Boosters and Mixed Schedules: Covid Vaccines at the 2-Year Mark

We’ve just passed the second anniversary of the release of the SARS-CoV-2 genome sequence, which was the starting gun for the Covid vaccine race. Back then, many said we’d be lucky to have “a vaccine” in 12 to 18 months. Now, according to the New York Times tracker, close to 30 vaccines have been rolled out, and there are more than 140 in clinical trials. Many more are in the pipeline, too. Too much is going on to dig into in a single post, so my 2-year roundup will be a series. First up, an overview of clinical trials and other studies on boosting and mixing vaccines.

While a distressingly huge proportion of the world’s people still haven’t had their first dose, a combination of waning immunity and variants has focused a lot of recent attention on boosters. Mixed vaccine schedules, on the other hand, have been critical ever since we’ve had a range of vaccines with uneven supply. Mixing vaccines isn’t only considered for logistical reasons, though. It can be done in hopes of improving immunity. The theory is that this could widen immune responses more than same-same vaccination, as vaccines are targeted at stimulating the immune system in different ways. Sputnik V was built this way from the start: although it’s called “a vaccine”, it’s actually a pair of them.

Better immune responses can be particularly critical to prepare us for some variants of concern. Some manufacturers are developing vaccines adapted for Omicron, but results of studies of these haven’t been reported yet. It’s not clear how many manufacturers are working on Omicron-adapted vaccines, though 2 mRNA vaccine manufacturers anticipate modified versions early this year (Moderna – February-March 2022; Pfizer – March 2022). Moderna is comparing its against other versions of its vaccine with 300-600 participants in each group – and they have included some blood test results for the Omicron-adapted version in a press release. Pfizer is comparing its with 1,420 participants: 615 people who have had 2 shots will get 1 or 2 Omicron-adapted boosters; 600 who have had 3 shots will get 1 Omicron-adapted shot; and 205 unvaccinated people will get 3 shots of Omicron-adapted vaccine.

As usual, I have a major focus on the results of clinical trials, particularly randomized trials. I put effort into being comprehensive there, but of course my collection is still likely to be incomplete. Interpreting the implications of other types of studies is increasingly complicated now that so many factors are in motion – for example, communities have wildly different rates of vaccination and vaccines used, as well as lengths of time since most people were vaccinated and in intervals between doses, and rates of people who have been infected and gained some immunity that way, and they’re facing different variants along the way. I searched for recent vaccine effectiveness studies for mixed schedules and after boosters, that had several characteristics: the data came from national data or major health systems, the study included efforts to reduce bias in the study, and, with a couple of exceptions, vaccine-specific results were reported.

As with my previous roundups, this post starts with an explanation of key technical terms and concepts. After that I’ve broken the information into the sections below, with links to navigate. Each section begins with a summary in bullet points – and there is an summary for the whole post, with some summary tables on boosters. There’s a key to the vaccine identifiers I use as well.

Finally, the term “booster” is complicated. In this post, boosters are doses that are additional to the original 1- or 2-dose courses of vaccine, even when it emerged that the vaccine’s complete schedule includes that additional dose.

• Overall summary
• Mix of vaccines for first 2 doses
• Third dose with the same vaccine
• Third dose with a different vaccine
• Boosters for single-shot vaccines
• Laboratory studies of response to Delta and Omicron after booster
• Fourth doses
• People with compromised immune systems
• Addendum 1: Key to vaccine names and identifiers
• Addendum 2: Notes on vaccine trial records and use
• Disclosures and links to other posts

Key terms used in this post:

• Homologous vaccine schedules have the same vaccine for each dose. When the doses aren’t all of the same vaccine, that’s called heterologous – what I’m calling “mixed” in this post. The first shot in a multi-dose vaccine schedule is called the prime: doses thereafter are boosts.
• Vaccine efficacy is a rate of risk reduction in symptomatic Covid-19 unless otherwise specified. Vaccine efficacy of 80% or 90% means if a vaccinated person is exposed to the virus, their risk of getting the disease is lowered by that proportion, so it depends on how high their risk of being exposed, and that varies. It’s not an absolute drop in percentage points. (Efficacy is for results on disease outcomes from phase 3 clinical trials; effectiveness studies follow that.)
• When available, a range of statistical certainty for efficacy is shown, eg 92% (CI: 88-95). The distance between 88% and 95% in this example is small: it means there is a lot of certainty that 92% is about what we can expect. However, the wider that range is, the more uncertain we are.
• The rate of efficacy set for whether a Covid vaccine works well enough is 50% (with a CI starting at 30% at least).
• And I have a post explaining the terms used, and assessment processes, for adverse events and safety in these trials – including the difference between “severe” and “serious”.

Overall summary

• Trials from the UK and Spain found that mixed 2-dose schedules of AZ and Pfizer produced higher immune responses than 2 doses of AZ (Com-Cov, Com-Cov2, and CombiVacS). The Com-Cov trials found the same for combinations of AZ and Moderna or Novavax, and Pfizer with Moderna or Novavax.
• All of the 10 community impact studies of third doses of the same vaccine, and around half of the 18 clinical trials, involve CoronaVac, Moderna, and Pfizer vaccines. These show that third doses of these vaccines can prevent disease and severe illness outcomes more effectively than 2 doses.
• The only large clinical trial of 3 doses with disease outcomes is for the Pfizer vaccine. There are clinical trials with immune response outcomes for Abdala, IMBCAMS’ unnamed inactivated vaccine, KCONVAC, Novavax, Soberana-2, Westvac Bio, ZyCov-D. Immune responses after third doses can be as high or higher than after the second dose.
• There are more than 100 trials of heterologous third doses underway, and results from the first 7 randomized trials reporting are included here, as well as results from 2 unrandomized trials, and 4 community impact studies, with 19 different vaccines. Most suggest a different vaccine booster is at least as good as same-same boosting, but often better, especially for vaccines that have lower effectiveness with a primary course. There are differences though, and some did not boost immunity, or not by much (such as those from Valneva and CureVac in the COV-BOOST trial).
• The most studied booster for a single-shot vaccine is a second shot of the J&J vaccine. An aerosolized version of CanSino’s single-shot adenovirus 5-based vaccine has been tested in a trial as a booster for CoronaVac, and is being tested in a 10,000-participant trial in China as a booster for some other vaccines too.
• I found 38 laboratory studies testing blood samples of vaccinated people for their ability to neutralize Delta and/or Omicron. Most test one or more of the 8 most-used vaccines. However, some address vaccines for which there’s no other data in this post, including variant-adapted versions of the Moderna, Sanofi, and Medigen vaccines, and a Sputnik Light booster for Sputnik V.
• There are at least 18 randomized trials underway for approaches to improve immunity for people with compromised immune systems. There are results for 4 of them – not enough to provide definitive answers to the major questions, but enough to provide encouragement that more effective vaccination schedules will be identified. For now, the most evidence is for going to at least 3 doses for mRNA vaccines.
• Reports of immune responses after 4 doses for the immunocompromised are emerging, but it’s very early days. At least 14 countries are now offering fourth doses to at least some people with compromised immune systems.
• At least 4 countries are offering 4 doses for a broader population. In the case of Cuba, that’s for their homegrown conjugate/protein subunit vaccines that have a 3-dose primary course – the fourth dose is the first “booster”. In Israel, it’s a fourth dose of Pfizer vaccine.

There are 3 major issues this post doesn’t address: vaccine outcomes specifically in people who have also been infected with the SARS-CoV-2 virus, outcomes in the under-18s, and adverse events after boosters and mixed schedules.

The studies in this post are almost exclusively in adults. An upcoming post in this 2-year-roundup series will focus on studies in children and adolescents.

Major safety concerns in rollouts of boosters haven’t been reported as far as I know. Adverse reactions appear to be similar to those from previous doses – see for example the results of COV-BOOST, a randomized trial with 7 vaccines, including mixed vaccine schedules and a non-Covid vax control group. And here are 3 larger studies of adverse reactions to third doses:

• A prospective study of 1,344 people in Israel who reported their reactions via an app on a smartwatch they were given. Their reports after a third dose of the Pfizer vax were similar to responses to the second dose.
• V-safe is a reporting scheme people in the US can sign up to. Among 12,591 people who reported on their responses to a third dose of either Pfizer or Moderna vaccines, local symptoms were more common than after dose 3, but there were fewer systemic ones.
• No major safety concerns with a second shot of J&J vaccine has been found in the Sisonke 2 study in South Africa, with over 230,000 healthcare workers boosted.

8 most used vaccines: how strong is the evidence?

Note: Covers the vaccine when it’s the first vaccination(s), not when it is a booster to a different vaccine. These tables includes my subjective ratings of the strength of the evidence, separate to the question of how well the vaccination schedule works – there’s more on that below, including supporting information.

