There’s been a big leap in the number of Covid vaccines known to have phase 3 results since my last catch-up post…
Wartime sanctions have short-circuited Sputnik V’s future in most of the world. The US Treasury described RDIF, the state-controlled intermediary behind the vaccine, as “a slush fund” for Russia’s president, and “emblematic of Russia’s broader kleptocracy”. RDIF vigorously rejects that, of course, but between its sanctioned status, and the general barriers to doing business with Russia and moving material out of the country, ongoing supply will be severely hampered. With less data being generated as a result, the evidence base may not get a whole lot better than it is now.
As I wrote here last year, the chain of clinical trials in Sputnik V’s development was riddled with problems. The lack of an adequate research trail plus questions about manufacturing quality were massive hurdles to critical authorizations, including the WHO’s and EU’s. With WHO’s follow-up factory inspections in Russia now postponed, and Germany deciding to freeze local production, the chances of authorization look even lower. From the start, there were major shortages, too, especially for Sputnik’s second shot. (The first shot is based on adenovirus 26, like J&J’s, and the second, on adenovirus 5, like CanSino’s.) That led to promoting the first shot as a stand-alone single-dose vaccine, Sputnik Light.
The upshot has been that this vaccine was less used, and studied far less, too. There was only a trickle of incomplete data from the Russian trials – the protocol and final results for the phase 3 trial were never published, and adverse reaction data wasn’t collected in the usual way in that trial, for example. And there are no publications for the late-stage trials of Sputnik Light, the intranasal use of the vaccine, or in under-18s. There was a flood of propaganda and claims, though, that makes scrutiny frustrating and dauntingly time-consuming.
By late last year, Sputnik V was way behind the major vaccines. The Big 5 are CoronaVac in first place, then Pfizer, Sinopharm’s Beijing vax, AstraZeneca, and Moderna. The first 4 of those account for more than 1.5 billion doses each, while Sputnik V was closer to 300 million. That’s about 2% of the world’s Covid vaccine production.
So how has the evidence panned out? Let’s start with team Sputnik’s claims. They badge it as “the world’s first registered COVID-19 vaccine with over 91.6% efficacy”, and also state its efficacy in Moscow was 97.6%. Actually, CanSino’s was the first vaccine authorized for use outside trials (in June 2020, initially for the military – Sputnik was registered in August). The preliminary results from Sputnik’s phase 3 trial included an efficacy rate of 91.6% against symptomatic disease (CI 86-95), in a 99% white population in Moscow. (The 97.6% comes from an uncontrolled study that’s never been published as far as I know.)
Efficacy that high would put Sputnik closer to the Moderna, Novavax, and Pfizer vaccines than to the other adenovirus-based vaccines. When you look at the efficacy results for the trials of other adenovirals, you need to keep in mind that unlike Sputnik’s Moscow trial, they were in far more diverse populations, and mostly included the emergence of variants of concern:
- AstraZeneca (US and Latin American trial) at 74.0% (CI 65-81)
- Single-shot CanSino at 57.5% (CI 40-70)
- Single-shot J&J at 56.3% (CI 51-61) and 2 shots at 75.6% (CI 56-99.9)
Team Sputnik now claims it’s the “world’s best vaccine”, especially against Omicron:
That data representation pretty much throws the rules of clinical research out the window. Data from the use of Sputnik V in San Marino is super-imposed over results of a Swedish matched control study. Team Sputnik doesn’t explain the San Marino data source, and I can’t find it (please let me know if you can!). Here are some of the reasons these 2 sets of data can’t be comparable enough to be presented in this way:
- The Swedish study is huge – over 1.6 million people, with a high proportion of Pfizer vaccinations, especially in those at high risk of Covid. The San Marino number must be small – it’s a microstate in Italy, with a population of less than 34,000 people. (As of May 2021, nearly 90% of those vaccinated there were with Sputnik.) These aren’t studies of equal weight in size or study design.
- The Swedish study is from January to October 2021, and the San Marino data is for a single month (November 2021).
- The Swedish study includes a Covid wave, while in November 2021, San Marino was in a plateau between Covid waves (source).
- The average time since people were vaccinated is likely to be very different in these groups. In the Swedish study, people were counted as vaccinated 14 days after their second dose, which is 3-7 weeks after the first: and people in the study had reached that point up to 9 months previously. San Marino didn’t start first doses of Sputnik till February 25, 2021 (with at least 3 weeks to second doses).
Omicron was identified in late November, so both these datasets are pre-Omicron, and they’re not the basis for the Sputnik claim of superiority against this variant. San Marino actually fared worse than most in the Omicron wave – though of course, a lot of other factors determine how a country fares in a Covid wave, not just which vaccine was used. You can see a chart showing San Marino, the surrounding country (Italy), Sweden, and several other countries in the sources below this post – including countries with similar vaccination rates, but different vaccines.
