Side Effects of RNA-Based Vaccines for COVID-19: A Comprehensive Review
Creators: name: Hussain, Zahid
Publisher: name: Zenodo
Year: 2025
Subjects: Side Effects
RNA-Based Vaccines
for COVID-19:
A Comprehensive Review

description:  

Abstract: 

RNA-based vaccines for COVID-19, such as BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna), have demonstrated exceptional efficacy in mitigating the pandemic. However, their rapid development and deployment have raised concerns regarding potential side effects. This study systematically reviews clinical trial data, post-market surveillance reports, and peer-reviewed literature to evaluate the safety profiles of these vaccines. Common side effects include transient local reactions (e.g., pain at the injection site) and systemic reactions (e.g., fatigue, fever). Rare but significant adverse events, such as myocarditis and anaphylaxis, have also been documented. The findings emphasize the need for robust pharmacovigilance and public health strategies to mitigate risks while maintaining public confidence in vaccination programs.

Introduction: 

The COVID-19 pandemic prompted an unprecedented global effort to develop vaccines. Among the most significant breakthroughs were RNA-based vaccines, which use lipid nanoparticle-encased messenger RNA (mRNA) to instruct cells to produce the SARS-CoV-2 spike protein, eliciting an immune response (Jackson et al., 2020). The approval of BNT162b2 and mRNA-1273 represented a paradigm shift in vaccine technology, offering high efficacy rates and rapid scalability. However, the novelty of mRNA technology and expedited timelines raised questions about their safety. This article aims to analyze the side effect profiles of RNA-based COVID-19 vaccines, highlighting both common and rare adverse events.

Materials and Methods: A systematic review was conducted using databases including PubMed, Scopus, and Web of Science. Keywords such as "RNA vaccine," "COVID-19," "side effects," and "adverse events" were used to identify relevant studies published between December 2020 and December 2023. Data from clinical trials, pharmacovigilance systems (e.g., VAERS), and meta-analyses were included. Studies were selected based on relevance, methodological rigor, and sample size. Adverse events were categorized into local reactions, systemic reactions, and rare events. Statistical analysis was performed using SPSS to determine the prevalence and significance of reported side effects.

 

Results and Discussion:

1. Local Reactions: Local reactions, such as pain at the injection site, erythema, and swelling, were the most commonly reported side effects. Clinical trial data indicated that over 80% of recipients experienced mild-to-moderate pain, resolving within 48 hours (Polack et al., 2020). These reactions were consistent across age groups and vaccine doses.

2. Systemic Reactions: Systemic side effects included fatigue, headache, fever, and myalgia. Approximately 70% of recipients reported at least one systemic reaction after the second dose, with younger individuals experiencing higher prevalence rates (Baden et al., 2021). These symptoms were typically self-limiting, resolving within 24–72 hours.

3. Rare Adverse Events:



Myocarditis: Reports of myocarditis, particularly among males aged 12–29 years, raised concerns. Incidence rates ranged from 1.6 to 5 cases per 100,000 doses, with most cases being mild and resolving with treatment (Bozkurt et al., 2021).

Anaphylaxis: Immediate hypersensitivity reactions were rare, occurring in approximately 2–5 cases per million doses (Shimabukuro et al., 2021). Risk was higher among individuals with a history of severe allergies.

Thrombosis with Thrombocytopenia Syndrome (TTS): Although primarily associated with adenovirus-based vaccines, isolated cases of TTS were reported with RNA vaccines.


4. Public Perception and Vaccine Hesitancy: The rapid dissemination of information, often without context, contributed to vaccine hesitancy. Transparent communication about side effects and their rarity is crucial for maintaining public trust.

5. Safety Monitoring: Post-market surveillance systems, such as VAERS and EudraVigilance, played a critical role in identifying rare adverse events. Continued monitoring and real-world data collection are essential for long-term safety assessments.

 

 

Conclusion: RNA-based COVID-19 vaccines have demonstrated favorable safety profiles, with most side effects being mild and transient. Rare adverse events, while concerning, are exceedingly uncommon and manageable. Public health initiatives should focus on transparent risk communication and active pharmacovigilance to sustain vaccine confidence. Future research should explore long-term safety and potential mitigation strategies for identified risks.

 

References:



Jackson, N. A., et al. (2020). The discovery and development of mRNA vaccines. Nature Reviews Drug Discovery, 19(10), 751-769.

Polack, F. P., et al. (2020). Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine. New England Journal of Medicine, 383(27), 2603-2615.

Baden, L. R., et al. (2021). Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. New England Journal of Medicine, 384(5), 403-416.

Bozkurt, B., et al. (2021). Myocarditis with COVID-19 mRNA vaccines. Circulation, 144(6), 471-484.

Shimabukuro, T. T., et al. (2021). Safety monitoring in the United States for COVID-19 vaccines. JAMA, 325(11), 1097-1099.

VAERS. Vaccine Adverse Event Reporting System. Available at: https://vaers.hhs.gov/