# Clinical Efficacy of Tozinameran in COVID-19 Prevention

## What clinical efficacy data support Tozinameran's prevention of COVID-19?

Randomized controlled trials enrolling over 46,000 participants and real-world observational studies including millions of individuals demonstrate that Tozinameran prevents COVID-19 with 91-95% efficacy against symptomatic infection and over 95% efficacy against severe disease, hospitalization, and death across age groups and SARS-CoV-2 variants.

## Abstract

Tozinameran demonstrated 95% efficacy (95% CI: 90.3-97.6) against laboratory-confirmed COVID-19 in phase 3 randomized controlled trials, with real-world observational studies confirming 91-95.3% effectiveness. Protection against severe outcomes was exceptionally high, with efficacy of 96.7% against severe disease, 94.3% against hospitalization, and 96.1% against COVID-19-related death. The vaccine also prevented asymptomatic infection with 89-91% efficacy. Efficacy declined gradually from 96.2% in the first two months to 83.7% after four months following the second dose, but a third booster dose administered at a median of 10.8 months restored efficacy to 95.3%. The vaccine maintained substantial protection across SARS-CoV-2 variants, including 100% efficacy against the B.1.351 (beta) variant in South Africa, 85-97% against B.1.1.7 (alpha), and 81-96% against Delta.

Efficacy was preserved across age groups from adolescents (100% efficacy) to adults aged 75 and older (82%), though immunocompromised individuals showed reduced effectiveness of 71%. The safety profile was favorable, with predominantly mild-to-moderate transient reactogenicity, low rates of serious adverse events similar to placebo, and no new safety signals identified with booster doses. These data provide robust evidence that Tozinameran prevents COVID-19 across diverse populations and variants, with particularly strong protection against severe disease, hospitalization, and death.

## Methods

We analyzed 10 sources from an initial pool of 200, using 8 screening criteria. Each paper was reviewed for 8 key aspects that mattered most to the research question.

### Paper search

We performed a semantic search across over 138 million academic papers from the Elicit search engine, which includes all of [Semantic Scholar](https://www.semanticscholar.org/) and [OpenAlex](https://openalex.org/).

We ran this query: "What clinical efficacy data support Tozinameran’s prevention of COVID-19?"

The search returned 200 total results from Elicit.

### Screening

We screened in sources based on their abstracts that met these criteria:

- **Primary Intervention**: Does this study investigate Tozinameran (BNT162b2, Pfizer-BioNTech COVID-19 vaccine) as the primary intervention?
- **Clinical Efficacy Outcomes**: Does this study report clinical efficacy outcomes for COVID-19 prevention with laboratory-confirmed infection as the outcome measure?
- **Study Design**: Is this study a randomized controlled trial, cohort study, case-control study, systematic review, or meta-analysis?
- **Comparative Design**: Does this study compare Tozinameran to placebo, other COVID-19 vaccines, or unvaccinated controls?
- **Study Population**: Does this study include participants of any age group eligible for Tozinameran vaccination?
- **Beyond Safety/Immunogenicity Only**: Does this study report clinical efficacy outcomes (not solely immunogenicity, safety, or adverse events without efficacy data)?
- **Human Clinical Research**: Is this a human clinical study (not an in vitro study, animal study, preclinical research, case report, case series, editorial, commentary, or opinion piece)?
- **Isolatable Tozinameran Effects**: Can the effects of Tozinameran be isolated in this study (i.e., is this not a vaccine combination study where Tozinameran effects cannot be separated)?

## Results

### Characteristics of Included Studies

| Study | Full text retrieved? | Study Type | Sample Size | Population | Geographic Location | Follow-up Duration | Predominant Variant |
|-------|---------------------|------------|-------------|------------|--------------------|---------------------|---------------------|
| F. Polack et al., 2020 | Yes | Randomized Controlled Trial, observer-blinded, placebo-controlled | 43,548 participants | Persons ≥16 years | Multinational | Median 2 months | Not reported |
| Stephen J. Thomas et al., 2021 | Yes | Randomized Controlled Trial, observer-blinded, placebo-controlled | 46,429 participants (44,165 aged ≥16 years, 2,264 aged 12-15 years) | Persons ≥12 years | Multinational | 6 months | B.1.351 (beta) in South Africa |
| E. Moreira et al., 2022 | No | Randomized Controlled Trial, placebo-controlled | 10,125 participants | Persons ≥16 years who received two doses ≥6 months prior | Not specified | Median 2.5 months | Not reported |
| Eric J Haas et al., 2021 | Yes | Observational study | 6.5 million residents | Residents of Israel ≥16 years | Israel | Median 7 weeks after second dose | B.1.1.7 (94.5% prevalence) |
| G. Chodick et al., 2021 | Yes | Historical cohort study | 1,178,597 individuals | MHS members ≥16 years | Israel | 7-27 days after second dose | Not specified |
| V. Hall et al., 2021 | Yes | Prospective cohort study | 23,324 participants | Healthcare workers ≥18 years (median age 46.1 years, 84% female) | England | December 2020 - February 2021 (approximately 2 months) | B1.1.7 (dominant) |
| Megan Wallace et al., 2022 | Yes | Systematic review and meta-analysis of observational studies | 26 studies included | Persons ≥16 years, general population and sub-populations | Various countries | Studies through August 2021 | Delta variant predominant in some studies |

### Efficacy Against Laboratory-Confirmed COVID-19

#### Primary Two-Dose Series Efficacy

| Study | Outcome | Time Point | Efficacy (95% CI) | Cases (Vaccine/Placebo) |
|-------|---------|------------|-------------------|------------------------|
| F. Polack et al., 2020 | Laboratory-confirmed COVID-19 | ≥7 days after dose 2 | 95% (90.3-97.6) | 8/162 |
| Stephen J. Thomas et al., 2021 | Laboratory-confirmed COVID-19 | Through 6 months | 91.3% (89.0-93.2) | Not specified |
| Eric J Haas et al., 2021 | Symptomatic COVID-19 | ≥7 days after dose 2 | 97.0% (96.7-97.2) | Incidence: 0.8 vs 32.5 per 100,000 person-days |
| G. Chodick et al., 2021 | COVID-19 | 7-27 days after dose 2 | 94% (88-97) | Not specified |
| Noa Dagan et al., 2021 | Documented infection | ≥7 days after dose 2 | 92% (88-95) | Not specified |
| V. Hall et al., 2021 | SARS-CoV-2 infection (PCR-confirmed) | ≥7 days after dose 2 | 85% (74-96) | Incidence: 4 vs 14 per 10,000 person-days |

The primary two-dose series demonstrated consistently high efficacy against laboratory-confirmed COVID-19 across both randomized controlled trials and real-world observational studies.

## Synthesis

The body of evidence for Tozinameran’s clinical efficacy in preventing COVID-19 demonstrates remarkable consistency across diverse study designs, populations, and geographic settings. The convergence of findings from phase 3 RCTs showing 95% efficacy and real-world observational studies in Israel showing 95.3% effectiveness provides strong support for the vaccine’s protection against laboratory-confirmed COVID-19.

Several apparent heterogeneities in the results can be explained by methodological and contextual factors. The observed waning of protection against infection over 6 months is addressed by booster doses that restore high-level immunity. The vaccine’s favorable safety profile, with predominantly mild and transient reactogenicity and no significant safety signals, supports its positive benefit-risk profile for preventing COVID-19 across diverse populations.