Vaccine	Billion doses delivered	Self booster	Other vax booster
CoronaVac (inactivated)	Close to 2	Strong	Strong
Pfizer (mRNA)	>1.5	Strong	Strong
Sinopharm Beijing (inactivated)	>1.5	Moderate	Moderate
AstraZeneca (AZ)/Covishield (adenoviral)	>1.5	Moderate	Strong
Moderna (mRNA)	Close to 0.5	Strong	Weak
Sputnik V (adenoviral)	<0.5	Weak	No evidence found
J&J (single-shot) (adenoviral)	<0.5	Strong	Moderate
Covaxin (inactivated)	<0.5	Weak	No evidence found

8 most used vaccines: overview of evidence on boosters

First vaccine	Evidence	My take
CoronaVac + CoronaVac	Vaccine effectiveness: National data from Chile (ca 165,000 triple-CoronaVac). Immune response: 1 placebo-controlled randomized trial (540 people); 1 randomized trial (1,205 people); 1 unrandomized study. 2 laboratory studies of blood after 3 doses – testing neutralization for Delta.	Overall evidence: Strong. Protection against disease outcomes may be high (eg 81% against hospitalization), though lower than with heterologous boost from some other vaccines (see below). Stronger immune response 2-4 weeks after dose 3 than after 2 doses. Response from lab studies was lower for Delta (none found for Omicron).
CoronaVac + other	Vaccine effectiveness: National data from Chile (>1.7 million people). Immune response: 2 randomized trials (420 and 1,205 people); 7 unrandomized studies or trials (mostly with AZ or Pfizer 3rd doses). 2 laboratory studies of blood after other Moderna and/or Pfizer boosts – testing neutralization for Delta and Omicron.	Overall evidence: Strong. Protection against disease outcomes apparently high (eg 90+% against hospitalization for AZ or Pfizer boost), which is higher than reports for homologous boost. Immune response was strong and higher than homologous boost for 3rd dose of AZ, low or high dose aerosolized CanSino, J&J, and Pfizer. Immune response after dose 3 of Moderna was also strong, and apparently higher than after a 3rd dose of CoronaVac. Response to Delta and Omicron were lower.
Pfizer + Pfizer	Vaccine effectiveness: Phase 3 trial (10,000 people); case-control studies from Israel (1, with >725,000 people), UK (1) and USA (2), and household transmission from Denmark; matched cohort study from Qatar; 2 community studies from the US. Immune response: 1 placebo-controlled phase 2 trial (549 people); 1 randomized phase 2 trial (2,878 people) with half & full dose 3 (non-Covid vax control & 6 other vaxes, COV-BOOST). 22 laboratory studies of blood after 3 doses – testing neutralization of Delta and/or Omicron.	Overall evidence: Strong. Effectiveness against symptomatic disease very high compared to placebo (around 95%) and compared to people with 2 doses months earlier (over 80% and over 90% for severe outcomes) (including Delta). Effectiveness at preventing severe disease or hospitalization in community studies very high, including for variants. Appears to lower risk of transmission/infection within households. Stronger immune response soon after dose 3 than soon after dose 2. May be similar for half or full dose Pfizer. Response was lower for Delta and Omicron.
Pfizer + other	Vaccine effectiveness data: UK case-control study with Moderna booster. Immune response: 1 randomized phase 2 trial with boosters by 6 non-Pfizer vaccines & control (COV-BOOST); 1 unrandomized trial with J&J or Moderna booster (NIH Mix & Match); 1 unrandomized trial with CoronaVac booster. 7 laboratory studies of blood (mostly after Moderna booster) – testing neutralization of Delta and/or Omicron.	Overall evidence: Strong. Protection after 3rd dose of Moderna may be higher than a 3rd dose of Pfizer. Immune response is increased by a Moderna dose 3 (in full or half dose) and may be as high or higher than with a BNT dose 3. J&J dose 3 increases immune response, but not by as much as Moderna and Pfizer doses. Immune response from dose 3 of CureVac and Valneva are lower again. Immune response was lower for Delta and Omicron.
Sinopharm Beijing + Sinopharm Beijing	Vaccine effectiveness: None included. Immune response: 1 phase 2 randomized trial (1,800 people). 2 laboratory studies of blood after 3 doses – testing neutralization of Delta or Omicron.	Overall evidence: Moderate. Stronger immune response soon after 3 doses than 2, but less of response for Delta and Omicron.
Sinopharm Beijing + other	Vaccine effectiveness: None included. Immune response: 1 phase 2 randomized trial, with Sinopharm recombinant NVSI as dose 3 (1,800 people); 1 unrandomized trial (with ZF2001 as booster). 2 laboratory studies of blood after boosters (Moderna, Pfizer, ZF2001) – testing neutralization of Delta and/or Omicron.	Overall evidence: Moderate. Stronger immune response soon after 3 doses than 2, but less of response for Delta and Omicron. A dose 3 of Moderna or Pfizer may greatly increase immune response, while a heterologous boost with Sinopharm’s recombinant (subunit) vaccine may achieve a similar response to a 3rd dose of Sinopharm’s inactivated Beijing vaccine. Less of a response for Delta and Omicron.
AstraZeneca (AZ) + AZ	Vaccine effectiveness: None included. Immune response: 1 randomized phase 2 trial (2,878) with 3 doses (non-Covid vax control & 6 other vaxes, COV-BOOST). 2 laboratory studies of blood after 3 doses – testing neutralization of Delta and Omicron.	Overall evidence: Moderate. A 3rd dose of AZ increases antibody but not cellular immune response, and antibody responses are lower than for boosts of CureVac (mRNA), J&J, Moderna, Novavax, and Pfizer. Immune response is lower for Delta and Omicron.
AZ + other	Vaccine effectiveness: UK case-control study of Pfizer 3rd dose (6,716 people); UK case-control study of Moderna or Pfizer booster. Immune response: 1 randomized phase 2 trial (2,878 people – COV-BOOST, 6 other vaxes). 4 laboratory studies of blood after Moderna or Pfizer booster – testing neutralization of Delta and/or Omicron.	Overall evidence: Strong. Effectiveness is high and similar to 3 doses of Pfizer after a 3rd dose of Moderna or Pfizer. Immune response is strong after a 3rd dose of CureVac (mRNA), J&J, Moderna, Novavax, and Pfizer, but not Valneva, and highest for Moderna and Pfizer. Response to Delta and Omicron were lower.
Moderna + Moderna	Vaccine effectiveness: 4 case-control studies (USA & household transmission, Denmark); Community studies (Qatar & USA). Immune response: 1 randomized phase 2a trial (results for subset of 20 people); 1 unrandomized trial (NIH “Mix & Match). 11 laboratory studies of blood after 3 doses – testing neutralization of Delta and/or Omicron.	Overall evidence: Strong. Effectiveness is very high. May be the most effective homologous 3-dose schedule. Appears to have vaccine effectiveness well over 90% for severe disease/hospitalization. Appears to lower risk of transmission/infection within households. Response was lower for Delta and Omicron.
Moderna + other	Vaccine effectiveness: None included. Immune response: 1 unrandomized trial (NIH “Mix & Match”). 6 laboratory studies of blood after other 3rd doses (mostly Pfizer) – testing neutralization of Delta and/or Omicron.	Overall evidence: Weak. Not enough evidence.
2-dose Sputnik V	Vaccine effectiveness: None included. Immune response: 1 laboratory study of dose 3 of Sputnik Light – testing for neutralization of Omicron.	Overall evidence: Weak. Not enough evidence.
2-dose Sputnik V + other	Vaccine effectiveness: None included. Immune response: None included.	Overall evidence: None included.
J&J + J&J	Vaccine effectiveness: 1 randomized placebo-controlled phase 3 trial (13,836 people); 1 case-control study from South Africa (69,092 people); community study from the US. Immune response: 1 randomized trial including a no-boost group (434 people); 1 unrandomized trial (NIH “Mix & Match”). None included.	Overall evidence: Strong. Effectiveness against symptomatic disease was high (around 75% globally and over 90% in the US) and very high for severe outcomes.
J&J + other	Vaccine effectiveness: None included. Immune response: 1 randomized trial with Moderna and Pfizer (434 people); 1 unrandomized phase 1/2 trial (NIH “Mix & Match”). 4 laboratory studies of Pfizer, or Pfizer or Moderna after J&J – testing neutralization of Delta and/or Omicron.	Overall evidence: Moderate. A booster (2nd) dose of Moderna or Pfizer may increase effectiveness to a similar level to Pfizer.
Covaxin + Covaxin	Vaccine effectiveness: None included. Immune response: 1 randomized placebo-controlled phase 2 trial (184 people).	Overall evidence: Weak. Some evidence of stronger immune responses soon after 3 doses than 2, with less response for Delta.
Covaxin + other	Vaccine effectiveness: None included. Immune response: None included.	Overall evidence: None included.

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Mix of vaccines for first 2 doses

Summary:

• This section includes results of 4 trials of 2-dose mixed vaccine schedules, as well as 4 preclinical trials and 2 community impact studies (a large nationwide study from Denmark, and a case-control study from Russia).
• 3 trials have compared schedules, 2 from the UK (Com-Cov and Cov-Cov2) and one from Spain (CombiVacS).
• The Com-Cov studies found that mixed doses of AZ and Moderna, Novavax, or Pfizer, and Pfizer with Moderna or Novavax, all produced immune responses that were higher than a 2-dose course of AZ. CombiVacS also found a higher immune response from AZ followed by Pfizer than a 2-dose course of AZ.

Background notes and sources:

In my post in July 2021, I was tracking the early case series of mixed 2-dose schedules. I have stopped gathering these, as clinical trial reports started to come in – they’re listed below. In addition, I’ve found 2 community impact studies of 2-dose mixed vaccine schedules:

• Denmark – AZ then Moderna or Pfizer: 136,551 people, study based on national registry data. Vaccine effectiveness against infection was 88% (CI: 83-92), with no people hospitalized or dying of Covid-19 (Gram 2021).
• Russia – Sputnik V: case-control study, with 1,198 cases and 2,747 controls in October during a Delta outbreak in St Petersburg, mostly Sputnik V/Sputnik Light. Sputnik Light (rAd26) is the first shot in the Sputnik V combination (rAd26 + rAd5). (Other vaccines were EpiVacCorona and CoviVac.) Vaccine effectiveness against symptomatic disease for Sputnik V was 58% (CI 50-64), and for Sputnik Light, 50% (CI 30-64) (Barchuk 2022).

