in Spanish (translation here) concurs. It discusses both the results seen in patients and the results of experiments where primate cells are infected with the virus and then treated with chloroquine. The conclusion is as follows:

Chloroquine can both prevent and treat coronavirus in primate cells…According to South Korean and China human treatment guidelines, chloroquine is effective in treating COVID-19. Given chloroquine’s human safety profile and existence, it can be implemented today in the U.S., Europe and the rest of the world.

Finally, a study published in the journal Nature confirms that when primate cells are infected by the virus that causes COVID-19, both chloroquine and an antiviral drug known as remdesivir were effective at fighting it. The researchers state:

Our findings reveal that remdesivir and chloroquine are highly effective in the control of 2019-nCoV infection in vitro. Since these compounds have been used in human patients with a safety track record and shown to be effective against various ailments, we suggest that they should be assessed in human patients suffering from the novel coronavirus disease.

Now, of course, these studies are far from conclusive. However, I expect that doctors will judiciously test the treatment on patients who volunteer for it. Hopefully, that will allow us to learn more. Perhaps an effective treatment is on the horizon!

More Thoughts on the New Coronavirus

An infographic adapted from one produced by the CDC (click for larger version)

A few readers have sent me questions regarding the coronavirus that is spreading across the world, so I thought I would make a post answering those questions and providing some resources you can use to deal with the issue. Please note, however, that I am neither a medical doctor nor a biologist. As a result, I don’t claim any expertise on the matter. However, there are some misconceptions about the virus that are easily cleared up, and there are some facts that anyone who can understand the scientific literature should share.

First, a few facts. The term “coronavirus” refers to a very large group of viruses that circulate mostly among mammals and birds. However, some are able to infect people. Most coronaviruses that infect people produce mild illnesses, but some (like this one) produce potentially fatal ones. The coronavirus that is in the news right now is one that has not been seen before. This is not unusual. When an animal is infected with two different versions of the coronavirus, they can mix together, producing a new (usually called “novel”) coronavirus. This particular novel coronavirus has been charmingly named SARS-CoV-2, and it causes the disease referred to as COVID-19. Because of that, it is sometimes referred to as the “COVID-19 virus.”

The reason it has been given the name SARS-CoV-2 is that its genetic sequences indicate it is very similar to the virus that caused the SARS outbreak of 2003. Based on that sequence, it is thought that the virus originated in bats, but it might have passed through another animal (possibly a scaly anteater) before infecting people. Most importantly, there is strong evidence against the idea that it was genetically engineered. This is because the way it infects people is quite different from what would have been predicted given our current knowledge about these viruses. In other words, it is very hard to believe that anyone knowledgable enough to engineer a virus would purposefully make the genetic sequences that end up allowing the virus to be so good at infecting people.

The illness caused by this virus is flu-like, but it is much more serious than the flu. The death rate caused by the flu changes from year-to-year, depending on the strains that circulate. However, on average, the flu has a death rate of about 0.1%. That means for every 1,000 people who get the flu, 1 will die. Even though that is a low death rate, a lot of people get the flu. As a result, millions of people die from the flu every year. We don’t know the death rate for this new virus, since we don’t really know how many people have actually been infected, but the best estimate so far is that the death rate is about 2%. That means this virus is thought to be 20 times more deadly than the flu virus.

Second, the resources. The infographic above has been adapted from one that was produced by the CDC. The university at which I teach has asked all its professors to post this electronically as well as wherever students might be found. It is basic, but nevertheless, it does contain some helpful information. This link will take you to the latest information regarding where the virus has been detected, how many people have been infected, and how many people have died.

In general, the best way to avoid being infected by this virus is to avoid other people and avoid going to places where it has been found. The virus spreads most effectively when an infected person is within a few feet of an uninfected person. However, it might also be transferred by surfaces. If someone sneezes on a surface and someone else touches that surface, the virus can be transferred to the hand. Then, if that person touches his or her mouth, nose, or eyes, it is possible for the virus to begin an infection. Thus, you need to wash your hands a lot and avoid touching your eyes, nose, and mouth in between washings.

The most important thing to remember is that while the illness caused by this virus has a death rate that is thought to be about 2% on average, it is significantly higher for elderly people, people who are already sick with something else, and people with weakened immune systems. Thus, if you show any of the signs of the illness (fever, cough, shortness of breath) and think you might have been in contact with someone who has the virus, you should seek medical help.

While there are several groups working on a vaccine to prevent the spread of the virus, the earliest a vaccine could possibly be ready would be at least a year from now. My guess, given that I am anything but an expert about these things, is that it will not be needed. The disease seems to have already plateaued in China, and I expect other countries to be a bit better at reducing the spread. Thus, I expect that the spread of the disease will slow down significantly before a vaccine can be approved for use. I could easily be wrong about that, however.