COVID Transmissions for 3-23-2021

Pfizer vaccine >90% effective against asymptomatic infection

Mar 23, 2021

Greetings from an undisclosed location in my new apartment. Good morning and welcome to COVID Transmissions.

It has been 491 days since the first documented human case of COVID-19. In 491, Aelle of Sussex sacked an old Roman fort at Anderitum and massacred the Romano-Brythons living there, during the ongoing Saxon invasion of formerly-Roman Britannia. Interestingly, nearly six centuries later, the invading Norman army, on the cusp of subjugating Aelle’s Anglo-Saxon descendants, camped in the ruins of the fort at Anderitum after landing at nearby Pevensey Bay on their way to the Battle of Hastings.

Some places are strategically important, and frequent sources of conflict. I am reminded of the sites in the SARS-CoV-2 spike protein, like position 501 and position 484, that seem to be frequent sites of mutation in many virus variants, as the virus independently evolves in different patients to escape immune responses.

We’ll talk a about that today, but the big headline is some important data showing an effect of the Pfizer mRNA vaccine on asymptomatic SARS-CoV-2 infections.

As usual, bolded terms are linked to the running newsletter glossary.

Keep COVID Transmissions growing by sharing it! Share the newsletter, not the virus. I love talking about science and explaining important concepts in human health, but I rely on all of you to grow the audience for this, which you can do by using this button here:

Share COVID Transmissions

Now, let’s talk COVID.

Israeli data: Pfizer vaccine is >90% effective against asymptomatic infection with SARS-CoV-2

Check this story out: https://www.reuters.com/article/us-health-coronavirus-pfizer-israel/pfizer-biontech-say-data-suggests-vaccine-94-effective-in-preventing-asymptomatic-infection-idUSKBN2B31IJ

Israel has become a lab for studying the effectiveness of the Pfizer-BioNTech mRNA vaccine, and we are starting to reap the data benefits with regular releases of findings. Israel is a valuable subject for a variety of reasons, but not least among the them is the combination of a national healthcare system (and thus unified records) with decades of mandatory national service (and thus even more unified records on each citizen). The availability of great medical and personal history on every citizen offers some deep opportunities to learn things about the effectives of vaccination on various groups.

This time, though, we are learning something that is not in a specialized subgroup with some rare characteristic. Instead, at a systemic level, Pfizer has announced that they now have data showing that their vaccine is about 94% effective at preventing asymptomatic infection with SARS-CoV-2. This is a finding of tremendous significance.

To me, the most insidious thing about the COVID-19 pandemic has been the potential for disease to spread through the air from asymptomatic people who are infected with the causative virus. This is quite unlike other deadly viruses; typically we expect that being contagious requires being symptomatic. For quite some time earlier in the pandemic, there was a lot of debate over whether asymptomatic spread even happens. That debate is long settled—it obviously does happen. If it it did not, it would have been substantially easier to contain, or even prevent, the pandemic.

Asymptomatic spread is a powerful driver of outbreaks during this pandemic. I have previously shared modeling work that looked at this: https://covidtransmissions.substack.com/p/covid-transmissions-for-1-8-2021

That work predicted that asymptomatic spread could be so influential that even if all symptomatic cases were eliminated, there would still be substantial new cases created by asymptomatic transmission. That was something that really worried me, because it was not at all clear early on that vaccines would be able to prevent asymptomatic spread. There was the possibility that vaccines would simply prevent serious disease and death, but still allow people to host the virus and spread it.

That would have been a real disaster for anyone in society who was unable to be vaccinated—either due to scarcity or due to medical conditions preventing vaccination. What we were looking for, really, was a vaccine that would not only prevent disease and COVID-19 death, but that would also prevent spread of the virus.

There were several intermediate possibilities as well—the vaccine might be 100% effective at preventing death from COVID-19, but maybe it would be 50% effective at slowing spread. It appeared from early data with the Moderna vaccine that this might be the case, with some (rather unreliable) data indicating a 2/3 reduction in capability to spread the virus.