Clinical* trials comparing schedules

* Includes 4 preclinical trials. (Trials in rough chronological order of announcement)

Vaccines	Schedule	Participants	Location(s)	Research phase
Sputnik V: rAd26-S (aka Sputnik Light) & rAd5-S	rAd26-S first; placebo control	19,866	Russia	Phase 3 trial, results.
AZ; Sputnik rAd26-S	Alternating	100 people	Belarus, Russia	In phase 1/2 trial. (Delayed – started September 2021.)
AZ; Sputnik rAd26-S	Alternating	100 people	Azerbaijan	In phase 1/2 trial. Some interim results on first 20 people in a press release.
AZ; Sputnik rAd26-S	Alternating	100 people	UAE	In phase 1/2 trial.
AZ; Imperial College saRNA	Single shots; alternating combination; usual 2-shot course	6 groups; 22 mice each	UK	Preclinical*, results.
AZ; Moderna; Novavax; Pfizer	Alternate boost starting with AZ or Pfizer (8 or 12 weeks apart)	1,050 people	UK	In phase 2 trial called Com-Cov (protocol). First results (AZ & Pfizer only); second results report (AZ & Pfizer only).
Gritstone ChAds (ChAdV68-S; ChAdV68-S-TCE); Gritstone saMRNAs (SAM-LNP-S; SAM-LNP-S-TCE)	Alternate boost	140 people	USA	In phase 1 trial.
CanSino; Sinovac’s CoronaVac	Alternate boost 3-6 months after 1 or 2 doses of CoronaVac	300 people	China	Phase 4 trial, start was planned for May 25.
AZ; Pfizer	AZ followed by Pfizer	600 people	Spain	In phase 2 trial called CombiVacS. First results.
AZ; Moderna; Pfizer	Same-same & alternating boost for mRNAs, 4 or 16 weeks apart; AZ first then mRNA boost, 4 or 16 weeks apart	1,200 people	Canada	Phase 2 trial, called MOSAIC, started on May 20.
Moderna; Pfizer	Alternating	400 people	France	Trial called ARNCOMBI, started on May 28.
AZ; Pfizer	Same-same (Pfizer 3-7 weeks apart, AZ 12 weeks apart); AZ followed by Pfizer (12 weeks apart)	3,000 people	Austria	Phase 2 trial, called HeVACC, started on May 10.
AZ; Moderna; Novavax; Pfizer	Alternate boost starting with AZ or Pfizer	1,050 people	UK	In phase 2 trial. Called Com-COV2 (protocol). Results. Omicron results for homologous schedule.
Sinopharm Beijing; 3 unspecified vaccines (adenoviral, protein, mRNA)	Sinopharm Beijing followed by a 2nd and 3rd shot of 1 of each 3 vaccines	48 mice	China	Results.
Moderna; Novavax; Pfizer	Alternate boost starting with Pfizer, 8-week interval	360 people (adolescents 12-16)	UK	In phase 2 trial. Called Com-COV3 (protocol).
Sinopharm Beijing (inactivated); ZF2001 (subunit)	Alternate 2-dose course (including homologous) or placebo; booster comparisons: homologous with 3rd heterologous dose, 3 doses of Sinopharm, placebo	83 mice	China	Preclinical. Results.
Moderna; unnamed intranasal vax from Yale Uni	Moderna or intranasal vax alone, intranasal vax after Moderna	Mice – number not reported	USA	Preclinical. Results.

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Third dose with the same vaccine

Summary:

• This section includes studies for 12 vaccines in 3 doses, including 18 trials comparing the third dose to a placebo, different dosage, or other vaccine, and 10 community impact studies.
• All of the community impact studies and around half of the clinical trials involve 3 of the most-used vaccines (CoronaVac, Moderna, and Pfizer). I found none for 3 doses of AZ, Covaxin, and Sputnik V, and one trial only for Sinopharm’s Beijing vaccine. (Studies for second doses of J&J are covered in the section on single-shot vaccines.)
• The other vaccines studied with 3 doses are Abdala, IMBCAMS’ unnamed inactivated vaccine, KCONVAC, Novavax, Soberana-2, Westvac Bio, ZyCov-D.
• With the exception of a large clinical trial of the Pfizer vaccine, the evidence from trials is for immune responses, not disease outcomes. Immune responses after third doses can be as high or higher than second doses.
• Community impact studies for 3 doses of CoronaVac, Moderna, Pfizer show that the third dose can prevent illness and severe outcomes more effectively than 2 doses.

Background notes and sources:

Large community impact studies with vaccine-specific results:

• Israel – Pfizer: case-control study with 728,321 people getting 3 doses (matched with the same number with 2 doses at least 5 months earlier) (Barda 2021). Vaccine effectiveness:
  • Hospitalization: 93% (CI 88-97)
  • Severe disease: 92% (CI 82-97)
  • Death from Covid-19: 81% (CI 59-97)
• UK – Pfizer: test-negative case-control study in 17,521 people over 50 or at clinical risk (Andrews 2021). Vaccine effectiveness:
  • Symptomatic disease, compared to people who had 2 doses only: 84.4% (CI 83-86)
  • Symptomatic disease, compared to unvaccinated people: 94.0% (CI 93-95)
• Qatar – Moderna, Pfizer: matched cohort study, adjusting for sex, age group, nationality group, and calendar week of second dose in over 2 million people with 2 doses and around 300,000 with 3 doses, predominantly Pfizer (Abu-Raddad 2022). Vaccine effectiveness compared to people with 2 doses for Omicron:
  • Moderna: 50.8% against disease (CI 43-57) – no one with either 2 or 3 doses developed severe/critical Covid or died from the disease
  • Pfizer: 50.1% against disease (CI 47-53), 100% against severe/critical Covid or death from it (CI 71-100)
• Chile – CoronaVac: uses national data sources, adjusting for several factors such as age for 165,449 people triple-vaccinated with CoronaVac (Araos 2021). Vaccine effectiveness comparing to unvaccinated people (from 14 days after dose 3):
  • Infection: 70.9% (CI 65-76)
  • Disease: 73.6% (CI 68-79)
  • Hospitalization: 80.8% (CI 73-87)
  • Intensive care: 85.1% (CI 70-93)
  • No deaths in triple-vaccinated people
• USA – J&J, Moderna, Pfizer: uses data from 25 state and local health departments representing 62% of the US population, adjusting for several factors, from April to December 2021 – through Delta and the rise of Omicron (Johnson 2022). The authors point out that they couldn’t adjust for people who were immunocompromised, who were the early group getting 3 doses. This reports includes calculations of weekly incidence of infection compared to an incidence of 348 for unvaccinated people (plus calculations of incidence rate ratio (IRR) – a measure of relative difference):
  • J&J: 26 per 100,000 – IRR 13.4 (CI 11-27) (for a single dose: 108 per 100,000)
  • Moderna: 20 per 100,000 – IRR 17.4 (CI 15-21) (for 2 doses: 75 per 100,000)
  • Pfizer: 27 per 100,000 – IRR 12.9 (11-15) (for 2 doses: 94 per 100,000)
• USA – test-negative case-control study with 23,391 cases and 46,764 controls (Accorsi 2022). Adjusted odds ratios (OR) for disease (a measure for comparing the odds of getting sick) – compared to unvaccinated – showed very low chance of getting sick, but higher with Omicron:
  • Moderna:
    • Delta OR 0.045 (CI 0.038-0.053)
    • Omicron OR 0.28 (CI 0.26-0.31)
  • Pfizer:
    • Delta OR 0.077 (CI 0.070-0.086)
    • Omicron OR 0.35 (CI 0.32-0.38)

• USA – test-negative case-control study from Kaiser Permanente Southern California, matching 5 people who tested negative against each of 6,657 who tested positive (56% with Omicron) – by age, sex, race/ethnicity, and specimen collection date (Tseng 2022). Vaccine effectiveness estimates (compared to unvaccinated and adjusted for a range of factors including BMI, history of Covid, medical center area):
  • 2 doses of Moderna:
    • Infection with Delta: 60.7% (CI 57-65) (from 83% up to 3 months down to 53% after 9 months)
    • Hospitalization with Delta: 98.0% (CI 87-99.7)
    • Infection with Omicron: from 30.4% (CI 5-49) up to 3 months down to 0% after 9 months (CI 0-2)
    • Hospitalization with Omicron data extremely uncertain (note the CI): 16.5% (CI 0-89) (unadjusted)
  • 3 doses of Moderna:
    • Infection with Delta: 95.2% (CI 93-96)
    • Hospitalization with Delta: no vaccinated person was hospitalized
    • Infection with Omicron: 62.5% (CI 56-68)
    • Hospitalization with Omicron: no vaccinated person was hospitalized

Large community impact studies with results that aren’t vaccine-specific:

England – mostly AZ first 2 doses, large proportion Pfizer, some Moderna, with Moderna or Pfizer third dose (both homologous and mixed vaccine schedules)

This is from a UK Health Security Agency report on variants (with data from November 27, 2021 to January 6, 2022). Vaccine effectiveness was estimated using a test-negative case-control study. There were 236,023 Delta cases and 760,647 Omicron:

• Vaccine effectiveness against symptomatic infection was lower than it was for Delta, and waned more rapidly for those without boosters.
• Vaccine effectiveness against hospitalization with Omicron (all vaxes combined):
  • 4 weeks or more after 1 dose: 58% (CI 37-72)
  • 2-24 weeks after 2 doses: 64% (CI 54-71)
  • 25 weeks or more after 2 doses: 44% (CI 30-54)
  • 2 weeks or more after 3 doses: 89% (CI 86-91) (from 92% in the first month to 83% at 10 weeks or more)

USA – Moderna, Pfizer: test-negative study based on data on 222,772 emergency/urgent care visits for Covid-like illness in 10 states (Thompson 2022). Almost all of the people with Covid in this study were infected with Delta (98%), the rest with Omicron. Vaccine effectiveness for the 2 mRNA vaccines combined against testing positive for Covid and being hospitalized (compared to unvaccinated):

• After 2 doses (from 2 weeks to 6 months earlier): 81% (CI 65-90)
• After 2 doses (6 or more months earlier): 47% (CI 39-70)
• After 3 doses: 90% (CI 80-94)

Denmark – Pfizer (85%), J&J (1%), and Moderna (14%).