The basis for the Sputnik claim about superiority of their vaccine against Omicron is a laboratory study of blood samples of vaccinated people that was a collaboration between the developers and an Italian laboratory (Lapa 2022). Another study by researchers independent of Sputnik analyzed Sputnik samples along with 6 other vaccines, and concluded the opposite: that Moderna and Pfizer vaccines induced the most response to Omicron, with Sputnik among the lowest – 5 out 12 samples had no relevant detectable neutralizing activity (Bowen 2022). (You can see all the laboratory studies on variants and Sputnik that I’ve found in the sources below this post.)
Trying to work out which vaccine is “the best” is now pretty much hopeless, especially with all possible combinations of vaccines out there. There isn’t going to be a head-to-head trial of all of them, which is really the only way to know with confidence. The studies we’ve got can’t really be compared to each other, especially when you take all the complex fluctuations from different variants, people who’ve had Covid mixed in, and with vaccine waning into account – and yes, Sputnik wanes, too (Lapa 2022, Ledesma 2022).
That said, we can be pretty confident that the Sputnik V adenovirus pair of shots is not the most effective option to immunize against Covid. Why? Because trials in Argentina found that a second shot of Moderna after the first Sputnik shot was superior to 2-shot Sputnik V (Macchia 2022). Moderna was also a better second shot than Sputnik’s own second shot in another study, though that one wasn’t a trial (Pereson 2022).
But back to Sputnik V. Can we put its effectiveness into perspective at all? That’s hard, because there are comparatively few studies of Sputnik V, and fewer still with study designs that can provide reliable results. I’ve detailed the handful of ones I’ve found that include results from multiple vaccines and effectiveness on symptomatic Covid or all infections below this post, which is the closest outcome to the central efficacy rate in Covid vaccine trials. In those, vaccine effectiveness for Sputnik V ranges from 58% to 95% – with the 58% from a more reliable study type and the 95% not. In the 2 more reliable studies that include non-Russian vaccines, Sputnik’s effectiveness against infection is similar to AstraZeneca’s (Bello-Chavolla 2022, Macchia 2021).
I discussed a study on responses to Omicron for people who’d been vaccinated with various vaccines above. There’s another study like that from Mexico, too, but looking at rates of seroconversion and adverse reactions after vaccination, not specifically about Omicron (Romero-Ibarguengoitia 2022). That study put Moderna and Pfizer well ahead of Sputnik V in people had never had Covid, but Moderna and Sputnik V ahead of Pfizer in people who had been infected. (The other vaccines in that study were AstraZeneca, CanSino, CoronaVac, and J&J.)
Which brings us to safety and adverse reactions. Two other adenovirus-based Covid vaccines cause some vaccine-induced thrombotic thrombocytopenia (VITT) – AstraZeneca and J&J. It’s a great example of the complexity of knowing how often relatively rare events happen, when they require high-end healthcare system diagnosis and reporting. Back in March, when this was first detected in Europe, UK authorities insisted there was no similar problem in the UK. Several countries suspended the vaccine to investigate, and as I wrote in The Atlantic at the time, in the UK, “Commentators and public-health experts called it ‘stupid, harmful, ‘quite dangerous,’ and a ‘magnificent example of European failure‘.” However, a month later the UK authority was saying it was happening there, too, at much the rate the Germans had said it was, and they withdrew their previous statement.
Is VITT related to adenovirus Covid vaccines, or are Sputnik and CanSino in the clear? I don’t think we know. As the authors of a study in Mexico wrote, the rate of VITT may be lower, or underdiagnosed, in low- and middle-income countries where adenoviral vaccines have been used the most. They found a higher rate of reported strokes after CanSino than other Covid vaccines, including AstraZeneca, J&J, and Sputnik. There’s not much else to go on.
What about other serious adverse events? Another study from Mexico concluded that the rate of Guillain Barré Syndrome after 5.8 million doses of Sputnik was similar to that for all the adenovirus-based vaccines. As you would expect, there have been case reports of serious adverse events after vaccination with Sputnik (like this and this for myocarditis), but I haven’t seen a thorough review of them. If the EU’s European Medicines Agency publishes an evaluation of Sputnik vaccine, we may get a better idea then.
There have been enough studies to get an idea of adverse reactions after Sputnik, and I’ve listed the ones I found in the sources below this post. It seems to be at the higher end of adverse reactions for Covid vaccines – less than Moderna and Pfizer, and roughly around where AstraZeneca and Novavax were in their trials.
Meanwhile, the Sputnik propaganda rolls on. In the English language media that I see, they are still bashing Pfizer and mRNA vaccines, while cherry-picking data on Sputnik V and Sputnik Light, and their claims are often passed on uncritically. They’re claiming to be the first nasal vaccine in the world since Sputnik was registered in Russia for nasal use. It wasn’t first, though. That already happened with an intranasal protein subunit vaccine in Iran last October. (More on the dozens of intranasal vaccines in the pipeline in my recent post.) RDIF was sanctioned, they claimed, because the US was “lobbied by a number of large Western pharmaceutical companies”. That doesn’t seem likely. A vaccine that possibly peaked at around 2% and wasn’t authorized in EuroAmerica was never much of a market threat.
