A few days ago Derek Lowe** over at In the Pipeline, had a short post about the dangers of apparent side effects being wrongly attributed to the Covid-19 vaccine(s) – ie. false side effects.

We’re talking about treating very, very large populations, which means that you’re going to see the usual run of mortality and morbidity that you see across large samples. Specifically, if you take 10 million people and just wave your hand back and forth over their upper arms, in the next two months you would expect to see about 4,000 heart attacks. About 4,000 strokes. Over 9,000 new diagnoses of cancer. And about 14,000 of that ten million will die, out of usual all-causes mortality. No one would notice. That’s how many people die and get sick anyway.

But if you took those ten million people and gave them a new vaccine instead, there’s a real danger that those heart attacks, cancer diagnoses, and deaths will be attributed to the vaccine. I mean, if you reach a large enough population, you are literally going to have cases where someone gets the vaccine and drops dead the next day (just as they would have if they *didn’t* get the vaccine).

We need to remain alert for this, and ensure that others understand this. Because people get sick and die constantly. As Lowe goes on to say:

The key will be whether they are getting sick or dying at a noticeably higher rate once they have been vaccinated. No such safety signals have appeared [during] the first [vaccine trails] … we should be seeing the exact opposite effects on mortality and morbidity as more and more people get vaccinated …
I certainly think mass vaccination is the most powerful method we have to knock that back down to normal. That’s going to be harder to do, though, if we get screaming headlines about people falling over due to heart attacks after getting their vaccine shots. Be braced.

Yes, we need to be alert and realistic, but not ignore possible side effects. Remember that in the UK possible adverse reactions to any pharmaceutical can be reported by patients as well as clinicians through the Yellow Card Scheme.

** Derek Lowe gained a PhD in organic chemistry from Duke University. Since 1989 he’s worked for several major pharmaceutical companies on drug discovery projects against schizophrenia, Alzheimer’s, diabetes, osteoporosis and other diseases.

[Warning: LONG READ]

Last week’s New Scientist carried several good articles on Covid-19 vaccines etc. If you have access to New Scientist or their website (which is paywalled) they’re worth reading. As usual, as they’re paywalled I’m going to be a little naughty and give you a key extracts from three of the articles. (Links to the articles are at the foot of the page.)

We can’t be certain the coronavirus vaccines will stop the pandemic

So things look good. But we are still a long, long way from a vaccine that will get us back to life as normal. That is in no small part due to the huge challenge of manufacturing, distributing and administering one … plus the reluctance of a significant minority of people to get vaccinated.

How long will immunity last? … We simply don’t know yet how long protection from any vaccine will last.

Vaccine efficacy does not always predict vaccine effectiveness … various reasons …a major one is that the deployment of a vaccine on the ground, to millions or billions of people, is much more challenging than administering it within a tightly regimented clinical trial. That is especially true of a two-shot vaccine that relies on people showing up to two appointments, often weeks apart.

The trials aren’t going to tell us what, if any, effect a vaccine has on severe illness … unless urgent changes are made to the way the trials are designed and evaluated, we could end up with approved vaccines that reduce the risk of a mild infection but do not decrease the risk of hospitalisation, [ICU] use or death. This seems outlandish, but … it comes down to the trials’ end point. In all the phase III trials, this is defined as the prevention of mild covid-19 symptoms … such a result tells us next to nothing about whether the vaccine is stopping infected people from getting really sick.

The trials appear designed to answer the easiest questions in the least amount of time, not the most clinically important ones … It is possible to do a Covid-19 clinical trial with severe disease as an end point … but it would be a major undertaking because that outcome is still quite rare. The studies do not have adequate numbers of patients to be able to reliably tell us if they prevent severe disease.

We don’t know how people who have had the virus and recovered will respond to any of the vaccines … We also don’t know whether the vaccines will put pressure on the virus to mutate.

The seemingly simple question “does this Covid-19 vaccine work?” is surprisingly hard to answer.

The Biggest Logistics Challenge in History: What will it take to get a covid-19 vaccine to the world?

Vaccines don’t save lives … Vaccination does.

When a Covid-19 vaccine is approved, it will trigger a staggeringly complex chain of events. These events must occur in perfect lockstep using a global supply chain that needs to reach even the planet’s most remote areas – the same supply chain that left parts of the world in desperate need of things like disposable gloves and protective equipment just months ago. The scale and magnitude of what we’re talking about doing is just unparalleled.

The key to overcoming complexity is planning and planning early.

How many people need to be vaccinated to end the pandemic depends on how effective the vaccine is, and how long the immunity it provides lasts … that figure [may be] 60 per cent. Given we now number 7.7 billion, and most of the vaccine candidates in late-stage trials require at least one booster, that is a staggering 9 billion or so doses.

