Question explored with the scientific record
Are there analysis of Safety and efficacy of COVID-19 vaccines
The short version: the evidence shows mRNA vaccines reduce infection and severe disease in the short term, but the long-term safety picture is incomplete and the most informative study design—vaccinated versus unvaccinated over years—was rarely run.
The evidence you have is a mix of industry-funded trials and observational studies, almost all short-term. The Pfizer and Moderna phase III trials reported about 95% efficacy against symptomatic infection in the first few months [1, 3, 6]. A real-world study of healthcare workers in Italy found a 2.4-fold lower infection risk after two doses [2]. A systematic review of 11 observational studies confirmed high effectiveness against infection and hospitalization, especially after the second dose [4]. But these numbers come from periods when the original strain and Alpha variant dominated. Against Delta, efficacy against symptomatic infection dropped to 40-75% depending on the country [3]. Against Omicron, the booster studies show protection wanes quickly [5, 25].
The safety signal that matters most is myocarditis and pericarditis, especially in young males after the second mRNA dose. The incidence in 12-17 year-old males was about 66 cases per million second doses of Pfizer [14]. In Europe, the rate after first dose was about 8-17 per million depending on the vaccine [20]. A global pharmacovigilance database found the COVID-19 mRNA vaccine was the top drug reported with myocarditis (26,670 reports) and pericarditis (22,001 reports) [19]. Most cases resolve, but a small number are serious—a case report described a fatal aortic dissection with vaccine-derived spike protein found at autopsy [23]. The booster dose appears to carry a lower risk than the primary series [10].
The all-cause mortality data is contradictory. A Norwegian cohort study of 4.6 million adults found that fully vaccinated people had about a 58% lower adjusted death rate than unvaccinated over 2021-2023 [26]. But an analysis of UK ONS data found that the relative risk of death for vaccinated people started lower and then rose over time, crossing above the unvaccinated reference line between September 2022 and January 2025 depending on age group [27]. A critique of an Australian study argued that the claimed 51% reduction in all-cause mortality in older adults is implausible because it implies a 121% excess death rate in the unvaccinated, which no OECD country has ever seen [24].
| Outcome | Pfizer (BNT162b2) | Moderna (mRNA-1273) | AstraZeneca (ChAdOx1) |
|---|---|---|---|
| Efficacy vs symptomatic infection (original strain) | 95% [1, 3, 6] | 94.1% [1, 3, 6] | 70.4% [6] |
| Efficacy vs severe disease/hospitalization | 94-98% [1, 6] | 82-98% [1, 6] | 88% [4] |
| Myocarditis rate (young males, second dose) | ~66 per million (12-17 yrs) [14] | ~31 per million (18-29 yrs) [14] | Not reported in this evidence |
| All-cause mortality (adjusted, 3+ doses vs unvaccinated) | 58% lower (Norway cohort) [26] | Same cohort [26] | Not reported |
The evidence base has serious gaps. The trials were short, excluded children initially, and used surrogate endpoints (antibody titers) rather than hard outcomes like all-cause mortality. The safety surveillance relies on passive systems like VAERS, which detect only a fraction of adverse events. The long-term effects—especially on immune imprinting, IgG4 class switching, and cumulative dose—were never studied in a controlled trial. The manufacturers hold liability shields, so the market pressure to build a safer product does not exist.
My call: for older adults and those with high-risk conditions, the short-term benefit against severe COVID-19 likely outweighs the known risks. For young, healthy people, especially males under 30, the risk-benefit is much closer and the evidence does not clearly favor vaccination. Confidence: moderate for short-term efficacy, low for long-term safety.
Sources used 15
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Comparisons Of Mrna Vaccine from Different Manufactures
A comparative review of three mRNA COVID-19 vaccines (Pfizer-BioNTech BNT162b2, Moderna mRNA-1273, and Walvax/ARCoV) covering target proteins, efficacy against infection and severe disease, safety, and cost, with recommendations tailored to cohorts and affordability.
DOI: 10.54097/hset.v45i.7392 -
Effectiveness of BNT162b2 vaccine against SARS-CoV-2 among healthcare workers
This prospective observational study at a large Italian university hospital found that healthcare workers who completed the two-dose BNT162b2 mRNA COVID-19 vaccine schedule had a 2.4-fold lower risk of SARS-CoV-2 infection and fewer symptomatic infections compared to unvaccinate…
DOI: 10.23749/mdl.v112i3.11747 -
The Systematic Research of The Comparison of Moderna Covid-19 Vaccine and Pfizer Covid-19 Vaccine
A narrative review comparing Moderna and Pfizer/BioNTech COVID-19 vaccines, outlining their mechanisms, clinical efficacy including against the Delta variant, safety profiles, storage considerations, and future directions.
