Understanding Covid-19 vaccines for the rest of us

The media machine is delighted to peddle sensational news, irrational fears and “opinions” coming from overnight experts — or worse movie and pop stars. So like many of us who just happen to have formal scientific training in the field, I alternate between depression and anger when listening to the news. I realize that this article will be out of the usual subjects we address here. But since family and friends had questions about the new Covid-19 vaccines, I guess that many have had too.

So, as someone who worked in medical research for his PhD, managed businesses in the pharma market, and who’s been consulting for medtech startups and big pharmas since 2008, I’d like to share a few things.

Don’t expect high level, intricate discussion from a business perspective. This is really about trying to share what I believe anyone should know really about vaccines and the current pandemic.

Let’s jump right in:

Q. Why should I rush to get a vaccine? The Covid-19 virus is not that dangerous anyway, it barely kills more people than the normal flu and this is just all blown out of proportion because of [ insert your rant on media, politicians, or big pharma].

Before even going back to actual data and science, let’s just consider this:

When was the last time all of the governments on the planet, from democrats to autocrats, from conservative to liberals, from rich to poor countries, decided all together around the same time to close down ALL economies? Whatever is your belief system or your source of information, just pause on that.

Now, why is Covid-19 such a huge threat?

First the fatality rate is extremely high. As I’m writing this, there have been more than 87 million people infected worldwide that we know of, and 1.88 million deaths. This means a global average IFR (infected fatality ratio) of 1.6%. And this number is obviously vastly underestimated, given that stats in countries like Africa, India or even Russia are just a fraction of the reality (India has only reported as much infections as Germany if you can believe this).

All the studies we’ve been compiling for months also show that the IFR varies from 0.5 to 2.2% depending on your age and few other factors. So yes, kids have it better but not that much and you shouldn’t expect that they will be safe at school for magical reasons (sorry about the bad news).

And also, before you ask, the IFR of the common flu is less than 0.1%. So the fatality rate is ten times lower, but most importantly the risk of getting the flu is also much, much lower. The Covid-19 currently infected about 10% of the world population, and we may hit 50 to 60% before the end of 2021. This is unprecedented.

Now, why is it somehow so difficult for some of us to grasp the extent of this pandemic?

I have a simple theory, which is that Covid-19 deaths are not spectacular. There is no airliner crashing in a 110 stories tall skyscraper downtown Manhattan playing on slow motion on TV, no kilometers-wide tidal wave sweeping over a nuclear power plant on one of Japan’s coast, no zombies running around and eating babies. Covid-19 deaths don’t make for good live TV. And as Stalin was famously reported saying: “The death of one man is a tragedy. The death of millions is a statistic.”

Of course talking to doctors and nurses in ICUs who have been witnessing for months people dying with lungs destroyed by the virus and drowning from inside might change your mind. I’m just saying.

Q. OK but why not just wait for herd immunity to kick in then?

This question is actually quite easy. We’re getting to 10% of the world population that has been infected up to now. Herd immunity would kick in at about 90% of the population getting infected, and it would be quite effective when reaching 95 to 98%. With what we know today, this would translate in 124.8 million people dying.

That’s about the size of Japan getting wiped off, or France plus UK (for reference the total number of deaths for WWII is estimated at 75 million). So no, I’m not sure that’s an option that anyone would consider beyond dangerous psychopaths.

But herd immunity is still important, and it’s achievable by a simple way: vaccination.

Q. But I don’t trust vaccines, how can introducing weakened viruses in my body be really safe?

It’s a concern that comes up very often, even if for no apparent reason.

The way vaccines work is very straightforward: a small part that is very specific of a target virus is isolated and introduced into the blood stream. From there our body a) knows it’s foreign element, b) take it away from our blood stream and c) start to program and grow an army of combatant cells to prepare in case we see more of it coming up. When we get infected again by the target virus, this army of combatants is already on the lookout and numerous enough to trash it swiftly.

All this is a natural process that occurs in everyone as soon as we are toddlers. But for some very aggressive viruses, our body is not fast enough to identify the invader, program defenses and build them up before it’s too late. This is where vaccines get useful. Vaccines don’t do much actually. They’re just a trick to kickstart our natural defenses and be prepared before we’re overwhelmed and get too sick to defend ourselves. .

And yes, the first vaccines that were produced were based on “inactivated viruses”. Basically you would destroy a batch of viruses, keep their shell and inject them in patients. It may seems dangerous, but is actually very straightforward and safe. Viruses are very simple organisms (they’re not even categorically classified as ‘living’). Don’t think of them as sturdy tortoises, but rather as flimsy soap bubbles. They can be airborne for a while or stick to surfaces, but they will burst by themselves very fast… unless they get inside us and start to replicate like crazy.