Danish registers were used to estimate infection rates in 11,937 households where someone tested positive for Covid, 2,225 with Omicron. The rate of secondary infections was 21% for Delta and 31% for Omicron. People who had boosters had a reduced chance of transmitting the virus (OR 0.72, CI 0.56-0.92 – not broken down by variant). They also had a lower chance of being infected: for Omicron (OR 0.54, CI 0.40-0.71) and for Delta (OR 0.38, CI 0.32-0.46).

There is also a preclinical trial with homologous and heterologous boosts of unspecified vaccines for Sinopharm’s Beijing vaccine (Zhang 2021).

Results from clinical trials comparing schedules

(Trials in rough chronological order of announcement)

Vaccines	Schedule	Participants	Location(s)	Research phase
Abdala	3-dose course at either short (14-day) or long (28-day) intervals in 2 doses, or placebo	792 people	Cuba	Phase 1/2. Results.
Westvac Bio’s recombinant vaccine	3-dose course at 14-day intervals in either low or high dosage, or placebo	168 & 960 people	China	Phase 1 & Phase 2 trials. Results.
Sinovac’s CoronaVac	2 doses CoronaVac (either 14 or 28 days interval) followed by medium or high vax dosage or placebo (either at 28 days as part of a 3-dose schedule or 6 months after a 2-dose schedule)	540 people	China	Phase 2 trial. Results.
Novavax	2 doses in a phase 2 trial, followed by another dose or placebo approximately 6 months later	210 people	Australia	Phase 2 trial. Results.
AZ, CureVac, J&J, Moderna, Novavax, Pfizer, Valneva	2 doses of AZ or Pfizer followed by either a 3rd of the same vax, or a dose of 1 of the 5 other vaccines (or a non-Covid vax control)	2,878 people	UK	Phase 2 trial. Called Cov-Boost (protocol). Results.
J&J, Moderna, Pfizer	2 doses Moderna or Pfizer or 1 dose J&J, followed by 1 dose of the same vaccine or 1 of the 2 other vaccines	458 people	USA	Unrandomized phase 1/2 trial, NIH “Mix and Match Study”. Results (reactions), results (immune response), FDA presentation.
Moderna	2 doses original formula in a phase 2 trial, followed by dose of original or adapted version in 1 of 2 dosages	186 people	USA	Phase 2a trial. Results for a subset of 20 people.
IMBCAMS; Stemirna	IMBCAMS, 2 doses (inactivated) followed by either IMBCAMS or Stemirna (mRNA) 6 months later	112 people	China	Unrandomized trial. Results.
AZ, CoronaVac, J&J, Pfizer	2 doses of CoronaVac followed by a 3rd dose of CoronaVac or AZ, J&J, or Pfizer	1,205 people	Brazil	Phase 4 trial. Results.
Soberana-2; Soberana-Plus	3 doses of Soberana-2 in low or high dosage or 2 doses with dose 3 of Soberana-Plus	100 people	Cuba	Phase 1 trial. Results.
Pfizer	3 or 4 doses of original formula, dose 3 of version adapted for Beta variant, or placebo	549 people	Germany	Phase 2 trial. Some results via EMA (page 13, version of product information Dec 15)
ZyCov-D	3-dose course or placebo 28 days apart	1,048 people (48 in phase 1)	India	Phase 1/2 trial. Results (phase 1).
Pfizer	Dose 3 in original or low-dosage or placebo after 2 doses at least 6 months previously	10,000 people (aged 12 or over)	Brazil, Canada, South Africa, US	Phase 3 trial. Preliminary efficacy result cited by FDA (page 6) (95.3%, CI 90-98)
Covaxin	2 doses of Covaxin, 3rd dose or placebo 7 months later	184 people	India	Phase 2 trial. Results.
Sinopharm Beijing, Sinopharm recombinant NVSI	2 doses of Sinopharm Beijing, followed by either the same vax or Sinopharm recombinant NVSI	1,800 people	UAE	Phase 2 trial. Results.
KCONVAC inactivated vax	3 shot schedule in a lower or higher dosage or placebo, 28 days apart	500 people	China	Phase 2 trial. Results.
CoronaVac, Pfizer	2-dose course of CoronaVac or Pfizer only, or followed by either the same vaccine or the other for dose 3	383 people	Chile	Unrandomized. Results.

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Third dose with a different vaccine

Summary:

• Over 100 trials of heterologous third vaccine doses are underway, for the vaccines already in wide use, and ones that haven’t yet been authorized for use. This section includes results from 7 randomized trials, 2 unrandomized trials and 1 preclinical trial, as well as 4 community impact studies.
• Most of the studies are suggesting that a heterologous third dose leads to as good immune responses than same-same boosters, but often better – especially for vaccines that have lower effectiveness with a primary course. However, there are differences, and some vaccines did not improve much, or at all, on same-same vaccination in some studies (such as those from Valneva and CureVac in the COV-BOOST trial).
• Most of the studies of alternative vaccines for booster doses involve the most-used vaccines, but other vaccines used in mixed schedule studies for third doses in people include:
  • Cuba’s 3-dose primary courses for Soberana (1, 2, and Plus);
  • From China, an unnamed inactivated vax from IMBCAMS, Stemirna’s mRNA, and 3 subunit vaccines, Sinopharm’s NVSI, and ZF2001;
  • Novavax, from the USA;
  • Valneva, an inactivated vaccine from a European company;
  • ZyCov-D, a DNA vaccine from India.
• CanSino has some results for its aerosolized version after CoronaVac – and the aerosolized vax is now in a phase 3 trial in China for 10,420 adults who were vaccinated with a 2-dose course of any of 4 inactivated vaccines, compared with a third dose of the inactivated vaccine (CoronaVac, KCONVAC, Sinopharm’s Beijing and Wuhan vaccines).

Background notes and sources:

There has also been a flood of mixed vaccine booster trials starting globally. I’ve now gathered trial registry entries for more than 100 in my collection – included either because they have a comparison group, or they are being undertaken by a vaccine’s manufacturer or government sponsor.

Results have started coming in, too. I found results reported for 7 randomized and 2 unrandomized clinical trials, as well as for 1 preclinical trial, of a third dose of a different vaccine. Details for all these are included in a table at the end of this section, with 8 observational studies with no comparison groups listed separately just before the table. Not included in those lists is another preclinical study with results, because some of the vaccines used in it aren’t specified – they are boosters after Sinopharm’s Beijing vax (Zhang 2021).

Large national community impact studies

• Chile – 2-dose CoronaVac followed by AZ or Pfizer, mid-October (Araos 2021). Uses national monitoring and a model with factors such as age for over 1.7 million people with a third dose of AZ and over 966,000 with Pfizer. (Note: Pfizer was rolled out to high risk people early in the campaign, so those people would have also been early to third doses. 3-dose CoronaVac results were included in previous section.) Vaccine effectiveness comparing to unvaccinated people (from 14 days after dose 3):
  • Infection:
    • 2-dose CoronaVac + AZ: 90.5% (CI 90-92)
    • 2-dose CoronaVac + Pfizer: 93.2% (CI 92-95)
  • Disease:
    • 2-dose CoronaVac + AZ: 93.6% (CI 93-94)
    • 2-dose CoronaVac + Pfizer: 95.0% (CI 93-96)
  • Hospitalization:
    • 2-dose CoronaVac + AZ: 97.1% (CI 96-98)
    • 2-dose CoronaVac + Pfizer: 91.2% (CI 87-94)
  • Intensive care:
    • 2-dose CoronaVac + AZ: 98.7% (CI 97-99)
    • 2-dose CoronaVac + Pfizer: 92.7% (CI 83-97)
  • Death: no deaths in triple-vaccinated people

• England – 2-dose AZ followed by Pfizer, data to late October (Andrews 2021). Test-negative case-control study with 6,716 people over 50 or at clinical risk. Vaccine effectiveness for symptomatic disease was 87.4% (CI 85-89) compared to people who had 2 doses only, and 93.1% (CI 93-95) compared to unvaccinated people.
• England – 2-dose AZ or Pfizer followed by Moderna or Pfizer, in December 2021 (UK Health Security Agency 2021). Test-negative case-control study, based on 98 hospitalizations of people aged 65 or older who had a third dose. Either vaccine pushed effectiveness for mild disease over 60%, dropping to around 50% at 5-9 weeks; for people who had Pfizer followed by Moderna, it was about an extra 5 percentage points. Protection against hospitalization, however, was high after the third dose – vaccine effectiveness (not broken down by vaccine):
  • 2-9 weeks after the third shot: 94% (CI 89-97)
  • 10+ weeks after the third shot: 89% (CI 80-95)

In addition, there’s a large study that didn’t have vaccine-specific results. As it included both mixed and same-vaccine boosters, it was included in the previous section – this is a duplication of my summary above:

The study is from a UK Health Security Agency report on Omicron (with data up to December 29, 2021) – mostly AZ first 2 doses, large proportion Pfizer, some Moderna, with Moderna or Pfizer third dose (both homologous and mixed vaccine schedules). Vaccine effectiveness was estimated using a test-negative case-control study (a case-control study of people getting tested for Covid). There were 373,924 cases (including 204,036 with Omicron):

• The risk of hospitalization was higher with Omicron than Delta. No comparison was shown with original virus (which was also less than Delta).
• Vaccine effectiveness against symptomatic infection was lower than it was for Delta, and waned more rapidly for those without boosters. It began waning about 10 weeks after the booster (third dose) for Omicron, as it did with Delta.
• Vaccine effectiveness against hospitalization with Omicron (all vaxes combined):
  • 4 weeks or more after 1 dose: 52% (CI -5 to 78)
  • 2-24 weeks after 2 doses: 72% (CI 55-83)
  • 25 weeks or more after 2 doses: 52% (CI 21-71)
  • 2 weeks or more after 3 doses: 88% (CI 78-93)

There are also 2 preclinical trials including third doses (Zhang 2021; Song 2022).

