A new study out of Denmark tried to measure the benefits of masks. It didn't go so well.

Social media has been abuzz this week over a new study out of Denmark about the effectiveness of masks on the risk of getting Covid-19. Depending on what news source you looked at, you might have heard that masks might not protect the people wearing them, or that wearing masks doesn’t prevent the spread of the virus. You might also have read the near-immediate backlash in which scientists pointed out all the evidence that masks really do work.

I read the study. It doesn’t prove anything, as even its own authors admit.

Let’s dig into the actual results just a bit to see what all the fuss is about.

The study was conducted in Denmark in April and May of this year, and what it tried to do (not very effectively) was to measure the effect of a recommendation to wear masks. That’s right, they weren’t really measuring the benefits of masks directly at all!

The study enrolled about 6000 volunteers, and for half of them they recommended wearing masks whenever they went outdoors. They also provided masks to those volunteers. For the other half, they didn’t do anything. At the time (March and April), Denmark was recommending social distancing, but universal mask wearing wasn’t recommended.

Quite a few people dropped out, so in the end they only had 4862 people in the two groups, about 2400 per group.

What did they measure? Well, they did an antibody test (far from perfect, but let’s not digress) at the beginning of June to see whether or not people were infected with SARS-CoV-2, the virus that causes Covid-19.

(Note that they DID NOT measure how well the masks might have protected anyone else in the community. They were only measuring whether a mask might protect the wearer.)

And the results? 42 people in the mask-recommendation group were infected, and 51 people in the no-recommendation group were infected. (That’s 1.8% versus 2.1% of each group.) So there was a small reduction, but it was not statistically significant, which means we really can’t say if the mask recommendation helped prevent infection.

The study authors admitted this themselves, writing: “the findings are inconclusive ... compatible with a 46% decrease to a 23% increase in infection.” In other words, the results could mean that masks reduce self-infections by 46% or increase them (bizarre as that sounds) by 23%.

In other words, this experiment doesn’t tell us much. If it weren’t about Covid-19, I doubt that the Annals of Internal Medicine would have published it. (A commentary by my colleagues at Hopkins and Stanford suggested that Annals was right to publish it, as long as scientists “carefully highlight the questions that the trial does and does not answer.”)

Now some big caveats. First, in the mask recommendation group, only 46% of the participants wore masks as recommended. Second, the study didn’t ask if anyone in the no-recommendation group wore masks. Third, the study relied on self-reporting to determine who was actually wearing their masks consistently–that is, they simply asked the participants to tell them how often they wore their masks.

What? Imagine if you were studying the use of seat belts to reduce injuries, and only 46% of the people you told to wear seat belts wore them properly. On top of that, imagine that you relied entirely on self-reporting to determine who was actually wearing the seat belts. This study design is nearly worthless if you want to know the true benefits of seat belts.

So the Danish mask study was inconclusive, as its own authors report. Therefore it would be a huge mistake, scientifically speaking, to take this non-result and conclude that masks do not protect you. It would be an even bigger mistake to conclude that the study showed that masks don’t benefit the community. Unfortunately, that didn’t stop these two Oxford University scientists from jumping to exactly that conclusion. They claimed, in an article in The Spectator, that the study showed that “wearing masks in the community does not significantly reduce the rates of infection.” This is dead wrong. The study wasn’t even measuring community rates of infection.

(For an excellent Twitter-take on what the study does not prove, see this thread from The Health Nerd.)

And as the CDC has documented, multiple studies have already shown that masks are highly effective at limiting the spread of Covid-19. And a study last summer pointed out that increasing the use of masks by just 15% “could prevent the need for lockdowns and reduce associated losses of up to $1 trillion” in the U.S. alone. So yes, it’s a good idea to wear a mask.

It’s also simply common sense that if you wear a mask, the amount of virus that you breathe in or out will be reduced. You’re not just protecting yourself, you’re also protecting everyone around you.

Until we can get this pandemic under control, we all need to wear masks in public. It’s utterly ridiculous that this has become a political issue, as it has in the U.S. To those who think mask wearing somehow limits their personal freedom: get over it. When you see a red light at a busy intersection, do you race through it because you need the “freedom” to drive like a crazy person? No. Civilized society requires everyone to follow some basic rules to protect each other, and during a pandemic, wearing a mask is one of them. And to those who think that wearing a mask somehow shows their civic virtue? No, that’s wrong too. To use the same example, stopping at a red light doesn’t prove that you’re virtuous.

