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.

Why you should trust the coronavirus vaccine

Let me start by making one thing clear: at the time of this writing, we don't have a scientifically validated vaccine for COVID-19. But more than 150 vaccines are being developed around the world, and many of them are already in advanced stages of testing.

So we'll have a vaccine soon, likely in a matter of months. And everyone should take it. I know I will.

Today I’m going to try to de-mystify vaccines a bit, in the hope that this might help people feel more comfortable with them.

Before explaining what a vaccine actually is, let me point out that vaccines are probably the single greatest medical advance in the history of human civilization. Vaccines have saved hundreds of millions of lives: prior to vaccines, people lived in fear of diseases like smallpox, which killed 300 million people in the 20th century alone. Thanks to the vaccine, we eradicated smallpox from the entire world in 1980. Polio is another dreaded disease that killed or permanently injured millions, until the 1950s, when Hilary Koprowski, Jonas Salk, and Alfred Sabin invented vaccines that protected against it. Today, no one in the U.S. or Europe worries about polio, and it too has nearly been eradicated worldwide.

What exactly is a vaccine? It’s a pretty simple concept. Our immune system has the remarkable ability to “remember” pathogens that we’ve been exposed to. So once you’ve been infected with some viruses or bacteria, you acquire immunity to those diseases that may last the rest of your life. A vaccine is basically a way to teach the immune system to recognize a pathogen without actually making you sick.

The simplest way to do this (conceptually) is to take a batch of viruses or bacteria, kill them so they’re harmless, and then just inject them into a person. The immune system then “sees” the proteins in the dead pathogens (because the proteins are still floating around), and it learns all it needs to know from these. Later on, if a live virus infects that person, her immune system will say “aha, I know you!” and will quickly surround and destroy the invaders.

Simple as it sounds, there are many complications with this process. One is that it’s often very hard to isolate and grow enough of the virus (or bacteria) for large-scale production. The viruses then need to be isolated, killed, and purified, which can be complicated and costly. For COVID-19, though, any cost is worth it.

Another, much newer way to make vaccines uses modern molecular technology to make RNA. There’s no need to isolate or grow the virus at all! This is how Moderna’s new mRNA vaccine works (see their whitepaper here).

The mRNA vaccine relies on the fact that we already know which protein in the SARS-CoV-2 virus is the most important one. It’s called the spike protein, so I’ll just call it Spike. Spike is what attaches to human cells and lets the virus infect them. We also know the sequence of the Spike gene: the sequence of the entire SARS-CoV-2 virus was released in early January, and we’ve now sequenced thousands of these viruses.

An mRNA vaccine simply uses the RNA itself, rather than dead viruses. Today we can synthesize RNA in large quantities, so if you take some of this RNA and inject it into a person, what happens? Well, our own cells will translate this RNA to produce the Spike protein. All by itself, the protein cannot possibly cause an infection. It’s analogous to having a motor without a car: you can’t go anywhere without the whole package.

But here’s the good part: our immune system will recognize Spike anyway, even without the virus, and it will remember this invader. So the RNA vaccine is, in theory at least, even safer than traditional vaccines, because live pathogens are never used in the production process. (Before the anti-vaxxers jump on me here, let me emphasize that traditional vaccines are incredibly safe.)

This is just one example: there are 23 vaccines already in human trials, and over 150 in development, using mRNA, proteins, and other approaches.

There are other ingredients in vaccines too: preservatives and adjuvants. Anti-vaxxers like to read vaccine ingredients and then claim that all sorts of harmful stuff is in there, but their claims are mostly just gross ignorance. Preservatives are there to prevent the growth of things like bacteria, so they make vaccines safer. And adjuvants like aluminum salts (the most common adjuvant) are ingredients that enhance the effectiveness of vaccines, meaning you can use a lower dose. Aluminum salts have a very long safety record.

So why don’t people trust vaccines? Largely because the anti-vaccine movement has spent years spreading misinformation and fear, and it is already pronouncing strong opposition to any coronavirus vaccine, regardless of the evidence. The New York Times reported this week that mistrust of future coronavirus vaccines could imperil public health, especially in the United States. Polls have shown that large proportions of Americans say they won't take a vaccine even when it's available, which is, frankly, kind of crazy. (It didn’t help when tennis player Novak Djokovic expressed doubts about whether he’d be willing to take any future coronavirus vaccine.) Last month, NIH’s Anthony Fauci said that the “general anti-science, anti-authority, anti-vaccine feeling” in the U.S. may seriously undermine the effectiveness of any future vaccine. Of course, this could change once we really do have a vaccine, and we should all hope it does. But the anti-vaxxers never let up.

It also doesn't help build trust when the Trump administration calls their vaccine program "Operation Warp Speed." This might have sounded exciting to some sci-fi fans in the White House, but to many people it sounds more like a devil-may-care approach that emphasizes speed over safety. 

So how do we establish trust in the new vaccines, which are probably coming just a few months from now? One way to reassure people is to publish all the numbers from the vaccine trials. A just-published study in NEJM on the Moderna vaccine (the RNA vaccine) provides exactly these numbers, and they look very good in terms of both safety and effectiveness. 

In that study, all 45 participants had a robust antibody response–a stronger response, in fact, than in many people who’d been infected with the virus itself. There were some side effects, including fever and chills, but all were graded as mild or moderate. The scientists looked at 3 different dosage levels, and the side effects were greatest in the highest dose–but the antibody response was perfectly adequate in the lower dosage levels. So the next phase of testing, already under way, is using the lower dosages.

