A review of COVID-19 vaccine effectiveness

A new study published on the medRxiv* preprint server systematically reviews vaccine efficacy and vaccine effectiveness (VE) of coronavirus disease 2019 (COVID-19) vaccines. This study reviews data including asymptomatic infection, infection, symptomatic disease, hospitalization, and death after vaccination. It also examines data for full and partial immunization courses, as well as VE against circulating SARS-CoV-2 variants of concern (VoCs).

Study:  A systematic review of COVID-19 vaccine efficacy and effectiveness against SARS-CoV-2 infection and disease. Image Credit: malazzama / Shutterstock.com

COVID-19 vaccination

The World Health Organization (WHO) declared COVID-19 a global pandemic on March 11, 2020. Since then, the causative agent, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has continued to spread globally at an alarming rate. The clinical severity of COVID-19 and its adverse effects on public health have resulted in the emergency use authorization (EUA) of over 20 COVID-19 vaccines in various countries around the world.

Several studies have shown that COVID-19 vaccines provide a high degree of protection against infection and disease. However, precise estimates vary, with studies differing in various factors including their design, outcomes measured, dosing regime, location, and circulating virus strains.

Several clinical studies have studied the safety and efficacy of these COVID-19 vaccines. They have been shown to protect against severe infection and death in fully vaccinated individuals.

Vaccine efficacy, which is calculated from randomized clinical studies, refers to the vaccine performance under ideal conditions. Comparatively, VE is calculated from observational studies and refers to the performance of the vaccine in a wider population or real-world data. In this study, the researchers use the abbreviation VE to refer to both, vaccine efficacy and vaccine effectiveness.

Several factors have contributed to the differences in VE estimations in different studies. It is important to observe the evidence for COVID-19 VE and understand the varied factors resulting in heterogenous VE data. This will help policy-makers to design effective COVID-19 vaccination campaigns.

Study design

This study provides a systematic review of COVID-19 vaccines as of August 2021.

The researchers looked for clinical trial efficacy results published in peer-reviewed scientific journals, preprint servers like medRxiv and bioRxiv, government public health agency websites, news articles, on the vaccine manufacturers’ websites, and in the databases of medical regulatory agencies like the United States Food and Drug Administration (FDA) or the European Medicines Agency (EMA).

Searches were conducted using the vaccine’s brand, trade, or research name. Through these searches, the researchers extracted VE data against any stage of infection.

VE data

The researchers included VE data from Phase III clinical trials for 13 vaccines within the WHO Emergency Use Listing evaluation process and real-world VE data for 5 vaccines with observational studies. The 13 vaccines included Oxford/AstraZeneca’s AZD1222, Bharat Biotech’s BBV152, BioCubaFarma’s Abdala, Soberano 2, and Soberano 2 Plus, Gamaleya Institute’s Sputnik V, Janssen’s Ad26.COV2.S, Moderna’s mRNA-1273, Novavax's NVX-CoV2373, Pfizer/BioNTech’s BNT162b2, Sinopharm Beijing’s BBIBP-CorV, Sinopharm Wuhan’s WIBP-CorV, and Sinovac’s CoronaVac. The vaccine efficacy of these vaccines against symptomatic COVID-19 ranged from 66-95%.

The researchers identified 58 real-world vaccine effectiveness studies covering five vaccines that included the BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), Ad26.COV2.S (Janssen/Johnson & Johnson), ChAdOx1 nCoV-19 (Oxford-AstraZeneca), and CoronaVac (Sinovac) vaccines. These observational studies provided VE data that was not available or estimated with high uncertainty in clinical studies. The data included effectiveness against more severe outcomes, any SARS-CoV-2 infection, asymptomatic infection, specific circulating SARS-CoV-2 variants of concern, and after only a single dose of two doses of the vaccine.

Vaccine effectiveness estimates were high for full vaccine courses and overlapped with the efficacy data from clinical trials. All studies indicate that vaccines are more efficacious at preventing severe infection or death compared to symptomatic COVID-19.

The degree to which the vaccine prevented any infection, and the degree to which partial courses prevented infection or disease, varied significantly by the vaccine administered.

Most vaccines provided high levels of protection against most SARS-CoV-2 variants of concern against severe outcomes. Some studies also provided evidence of slight reductions in VE for infection or mild disease with the Beta and Delta strains. There was not much data on VE against death or asymptomatic infection and against the Gamma variant.

VE components not addressed in this study

Individuals with prior infection demonstrate robust immunity after a single vaccine dose. This can affect the VE estimations; however, this factor was not discussed in the current study.

There is a reduction in VE over a period of time. Most studies included in this review were conducted shortly after vaccination. New studies that examine the waning are lacking.

Thirdly, many COVID-19 vaccines are multi-dose vaccine regimens; thus, the time interval between the first dose and follow-up doses may affect VE. In real-world data, this interval varies among individuals due to policies in certain countries. Some countries have also adopted flexible policies allowing for “mixing and matching” of doses. Taken together, these differences in dosing regimens, although they were not discussed in the current study, can also affect VE.


Data from different studies demonstrate that COVID-19 vaccines provide high levels of protection against severe disease and death. They also protect against infection and mild disease, even for major SARS-CoV-2 VoCs.

While vaccination protects against severe COVID-19 and death at the individual level, it also helps in reducing transmission of the virus at the population level.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Dr. Shital Sarah Ahaley

Written by

Dr. Shital Sarah Ahaley

Dr. Shital Sarah Ahaley is a medical writer. She completed her Bachelor's and Master's degree in Microbiology at the University of Pune. She then completed her Ph.D. at the Indian Institute of Science, Bengaluru where she studied muscle development and muscle diseases. After her Ph.D., she worked at the Indian Institute of Science, Education, and Research, Pune as a post-doctoral fellow. She then acquired and executed an independent grant from the DBT-Wellcome Trust India Alliance as an Early Career Fellow. Her work focused on RNA binding proteins and Hedgehog signaling.


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