It’s just a mask. It’s not a political statement. Get over it.

New Alzheimer's disease fails, then works, then fails again


 Alzheimer’s disease is one of the most devastating conditions of old age. By recent estimates, more than 5 million people in the U.S. have Alzheimer’s, and managing the disease will cost over $300 billion in 2020. As the population ages, this problem is growing worse, and yet we still have no effective treatment.

You might have seen rosy-looking ads for Alzheimer’s treatments, but nothing really works, not yet at least. That’s why many people were excited about the possibilities of a new drug, aducanumab, that showed early signs of being able to reduce the accumulations of “plaques” in the brain.

Background: in people with Alzheimer’s, a protein called beta-amyloid accumulates in the brain, forming plaques that seem to disrupt brain function. (This hypothesis is not fully proven, but it is widely considered credible.) Thus one way that we might treat Alzheimer’s would be to reduce or eliminate beta-amyloid plaques. That’s what Biogen’s new drug, aducanumab, is intended to do.

Biogen has run two separate trials, called “EMERGE” and “ENGAGE,” to test whether or not aducanumab (ADU for short) worked.

Here’s where things get murky. Back in March of 2019, both trials were halted due to “futility,” because ENGAGE was showing no benefits for the new drug. In EMERGE, the high-dose patients seemed to be getting some benefit, but Biogen had specified ahead of time that if either trial was failing, that would mean the drug wasn’t working. Thus they halted the trials, disappointing as it was.

Fast forward to October of 2019, though, and Biogen had a new story. They went back and looked at a subset of the patients in ENGAGE (the study that had failed), and said that there was a benefit after all, if they looked only at the high-dose patients. This past July, Biogen went to the FDA and applied for approval for ADU.

Just this past week, two very conflicting announcements about ADU appeared. First, on Wednesday, the FDA’s internal scientists released a very rosy report, saying that the data from one of the trials were “robust and exceptionally persuasive.” For the second trial, the scientists said that even though the drug initially seemed to fail, a closer review led them to conclude that overall, ADU did provide a benefit.

Biogen shares rose 45% that day, adding $17 billion to the company’s value.

Then on Friday, a panel of independent, external scientists released their conclusions, which resoundingly rejected the drug. The external panel said that the data from the two trials was unconvincing, and they pointed out “multiple red flags” in the analysis.

(Trading in Biogen stock was halted during the Friday meeting, but at the end of the day it was close to the high it reached on Wednesday.)

So what happened? It appears to be a classic case of cherry-picking: when the data from the ENGAGE study didn’t pan out, the company re-analyzed a subset of the data and found a more-positive picture.

That’s not really kosher, as explained by a separate group of scientists in a paper published just a few days ago in the journal Alzheimer’s & Dementia. In this paper, David Knopman and colleagues, from the Mayo Clinic and Stanford Medical School, analyzed data that Biogen has released from its two trials. (The trials haven’t been published, but some of the findings were released in a publicly-available slide presentation that the authors relied upon.)

Knopman and colleagues explained that after two conflicting trials, there simply isn’t enough evidence that ADU works, and they also offer alternative explanations for the positive findings. They argue that the best Biogen can do is to “perform another trial of high‐dose ADU of at least 78‐weeks duration,” which could determine whether or not the positive results were real or just coincidence.

It’s somewhat mysterious that the FDA’s internal panel released their rosy report about ADU on Wednesday, only to be slapped down just two days later by an independent outside panel of scientists. After reading the negative views of the external panel and the analysis in the paper by Knopman and colleagues, I’m very skeptical that ADU has any clinically significant effect. If it had a truly robust effect, it simply wouldn’t be so hard to tease it out.

So we still don’t have a good treatment for Alzheimer’s, but the world still needs one.

The newest member of the coronavirus task force is giving out terrible advice


Why shouldn’t we trust the advice of an M.D. from Stanford University? Because he’s unqualified, that’s why.

As everyone with a pulse knows, the U.S. has handled the coronavirus pandemic very, very badly. Tragically, over 220,000 people have died, and our rate of deaths per capita is higher than any other country in the world.