For viruses that are less dangerous — but annoying to get, like measles, it’s even possible to use attenuated viruses. Viruses that are not destroyed but knocked down enough that they won’t reproduce or super slowly. Again, the trick is to get in contact as safely as possible with the target virus and speed up our natural defenses.

For dangerous viruses like Covid-19 this is a different story. We take them completely apart and just use a very specific part of them as a signature. Think of it at training dogs at sniffing grenades by using just the pin.

The Pfizer / BioNTech vaccine even goes an extra mile and doesn’t use any part coming Covid-19, but it’s a small program (a RNA messenger) than some of our cells will use to create a single artificial part of the outside of the virus. You probably have in your mind by now what Covid-19 looks like? A kind of balloon with spiked heads? Well, the program is making some of our cells to assemble this spiked head, which will be the virus signature that will allow us to train our defense cells. (Now it’s not even an actually grenade pin, but just a plastic replica.)

But there is another component in vaccines that is called an adjuvant and that you may worry about.

The adjuvant is the juice added to accelerate even more the reaction of our body to the small signature part of the virus making the vaccine. They are specially important for people with bad immune systems (because of a cancer treatment for example), or simply because over time, past 50, our bodies start to be less efficient at dealing with… anything, really.

In 90 years of vaccination, the only cases of minor problems with adjuvants were reported in the early days when substances like aluminum were used by rule of thumb. It was not entirely prehistoric times, but for context US and Europe were discovering TV and landlines phones were just starting to be mainstream.

So is there a risk there for you? Sure, why not? The risk we are talking about is pretty much you being on the sinking Titanic and discussing the benefit of putting on a life jacket in case you’d have a reaction to the plastic. All jokes aside, vaccines have been the most documented and used medical products on the planet since ever. Consider it’s reassuring that we are thorough enough to know about a few dozens extreme cases over billions of people during the last decades.

And the last thing we need to discuss in term of risk, is the probability that you still have a reaction to the vaccine because your immune system is triggered.

These reactions are far much more common. A few percent of the population will get tired, have a red patch at the injection point or maybe even a light fever for a day or two. That’s actually great news. It means that your body has seen the vaccine and is working on it. Producing a small army of cells against the real virus is an active process. It’s just like having sore muscles after coming back from the gym after your vacations. Your body has to adjust and might be bitching about it.

Q. Vaccines usually require more than 10 years to be developed and approved. Getting one out in less than 1 year can only mean things have been rushed and I won’t trust this vaccine

Ah yes, it’s rather unprecedented (but not entirely) and that’s actually a very exciting thing about this vaccine and the way public healthcare organizations and private pharma companies worked together. And if you heard many times over that a typical vaccine development requires 8 to 12 years. So it may seem difficult to believe we got several Covid-19 vaccines within a year. Well, they are actually 3 key reasons why we got there so fast.

(1) The science was essentially ready.

If you unpack the complex timeline of getting a vaccine to the population there are 3 big steps :

• The research phase to find an immunity trigger against the virus;

• The clinical phase where the potential vaccine efficiency is assessed;

• The production and distribution phase.

The research phase is always potentially the longest. For instance, we’re still trying to find a first serious vaccine for the AIDS / HIV retrovirus that was discovered in 1981! And in 1918 when the Influenza virus responsible for the so-called Spanish Flu hit us and caused between 20 and 50 million deaths worldwide (stats post-WWI were not exactly precise) we were also defenseless. We had to wait more than 20 years, in 1940, to find a first effective vaccine against the Spanish Flu.

But now, when we meet this specific family of viruses, we have a solid recipe to get vaccines out. Recently, in 2009, we met another Influenza virus called H1N1 (you might remember it), and we were able to develop a specific vaccine within a year.

Well, Covid-19 is like this. It’s not an Influenza virus, but a Coronavirus. And this family of viruses is responsible for the common cold, but also of other infections that we already had to fight off in the past (such as SARS “Bird Flu” in 2002, or MERS “Middle-East” virus in 2012). Long story short, we’ve been working on these suckers since 1968!

So for medical research, coronaviruses are like potatoes. We know how they work very, very well. Despite the impression you might have that we “magically” got several vaccines out of the lab in just a few months, we didn’t. We’re just collecting the dividends of 50 years of research.

So yes, even if it wasn’t guaranteed, it was pretty much expected that we would get there as fast as we did.

(2) There never was so many labs working on a vaccine

There second reason we got there so fast is pretty straightforward: it’s the first time in history that so many people work at the same time on the same virus. All the big, small and medium pharmaceutical companies understood very quickly a simple equation: huge pandemic worldwide x relatively simple science = gold rush.

Sure enough, we ended up with more than 60 labs working on Covid-19 with more than 90 candidate vaccines already developed in April 2020.