Now, the data from Israel with the Pfizer vaccine suggest that prevention of asymptomatic infection—and thus prevention of asymptomatic transmission—is on par with prevention of disease and COVID-19 death, all of which were in the 90s for vaccine effectiveness percentage points. That is tremendous news, because it suggests—for this particular vaccine, at least—that a vaccinated person is not just protected, they are also protective. As an unvaccinated person—for now—I am convinced that I am safer around someone who has received the Pfizer vaccine than I am around someone who is unvaccinated.

Also remarkably, in this dataset, unvaccinated people were 44 times more likely to get COVID-19 and 29 times more likely to die of COVID-19 than people who were vaccinated. Truly the existence of vaccines is a game-changer.

That said, we must keep in mind that we have a press release from Pfizer backing all of this up, and it would be really great to be able to see the data in some kind of published, peer-reviewed form. However, the Israeli Ministry of Health has in the past released other data that had the same general trends and tendencies as what Pfizer has now announced, so I feel pretty confident that these conclusions will, at least approximately, bear out in the final results.

With this information available I feel really very good about future prospects. I do not think that this phenomenon will prove to be unique to the Pfizer vaccine, and it is likely that the other available options also have potent effects on asymptomatic infection and ultimately on the spread of disease. I feel hopeful about this.

One thing that still bothers me, though, is the prospect of variants that might be able to escape. Which brings me to our next story.

An immunosuppressed case study shows how concerning variants may emerge

A reader sent me this story and asked me to comment: https://www.npr.org/sections/goatsandsoda/2021/02/05/964447070/where-did-the-coronavirus-variants-come-from

The story documents a particular patient case—an immunosuppressed patient, taking immunosuppressants for an autoimmune condition—where the patient had a chronic SARS-CoV-2 infection for five months before they finally succumbed to disease.

This type of situation is not a new story, though this is one of the first such patients to have been documented in the medical literature for SARS-CoV-2. Still, in many other infectious diseases, the ongoing HIV pandemic has offered up a lot of depressing information on how pathogens can escape host immune systems if those immune systems are suppressed.

You see, under normal conditions, the immune system uses an array of weapons to attack invaders. Antibodies are one tool, but there are various other options that are also employed. These include directly toxic chemical warfare, cell-driven approaches where killer cells attack sites of infection to destroy the pathogens, and even systemic metabolic programs that make the body more hostile to infection. Each of these tactics contributes to an overall strategy that works more often than it fails: make the body completely hostile to the invader, even if it means doing some damage to the host, because the host can survive a little damage and the invader can’t—at least not when it is being attacked on all fronts.

It’s not all that different from a war, really. In military strategy, there is an advantage to using a mixture of types of tactics to drive an overarching strategy. A military that is composed entirely of tanks is weak to specific other tactics; planes, anti-tank mines, barriers that tanks cannot pass, etc. However, if you take those tanks and support them with units that have other tactical capabilities, such as air support, infantry that can destroy tank traps, and other specialist forces, you create something that can overcome those weaknesses to adapt and press the attack.

A host body has infinitely more resources than an invading virus. This is both why the virus needs the host, and also the host’s greatest advantage against the virus, because it means the host can use a wide array of tactics to fight the virus. Compared to the virus’s zero cells, I have trillions of cells. Compared to the virus’s zero methods of making cellular energy to drive life processes, I have an entire suite of genetics, evolved over billions of years, to make so much energy that I have to store the excess. If even a fraction of my resources are turned to defeating a virus, there is a good chance that I will succeed. In fact, I can afford to burn some of what I have—including destroying my own cells—to turn back an invader. Viruses, especially early in infection, do not usually have such luxuries.

Given these limitations, if my immune system can marshal a response that attacks the invader in many different ways, it becomes hard for that invader to adapt. Imagine that with each generation, the virus mutates enough times within its host to escape one aspect of the immune response. This doesn’t do all that much if the immune system has ten other tactics that can also destroy the virus and contain infections. A fantastic mutation that allows the virus to escape antibodies will not survive to do its work if a killer cell swoops in and gobbles it up.

However, in the immunosuppressed patient, fewer tactics are being used. The response is suppressed and weaker. The virus has more chances for useful mutations to survive and replicate—and more opportunities to achieve a foothold.