The Trump administration established a coronavirus task force back in the spring, supposedly led by VP Mike Pence. For a long time, the task force included Dr. Anthony Fauci, a world-renowned expert on viruses who is also the Director of the NIH’s infectious disease institute, where he has worked for 40 years. Despite the frequently erroneous and misleading statements by President Trump, Dr. Fauci consistently gave the public advice that was both scientifically and medically accurate. He never promised that the virus would simply disappear, and he urged everyone to wear masks and avoid unnecessary contact with others. He also warned against re-opening businesses too quickly.

Trump didn’t like that, so he pushed Fauci to the sidelines in favor of someone whose advice matched what he wanted to hear.

Enter Scott Atlas. Atlas is a Fellow at the right-wing Hoover Institute at Stanford University, where he studies health care policy. He’s also an M.D., a radiologist who specializes in MRIs. Notably, he has no special expertise on viruses, vaccines, or epidemiology.

Atlas has pushed for schools to reopen and for college sports to resume, against the advice of public health experts. Just last week, he tweeted that masks don’t work, a claim that was so outrageous and dangerous that Twitter took it down. (To be precise, Atlas’s tweet was “Masks work? NO”.) Another coronavirus task force member, Dr. Deborah Birx, said she felt “relief” that Atlas’s tweet was removed.

Perhaps Atlas is so convinced of his own brilliance–after all, Stanford is one of the world’s top universities, and he wason the faculty there–that he thinks he’s an expert on everything. But a good scientist would pay attention to the recommendations of others who are clearly more qualified, and Atlas has not done that. For example, he has argued, against the evidence of experts, that “low-risk groups getting the infection is not a problem” (wrong–they can spread the infection to high-risk groups) and that only people with symptoms should get tested (very bad idea, given that many people are asymptomatic).

Alarmed at the harm that Atlas’s advice has been causing, a group of more than 70 of his Stanford colleagues, including world-renowned experts in infectious diseases, epidemiology, and health policy, published an open letter decrying Atlas’s bad science. Their statement read, in part:

“... we have both a moral and an ethical responsibility to call attention to the falsehoods and misrepresentations of science recently fostered by Dr. Scott Atlas, a former Stanford Medical School colleague. Many of his opinions and statements run counter to established science and, by doing so, undermine public-health authorities and the credible science that guides effective public health policy.”

Atlas responded by threatening to sue his Stanford colleagues over their letter, and in response to that, an even larger group of Stanford professors released a statement saying they wouldn’t be intimidated. The second letter, with over 100 signatories, stated:

“We believe that his [Atlas’s] statements and the advice he has been giving fosters misunderstandings of established science and risks undermining critical public health efforts.”

My bottom line: Atlas is a bad scientist, apparently far more interested in power and influence than in public health. I’m not commenting on his skills as a radiologist, which are irrelevant here. (He might be an outstanding radiologist.) However, he’s providing advice to the U.S. government that contradicts the advice of scientists who are far more qualified than he is, and when they pointed that out, rather than buttressing his arguments with data, he threatened to sue. That is not the behavior of a good scientist.

To those who think that this disagreement means there are two sides to the issue, I urge you to think again. Science and medicine are highly specialized. Just as you wouldn’t want a virologist to read your MRI scan, you wouldn’t want a radiologist (Atlas) to decide on the best way to treat the Covid-19 virus. So when a radiologist (Atlas) disagrees with a virologist (Fauci) over a virus, guess who’s most likely to be right?

It’s unfortunate that the current administration has chosen to heed the advice of someone who tells them what they want to hear, rather than someone who truly has the qualifications to advise them.

Can the SARS-CoV-2 virus damage the brain?

A certain very famous politician came down with Covid-19 recently, and has been acting even more erratically than usual. This has led a number of pundits (and some doctors) to speculate that this politician’s behavior might be a symptom of his ongoing infection. Could this be true?

Well, maybe. Most of the attention around Covid-19 has been focused on the damage that the SARS-CoV-2 virus causes in the lungs, which can lead to difficulty breathing, the need for a respirator, and even death. The virus has the ability to replicate explosively in a person’s lungs, not only causing serious damage but also triggering an over-reaction by the immune system, a so-called “cytokine storm” that itself can kill you, even if the virus doesn’t.

