Review on the Safety and Efficacy of COVID-19 Vaccines Approved in Saudi Arabia

SARS-CoV-2 was first reported in Wuhan, China, and rapidly spread worldwide, causing a global pandemic with high mortality, particularly among the elderly and those with comorbidities. While multiple treatments have been investigated with mixed results, widespread vaccination is considered key for achieving herd immunity, reducing morbidity and mortality, and minimizing social and economic burdens. Vaccines generally induce minor and manageable side effects; rare serious events (e.g., hepatitis, renal failure, thromboembolic events, anaphylaxis) have been reported but at rates comparable to other medical interventions and often associated with vaccine design, manufacturing, genetic predisposition, or comorbidities. Several vaccines received WHO emergency use authorization during the pandemic (e.g., Pfizer, Moderna, AstraZeneca, Sputnik, Sinopharm). Reports of rare post-vaccination adverse events, including pathological clotting, prompted cautions for individuals with allergies and highlighted knowledge gaps for specific populations (pregnant/lactating persons, children under 18, and severely ill patients). As vaccination expanded, new adverse events were recorded, underscoring the need for comprehensive synthesis. This study systematically reviewed the safety and efficacy of four vaccines approved in Saudi Arabia: AstraZeneca, Pfizer, Moderna, and Janssen.

Prior literature indicates that COVID-19 vaccines commonly cause local reactions (pain, inflammation, warmth, redness) and systemic reactions (fever, chills, headache, myalgia, fatigue). Mechanistically, innate immune responses shortly after vaccination involve cytokines, chemokines, and prostaglandins that lead to vasodilation, nerve irritation, inflammation, and pain; these responses can be more pronounced after subsequent doses and are not necessarily correlated with antibody levels. Vaccine platform types include whole-virus (inactivated/attenuated), protein subunit, viral vector, and nucleic acid (DNA/RNA). Moderna and Pfizer use mRNA platforms requiring stringent cold-chain storage; AstraZeneca and Janssen are adenoviral vector vaccines. Prior reports also noted rare but serious events (e.g., thrombotic events with some vector vaccines, anaphylaxis, myocarditis/lymphadenopathy with mRNA vaccines), emphasizing ongoing pharmacovigilance. WHO considers an efficacy threshold of approximately 60% acceptable for pandemic use; many pivotal trials reported higher efficacy, especially for mRNA vaccines.

Design: Systematic review conducted according to PRISMA guidelines and the five-step approach outlined by Khan et al. Databases and search: PubMed, SCOPUS, Web of Science, and BIOSIS were searched from January 2021 to September 2022. Keywords included combinations of: COVID-19 vaccine OR Coronavirus vaccine OR Corona vaccine AND Safety AND Efficacy AND Clinical Trials OR Human Trials AND Approved. Study selection: Independent screening targeted four COVID-19 vaccines approved in Saudi Arabia: AstraZeneca (ChAdOx1 nCoV-19), Pfizer/BioNTech (BNT162b2), Moderna (mRNA-1273), and Janssen (Ad26.COV2.S). Two-step screening included title/abstract screening followed by full-text review. Discrepancies were resolved via discussion with a supervisor/subject expert. Eligibility criteria (inclusion): - English-language articles with detailed vaccine type and volunteer information (with consent). - Cross-sectional studies published 2019–2022. - Human studies evaluating COVID-19 vaccine safety and efficacy. - Studies reporting dose, timing, adverse reactions, and clear procedures for effectiveness assessment. - Publications in reputed journals with comprehensive statistical methods and significance reporting. Exclusions: Overlapping datasets, duplicate reports, studies with non-extractable data, and studies not meeting inclusion criteria. Data extraction: Performed independently using a pre-organized sheet capturing study design, population characteristics, and outcomes (safety and efficacy data). Quality assessment: Newcastle–Ottawa Scale (cross-sectional studies) assessing sampling, statistical analysis, exposure/outcome assessment, controls, response rates, and appropriateness of statistical tests. Reviewers assessed quality independently; disagreements were resolved through discussion.

