COVID Transmissions for 5-10-2021

Another way to look at Sputnik V

Greetings from an undisclosed location in my apartment. Welcome to COVID Transmissions.

It has been 539 days since the first documented human case of COVID-19. In 539, the resurgent Roman Empire (aka the Byzantine Empire) ran into trouble in its reconquest of Italy, losing the city that today we know as Milan.

Much like the Byzantine Empire’s attempt to retake the world, I hope recent surges in COVID-19 are just the last lashing out of this scourge before it fully declines.

Today we’ll discuss the Gamaleya Sputnik V vaccine drama again, and I share some reports on vaccine efficacy against different variants of concern, this time focusing on the Novavax and Pfizer vaccines.

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

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Now, let’s talk COVID.

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Updates on vaccine efficacy against variants

Two reports appeared recently in The New England Journal of Medicine looking at the efficacy of two vaccines against COVID-19 variants.

The first looks at the efficacy of the Pfizer-BioNTech vaccine against B.1.1.7 and B.1.351 variants, using a study population in Qatar, where both variants circulate: https://www.nejm.org/doi/full/10.1056/NEJMc2104974

In the case of both variants, the vaccine was highly effective (at least 72%) against disease. It was also highly effective against severe disease. This is just a letter to the editor, but it’s reassuring regarding the efficacy of this vaccine that has been deployed through much of the developed world.

The other report details a Phase 2 trial of the Novavax vaccine against the B.1.351 variant in South Africa: https://www.nejm.org/doi/full/10.1056/NEJMoa2103055

Here, the efficacy does look a bit worse, but we are talking only about efficacy against disease. I’m actually a little annoyed about the paper not talking much about severe cases. Basically, the top-line results here suggest about a 50% efficacy against the B.1.351 variant, but this was slightly confounded by the presence of patients with previous COVID-19 exposure and also the presence of patients with HIV in the sample. In patients with no previous COVID-19 exposure who were HIV-negative, it appeared that efficacy was around 61%.

This is a bit lowered from the original Novavax trial, but it’s still efficacy, and this is only a Phase 2 trial. The Novavax product has a lot of advantages, including no requirement for freezing the product. This could make it another on the list of good options to vaccinate the world, but to really be deployable everywhere, it needs efficacy against concerning variants. These data suggest that it has that efficacy, which is good news, though it does seem to be a bit worse than anyone would like.

I’m sure we’ll learn more as trials advance, but I wanted to provide an update via these two reports.

Further developments with the Sputnik V vaccine

Recently, Brazil’s regulator ANVISA rejected the Sputnik V vaccine by Russian vaccine maker Gamaleya, based on a list of 50 objections to their regulatory filings. One of the key objections was that the vaccine delivered had a replication-competent adenovirus vector. In response to the objections, the official Russian government mouthpiece promoting the vaccine lashed out at ANVISA, and made some outlandish claims about the Sputnik V vaccine, including extremely high claims of efficacy.

I’ve been covering this story and promised to follow up, so I wanted to mention that I listened to last week’s episode of This Week in Virology (TWiV), which went into great detail on Gamaleya’s regulatory filings up against ANVISA’s objections. I like TWiV’s approach, because they assumed good faith on behalf of both ANVISA and Gamaleya, making the point that the Russian scientific establishment is world-renowned and that the Brazilian government’s vaccination campaigns have also been historically world-renowned.

Looking at the data available from Gamaleya, the TWiV team felt that there was no evidence within the filing that the vaccine was replication-competent. Likewise, they felt that there was no evidence that ANVISA had presented to the contrary. Instead, they interpreted ANVISA’s objection on this matter as an objection to the statement in the Gamaleya report that there were “less than” 50 replication-competent particles in each dose of Sputnik V. This statement appears to have originated, according to the TWiV hosts, with the fact that scientists never ever can say we have truly ruled something out. I myself cannot tell you that unicorns don’t exist. All that I can tell you is that in all my travels, I’ve never found one.

Likewise, the Gamaleya filing explored the possibility of replication-competent virus by using a dilution series of their virus. This dilution series had only a fixed number of steps, such that they could only determine if there were more than 50 replication-competent particles in the original sample. This is pretty normal; every experiment has a limit of detection. There is no way to perfectly dilute a sample until you can be certain it had none of what you’re looking for in the original. Since virus particles do not perfectly distribute themselves inside fluids, there’s always some chance that the small fraction you diluted didn’t take up particles that were present. Much of science is playing the odds.

So, scientists tend to be pretty reserved in what we say. My statement on unicorns comes to mind again. Here, it looks like Gamaleya felt comfortable using out that there were more than 50 particles per dose that could replicate, and they thought this would be sufficient. Apparently, ANVISA did not find it be sufficient, and may even have misinterpreted this aspect of their filing. Thus, they objected.

This might have been resolved as part of a normal regulatory dialogue, except that the Russian government boosters of Sputnik V took ANVISA’s objections—a normal part of regulatory processes—as a personal attack on their country’s achievement. Their hostile response led to an escalation of the situation to where the normal regulatory discourse was blown out of proportion and their product ultimately rejected.

At least, this is TWiV’s interpretation of the situation, which you can listen to for yourself here:

Look, I’m not sure that the TWiV hosts have entirely the right read on this either, but their contribution is to offer a third way where ultimately a miscommunication of data, handled inappropriately by the Russian government, led to an international incident an the rejection of a much-needed vaccine.

I don’t know if this is the correct narrative, but I think it’s important to tell you all the whole story.

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

Mother’s Day

Yesterday we had a little get together with my sister and parents on our terrace, complete with bagels and lox from the best places on the Upper West Side of Manhattan. Being a group of fully-vaccinated people, we could have done this inside, but outside is safer even for the vaccinated and the weather was beautiful for the first half of the day.

Also, while we didn’t technically need masks for COVID-19, my mother did wear one—because she’s getting over a bacterial bug she caught from my grandniece. I’m telling you all this because I think it was really good practice on her part, and something we can all learn from. These masks we’ve all been using have a purpose after COVID-19 ends: you can also use them to keep other people from catching other respiratory infections you might have gotten. We might all do well to keep this in mind going forward. If you’re sick with anything, you’d best stay home—but if you have to go out, you’ve got a mask you can wear to keep others that much safer.

Anyways, it was a great way to celebrate and more than just a teachable moment on infection control.

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After press time for Friday’s edition, someone left a comment about potential vascular effects of COVID-19 in children, but they deleted the comment before I was able to reply. Still, I wanted to provide a general point about this: I expect most vascular effects of COVID-19 in patients of all ages to be transient effects that repair themselves over time. In some cases these repairs may come slow, but I think in general patients will recover from COVID-19-mediated vascular damage. I wouldn’t compare this damage to progressive or degenerative heart conditions that are developed through life due to a combination of lifestyle, injury, and genetics. Those are more complex conditions that take years to develop and thus consequently can take years to ameliorate—if that is even possible. I don’t expect a similar scenario to emerge following a transient virus infection.

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.

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Part of science is identifying and correcting errors. If you find a mistake, please tell me about it.

Though I can’t correct the emailed version after it has been sent, I do update the online post of the newsletter every time a mistake is brought to my attention.

No corrections since last issue. 

See you all next time.

Always,

JS