Landscape review of active vaccine safety surveillance activities for COVID-19 vaccines globally.

Background: Evidence of COVID-19 vaccine safety relied upon the global vaccine monitoring infrastructure due to shortened clinical development timelines and emergency use licensure. Differences in AVSS capacity between high-income countries (HICs) versus low- and middle-income countries (LMICs) were known prior to the pandemic.

Objective: To assess the global landscape of COVID-19 vaccine AVSS activities to identify gaps in safety evidence generation across vaccine products and populations with a focus on LMICs.

Methods: A cross-sectional survey was conducted in January 2022 on AVSS activities evaluating adverse events following immunization (AEFI). Data collected included country, targeted population, COVID-19 vaccine product(s), design of surveillance/monitoring activities or study, and AEFIs to be monitored.To supplement these findings, we conducted a literature review of COVID-19 vaccine safety activities published in PubMed through January 2023. Observational activities assessing AEFI, specifically adverse events of special interest (AESI), following routine use of COVID-19 vaccines in medical practice were included; systematic reviews, benefit/risk assessments, clinical trials, and case reports/series were excluded.

Results: The survey, completed by 34 respondents and compiled with reviews of 7 publicly available Risk Management Plans from five vaccine manufacturers, identified 79 monitoring activities in HICs, 24 in LMICs, and 9 in multiple regions. Most activities in LMICs were planned cohort event monitoring (CEM) studies (n = 18); two multi-national hospital-based sentinel surveillance studies for AESI were ongoing. Activities in LMICs evaluated multiple COVID-19 vaccine products simultaneously and were sponsored by health authorities. The literature review identified 1245 unique citations, of which 379 met inclusion criteria. The majority evaluated vaccines primarily used in high-income countries: Pfizer BioNTech (Comirnaty; n = 303), Moderna (mRNA-1273; n = 164), AstraZeneca (AZD1222; n = 126), and Janssen (Ad26.COV2.S); n = 62); 14 citations assessed vaccines used exclusively in LMICs: Sinovac (CoronaVac), Beijing CNBG (BBIBP-Corv), Bharat (Covaxin), SII (Covashield), and Gamaleya (Gam-Covid-Vac) vaccines.

Conclusions: Robust safety evidence for input into benefit/risk assessments is likely unavailable for most COVID-19 vaccines used primarily in LMICs due to emphasis on cohort event monitoring methods. Goals for equitable vaccine access should be coupled with investment and support for building infrastructure and capacity for safety evidence generation to inform policy and regulatory decisions at local levels.