However, numerous reports have shown that the virus gets into many other tissues besides the lungs, including the brain. Just this week, a new study out of Northwestern University School of Medicine found that over 80% of patients with Covid-19 had at least some neurological symptoms. 80% is a startlingly high number.

While that sounds alarming, let’s look at the details. The new study looked at 509 Covid-19 patients, all of them admitted to hospitals in Chicago. These were “consecutive” patients, meaning that the investigators didn’t cherry-pick their subjects, but just took 509 in a row. That seems sound.

Most of the symptoms, although definitely affecting the brain, were mild. 38% of the symptoms were headaches, and 44% were “myalgias”, which refers to aches and pains throughout the body. (Note that some patients had more than one type of symptom, so the numbers in the study add up to more than 100%.)

However, 32% of the patients had encephalopathy, which can be much more serious than a simple headache. According to NIH, encephalopathy can involve:

“loss of memory and cognitive ability, subtle personality changes, inability to concentrate, lethargy, and progressive loss of consciousness.”

Does this sound like any of the behaviors we’ve seen in our most famous infected politician?

The new study is not the first one to report neurological symptoms caused by Covid-19. Back in July, a research team from University College London reported multiple cases of neurological problems in their cohort of 43 patients. They observed not only encephalopathy (in 10 patients), but also encephalitis in 12 other patients and strokes in 8 more. Some of the patients in that study were reported as experiencing “delirium/psychosis,” and strokes often cause permanent brain damage. Clearly, the SARS-CoV-2 virus can cause serious health problems, and disturbing behavioral changes, if it gets into the brain.

None of this means that any current political leader is experiencing an altered mental state. We don’t have a direct test that measures whether the virus is present in a person’s brain, so all we can do is observe symptoms and make inferences from those. The best available evidence today, though, shows that for anyone with Covid-19, neurological problems are definitely something we should be worried about.

Why do the Covid-19 vaccine trials take so long?

The whole world is waiting for a Covid-19 vaccine. More than 100 different vaccines are being investigated, and 42 of them are already being tested in humans, which is lightning-fast progress in the world of vaccine development.

11 vaccines are already in Phase 3 trials, which use thousands of volunteer subjects to test whether a vaccine really works. If any of these 11 trials are successful, as many scientists expect them to be, then the world might finally begin the process of opening back up.

By all accounts, though, we’re still a few months away from having an approved vaccine. Why does this take so long? Today I’ll try to answer this question. A little math is involved, but we don’t need much to get the basic idea across.

In a Phase 3 trial, we give the vaccine to large numbers of people to see if it works. Some of the 11 current trials use as many as 40,000 volunteers, so let’s use that number for the sake of discussion. In the trial, we might give the real vaccine to half the volunteers–20,000 people–and give a placebo to the other 20,000. A placebo is a harmless shot, typically just saline solution, that won’t have any effect. The volunteers don’t know if they’re getting the real thing; this is called “blinding.”

Then we wait. Here’s the problem: we don’t infect anyone intentionally, so we have to wait for naturally-occurring infections, and it might take a long time to see those. Subjects just go about their lives, and if they get sick, the study records that fact.

So the question is, how many people in each group of 20,000 will be infected in the first week? The first month? Two months? The answer is that we simply don’t know. To speed things along, scientists running the trials try to select volunteers who are more likely than most people to get infected, but we can’t really control the number of people who get sick.

Let’s suppose that after just one week of a trial, 3 people in the placebo group come down with Covid-19, and no one in the vaccine group gets sick. So far so good, right? But we can’t possibly conclude that a vaccine works based on just 3 cases. Statistics tells us that those 3 cases might have just happened by chance. (More precisely, if 3 cases occur in the 40,000 subjects, and if the vaccine doesn’t work at all, then there’s still a 12.5% chance that all 3 cases will occur in the placebo group.)

Suppose that 2 months roll by, and now we have 100 people in the placebo group who got sick, and only 10 infections in the vaccine arm. This is much, much better: without going into the math, a difference of 100 versus 10 would be highly significant, suggesting that the vaccine reduced cases by 90%.