- Study yield: 360 records screened; after deduplication and screening, 153 articles were selected for full assessment; 18 articles were analyzed in detail for safety and efficacy. - Participant characteristics across vaccines: • Sex distribution tested: AstraZeneca 60.29% male/39.7% female; Pfizer 51.07% male/48.9% female; Moderna 52.22% male/47.74% female; Janssen 55.14% male/44.85% female. • Age groups included: AstraZeneca 18–65 years 84.4%, >65 years 15.25%; Pfizer 18–65 years 78.41%, >65 years 21.58%; Moderna 18–65 years 75.17%, >65 years 24.82%; Janssen 18–65 years 76.53%, >65 years 23.49%. - Common local reactions (overall ranges across studies): pain at injection site 40–70%, redness 16–30%, swelling 18–39%, tenderness 20–40%. • First dose local pain (per vaccine): AstraZeneca 50.6%, Pfizer 61.8%, Moderna 71.2%, Janssen 69.5%. • Second dose: increases in several local reactions except local pain (AstraZeneca 37.8%, Pfizer 48.6%, Moderna 59.2%), tenderness 20% (AstraZeneca), swelling 17.5% (Pfizer), redness 21.9% (Moderna). • Booster dose: more redness (AstraZeneca, Moderna, Janssen), swelling (Janssen), and tenderness (Pfizer, Moderna); lower frequencies of local pain (AstraZeneca, Janssen), swelling (Moderna), and tenderness (Janssen) vs prior dose. - Common systemic reactions (overall ranges): fever 40–60%, chills 12–23%, fatigue 44–65%, headache 30–42%, muscle pain 15–40%. • AstraZeneca (dose 1): fatigue 50.7%, headache 41.9%, fever 38.9%; dose 2 reactions reduced except fever 42.8%. • Pfizer (dose 1): fatigue 61.8%, fever 56.9%; dose 2: fatigue 65.8%, fever 57.2%. • Moderna (dose 1): fever 40.9%, fatigue 38.5%; dose 2: fatigue 49.2%, fever 52.5%. • Janssen (single dose): fatigue 43.8%, muscle pain 39.7%, fever 33.9%. • Second dose increases vs first: chills (AstraZeneca 23.1%, Pfizer 19.5%, Moderna 15.2%), muscle pain (AstraZeneca 19.7%, Moderna 20.8%), headache (Pfizer 41.6%, Moderna 40.1%). Booster dose effects: increases in fever (Moderna, Janssen), chills (Pfizer, Moderna), muscle pain (AstraZeneca, Janssen), and fatigue (all vaccines); decreases in chills (AstraZeneca, Janssen), headache (AstraZeneca, Janssen), and muscle pain (Pfizer, Moderna) vs previous doses. - Efficacy by sex: • Males: AstraZeneca 72.1%, Pfizer 95.3%, Moderna 95.5%, Janssen 69.8%. • Females: AstraZeneca 74.8%, Pfizer 93.9%, Moderna 93.4%, Janssen 67.3%. - Efficacy by age group: • 18–65 years: Pfizer 94.6%, Moderna 93.4%, AstraZeneca 76.2%, Janssen 74.7%. • >65 years: AstraZeneca 88.1%, Pfizer 96.5%, Moderna 100%, Janssen 79.1%. - All four vaccines exceeded the WHO efficacy threshold (~60%). - Quality: Included studies were generally rated as good quality on the Newcastle–Ottawa Scale (many scoring 7–9 stars).

This systematic review synthesized safety and efficacy data for AstraZeneca, Pfizer, Moderna, and Janssen vaccines approved in Saudi Arabia. The findings indicate that common local (injection-site pain, swelling, tenderness, redness) and systemic (fatigue, fever, headache, myalgia, chills) reactions occur across vaccines, often more pronounced after the second dose and with some increases after booster doses. These patterns align with innate immune activation (cytokines, chemokines, prostaglandins) and immunologic priming with subsequent doses. Efficacy analyses showed that all four vaccines surpassed the WHO’s minimum threshold, with mRNA vaccines (Pfizer, Moderna) demonstrating the highest efficacy in both sexes and across age groups. Notably, efficacy appeared highest among participants older than 65 years for all vaccines, potentially reflecting behavioral or exposure differences in this population. Platform differences help contextualize safety and logistic considerations: mRNA vaccines require stringent cold-chain storage and have been associated with events such as lymphadenopathy and myocarditis, whereas adenoviral vector vaccines have rare thrombotic events. Overall, the balance of benefits supports vaccination, while rare serious adverse events underscore the need for vigilant pharmacovigilance and tailored guidance for special populations (pregnant/lactating individuals, those under 18, and people with severe illness or allergies).

This systematic review of four COVID-19 vaccines approved in Saudi Arabia found that typical local and systemic reactions are common and generally manageable. All vaccines met or exceeded WHO’s efficacy threshold, with mRNA vaccines showing the highest efficacy. Rare but serious adverse events (e.g., anaphylaxis, thrombotic events) have been reported, warranting careful monitoring, especially as booster doses are administered. More comprehensive studies across diverse populations, including controlled challenge studies, are needed to fully establish long-term safety and efficacy and to guide booster strategies.

The review relied on published studies up to late 2022, during a rapidly evolving evidence landscape; newer data may alter estimates of safety and efficacy. Heterogeneity across study designs, populations, and outcome reporting limits direct comparability and may introduce bias despite quality assessments. Some subgroups (pregnant/lactating individuals, those under 18, severely ill or immunocompromised patients) remain underrepresented. Rare adverse events are difficult to quantify precisely in the included studies and require ongoing pharmacovigilance. Booster dose effects were incompletely characterized for all populations and comorbidity groups.