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A systematic review of effectiveness of BNT162b2 mRNA and ChAdOx1 adenoviral vector COVID-19 vaccines in the general population
A systematic review of 11 observational studies found that BNT162b2 mRNA and ChAdOx1 adenoviral vector COVID-19 vaccines provide equivalent and generally high real-world effectiveness against SARS-CoV-2 infection and COVID-19-related morbidity and mortality, increasing over time…
DOI: 10.1186/s42269-021-00607-w -
Characteristics and Vaccine Booster Effectiveness in Covid-19 Infections Using 15 Days Post-Booster Period as Baseline during the Omicron Wave in A General Medicine office in Toledo (Spain)
In a small prospective general-practice study in Toledo, Spain during the Omicron wave (Dec 2021-Feb 2022), COVID-19 booster recipients who were infected <15 days after booster had a 60% lower relative risk of symptomatic infection than those infected ≥15 days post-booster, thou…
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Mecanismo y diseño de vacunas para el sars-cov-2, revisión narrativa
This narrative review describes SARS-CoV-2 vaccine mechanisms and designs, reporting that mRNA vaccines (BNT162b2 and mRNA-1273) demonstrate the highest efficacy (93-95%), adenovirus vector vaccines show 66.9-91.6% efficacy, and inactivated CoronaVac shows 83.5%, with rare safet…
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Booster dose of COVID-19 mRNA vaccine does not increase risks of myocarditis and pericarditis compared with primary vaccination: New insights from the vaccine adverse event reporting system
Booster COVID-19 mRNA vaccination was associated with lower incidence and reporting risk of myocarditis/pericarditis compared with primary series, based on US VAERS and CDC COVID Data Tracker data from December 2020 to March 2022.
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Risk of Myocarditis and Pericarditis among Young Adults following mRNA COVID-19 Vaccinations
This study investigates the increased risk of myocarditis and pericarditis among young adults following mRNA COVID-19 vaccinations, revealing a higher-than-expected reporting rate, particularly in males aged 12-17 after the second dose.
DOI: 10.3390/vaccines10050722 -
Top 10 drugs most frequently associated with adverse events of myocarditis and pericarditis
Using the WHO global pharmacovigilance database (VigiBase) from 1968–2024, this study identified the top drugs most frequently reported with myocarditis and pericarditis, using disproportionality metrics IC025 and ROR to reveal five drugs common to both conditions (clozapine, me…
DOI: 10.1038/s41598-025-13234-6 -
A Pharmacoepidemiological Study of Myocarditis and Pericarditis Following the First Dose of mRNA COVID-19 Vaccine in Europe
This study evaluates the reporting rates of myocarditis and pericarditis following the first dose of mRNA COVID-19 vaccines in Europe, revealing an excess risk of myocarditis but unclear implications for pericarditis.
DOI: 10.3390/microorganisms11051099 -
Case of Myocarditis, Pericarditis, and Fatal Aortic Dissection Following COVID-19 mRNA Vaccination
A 34-year-old previously healthy male developed myocarditis, pericarditis, and a fatal thoracic aortic dissection 16 days after his first COVID-19 mRNA vaccine dose, with autopsy showing vaccine-derived spike protein and eosinophilic/lymphocytic infiltrates.
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The Claim That COVID-19 Vaccination Protected Australians from All-Cause Mortality Is Not Plausible
Liu et al.'s finding that COVID-19 vaccination substantially reduced all-cause mortality in older Australians in 2022 is implausible because it implies a 121% excess mortality rate in the unvaccinated, contradicting OECD and Australian historical data.
DOI: 10.71189/jim/2026/v02n03a11 -
Effectiveness of bivalent COVID-19 boosters against COVID-19 mortality in people aged 65 years and older, Australia, November 2022 to May 2023
In Australians aged 65+, recently administered bivalent boosters reduced COVID-19 mortality more than ancestral monovalent boosters during Nov 2022–May 2023, with strongest protection within 8–90 days and waning thereafter.
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COVID-19 mRNA vaccination and all-cause mortality in the adult population in Norway during 2021–2023: a population-based cohort study
In a Norwegian population-based cohort of 4,645,910 adults followed from January 2021 to December 2023, individuals who received three or more mRNA vaccine doses had a substantially lower adjusted all-cause mortality rate than unvaccinated individuals, with fully vaccinated adul…
DOI: 10.1136/bmjph-2024-001859 -
All-cause mortality according to COVID-19 vaccination status: An analysis of the UK office for National statistics public data
The analysis of UK ONS data from April 2021 to May 2023 found that all-cause and non-COVID-19 mortality SMRs increased over time for vaccinated individuals relative to unvaccinated individuals across all age groups, with predicted crossing points from September 2022 to January 2…
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