But what if 2 months roll by and the placebo group only has 10 cases? Even if the vaccine group has zero cases, such a small number is not going to be enough to give us confidence that we have an effective vaccine. We want to see as many cases as possible–but we can’t force the issue. We have to wait.

In the US, the FDA has announced that a vaccine has to protect at least 50% of people in order to be declared effective. This means we need to see enough cases in to be confident that a vaccine confers that degree of protection. 50% is a pretty low bar, but so far none of the trials have announced even preliminary results showing that they’ve met that standard.

(Aside: “blinding” is really important in these trials. If subjects know they’re getting a placebo, they might be extra-careful to avoid exposure to the virus. This would artificially depress the number of cases in the placebo group. Conversely, if they know they’re getting the vaccine, they might be more reckless, increasing the exposures and cases in that group. In order for the results to be valid, we need all the subjects to behave the same.)

A faster option? There is a way to speed up this process: a “challenge” trial, where subjects are intentionally infected with the virus. The UK is preparing to start such a trial in January, first administering vaccines to healthy volunteers, and then exposing them to the SARS-CoV-2 virus about a month later. This is a far faster way to determine if a vaccine is working, but it creates serious ethical quandaries, because we don’t have a cure for the virus. If the world has an effective vaccine in January, I expect that the challenge trial will be cancelled. That wouldn’t be a bad outcome.

A new Russian Covid-19 vaccine looks promising, but did they fabricate some of their data?

Last week, a team of Russian scientists published the results of two phase 1/2 vaccine trials for a new Covid-19 vaccine developed in Russia. The study appeared in The Lancet, one of the world’s leading medical journals.

This vaccine has already received tremendous attention after Russian leader Vladimir Putin announced they would start administering it widely, before any phase 3 trials were under way. As I wrote last month, it’s not a good idea to skip these Phase 3 trials.

Nevertheless, the results from the early stage trials of both vaccines look quite good. Although the trials were small, with just 76 subjects, 100% of the subjects had a strong antibody response, and none of them had anything more than mild reactions to the vaccine. This suggests that both vaccines might be effective, although it’s too soon (after just 76 people) that it will be safe on a large scale.

There’s another problem, though.

Within 3 days of the paper’s publication, Enrico Bucci from Temple University described a series of apparent duplications in the figures presented in the Russian paper. He published his findings on his website as a “note of concern” that dozens of other scientists have signed.

I’ve read the paper and looked at all the figures, and it’s clear that something is wrong with the data.

Let’s look at one example to see what is going on. Here’s a small part of Figure 2A from the paper:

Each little column of dots shows a distinct group of 9 subjects, where the height of a dot indicates the level of antibodies found in that subjects. Notice that the 9 subjects in the red box (boxes added for emphasis) on the left have an identical pattern to those in the box on the right. These are completely independent subjects, and such a pattern is exceedingly unlikely.

It’s possible that this happened by chance, but then the problem is that this isn’t the only apparently duplication. Prof. Bucci identified at least 13 instances where sets of results are identical or near-identical between two different time points or two different sets of subjects. The other duplications look a lot like the one shown here.

The simplest explanation is that the data for some of the experiments were simply copied over from other experiments. As reported in The Moscow Times, the lead author of the study, Denis Lugonov, said there were no errors in the data. Because the authors of the Russian study didn’t provide their raw data, and The Lancet didn’t require it, other scientists can’t really check.

What are we to make of this? The details of the study are clearly explained, and the Russian vaccines use a design (an adenovirus modified to contain the SARS-CoV-2 spike protein) that is similar to other vaccines that so far seem safe and effective. Thus it’s quite possible that this vaccine will work–and it will be good for the world if it does. But the questionable data raise questions about whether the scientists behind this phase 1/2 trial have really done all of the experiments that they describe. The study concludes by noting that a phase 3 clinical trial with 40,000 participants is planned. Let’s hope that one yields positive–and genuine–results.

[Hat tip to Retraction Watch for drawing my attention to this study.]

Can we re-grow cartilage in damaged knees? A new Stanford study offers hope

Knee pain is one of the most common afflictions among athletes and among older people in general. I’ve written about treatments for knee pain before, specifically about the many so-called alternative therapies that just don’t work.

(Quick review: the supplements glucosamine and chondroitin don’t work. Injections of hyaluronic acid don’t work. Acupuncture really doesn’t work. Simple pain relievers like ibuprofen work, but only for a short time.)