Pfizer and BioNTech plan to make enough doses to vaccinate 25 million people by the end of 2020, and 630 million people in 2021 … Making all this vaccine requires a lot of upfront cash.

The US government has invested $6.5 billion in Covid-19 therapeutics and vaccines … [and] … will own more than 700 million doses from at least six different companies. The UK government has signed [deals] agreeing to buy a total of 340 million doses at set prices from at least six firms.

Once vaccines have been approved and manufactured … the challenge remains to package, ship and administer them to more people and in a shorter … time than ever before. While supplies like alcohol swabs, gloves, bins for used needles, pallets, plastic wrap and syringes can all be made by a wide array of manufacturers, the scale of the demand may be hard to cope with.

One of the challenges … is that vaccines are shipped by air and can arrive almost anywhere on the planet in one to three days. Syringes, being bulkier and with a shelf life of around five years, are typically sent by boat and truck. They can take two to four months to reach their destination.

Covid-19 vaccines will be stored and shipped in special glass vials. These are resistant to shattering at temperature extremes and less chemically reactive than standard glass … almost exclusively made from borosilicate glass. The main worry is that this glass requires special sand … and a breakdown at any point in the chain could bring vaccination efforts to a halt.

Once the vials are filled, they will need to be distributed – and quickly. The … airline industry … has estimated that providing a single dose to everyone on the planet would require enough vaccine to fill 8000 Boeing 747 cargo planes.

How they are transported is another challenge: all 12 of the leading vaccine candidates will need to be kept cold to stabilise the sensitive ingredients. Moderna’s [vaccine] will need to be stored at -20°C, a temperature that can be reached by most household freezers. [Pfizer’s] vaccine will need to be far colder: -70°C. That requires special freezers that can reach -80°C, the kind used to store things like bacterial cells in labs or sperm in fertility clinics. Pfizer has designed new insulated, suitcase-sized containers that will be packed with dry ice to maintain temperatures below -70°C and can keep the vaccine stable for up to 15 days. Each container can hold up to 4875 doses and will need to be refilled with 23 kilograms of dry ice every five days.

At some air hubs in the US and Europe, UPS is building freezer farms. Each of the 600 freezers in one of its farms will be able to hold 48,000 doses of vaccine.

Things get trickier when products are on the road … it gets most difficult in the “last mile” … In low and middle-income countries, drivers on motorbikes typically deliver vaccines and other medical products to villages in remote areas.

More worrisome are unanticipated shortages … there are a lot of hypotheticals and you have to plan and prepare for all of them … you need to have the right infrastructure and capacity in place to handle what’s going to be a relatively short, sharp shock to the supply system … coordinating the administration of a vaccine and booster on a global scale isn’t something the world has experience with … at [the scale] needed to open up society.

Political challenges to overcome, not least the willingness of people to actually get vaccinated.

In the UK … there are concerns that changing trade agreements under Brexit could delay the transit of vaccines or even leave them stranded at the border.

As long as we leave a region or country without access, the virus will come back

Heidi Larson interview: How to stop covid-19 vaccine hesitancy

One of the reasons rumours and misinformation are getting more traction now is because we have a lot of uncertainty. Things are changing every day, and people are anxious and want an answer. We have a perfect storm for rumour spread.

In the UK, the US and other countries, in May only 5 per cent said they would definitely not take a vaccine. Now, that’s up to more like 15 per cent.

Across the UK and US is if you are lower income … you are non-white and female, you are more likely to refuse a Covid vaccine … These communities could benefit the most but they are the least trusting of government.

We don’t have a misinformation problem as much as we have a relationship problem [between the public and health systems].

What reasons do people give for not wanting to use the vaccine?
Safety … It’s “too new” … Could we get long covid from the vaccine?

We have to do a better job of explaining why things are moving faster. We are not short-cutting old processes. It’s because we have brand new [vaccine] platforms, new technology.

On the health authority side you get more formalistic “everybody do this” messages, it’s almost monotone. The public has a lot of different questions. So when they hear the same message they think we [public health officials] really don’t hear them, that’s not answering their questions.

The Covid response is a real opportunity to change [health authorities’] relationship with the public. If we rebuild our relationship with the public so they feel we are a caring, listening health authority or government, that will make a huge difference.

https://www.newscientist.com/article/mg24833093-100-we-cant-be-certain-the-coronavirus-vaccines-will-stop-the-pandemic/
https://www.newscientist.com/article/mg24833093-800-what-will-it-take-to-get-a-covid-19-vaccine-to-the-world/
https://www.newscientist.com/article/2259876-heidi-larson-interview-how-to-stop-covid-19-vaccine-hesitancy/