We already believe that we have seen this phenomenon at work; the emergence of the B.1.351 variant is thought to have occurred in an immunosuppressed patient somewhere in South Africa, as we have discussed in this newsletter before. This variant contains mutations that we believe serve to help the virus escape antibody-based immunity. We know that antibodies are not the only tactic in the immune response, but to evolve such a capability means the virus has fewer tactics that it must overcome.

Thankfully, this is not an all-or-nothing scenario. These mutations do not utterly defeat every single antibody that a host can produce. They just make it harder for antibodies to earlier variants of the virus to be effective against the newer variants. Eventually, a healthy immune system is able to catch up to these new variants too—provided the virus doesn’t do too much damage, or develop new useful mutations that help evade other immune system tactics. With every new variant, we see some possibility of something truly dangerous, though so far, all we have seen are things to keep a close eye on, and nothing that spells complete doom and gloom.

The new variants would be particularly concerning if the protection that vaccines offer is particularly reliant on antibodies, something we are not 100% sure about either way right now. Still, it is better for variants that escape any immune tactic, even to a small degree, not to emerge. This is something we want to prevent.

In the case report in the linked story, we see common patterns of mutation appeared in one immunosuppressed patient who was studied closely. Specific sites that are mutated in numerous variants of concern—ones that I have my eye on are positions 501 and 484 in the spike protein—also emerged with mutations in this patient case.

Keep in mind that these mutations are random. The virus has no intelligence and no agency driving these changes. They emerge with regularity in certain types of patients not because the virus is choosing to do something, but because it produces many random mutations, and the pressures applied by the human immune system through the generation of antibodies and other responses do the choosing. They “select for”—as in “natural selection—the mutations that best allow the virus to survive and replicate. What we are seeing, when we see these regularly emerge, is a list of those mutations that most easily help to evade important immune responses.

We see them in immunosuppressed patients because the weakened immune responses in these patients make them the ideal unintentional laboratory for these types of natural experiments. By turning down the heat a little bit, if that’s how I may be allowed to refer to reduced intensity of the immune response, patients who are immunosuppressed become a perfect incubator for new mutations to survive.

As these mutations accumulate, they produce new variants that are of greater threat to those who are not immunosuppressed. So far, we have only seen this to a limited extent. Known variants are better at defeating immune responses, but not in truly substantial ways that fully differentiate them into new strains of virus that could cause distinct epidemics even in people with acquired immunity (either from vaccination or from infection).

Instead of seeing these variants as potential causes of a tremendous wave of new infections, I feel they are better seen as a warning shot for us all. We know that eventually, mutations might accumulate to produce a totally new strain. That possibility has been realized in other viruses, and we see the early steps down that road in SARS-CoV-2 through these variants. But we are not there yet.

So the best thing that we can do is try to contain the pandemic while we can still prevent the emergence of a totally new strain, during this time where there are just minor variants appearing that have small advantages over their predecessors. If we widely vaccinate, if we take well-known precautions like distancing and masking, and if we take the very sensible step of protecting immunosuppressed people from infection, we can do it.

It’s like I said yesterday—with the tools that we have, the fight against COVID-19 is ours to lose. So, let’s try our best to win instead.

What am I doing to cope with the pandemic? This:

Watching: Staged, series 2

David Tennant and Michael Sheen are back in the second series of their show about life in quarantine, and it continues to be a delightful exploration and parody of what happens to a performer’s mind when they have no one to perform for. It is a deep-dive into neurotic hilarity, and very relatable to the world we’ve lived in through this pandemic.

I recommended the first series, and now that I’ve watched the second, I have to recommend it, too.

I owe a number of you comment replies, email replies, or coverage of specific news stories—I have not forgotten these! Give me a few days to get back into the swing of things after my brief hiatus.

You might have some questions or comments! Send them in. As several folks have figured out, you can also email me if you have a comment that you don’t want to share with the whole group.

Join the conversation, and what you say will impact what I talk about in the next issue.

Also, let me know any other thoughts you might have about the newsletter. I’d like to make sure you’re getting what you want out of this.

Viral Transmissions

Discussion about this post