The problem is that cartilage, which provides a cushion between the large bones of the upper and lower leg, doesn’t regenerate itself. When you have cartilage damage, either from an injury or just wear and tear, you lose that cushion and you get pain and inflammation. Because the cartilage doesn’t really heal, if the damage gets severe, you might eventually need a knee replacement.

There is hope, though. For years now, I’ve been following stem cell research to see if it offers the promise to truly regenerate cartilage (or any other tissue, for that matter). Stem cells are special types of cell that can generate all of the different cells in our bodies, from blood cells to heart cells to lung cells to cartilage. Back in 2006, scientists made a major breakthrough when they discovered how to turn normal cells back into stem cells. Ever since, scientists have been exploring how to turn stem cells into just what we want them to be.

To repair damaged cartilage, what we’d really like is fresh new cartilage grown from our own stem cells. This is what a new study out of Stanford University, just published in the journal Nature Medicine, promises to do.

Here’s how it works. It turns out that the ends of our leg bones do contain stem cells, and if the bones are damaged, those stem cells will create new cells in response. The problem is that the new cells are basically scar tissue, not cartilage. The scar tissue wears out pretty quickly, and doesn’t provide the cushioning that cartilage does.

Stimulating the stem cells to get started is easy, if a bit crude: orthopedic surgeons already do this by drilling very tiny holes in the ends of the bone, a technique called microfracture. This provides some pain relief when the scar tissue appears, but it’s only temporary.

The Stanford team, led by Matthew Murphy, Charles K.F. Chan, and Michael Longaker, decided to use some of the latest findings about stem cells to steer the cells in a different direction after microfracture surgery. They did this by adding two proteins to the ends of the bones. The first one was BMP2 (bone morphogenetic protein 2), which encourages the stem cells to make new bone cells. They also added a second protein, VEGFR1 (vascular endothelial growth factor), which halts the process of bone formation in a way that leaves cartilage instead.

What’s exciting about this therapy is that it actually worked! New cartilage grew from the stem cells, and it appeared to reduce pain. The big caveat here, and this bears emphasis, is that the experiments were done in mice–and many studies that work on mice fail to reproduce in humans. Recognizing this limitation, the Stanford team also conducted experiments using human cells that had been transplanted into mice, showing that the treatment did indeed create human (not mouse) cartilage.

Next up will be studies in humans, to see if this works as well in people as it did in mice. If it does, another big advantage, as Prof. Longaker pointed out, is that both BMP2 and VEGF have already been approved by the FDA for other uses. This should make it easier to get approval for the new treatment as a therapy for aching knees. He suggested that, eventually, doctors might:

“follow a ‘Jiffy Lube’ model of cartilage replenishment. You don’t wait for damage to accumulate — you go in periodically and use this technique to boost your articular cartilage before you have a problem.”

So when can we get this new cartilage-healing treatment? More studies will likely take years.

Well, as Dr. Robert Marx pointed out in the NY Times, there’s nothing to stop orthopedists from trying this treatment out right away, because the drugs required are already on the market. Thus long before we see convincing evidence that it works in humans, doctors might be trying this out. For a patient who has deteriorating cartilage, if given the choice between waiting many years to see how the studies turn out versus trying a promising new treatment right away, the temptation might be too great to resist.

This is where things get tricky. There are already numerous orthopedic practices offering “stem cell therapy for knees” along with “platelet-rich plasma,” which they will inject right into your knees (for a price, of course). It took me less than 30 seconds of Googling to find dozens of practices offering these therapies, with assurances that they “repair the knee naturally ... by stimulating the creation of cartilage.” Note that these clinics are not using the new Stanford technique (not yet, at least), and there’s no good evidence that these injections will re-grow cartilage, despite the testimonials on many websites. So for anyone looking for knee pain treatments, caveat emptor.

Let’s hope this new treatment method works. For those of us (including myself) with aching knees, this new therapy is the most promising one I’ve seen in a very long time.

Some odd truths about viruses, and about the COVID-19 viruse

The virus that has devastated the world this year, SARS-CoV-2, is not a living organism. Viruses are not alive. Think of them instead as biological machines, incredibly small ones.