All this isn’t just background noise. Propaganda can have real consequences. In the end, its effects, combined with the problematic drug development program, manufacturing quality problems, and the harm caused by not delivering second doses on a major scale in places like Argentina, will make it hard to assess the full impact of this vaccine.
Disclosures: My interest in Covid-19 vaccine trials is as a person worried about the virus, as my son is immunocompromised: I have no financial or professional interest in the vaccines. I have worked for an institute of the NIH in the past, but not the one working on vaccines (NIAID). More about me.
Sputnik IV’s re-entry didn’t go as planned – a 20-pound chunk of it landed in the US. My cartoon includes a photo of the spot in Wisconsin, by Justin M. Skiba via Wikimedia Commons. Chart from Our World in Data is CC BY. The cartoons are my own (CC BY-NC-ND license). (More cartoons at Statistically Funny.)
You can read more about how I search for studies in this post. Here’s a list of the sources included below:
- Our World in Data chart showing cumulative Covid deaths relative to population size in several countries from January 2021 to April 17, 2022
- Laboratory studies on Sputnik response to variants
- Community effectiveness studies including Sputnik V and other vaccines
- Studies on adverse reactions
Our World in Data, cumulative Covid deaths per million in several countries from January 2021 to April 17, 2022
Laboratory studies on Sputnik responses to variants
As with other vaccines, laboratory tests of blood samples show reduced immune responses to variants:
- Alpha and Beta (Ikegame 2021)
- Beta (Byazrova 2021)
- Beta and Delta (Gushchin 2021, Sapkal 2022)
- Alpha, Beta, Delta, Gamma, and Lambda (Ledesma 2022)
- Delta (Komissarov 2022 – Sputnik Light)
- Gamma (Blanco 2021, also reported Córdoba University and Ministry of Health Working Group 2021)
- Omicron (Bowen 2022, Cameroni 2021, Dolzhikova 2021, Lapa 2022 – manufacturer)
Community effectiveness studies including Sputnik V and other vaccines
|Study (place)||Study details||Results|
(St Petersburg, Russia)
1,198 with symptomatic Covid, Delta outbreak
|Effectiveness against symptomatic Covid (adjusted)|
Sputnik: 58% (CI 50–64)
Sputnik Light: 50% (CI 30–64)
CoviVac: 38% (CI 0-62)
EpiVacCorona: -40% (CI -191–33)
|Effectiveness against infection|
Moderna: 91.5% (CI 90-92)
J&J: 82.2% (CI 81-83)
AstraZeneca: 80.8% (CI 80-81)
Pfizer: 80.3% (CI 80-81)
Sputnik: 78.7% (CI 78-79)
CoronaVac: 71.9% (CI 71-73)
CanSino: 70.5% (CI 70-71)
(Buenos Aires, Argentina)
>540,000 people aged 60+ with at least 1 dose, >83,000 with 2 doses
|Risk of Covid infection in double-vaccinated people|
Risk similar for Sputnik V and AstraZeneca (hazard ratio 1.05; CI 0.80-1.37)
Increased risk for Sinopharm Beijing vaccine
(hazard ratio 1.65; CI 1.40-1.93)
Note: There was an earlier analysis in the same population (and therefore a smaller group), looking at mortality only (Ministerio de Salud Argentina 2021)
(Vojvodena province, Serbia)
>130,000 people aged 60+ with 2 doses
|Effectiveness against symptomatic disease*|
Pfizer: 99.0% (CI 98-100)
Sputnik: 95.0% (CI 92-97)
Sinopharm Beijing: 86.9% (CI 86-88)
* Not clear
> 3.7 million people with 2 doses
|Effectiveness against infection|
Sputnik V: 85.7% (CI 84-87)
Pfizer: 83.3% (CI 83-84)
AstraZeneca: 71.5% (CI 69-74)
Sinopharm Beijing: 68.7% (CI 67-70)
Studies on adverse reactions
Each includes the most commonly reported systemic adverse event (as I did previously with phase 3 trials for other vaccines):
- Babamahmoodi 2021 (Iran) – 51% fatigue
- Blanco 2021 (Brazil) – 47% hyperthermia (raised temperature), 42% muscle pain
- Montalti 2021 (San Marino) – 32% asthenia (fatigue – 4% severe)
- Pagotto 2021 (Argentina) – 68% new or worsened muscle pain
- Romero-Ibarguengoitia 2022 (Mexico) 37% fever (includes 4 vaccines)
- Zahid 2021 (Bahrain) – 37% fever (includes 4 vaccines – Sputnik and AstraZeneca had roughly similar levels)