Sources: Results from studies* comparing schedules

* Includes one study of before and after a booster. (Trials in rough chronological order of announcement.)

Vaccines	Schedule	Participants	Location(s)	Research phase
IMBCAMS; Stemirna	IMBCAMS, 2 doses (inactivated) followed by either IMBCAMS or Stemirna (mRNA) 6 months later	112 people	China	Unrandomized trial. Results.
Soberana-1; Soberana-Plus	2 doses of Soberana-1 in high dosage followed by either a 3rd high dosage Soberana-1 or a low-dosage Soberana-Plus	60 people	Cuba	Phase 1 trial. Results.
Soberana-2; Soberana-Plus	3 doses of Soberana-2 in low or high dosage or 2 doses with dose 3 of Soberana-Plus	100 people	Cuba	Unrandomized phase 1 trial. Results.
Soberana-2; Soberana-Plus	2 doses of Soberana-2 with 3rd dose of Soberana-Plus, or placebo	810 people	Cuba	Phase 2 trial. Results (part 2b).
Soberana-2; Soberana-Plus	2 doses Soberana-2, or 2 Soberana-2 plus a 3rd dose of Soberana-Plus, or placebo	44,031 people	Cuba	Phase 3 trial. Results.
AZ; CureVac; J&J; Moderna; Novavax; Pfizer; Valneva	2 doses of AZ or Pfizer followed by either a 3rd of the same vax, or a dose of 1 of the 5 other vaccines (or a non-Covid vax control)	2,878 people	UK	Phase 2 trial. Called Cov-Boost (protocol). Results.
J&J, Moderna, Pfizer	2 doses Moderna or Pfizer or 1 dose J&J, followed by 1 dose of the same vaccine or 1 of the 2 other vaccines	458 people	USA	Unrandomized phase 1/2 trial, NIH “Mix and Match Study”. Results (reactions), results (immune response), FDA presentation.
AZ, CoronaVac, J&J, Pfizer	2 doses of CoronaVac followed by a 3rd dose of CoronaVac or AZ, J&J, or Pfizer	1,205 people	Brazil	Phase 4 trial. Results.
Sinopharm Beijing, Sinopharm recombinant NVSI	2 doses of Sinopharm Beijing, followed by either the same vax or Sinopharm recombinant NVSI	1,800 people	UAE	Phase 2 trial. Results.
CanSino, CoronaVac	2 doses of CoronaVac followed by low or high dose aerosolized CanSino vaccine	420 people	China	Phase 1/2 trial. Results.
CoronaVac, Pfizer	2 doses of CoronaVac, followed by CoronaVac or Pfizer (and an unvaxed group)	68 people	Turkey	Unrandomized. Results.
CoronaVac, Pfizer	2 doses of CoronaVac, followed by Pfizer in one of 2 dosages or intradermal	91 people	Thailand	Unrandomized phase 1 trial. Results.
AZ, CoronaVac, Pfizer, Sinopharm Beijing	2-dose course of CoronaVac followed by AZ, Pfizer or Sinopharm Beijing	177 people	Thailand	Unrandomized trial. Results.
AZ, CoronaVac	2-dose course of CoronaVac or AZ, or 2-dose course of CoronaVac followed by AZ	549 people	Thailand	Unrandomized trial. Results.
CoronaVac, Sinopharm Beijing, ZF2001	2-dose course of CoronaVac or Sinopharm Beijing, followed by ZF2001 or no booster	122 people	China	Unrandomized trial. Results.
CoronaVac, Moderna	2-dose course of CoronaVac followed by Moderna	304 people	Indonesia	Study of samples before and after booster. Results.
CoronaVac, Pfizer	2-dose course of CoronaVac followed by Pfizer, or 2-dose course of Pfizer	141 people	Dominican Republic, USA	Unrandomized. Results.
CoronaVac, Pfizer	2-dose course of CoronaVac or Pfizer only, or followed by either the same vaccine or the other for dose 3	383 people	Chile	Unrandomized. Results.

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Boosters for single-shot vaccines

• Boosters are being studied for all 3 of the single-shot Covid vaccines, mostly for the J&J vaccine.
• There are some results of boosters for both the CanSino and J&J vaccines. I could find none for Sputnik Light (other than the data for the original Sputnik V schedule of the same vaccine followed by a shot of a different vaccine).
• The evidence for boosting the J&J vaccine is strong. There is strong data for either a second shot of J&J, and moderate evidence for Moderna and Pfizer boosters.
• An mRNA booster shot after J&J may be as effective as a fully mRNA 3-dose course. A second shot of J&J appears to be somewhat less effective, although still very high against hospitalization or severe disease (from 85% to over 90%).
• There has been a trial of boosting the CanSino vaccine with an aerosolized version, where it increased immune responses more than a second shot of the vaccine.
• Reactions to booster shots are similar to those expected for the vaccines. No major safety concerns have been reported so far for the biggest ongoing study of a second J&J shot (Sisonke 2, with over 230,000 healthcare workers).

There are 3 vaccines used as a single shot, all of them based on adenovirus vectors: CanSino (adenovirus 5), J&J (adenovirus 26), and Sputnik Light (adenovirus 26). Sputnik Light is also the first shot of Sputnik V, where it is paired with a vaccine based on adenovirus 5 that has had greater manufacturing/supply problems than the first shot.

Almost all the results I could find are for boosting the J&J vaccine. There is data from Chile for a very small number of people who were boosted after CanSino – 5 with AZ and 100 with Pfizer (Araos 2021). The estimated vaccine effectiveness against from 28 days after that second dose was 52.3% against disease (CI 49-55), 83.7% against hospitalization (CI 77-89), and 95.4% against admission to intensive care (CI 86-99).

There are at least 7 trials comparing boosters for these vaccines to placebo or other vaccines (details in a table at the end of this section), and another with no comparison group – the Sisonke 2 (TOGETHER) study in healthcare workers in South Africa. That’s for the J&J vaccine, as most of the trials are. Some results have been reported for 4 of the comparison trials as well as for Sisonke 2 – all for J&J. There are also results from a study of a second shot for some of the participants in the early phase trials for the single shot. My summaries of these follow.

Study results:

• ENSEMBLE 2 – randomized placebo-controlled trial of 2-dose J&J: There’s only a press release from J&J on interim results so far. The booster shot came 2 months after the first, and the study has 13,836 participants around the world. Vaccine efficacy from 14 days after the booster was reported when only 29% of people had at least 2 months follow-up:
  • Against moderate to severe disease (analogous to “symptomatic disease” in other studies): 75% (CI 55-87);
  • Against moderate to severe disease in the US only: 94% (CI 58-100);
  • Against severe or critical Covid-19 globally: 100% (CI 33-100) (no one in the boosted group vs 8 in the placebo arm).
• NIH Mix and Match Study: The study arm with J&J first-dose had 150 participants. They got a booster of J&J, Moderna, or Pfizer at varying intervals. Researchers reported results for measurements of immune response and reactions. For a cut-off set to correspond with around 90% vaccine efficacy against symptomatic disease*, an mRNA booster after J&J was similar to that for a full mRNA course with mRNA booster was lower. (This wasn’t a randomized trial, so it wasn’t set up to test whether there was a difference.)
  • * post‐boost neutralizing geometric mean IU50/mL levels of >100
• SWITCH trial: 434 healthcare workers in the Netherlands who had had single-shot J&J were randomized to no boost or one of J&J, Moderna, or Pfizer. The researchers reported results for measurements of immune response and reactions. A boost with J&J increased signs of immunity, but not as much as an mRNA booster.
• Sisonke 2: Researchers for this non-comparison trial in South Africa used a test-negative case-control study to estimate vaccine effectiveness of a second dose of J&J given 6-9 months after the first to 69,092 healthcare workers. Adjusted effectiveness estimate against hospitalization rose to 85% (CI 54-95) after 1-2 months. Over 230,000 Sisonke participants got their second J&J shot and no major safety concerns have been reported so far.
• Later boosting of early single-J&J trial participants: Researchers reported measurements of immune response for 137 people in Europe and the US, 6 months after they had participated in phase 1 or 2 trials. They concluded that immune response had stayed “largely stable”, and a low or the same dosage as previously elicited a fast increase in antibodies.