What, exactly, is a virus? Many people outside the world of science and medicine don’t really know, so today I’m going to describe just a few of their essential features.

Viruses have, in general, just two functions: they invade your cells, and then they borrow your own cells’ machinery to copy themselves. (Note: for simplicity I’m describing viruses that infect humans, but in reality they infect pretty much every living thing, from bacteria to plants to animals.) After making many copies, they break out, usually destroying the cell they’ve invaded, and do it again.

Here’s a weird thing about viruses. All living things on this planet are made from instructions encoded in DNA. Some viruses are also made of DNA, but many are made of RNA instead. RNA is a lot like DNA, but it doesn’t have that famous double-stranded helix structure; instead, it’s just a single strand.

Now consider how small they are. The Covid-19 virus, SARS-CoV-2, has just 29 genes that are encoded in just under 30,000 letters of RNA. Other viruses can be even smaller: the influenza virus has just 10 genes, encoded in 13,588 letters of RNA. In contrast, the human genome has about 3 billion letters of DNA, and over 20,000 genes. In other words, our genome has 100,000 times more information encoded in it than the Covid-19 virus.

And yet these simple machines with a handful of genes can destroy us. Think of it like throwing a wrench into a running engine: the wrench is simple, but that doesn’t mean it can’t gum up the works of a far more complicated device. So too with viruses and their hosts.

It’s not just that they have a small genetic code: viruses are also physically small. So small, in fact that they cannot be seen under a normal microscope. Bacteria are huge compared to viruses; in fact, bacteria suffer viral infections just like humans do.

(Aside: the exciting new technology known as CRISPR is actually a mechanism created by bacteria to fight off viral infections!)

One consequence of virus’s tiny size is that when the 1918 flu pandemic swept the world, no one knew it was caused by a virus. Scientists didn’t have the technology to see a virus at that time. The influenza virus–the true cause of flu–wasn’t discovered until 15 years later, in 1933.

(Another aside: a bacterium called Haemophilus influenzae was given its name because scientists thought it caused the flu. It doesn’t. It does cause ear infections and sometimes-deadly meningitis, though, and for that reason the Hib vaccine, which prevents infection from this bacterium, is a critical part of the childhood vaccine schedule.)

Another odd fact about viruses: they’re not cells. They don’t have a proper cell wall, as such, just a shell made out of a few proteins. The shells encapsulate the tiny genetic code of the virus. We call them “particles” for lack of a better word.

Viruses are everywhere, and they are far more numerous than bacteria. Bacteria, in turn, are far more numerous than plants and animals. Viruses are also devastatingly effective at what they do (infecting living cells and hijacking those cells to make more viruses), which is why we will never rid ourselves of them.

While we can’t get rid of them, we can fight the viruses that cause human diseases like Covid-19. The best way to do that is to prevent viruses from invading our cells. How? There’s only one good way that we know of so far, and that’s to use the human immune system to fight them off at the molecular level. (While viruses are simple, the immune system is really complicated. I can’t possibly explain it here, but check out Ed Yong’s recent story at The Atlantic for an excellent attempt to de-mystify the immune system.)

This is where vaccination comes in. When a virus invades us, our immune system creates custom-designed cells (see that Ed Yong article) that recognize and destroy the virus. Then it becomes a race: if the immune system wins, it destroys all of the viral particles. If the virus overwhelms the host, the result can be fatal.

For Covid-19, most people mount an immune response quickly enough to avoid getting seriously ill. However, for those that don’t, the results are extremely serious. A vaccine works by “showing” the immune system part of the virus, but doing this in a way that isn’t actually an infection. One strategy used by several of the Covid-19 vaccines under development is to just package up one of the SARS-CoV-2 proteins, without the rest of the virus. The vaccine itself will prime the immune system to recognize the Covid-19 virus without actually causing an infection. Then, if that person is actually infected, the immune system swings into action quickly, and fights off Covid-19 before it ever gets established.

So that’s it. Covid-19 is caused by a tiny, sub-microscopic biological machine, a virus with just 29 genes. The virus can be ruthlessly effective, but our immune system can wipe it out if we give it the right clues. Let’s hope we’ll have a vaccine soon.

Disclaimer: the content on this site is my personal opinion and is independent of my affiliation with Johns Hopkins University.