Key messages

– Most vaccines reduce, or probably reduce, the number of people who get COVID-19 disease and severe COVID-19 disease.

– Many vaccines likely increase number of people experiencing events such as fever or headache compared to placebo (sham vaccine that contains no medicine but looks identical to the vaccine being tested). This is expected because these events are mainly due to the body's response to the vaccine; they are usually mild and short-term.

– Many vaccines have little or no difference in the incidence of serious adverse events compared to placebo. 

– There is insufficient evidence to determine whether there was a difference between the vaccine and placebo in terms of death because the numbers of deaths were low in the trials.

– Most trials assessed vaccine efficacy over a short time, and did not evaluate efficacy to the COVID variants of concern. 

What is SARS-CoV-2 and COVID-19?

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is the virus that causes COVID-19 disease. Not everyone infected with SARS-CoV-2 will develop symptoms of COVID-19. Symptoms can be mild (e.g. fever and headaches) to life-threatening (e.g. difficulty breathing), or death.

How do vaccines prevent COVID-19?

While vaccines work slightly differently, they all prepare the body's immune system to prevent people from getting infected with SARS-CoV-2 or, if they do get infected, to prevent severe disease.

What did we want to find out?

We wanted to find out how well each vaccine works in reducing SARS-CoV-2 infection, COVID-19 disease with symptoms, severe COVID-19 disease, and total number of deaths (including any death, not only those related to COVID-19).

We wanted to find out about serious adverse events that might require hospitalization, be life-threatening, or both; systemic reactogenicity events (immediate short-term reactions to vaccines mainly due to immunological responses; e.g. fever, headache, body aches, fatigue); and any adverse events (which include non-serious adverse events).

What did we do? 

We searched for studies that examined any COVID-19 vaccine compared to placebo, no vaccine, or another COVID-19 vaccine.

We selected only randomized trials (a study design that provides the most robust evidence because they evaluate interventions under ideal conditions among participants assigned by chance to one of two or more groups). We compared and summarized the results of the studies, and rated our confidence in the evidence based on factors such as how the study was conducted.

What did we find? 

We found 41 worldwide studies involving 433,838 people assessing 12 different vaccines. Thirty-five studies included only healthy people who had never had COVID-19. Thirty-six studies included only adults, two only adolescents, two children and adolescents, and one included adolescents and adults. Three studied people with weakened immune systems, and none studied pregnant women.

Most cases assessed results less than six months after the primary vaccination. Most received co-funding from academic institutions and pharmaceutical companies. Most studies compared a COVID-19 vaccine with placebo. Five evaluated the addition of a 'mix and match' booster dose.

Main results 

We report below results for three main outcomes and for 10 World Health Organization (WHO)-approved vaccines (for the remaining outcomes and vaccines, see main text). There is insufficient evidence regarding deaths between vaccines and placebo (mainly because the number of deaths was low), except for the Janssen vaccine, which probably reduces the risk of all-cause deaths. 

People with symptoms

The Pfizer, Moderna, AstraZeneca, Sinopharm-Beijing, and Bharat vaccines produce a large reduction in the number of people with symptomatic COVID-19.

The Janssen vaccine reduces the number of people with symptomatic COVID-19.

The Novavax vaccine probably has a large reduction in the number of people with symptomatic COVID-19.

There is insufficient evidence to determine whether CoronaVac vaccine affects the number of people with symptomatic COVID-19 because results differed between the two studies (one involved only healthcare workers with a higher risk of exposure).

Severe disease

The Pfizer, Moderna, Janssen, and Bharat vaccines produce a large reduction in the number of people with severe disease.

There is insufficient evidence about CoronaVac vaccine on severe disease because results differed between the two studies (one involved only healthcare workers with a higher risk of exposure).

Serious adverse events

For the Pfizer, CoronaVac, Sinopharm-Beijing, and Novavax vaccines, there is insufficient evidence to determine whether there was a difference between the vaccine and placebo mainly because the number of serious adverse events was low.

Moderna, AstraZeneca, Janssen, and Bharat vaccines probably result in no or little difference in the number of serious adverse events. 

What are the limitations of the evidence?

Most studies assessed the vaccine for a short time after injection, and it is unclear if and how vaccine protection wanes over time. Due to the exclusion criteria of COVID-19 vaccine trials, results cannot be generalized to pregnant women, people with a history of SARS-CoV-2 infection, or people with weakened immune systems. More research is needed comparing vaccines and vaccine schedules, and effectiveness and safety in specific populations and outcomes (e.g. preventing long COVID-19). Further, most studies were conducted before the emergence of variants of concerns.

How up to date is this evidence?

The evidence is up to date to November 2021. This is a living systematic review. Our results are available and updated bi-weekly on the COVID-NMA platform at covid-nma.com.