A Systematic Review of Coronavirus Disease 2019 Vaccine Efficacy and Effectiveness Against Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Disease

Abstract

Billions of doses of coronavirus disease 2019 (COVID-19) vaccines have been administered globally, dramatically reducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) incidence and severity in some settings. Many studies suggest vaccines provide a high degree of protection against infection and disease, but precise estimates vary and studies differ in design, outcomes measured, dosing regime, location, and circulating virus strains. In this study, we conduct a systematic review of COVID-19 vaccines through February 2022. We included efficacy data from Phase 3 clinical trials for 15 vaccines undergoing World Health Organization Emergency Use Listing evaluation and real-world effectiveness for 8 vaccines with observational studies meeting inclusion criteria. Vaccine metrics collected include protection against asymptomatic infection, any infection, symptomatic COVID-19, and severe outcomes including hospitalization and death, for partial or complete vaccination, and against variants of concern Alpha, Beta, Gamma, Delta, and Omicron. We additionally review the epidemiological principles behind the design and interpretation of vaccine efficacy and effectiveness studies, including important sources of heterogeneity.

Keywords: COVID-19; SARS-CoV-2; systematic review; vaccine effectiveness; vaccine efficacy.

Figure 1.

Local context of Phase 3 clinical trials of coronavirus disease 2019 (COVID-19) vaccines. For each country, the time period (2020-2021) during which outcomes were observed during each vaccine trial is shaded gray. For each 2-week period, the average daily incidence of reported cases is shown (height of bars) [225]. The contribution of each major variant of concern to total case counts is estimated from the reported fraction of sequenced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) samples belonging to that strain (fill color) [226]. Figure includes only vaccine trials described in published or preprint reports, trial sites with at least 10 000 individuals from the general adult population, and countries regularly reporting SARS-CoV-2 lineages to the GISAID database.

Figure 2.

Vaccine efficacy against symptomatic coronavirus disease 2019 (COVID-19), from Phase 3 clinical trials. Each efficacy value is for the complete vaccine course (1 dose for Ad26.COV2.S/Janssen and Ad5-nCoV/CanSinoBio, 3 doses for BioCubaFarma/Abdala and Soberana02+/BioCubaFarma, and 2 doses for all others). Two vaccines which withdrew from the World Health Organization Emergency Use Listing evaluation process but completed Phase 3 trials were not included (CureVac’s mRNA vaccine CVnCoV, reporting 48% efficacy [224], and Kazakhstan RIBSP’s inactivated virus vaccine QazCovid-in, reporting 82% efficacy [227]).

Figure 3.

Vaccine efficacy and effectiveness estimates for BNT162b2, a 2-dose mRNA vaccine developed by Pfizer/BioNTech. (A) Efficacy and/or effectiveness against death, severe disease, or symptomatic disease. (B) Efficacy and/or effectiveness against any or asymptomatic infection. Estimates are colored by the viral variant against which the vaccine efficacy or effectiveness value was measured. Solid markers are estimates from randomized clinical trials (efficacy values), and open markers are estimates from observational studies (effectiveness values). The source of each estimate is given by the labels on the left side (“(reference number) Country, population”). Within each disease severity level, estimates are ordered alphabetically by country and then by population.

Figure 4.

Vaccine efficacy and effectiveness estimates for mRNA-1273, a 2-dose mRNA vaccine developed by Moderna. Estimates are colored by the viral variant against which the vaccine efficacy or effectiveness value was measured. Solid markers are estimates from randomized clinical trials (efficacy values), and open markers are estimates from observational studies (effectiveness values). The source of each estimate is given by the labels on the left side (“(reference number) Country, population”). Within each disease severity level, estimates are ordered alphabetically by country and then by population.

Figure 5.

Vaccine efficacy and effectiveness estimates for AZD1222, a 2-dose viral vector vaccine developed by AstraZeneca. Estimates are colored by the viral variant against which the efficacy or effectiveness value was measured. Solid markers are estimates from randomized clinical trials (efficacy values), and open markers are estimates from observational studies (effectiveness values). The source of each estimate is given by the labels on the left side (“(reference number) Country, population”). Within each disease severity level, estimates are ordered alphabetically by country and then by population.

Figure 6.

Vaccine efficacy and effectiveness estimates for 2 viral vector vaccines: (A) Ad26.COV2.S, a single-dose vaccine developed by Janssen/Johnson & Johnson, and (B) Sputnik V, a 2-dose vaccine developed by Gamaleya Institute. Estimates are colored by the viral variant against which the efficacy or effectiveness value was measured. Solid markers are estimates from randomized clinical trials (efficacy values), and open markers are estimates from observational studies (effectiveness values). The source of each estimate is given by the labels on the left side (“(reference number) Country, population”). Within each disease severity level, estimates are ordered alphabetically by country and then by population.

Figure 7.

Vaccine efficacy and effectiveness estimates for three 2-dose inactivated virus vaccines: (A) CoronaVac, developed by Sinovac (B) BBIBP-CorV, developed by Sinopharm Beijing, and (C) BBV152, developed by Bharat Biotech. Estimates are colored by the viral variant against which the efficacy or effectiveness value was measured. Solid markers are estimates from randomized clinical trials (efficacy values), and open markers are estimates from observational studies (effectiveness values). The source of each estimate is given by the labels on the left side (“(reference number) Country, population”). Within each disease severity level, estimates are ordered alphabetically by country and then by population.