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The need for the safety monitoring of the COVID-19 vaccine is unprecedented. It is an ongoing process starting from different phases of clinical trials and continued to post-marketing to tackle the emergency used authorized COVID-19 vaccines across the world. Rapid detection, exchange, prioritization, and assessment of safety signals based on available real-world data, surveillance of Adverse events following immunization (AEFI), and adverse event of special interest (AESI) by studying the observed/expected cases. Enhanced collaboration, and availability of resources, tools, and methods will add to the lessons learned from previous experiences.