Unexpected Adverse Reactions Reported for COVID-19 Vaccines: A Descriptive Analysis of Spontaneous Reports Received by a Portuguese Regional Pharmacovigilance Unit: An International Journal of Medical Toxicology and Drug Experience

ABSTRACT

Background/Introduction: The approval of COVID-19 vaccines has been based on fast clinical development programs leading to limited knowledge on safety data [1]. Unexpected adverse drug reactions (ADRs), including rare ADRs or delayed ADRs from long-term exposure, may occur [2]. Moreover pre-marketing clinical trials do not have power to detect all ADRs, thereby highlighting the need to analyse post-marketing spontaneous reports (SRs). Objective/Aim: To identify unexpected ADRs associated with COVID-19 vaccines spontaneously reported to the Regional Pharmacovigilance Unit of Coimbra in Portugal (UFC). Methods: SRs of ADRs associated with COVID-19 vaccines received by UFC between 30/12/2020 and 30/04/2021 were included. ADRs were coded with MedDRA®, v.24 (System Organ Classification [SOC] and Preferred Term [PT]). ADRs were classified as "expected" or "unexpected" according to their description on the vaccines Summary of Product Characteristics (SmPC). Further, each unexpected ADR was classified as an important medical event (IME) according to the list from the European Medicines Agency (EMA). Results: A total of 771 SRs, of which 262 SRs (34%) contained a total of 420 unexpected ADRs were received. For Comirnaty®, out of 287 unexpected ADRs, 26 (9.1%) were IME. The most frequently reported IMEs were angioedema (n = 2;7.7%), bradycardia (n = 2;7.7%), death (n = 2;7.7%), deep vein thrombosis (n = 2;7.7%), ischaemic stroke (n = 2;7.7%), and seizure (n = 2;7.7%). The remaining ADRs (acute kidney injury, cardio-respiratory arrest, cerebrovascular accident, corneal opacity, haemorrhagic stroke, hypertensive crisis, laryngeal oedema, loss of consciousness, pneumonia, pulmonary oedema, sepsis, status epilepticus, tongue paralysis and upper gastrointestinal haemorrhage), had one report each (n=14;53.8%). Of the 121 unexpected ADRs reported for Vaxzevria®, 20 were IME (16.5%). The most frequently reported IMEs were ischaemic stroke (n = 5;25.0%), and conjunctival haemorrhage (n = 3;15.0%). The remaining ADRs (acute myocardial infarction, altered state of consciousness, angina pectoris, arrhythmia, death, guillain-Barre syndrome, hypothermia, mesenteric vein thrombosis, monoplegia, pericarditis, syncope and truncus coeliacus thrombosis), had one report each (n = 12;60.0%). Twelve unexpected ADRs were reported for the Moderna COVID-19 vaccine®, of which 4 IMEs (33.3%), corresponding to cerebrovascular accident (n = 1;25.0%), conjunctival haemorrhage (n = 1;25.0%), death (n = 1;25.0%) and retinal artery occlusion (n = 1;25.0%). Conclusion: A considerable proportion of SRs received by UFC contained unexpected ADRs, among which 11.9% were IMEs. These results highlight the value of post-marketing spontaneous reporting to identify unknown ADrs and to better characterize the safety profiles of newly approved COVID-19 vaccines, as well as their benefit/risk ratios.