This was a phase 1 study, but it's very encouraging. If these results hold up in a large group–a question that is being tested now, in a phase 3 study–we'll have a working vaccine. 

And if you want to know more about this trial, you can read about it at the public NIH site,

Many if not all of the vaccines being developed in Europe and the U.S. are going through the same kind of scrutiny, and we’ll be able to see the results of those tests too. This is how we generate trust in the results: share them openly. I’m very re-assured by what I’ve seen so far.

The bottom line: vaccines work, and our methods for testing them are rigorous and thorough. With a little luck, the world will have multiple COVID-19 vaccines by the end of 2020. Once we have enough people vaccinated, our long nightmare with the coronavirus pandemic will come to an end.

It's not okay to open universities without universal coronavirus testing

Paper strip COVID-19 test developed at MIT
and the Broad Institute

Over the past week, many universities, including my own Johns Hopkins University, announced plans for re-opening this fall. As expected, almost all of them will re-open.

Most of the plans for re-opening are entirely predictable, involving lots of social distancing rules, but in some cases they appear to reflect a mindset that seems more driven by fear of legal liability then genuine concern for everyone's health. If they really care, universities should offer testing to everyone on campus–students, faculty, and staff–and they should make the tests frequent and mandatory. So far, most are not doing this, with exceptions including Cornell University, Yale University, MIT, Dartmouth, and a few others. (Many schools, including Hopkins, haven’t announced a testing plan but yet implement one. Duke and Penn have announced that students will at least be tested initially upon their return.)

It's not really that hard, and it's not that expensive, to offer testing to all students. Let me explain.

Most universities (I've read a dozen or more re-opening plans, but I'll go out on a limb and say "most") plan to open with a mixture of in-person and online classes. In-person classes will be smaller, with students spaced apart in large rooms, and masks required. Larger lectures will be offered online, much as we did this past spring. Universities are also offering students the opportunity to opt out and take a temporary leave of absence if they're not comfortable returning.

Universities know that most students will opt to return. After all, what else can they do? In a normal world, students could take time off to travel, or pursue an internship, or study elsewhere; but in our COVID-infected world right now, there's simply nowhere to go.

So the students will return, and universities will require them to agree to practice social distancing, wear masks, blah blah blah. The students will agree to all these restrictions, and then they will behave like college students everywhere.

In other words, students will get together without masks, party late into the night, and generally share whatever infections any of them have. Luckily for students, the 18-24 year-old age group has very low risk of serious illness from COVID-19. Most of them will recover quickly.

The same is not true for faculty, staff, and the communities around our universities. Many of us (myself included) are far more vulnerable to serious complications if we get infected, and students will unintentionally be vectors for spreading the virus. Without testing in place so that we know who's infected, this is highly likely to happen.

We could greatly reduce the risk of viral transmission if we had universal testing of everyone on campus. This would have to be followed by contact tracing, which we can do with a smartphone app, and isolation of infected individuals. There are now several ways to offer coronavirus testing, and perhaps the most promising is a simple, saliva-based test that only costs a few dollars.

These new tests are based on very elegant CRISPR technology designs; one was described publicly by scientists from MIT, the McGovern Institute, and the Broad Institute in early May (with a preliminary version in February), and another was described publicly by scientists from UC San Francisco and Mammoth Biosciences in mid-February. At least 3 companies–E25Bio, Mammoth Biosciences, and Sherlock Biosciences–are now gearing up to manufacturer these tests, and the cost will be just one to five dollars.

The new paper-strip test couldn't be much simpler: you simply spit into a tube, and then place a specially-treated paper strip into the saliva. (Several other variants on this process are in development.) After some simple processing using inexpensive, widely available equipment, the strip then changes color if the coronavirus is present. The whole process takes under an hour

An alternative to the paper strips is a home-grown virus detection process using modern DNA and RNA sequencing technology. Most major universities (including my own) have this expertise on campus. Working with colleagues at Hopkins, we estimated that we could "roll our own" large-scale testing technology for about $10 per test, with 12-hour turnaround time, and that we could test everyone at least once a week. Not as good as the paper strips, but far better than doing nothing.

Meanwhile, the only FDA-approved tests, based on RT-PCR technology, use nasal swabs, which are far more invasive and difficult to use (you have to stick those swaps deep into the nasal cavity), and cost $50-$100 per test. Either of these reasons suffice to make nasal swab testing impractical as a universal testing method. 

I've already heard objections to these newer tests. The most common refrains are (1) they sometimes have false negatives, meaning that an infection is not detected, and (2) they're not FDA approved. To both of these I have the same response: so what? Is it better to bring back thousands of students, to mix and mingle with hundreds (or thousands) of faculty and staff, and not provide any testing at all? No.

Without a cheap, FDA-approved test, universities have an excuse to take the easy way out: bring everyone back, make them promise to socially distance, and don't offer any testing. Under this scheme, we won't have any way to know who's infected. Many professors and university employees have expressed alarm, and some have signed petitions asking for the right to teach remotely

I agree that universities should re-open this fall–indeed, I think it's imperative to do so, in order to start bringing the world back to normalcy. But universities can't keep pretending that a set of social distancing rules, combined with a mix of online and in-person classes, is enough. 

Many of us don't care if the coronavirus test is FDA approved, and we know it's not perfect. The tests are already quite good, as peer-reviewed papers have shown, and they'll get better. Universities can offer these tests or others to everyone on campus. Cornell University has announced that it will do so, as have Yale, MIT, and Dartmouth. I hope every other college and university, including my own, will do the same.