Clinical trials comparing schedules

(Trials in rough chronological order of announcement)

Vaccines	Schedule	Participants	Location(s)	Research phase
J&J	2 doses of J&J	13,836 people	Belgium, Brazil, Colombia, France, Germany, Philippines, South Africa, Spain, UK,content US	Phase 3 trial. Called ENSEMBLE 2 (protocol). Press release results only.
CanSino; ZF2001 (protein subunit)	CanSino followed by ZF2001 or a flu vax as a control group	120 people	China	In phase 4 trial.
ImmunityBio; J&J; Moderna; Pfizer	ImmunityBio vax (injected or oral) as a booster after course of J&J, Moderna, or Pfizer	540 people	US, possibly South Africa	Phase 1 trial.
J&J; Moderna; Pfizer	2 doses Moderna or Pfizer or 1 dose J&J, followed by J&J, Moderna, or Pfizer	458 people	USA	Unrandomized phase 1/2 trial, NIH “Mix and Match Study”. Results, FDA presentation.
J&J; Moderna; Pfizer	J&J single shot, or J&J followed by J&J or mRNA	432 people	Netherlands	Trial. Called SWITCH. Results.
Genexine, Sputnik Light and others	Vaccines in use, including presumably single-shot Sputnik Light, followed by a shot of Genexine DNA vax or placebo	14,000	Indonesia and Argentina	Phase 2/3 trial.
CanSino	CanSino single shot followed by inhaled CanSino vax or placebo	13,000	Not reported	Phase 3 trial. Called SeiHOPE.

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Laboratory studies of response to Delta and Omicron after booster

Summary:

• Based on the vaccine effectiveness studies in previous sections, several boosted vaccines and mixed vaccine schedules have been shown to be very protective against disease and hospitalization caused by Delta and Omicron. And a study of household contacts in Denmark found that people who had a booster had a lower chance of getting infected by, or transmitting, the variants (mostly Pfizer vaccine, some Moderna, very few J&J).
• There have also been at least 38 reports of laboratory studies testing blood samples for ability to react against Omicron and/or Delta that include data on boosted vaccination (all listed below). These also suggest boosted Covid vaccines in their original formulations may still offer protection against harm from these variants, although less than for the original virus.
• Most of these studies test blood samples from people vaccinated with one or more of the 8 most-used vaccines, sometimes in schedules not included in other studies above. Some of the studies include tests of vaccines with no other data in this post:
  • Moderna’s versions adapted for the Beta and Omicron variants (and a multivalent version);
  • A Sputnik Light booster for Sputnik V;
  • Sanofi’s subunit vaccine (including a version adapted for the Beta variant) and the company’s mRNA vaccine; and
  • Medigen’s subunit vaccine (including a version adapted for the Beta variant).

Sources:

Vaccine(s)	Type of study	Variants of Concern	Results
3rd dose of Sinovac’s CoronaVac	Humans, blood tests	Beta, Gamma, Delta	Wang (Sept 5)
3rd dose of Moderna’s vax, either adapted for Beta or original or multivalent (combination of original and adapted in one dose)	Humans, blood tests	Beta, Gamma, Delta	Choi (Sept 15)
3rd dose of Sanofi’s protein subunit vax (original & version adapted for Beta), after doses of that vax or their mRNA vax	Preclinical, non-human primates	Alpha, Beta, Gamma, Delta	Pavot (Sept 21)
2nd or 3rd dose of Medigen’s protein subunit vax adapted for Beta, after dose(s) of original, and 3 doses of original	Preclinical, non-primates	Alpha, Beta, Gamma, Delta	Kuo (Oct 15)
3rd dose of Sinovac’s CoronaVac	Humans, blood tests	Alpha, Beta, Delta	Yue (Oct 19)
3rd dose of Moderna, either adapted for Beta or original	Preclinical, non-human primates	Beta, Delta, Epsilon, Gamma, Iota	Corbett (Oct 21)
3rd dose of Sinopharm’s Beijing vax	Humans, blood tests	Beta, Delta, Lambda	Ju (Nov 10)
3rd dose of Pfizer	Humans, blood tests	Delta, Omicron	Basile (Dec 13)
2 or 3 doses of Pfizer, 1 dose of J&J, or 1 or 2 doses of Moderna	Humans, blood tests	Omicron	Schmidt (Dec 13)
2-dose course of Moderna followed by half-dosage Moderna	Humans, blood tests	Beta, Omicron	Doria-Rose (Dec 20)
3rd dose of Moderna in half and full dosages, original, adapted for Beta or Omicron, or multivalent	Humans, blood tests	Omicron	Moderna press release (Dec 20)
2-dose course of Sputnik V (Sputnik Light [rAd26-S] followed by second Sputnik V vaccine [rAd5-S]), followed by another dose of Sputnik Light	Humans, blood tests	Omicron	Dolzhikova (Dec 21)
3rd dose of Moderna or Pfizer in people with multiple sclerosis on anti-CD20 treatment	Humans, blood tests	Delta, Omicron	Madelon (Dec 21)
2 doses of Novavax followed by a 3rd dose	Humans, blood tests	Delta, Omicron	Novavax press release (Dec 22)
3 doses of Pfizer	Humans, blood tests	Delta, Omicron	Hoffmann (Dec 23)
3rd dose of Pfizer	Humans, blood tests	Delta, Omicron	Ariën (Dec 24)
2 or 3 doses of Pfizer	Humans, blood tests	Delta, Omicron	Lusvarghi (Dec 28)
2-dose course of AZ, Moderna or Pfizer or single-shot J&J; dose of Pfizer after 2-dose Moderna or single-shot J&J	Humans, blood tests	Beta, Delta, Omicron	GeurtsvanKessel (Dec 29)
2-dose course of CoronaVac followed by a dose of Pfizer	Humans, blood tests	Delta, Omicron	Perez-Then (Dec 29)
2-dose course of AZ, Moderna or Pfizer; 3rd dose of Pfizer after AZ, Pfizer or Moderna 2-course; 3rd dose of Moderna after AZ 2-course; Moderna or Pfizer dose after single-shot J&J	Humans, blood tests	Omicron	De Marco (Dec 30)
2-dose course of Pfizer followed by 3rd dose of J&J or Pfizer	Humans, blood tests	Omicron	Tan (Dec 30)
2-dose courses of Pfizer or Moderna or 3rd dose of Moderna or Pfizer	Humans, blood tests	Beta, Omicron	Carreño (Dec 31)
2-dose course of Moderna or Pfizer or single-shot J&J; booster dose of Moderna or Pfizer	Humans, blood tests	Delta, Omicron	Saharia (Jan 1)
3-dose course of AZ or Pfizer	Humans, blood tests	Alpha, Beta, Gamma, Delta, Omicron	Dejnirattisai (Jan 3)
2-dose course of AZ, Moderna, or Pfizer; 2-dose course of AZ or Pfizer with 3rd dose of Moderna or Pfizer	Humans, blood tests	Alpha, Delta, Omicron	Willett (Jan 3)
2-dose courses of AZ, Moderna and/or Pfizer with 12-week interval; 2-dose course of Pfizer with short interval with 3rd dose of Moderna or Pfizer	Humans, blood tests	Delta, Omicron	Belik (Jan 5)
2-dose courses of Moderna or Pfizer or single-shot J&J; additional mRNA vax (as 3rd after mRNA or 2nd after J&J), either homologous or heterologous	Humans, blood tests	Delta, Omicron	Garcia-Beltran (Jan 6)
2-dose courses of CoronaVac or Sinopharm Beijing with 3rd dose of either Moderna or Pfizer	Humans, blood tests	Beta, Delta, Omicron	Zuo (Jan 6)
2-dose courses of AZ or Pfizer with third dose of Pfizer	Humans, blood tests	Delta, Omicron	Faustini (Jan 8)
1 to 3 doses of Moderna or Pfizer	Humans, blood tests	Beta, Delta, Omicron	Banerjee (Jan 13)
2-dose course of Sinopharm Beijing; 3-dose course of Sinopharm Beijing or 3rd dose of ZF2001	Humans, blood tests	Omicron	Wang (Jan 15)
2-dose course of Moderna or Pfizer with 3rd dose of Moderna or Pfizer	Humans, blood tests	Omicron	Jergovic (Jan 16)
3-dose course of Pfizer	Humans, blood tests	Beta, Delta, Omicron	Muik (Jan 18) (by BioNTech/Pfizer)
2-dose course of CoronaVac or AZ, or 3-dose course of AZ	Human, blood tests	Alpha, Beta, Delta, Omicron	Suntronwong (Jan 18)
3-dose courses of Moderna or Pfizer	Human, blood tests	Beta, Delta, Omicron	Walls (Jan 19)
3-dose course of Pfizer	Human, blood tests	Omicron	Wu (Jan 19)
2- and 3-dose courses of Pfizer	Human, blood tests	Omicron	Xia (Jan 22)
2-dose courses of AZ or Pfizer, 3rd dose Pfizer in people with cancer	Human, blood tests	Omicron	Fendler (Jan 25)

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Fourth doses

Summary:

• Other than a small pilot within another trial for people with compromised immune systems, I could find no randomized trials underway of fourth doses of Covid vaccine. A study is underway in Israel for the Pfizer vaccine – but I could find no public details of the study’s design.
• I found 3 published reports of measurements of immune system response in immunocompromised people who received an mRNA fourth dose in France.
• At least 14 countries are recommending fourth doses for at least some people with compromised immune systems, at least 4 of which are extending fourth doses to older people and some others.

Background notes and sources:

The WHO’s interim statement on boosters stresses the need to consider global equity, virus evolution, and the prolongation of the epidemic alongside evidence of benefit to individuals and protection of healthcare systems (December 2021). WHO considers a third dose for people with compromised immune systems as part of the primary vaccination series for them, not “a booster”. They stress the need for country’s decisions to be informed by evidence. The WHO’s director has called for a moratorium on extending booster programs until there is a minimum level of vaccination globally:

90% of high-income countries have reached the 10% #COVID19 vaccination target; 70%+ have reached the 40% target. Not 1 low-income country has reached either target. This is why I call for a booster moratorium extension until the end of 2021.https://t.co/DGXyAJvD5i #VaccinEquity pic.twitter.com/fU8jejdR0K

— Tedros Adhanom Ghebreyesus (@DrTedros) September 8, 2021

We've updated our end-of-year projections for global vaccination targets.

