Network analysis of adverse event patterns following immunisation with mRNA COVID-19 vaccines: Real-world data from the European pharmacovigilance database EudraVigilance

Renato Ferreira Da Silva ^1* Mariana Lobo ¹ Ana Pereira ¹ Manuela Morato ² Jorge Junqueira Polónia ¹ Inês Ribeiro-Vaz ¹

• ¹ Faculty of Medicine, University of Porto, Porto, Portugal
• ² LAQV/REQUIMTE, Faculty of Pharmacy, University of Porto, Porto, Portugal

Objectives: To analyse real-world safety data of mRNA COVID-19 vaccines within the European Economic Area (EEA), using Individual Case Safety Reports (ICSR), and to evaluate the variability in safety profiles between different vaccine versions. Methods: We utilised EudraVigilance data from January 1, 2020, to December 31, 2023, focusing on Moderna (Spikevax) and Pfizer/BioNTech (Comirnaty) vaccines against COVID-19. We performed descriptive statistics, co-occurrence analysis, and correspondence analysis to identify patterns and clusters of adverse events following immunisation (AEFI). Results: We retrieved 993,199 ICSR (Moderna: 394,484; Pfizer: 605,794), with most reports related to women patients (69%) and non-healthcare professionals (65%). A total of 10,804 distinct AEFI terms were described across the retrieved ICSR, with a cumulative occurrence frequency of 3,558,219 (Moderna: 1,555,638; Pfizer: 2,031,828). The most prominent serious clusters included headache, fatigue, pyrexia, myalgia, arthralgia, malaise, nausea, and chills, which frequently co-occurred with vaccination failure. Specific AEFI like fever, chills, malaise, arthralgia, injection site pain, inflammation, and warmth were more often linked to Moderna, while Pfizer was more commonly associated with vaccination failure, menstrual disorders (heavy menstrual bleeding and dysmenorrhea), and hypoesthesia. In older adults, serious clusters included confusional states, cerebrovascular accidents, and myocardial infarctions, while myocarditis and pericarditis were noted in younger males. Although rare, serious systemic AEFI, like anaphylactic reactions, were identified but require further causality evaluation. Conclusions: The overall safety of mRNA COVID-19 vaccines for mass vaccination is supported, but continuous pharmacovigilance remains essential. Identified clusters of AEFI, particularly serious and systemic ones, although rare and potentially influenced by other underlying causes, underscore the need for continuous monitoring and further epidemiological investigations to explore potential causal relationships.