And it was probably even a way larger number. You might have noticed that Pfizer who got the first vaccine out, didn’t find the vaccine by itself. They worked with a German company called BioNTech where the science was done. But Pfizer was not only working with them, they were probably monitoring dozens of other private labs.

Not accounting for India, China or Russia, my rough calculation is as such: take all the 7 big pharma in the game (Johnson & Johnson, Pfizer, Roche, Novartis , Merck, GlaxoSmithKline and Sanofi), multiply by 30-50 private labs plus their own teams, and you get in reality between 250-500 labs competing together to be the first.

And a “lab” like BioNTech is not 6 people, but more than 1,000.

I can’t imagine a larger mobilization of researchers in our whole history. Maybe not even for cancer research. Huge market and easy science combined together is a powerful motivator…

(3) Millions of patients to pick from for trials and swats of public money

Then there is the second phase of putting a vaccine in the market, which is the clinical trials. This phase can also be terribly long because it’s usually difficult to find enough patients to test.

You see the trials themselves are not that long, but they require step after step more and more people infected by the virus to voluntary enroll. And that’s usually a big bottleneck for studies. But hey, obviously not with Covid-19 and already millions of people infected and hospitalized in the first few months.

Another difficulty causing tons of delays is that pharmaceutical companies just don’t want to lose money on trials.

Trials are very expensive and usually only 5-10% of the potential vaccines get through. So pharmaceuticals companies don’t rush. They cautiously do a first step and if it goes well, they invest more money and finance the next step and so on. And we’re not even talking production yet, which might happen years later!

But given the impact of Covid-19 in the global economy, governments all around the world (and now famously the US with operation “Warp Speed”) did something incredible. They told key pharmaceutical companies: don’t try to be smart about it, just go ALL IN. Take all your best shot at a vaccine, produce them already and do all the tests. We will pay the bills, in exchange for being able to have X amount of the one vaccine that will work, reserved for us.

Pharmaceutical companies didn’t had to be told twice, they did went trough production and testing immediately. For them I was like being allowed to bet on all the numbers at the same time at the casino and to pay for only one bet in the end. Pretty sweet deal if you ask me.

Of course in the end, will be fitting the hefty bill with our taxes for the next 10 to 20 years.

Q. If enough are vaccinated around me, then I surely don’t need to be in rush to get the vaccine myself?

As we explained, herd immunity is critical and can only be reached by mean of vaccination when 90% of the population gets its shot.

If you’re getting supremely selfish about this and decide not to get vaccinated in case there is a slight chance you feel under the weather for 48h, you willingly decide to be potentially a risk factor for everyone around. This means your family, the bus driver, your kids, their teachers, etc.

Now OK, why not being a dangerous asshole? I’d say, Just be consistent then. Stay boarded in your attic until the end of 2021 (most probably mid-2022) before enough gets vaccinated around you and you can be safe. The other way doesn’t work, because only people with a vaccine will be protected, and as you might discover in your local news vaccination is definitively a long and difficult logistics.

Q. OK, but if I have to get vaccinated, right now we have vaccine X planned, and I would rather get vaccine Y because [insert your professional opinion about RNA protein synthesis pathways or the statistical relevance of mutagenic zoonoses]?

There are several vaccines that start to be distributed all over Europe as we speak. All of them have been approved with the same rigorous testing as any other vaccine. Plain and simple. Specially at the scale of vaccination we are talking, there is not a single pharmaceutical company that could afford the slightest misstep, or the stock market will crash and burn them to the ground.

As of today, I would personally believe that the Pfizer/BioNTech vaccine using the new RNA methodology is even the safest. Because initally this technology was not developed with Covid-19 in mind (it’s been worked on for many years, way before the current pandemic), but it was developed for its potential at tackling cancer. This is where the big money will be for these guys, so they have even more skin in the game on this one. .

That being said, after working for about ten years in medical distribution and medical safety protocols with hospitals all over Europe, I can give you a simple advice — exactly the same one I gave to my mom:

Just. Get. Vaccinated. As. Soon. As. Possible.

The reason is (and it might seem counter intuitive) that the earliest you get your shot, the less sloppy the distribution protocol with be, and the more chances you will have got a vaccine that was stored in proper conditions (meaning the most effective one). In a few months from now, boredom and routine will kick in, subcontractor staff will be on boarded, shortcuts will be taken, and it might be a little more dicey.

In the Netherlands, Stéphanie and I are supposed to have a chance at getting our Covid-19 vaccine starting in April. But it will be most probably this summer or later in September. This is not such a good news, so if you can get a shot earlier, by any mean take advantage of this chance.

OK, that’s it. I hope that this article might be useful for you, your family or friends. If you think that something is missing or that I made it too simple or too complex, please drop me a line. I’ll be happy to adjust and improve.

Take care.