We now project that 116 countries (including the US, Indonesia, Pakistan, Nigeria, Russia) are not on track to have fully vaccinated 70% of their population by mid-2022.

Read more: https://t.co/K7QxnfwYTV pic.twitter.com/ipS85D50Xp

— Edouard Mathieu (@redouad) January 13, 2022

There isn’t data from randomized trials to test the results of having 4 doses. The level of risk exposure to Covid-19 and vaccine effectiveness is very different for people with compromised immune systems, though. The following section in this post covers randomized trials for them – but only 1 of those includes fourth doses, and that part is only a pilot study. So it isn’t designed to answer questions about fourth dose effectiveness.

However, some reports of outcomes have been published for people with compromised immune systems – all from France – with fourth doses of Moderna or Pfizer vaccine:

• 92 people with kidney transplants after a weak response to their third (Caillard 2021)
• 67 people with kidney transplants after a weak response to their third (Benotmane 2021)
• 37 people with kidney transplants in France given a fourth dose of Moderna or Pfizer (Kamar 2021)

A study is reportedly underway in Israel at Sheba Medical Center under the auspices of the Ministry of Health. Ultimately intended to include 6,000 participants according to unconfirmed media reports, results showing an increase in antibodies in the first week after a fourth dose in 154 healthcare workers who had low antibodies reportedly led to the decision to widen access to fourth doses. I couldn’t find a detailed report of these results. There are media reports that antibodies were 5 times as high, which isn’t informative in a group of people who had low antibodies to start with: we don’t know their antibody levels before the extra dose, or how many of the 154 people reached an adequate level of antibodies, for example. Later media stories, still without a release data, indicate that the fourth dose wasn’t proving to be very effective at preventing Omicron infection in that group (and don’t mention an expanded study).

On January 24, the Ministry released a statement with interim data from a comparison of about 400,000 people over 60 receiving fourth doses with about 600,000 with a third dose 4 or more months previously. They reported that the rate of serious illness was 3 times as high for those without the fourth dose, and double the infection rate: it was a week’s data, without data on the rates themselves, so we don’t know what how big this difference actually was – and the uncertainty around the estimates is high. (Thanks to Yaron Kaplan for translation.)

Several countries have begun to offer fourth vaccine doses to restricted groups of people, including (in alphabetical order):

• Australia: for severely immunocompromised people.
• Belgium: for the immunocompromised.
• Canada: for moderately or severely immunocompromised people.
• Chile: for the immunocompromised, healthcare professionals, and for people over 55 from February 7.
• Cuba: nationwide (apparently except for people who have recovered from Covid-19) – reportedly close to half the country has had a fourth dose. (Note: the primary course of Cuban vaccines is 3 doses, so the fourth dose is the first booster.)
• Denmark: for the highly vulnerable.
• Dominican Republic: for the immunocompromised, medically vulnerable, healthcare and pharmaceutical personnel, and people over the age of 60 – and then more widely, 6 months after the third dose.
• France: for the immunocompromised.
• Greece: for the immunocompromised.
• Israel: for the immunocompromised, and from January 2, healthcare workers and people over 60 as well. Health Ministry advisory panel recommended extension to all adults – expected to be introduced.
• Spain: for the immunocompromised (announced January 13).
• UK: for the immunosuppressed.
• US: some moderately or severely immunocompromised.
• Uruguay: for the immunocompromised from the second quarter of 2022.

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People with compromised immune systems

Summary:

• Response to vaccines varies greatly for people with compromised immune systems, though it varies from not at all, to a great deal for different groups, depending on factors like particular forms of immunosuppressive medication is being used.
• Vaccine effectiveness is therefore often reduced for people with compromised immune systems. On average, for AZ, Moderna, and Pfizer vaccines, it could be lower by 10 or 20 percentage points for infection or disease (based on 2 community impact studies).
• A variety of approaches are being tried and studied for improving immunity in people at risk from immunocompromise:
  • Additional doses of vaccine;
  • Mixed vaccine schedules;
  • Temporarily modifying or discontinuing immunosuppressive treatment around vaccination;
  • Prophylactic (preventive) monoclonal antibodies when a person has a poor response (background here and here);
  • Exploring whether some treatments related to the condition, not Covid, are protective;
  • Comparing the effectiveness of vaccines to see if any are preferable; and
  • At least one vaccine has been developed specifically for people with cancer.
• It’s early days for evidence from trials on these interventions. There are at least 19 randomized trials underway, involving 6 vaccines (mostly Moderna and Pfizer). These trials are mostly testing third doses (or second for single-shot J&J) and/or mixing vaccines or temporarily discontinuing treatment.
• Only 1 of these trials includes a group getting a fourth dose, and it’s possible in another. Early reports of fourth doses for immunocompromised people in France show improved measurements of immune response in many people who had inadequate or no discernible response to 3 doses, but not all.
• Results have been reported for 4 trials, with the authors concluding there was evidence of benefit and safety for each. (I haven’t evaluated these trials, or the non-randomized studies on the same questions.) The trials are:
  • temporary reduction of methotrexate in people with rheumatoid arthritis around CoronaVac vaccination (138 participants);
  • third dose either of the same mRNA vaccine or AZ for people on rituximab who did not seroconvert after 2 doses of Moderna or Pfizer vaccines (60 participants);
  • third dose of Moderna vaccine in people with solid organ transplants (120 participants); and
  • third dose of vaccine (J&J, Moderna, or Pfizer) for people with kidney transplants who had not developed spike protein antibodies after 2 doses of Moderna or Pfizer vaccines (197 participants).

Background notes and sources:

In previous posts, I had been cataloging studies reporting on responses to vaccination for people with compromised immune systems. There are now far too many of these to keep up with in that way: it’s both too difficult to be sure that you’ve found all the most critical datasets and studies, and because there are so many, they need to be distilled – which requires considerable effort and disease/medicine content expertise. To give you an idea of how complex this is, at one point, studies of responses to the first dose of a vaccine in people on dialysis reported ranged from 18 to 41% (with an outlier at 84%) – and that was back in April 2021.

Outcomes depend on a complicated variety of factors, including health problems, specific treatments, as well as how response to vaccine is measured and when (response can be slower). And all of that can vary from vaccine to vaccine, though the underlying issue – weaker overall response for many people – holds for all vaccines. As a Etemadifar and colleagues put it in a report on multiple sclerosis and the Sinopharm Beijing vaccine: “same story, different vaccine”. And Carr and colleagues, studying Omicron and people on hemodialysis, conclude that the number of doses needed may differ because of variants.

Then there are issues related to design of studies and accessible data and patients that add complexity: some studies will have more biases baked in than others. All of that has to be taken into account when you start to consider varying results. For my summary, I relied particularly on these 2 community impact studies, which include estimates of vaccine effectiveness for people with compromised immune systems:

• Vaccine effectiveness against symptomatic Covid-19 for up to 2 months after the second dose of 60.0% (CI -64-90) for the AZ vaccine, and 59.6% (CI 18- 80) for the Pfizer vaccine. From a nationwide study of people at clinical risk from Covid based on data from general practice in England and Covid testing data (Whitaker 2022); and
• Vaccine effectiveness against infection with Delta and Omicron after a third dose of Moderna vaccine of 72.2% (CI 12-91) compared to 95.7% in non-immunocompromised people (CI 94-97). From a test-negative case-control study from Kaiser Permanente Southern California (Tseng 2022).

There’s another large-scale observational study tackling these questions on immune response in the UK, called the OCTAVE trial – you can see their first early results here, and there’s a page that will keep track of lay summaries of study materials and results from OCTAVE, too.

I am still trying to keep track of the recently emerging studies on fourth doses: the small handful I’ve found are listed in the section on fourth doses above. Mostly, though, I’m now concentrating on evidence from randomized trials for interventions to improve outcomes for people with compromised immune systems. I’ve gathered randomized trials I’ve found in the table below, whether or not they have results. It’s very early days for this evidence. A special mention, though, to the UK’s MELODY study. Researchers aim to recruit 35,000 people with compromised immune systems after a third vaccine dose, and follow them for 6 months: people with solid organ transplants, blood cancer, or on immunosuppressive medication for rare autoimmune diseases.

Randomized trials comparing interventions for people with compromised immune systems

(Trials in chronological order of announcement)

Vaccines	Schedule	Participants	Location(s)	Research phase
CoronaVac	Randomized to not take the 2 doses of methotrexate due after vax or continue treatment as usual	138 people with stable rheumatoid arthritis using methotrexate	Brazil	Results.
Moderna, Pfizer	Head-to-head trial of 2-dose courses of Moderna vs Pfizer	700 people with HIV or transplants	Switzerland	Phase 3 (protocol).
AZ, Moderna, Pfizer	2 doses of Moderna or Pfizer vax, randomized to either a 3rd dose of the same vax or a dose of AZ	60 people on rituximab who did seroconvert after 2 doses of mRNA vax	Austria	Phase 2. Results.
Moderna	2 doses of Moderna a month apart, randomized to either a 3rd dose 2 months later or placebo	120 people with solid organ transplants	Canada	Phase 4. Results.
J&J, Moderna, Pfizer	2 doses of Moderna or Pfizer vax, randomized to a 3rd dose of J&J, Moderna, or Pfizer. (With pilot study of 4th dose.)	197 people with kidney transplants who had not developed spike antibodies after 2 doses of mRNA vax	Austria	Phase 4. Results.
Pfizer	Randomized to reduction of mycophenolic acid plus 3rd dose of Pfizer vax or 3rd dose only	504 people with kidney transplants with inadequate humoral response after 2 doses of Pfizer vax	Israel	Phase 4. Called BECAME (protocol).
AZ, Moderna, Novavax, Pfizer	Randomized to a 3rd dose of Moderna, Novavax, or Pfizer	1,200 people with compromised immune systems who had a poor response to AZ or Pfizer vaxes	UK	Phase 3. Called OCTAVE DUO.
City of Hope, J&J*, Moderna, Pfizer	Randomized to 2 doses 28 days apart of either of City of Hope vax or a US-authorized vax (* not clear if J&J included)	240 people with blood cancer and stem cell transplant or cellular therapy	US	Phase 2.
J&J, Moderna, Pfizer	2-dose course of Moderna or Pfizer, or single-shot J&J, randomized to a dose of 1 of the 3 vaccines, with or without stopping some immunosuppressive treatments before and shortly after vaccination	600 people with any of 5 autoimmune diseases (including rheumatoid arthritis and MS), on immunosuppressive treatment, and with suboptimal response to any of the 3 vaccines	US	Phase 2.
AZ, Moderna, Pfizer	Randomized to 2-week break from methotrexate or not while receiving booster dose	560 people with autoimmune disease (including rheumatoid arthritis) who have had methotrexate for at least 3 months	UK	Phase 3/4. Called VROOM.
Moderna, Pfizer	2 doses of Moderna or Pfizer vax, randomized to a third dose of the same or the other vax.	300 people with kidney transplants or on dialysis who had a poor response to 2 doses of mRNA vax	Canada	Phase 2/3. Called Boost Kidney.
J&J, Moderna, Pfizer	2-dose course of Moderna or Pfizer, or single-shot J&J, followed by dose 3 of Moderna	171 people with hematological (blood) cancers who had a poor response to any of the 3 vaccines	US	Phase 2 (unrandomized).
J&J, Moderna	People on triple immunosuppressive therapy: randomized to 3rd dose of Moderna, with or without discontinuation of mycophenolate mofetil (MMF) or mycophenolic acid (MPA); others randomized to 3rd dose of Moderna, 3rd and 4th dose of Moderna, or J&J	460 people with kidney transplants who did not seroconvert after 2 doses of Moderna	Netherlands	Phase 4. Called RECOVAC.
J&J, Moderna	Head-to-head trial of J&J vs Moderna for 3rd dose	386 people with solid organ transplants who have had 2 doses of Moderna vax	Spain	Phase 3. Called REIN-TX.
J&J, Pfizer	Head-to-head trial of J&J vs Pfizer for 3rd dose	200 people with solid organ transplants who have had 2 doses of Pfizer vax	US	Phase 3.
Moderna, Pfizer	Randomized to no change in immunosuppression for 3rd dose of mRNA vax or to reduction in dose of mycophenolate mofetil/mycophenolic acid (MMF) or azathioprine before and after mRNA vax	50 people with kidney transplants	US	Phase 4. Called ADIVKT.
J&J, Moderna, Pfizer	Randomized to homologous booster (2nd dose for J&J, 3rd dose for Moderna and Pfizer) or heterologous booster (2nd dose of mRNA if originally J&J, 3rd dose of J&J if originally mRNA)	60 people with multiple sclerosis	US	Phase 4.
CoronaVac	2 doses of CoronaVac alone or 3 doses of CoronaVac or 2 doses of CoronaVac plus a double-dosage 3rd shot	240 people with pulmonary tuberculosis	China	Phase 4.
J&J after Moderna or Pfizer	People with low protein spike test after 2 or 3 doses of Moderna or Pfizer, randomized to a dose of J&J (with or without change in immunosuppression medication); if response still low, randomized to a further J&J dose, again with or without medication change	1,200 people with kidney transplants	US	Phase 3.

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~~~~

All my Absolutely Maybe Covid-19 vaccine posts

All previous Covid-19 posts at Absolutely Maybe

My posts at The Atlantic, at WIRED, and debunking posts at my personal website.

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.

The cartoons are my own (CC BY-NC-ND license). (More cartoons at Statistically Funny.)

Correction, February 7, 2022: The authors and link to the effectiveness study for Sputnik V had been missing (Barchuk 2022), and the original said the study was done in Moscow, not St Petersburg.

Update, February 8: Added additional trial registered for people with immunocompromise.

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Key to vaccine names and identifiers

Bold = the identifier used in this post

Commonly used name(s)	Main manufacturer	Technical identifier used by manufacturers
Abdala	Center for Genetic Engineering and Biotechnology (CIGB) Cuba	CIBG-66I
AZ, Vaxzevria, or Covishield (version by Serum Institute of India)	AstraZeneca (AZ) England	ChAdOx1 nCoV-19, ChAdOx1-S, AZD1222
Covaxin	Bharat Biotech India	BBV152
Pfizer or Comirnaty	BioNTech(BNT) and Pfizer Germany and US	BNT162b
CanSino or Convidicia	CanSino Biologics China	Ad5-nCov
	City of Hope Medical Center (developed with NCI, the NIH’s National Cancer Institute) US	COH04S1
CureVac	CureVac Germany	CVnCoV/CV2CoV
Soberana-1 Soberana-2 Soberana-Plus	Finlay Institute for Vaccines Cuba	Finlay-Fr-1 Finlay-Fr-2 Finlay-Fr-1A
Sputnik V and Sputnik Light	Gamaleya Research Institute of Epidemiology and Microbiology Russia	Sputnik V is Gam-COVID-vac, with 2 components: rAd26-S (Sputnik Light) and rAd5-S
	Genexine and SL VaxiGen South Korea	GX-19
	Gritstone Bio (developed with NIH’s NIAID) US	ChAdV68-S/-TCE GRT-R910 – saMRNA: SAM-LNP-S/-TCE Note: ChAd = Chimpanzee Adenovirus SAM/saMRNA = self-amplifying mRNA S = Spike TCE = T cell epitopes
Covac1	Imperial College London (Imperial College saRNA) England	LNP-nCoVsaRNA
	Institute of Medical Biology, Chinese Academy of Medical Sciences (IMBCAMS) China
J&J or Janssen	Janssen/Johnson & Johnson (J&J) Belgium and US	Ad26.COV2-S
Moderna or Spikevax	Moderna (developed with NIH’s NIAID) US	mRNA-1273
Novavax or Nuvaxovid	Novavax US	NVX-CoV2373
	Shenzhen-Kangtai Biotechnology and Beijing Minhai Biotechnology China	KCONVAC
Sinopharm	Sinopharm, Beijing Institute of Biological Products China	BBIBP-CorV
	Sinopharm, National Vaccine and Serum Institute (NVSI) (Sinopharm recombinant NVSI) China	NVSI-06-07
CoronaVac	Sinovac China
	Stemirna Therapeutics China	mRNACOVID-19
Valneva	Valneva France	VLA2001
	Westvac Bio China	Recombinant COVID-19 Vaccine (Sf9 Cells)
	Anhui Zhifei Longcom Biopharm (developed with Chinese Academy of Sciences) China	ZF2001
	Zydus Cadila India	ZyCov-D

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Notes on vaccine trial records and use

Source records are in my public Zotero collection of Covid-19 vaccines that have any published preclinical or clinical results (or preprints), or that are in phase 3 trial (more details below, including how to use it) for general populations. It also includes the matched control studies I featured in a couple of posts. Please let me know if you find any I’ve missed! On January 26, the collection included 1,255 entries:

• 275 vaccines/groups with published or posted results;
• 35 records for trial protocols, for 11 vaccines and Com-COV (including 1 vaccine with additional protocol versions in a clinical study report package);
• 347 preclinical preprints/articles;
• 166 preclinical or serum studies of vaccines and new variants;
• 423 trial registry entries associated with these vaccines;*
• 165 clinical trial preprints*/articles/letters:
  • 46 for phase 1 trials;
  • 32 for phase 1/2 trials;
  • 34 for phase 2 trials;
  • 7 combined reports of phase 2/3 trials;
  • 3 combined reports of phase 1 to 3 trials (including a submission to regulatory agency);
  • 28 reports from phase 3 trials (for 15 vaccines, including 2 with 2 vax components);
  • 7 reports on phase 4 trials;
  • 4 author replies to letters to the editor about their publications (for 3 vaccines);
  • 4 errata notices for 4 vaccines (including 1 with 2 vax components);
• 54 trial efficacy readouts (press releases or website);
• 30 documents reporting on or reviewing phase 3 data at regulatory agencies;
• 4 full clinical study report packages;
• 4 termination notices, for 4 vaccines (all but one of which have other records in this collection);
• 24 reports of 23 featured community impact studies, for 5 vaccines (This was only done for a short time);
• Records for 21 vaccines tagged as trials including children/teenagers;
• Records for 7 vaccines tagged as adapted for variant.

* May not include all entries where a trial is registered in multiple registers, a preprint is posted to multiple servers. There can be multiple records for one study if I happened to pick up that a published version is substantially different to a preprint.

Notes on the collection 

This is a publicly accessible collection I update regularly. It includes any Covid-19 vaccine with published preclinical, clinical trial results, or trial protocols. If a phase 3 trial starts (or is about to) without any prior publications for the vaccine, the vaccine is added. Once a vaccine is in the collection, clinical trial register entries for that vaccine are also added.

When trials are registered in more than clinical trials registry, the multiple records may or may not be in the collection: If I have located a record in ClinicalTrials.gov, I do not hunt for additional registrations. For my own convenience in keeping an overview of vaccine progress, when preprints appear later in journals, I replace the original record with the journal article. Preprints may also be uploaded to multiple preprint servers: rather than check if versions have differed, I keep the first preprint in the collection (sometimes over-written with updates in the same server), unless I saw that a version that seems markedly different.

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