Introduction: The coronavirus disease 2019 (COVID-19) pandemic was a global outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The rapid authorization of mRNA COVID-19 vaccines was a pivotal milestone, addressing an unprecedented global public health crisis. Following Phase III clinical trials, there was a regulatory need for information on real-world vaccine effectiveness (VE) and durability of protection. Methods: A series of cohort studies and test-negative case-control studies were conducted at Kaiser Permanente Southern California (KPSC) to evaluate the VE of the Moderna COVID-19 vaccine as a regulatory commitment to multiple health authorities globally. KPSC’s electronic health record captures comprehensive information on patient care, including vaccinations, diagnoses, lab tests, procedures, and pharmacy records across all care settings. Exposures included the 2-dose primary series, monovalent booster dose, and bivalent dose. Outcomes included SARS-CoV-2 infection, COVID-19 hospitalization, and COVID-19 in-hospital death. Results: From 2021 to 2024, ten analyses were performed and showed that the vaccine was initially highly effective in preventing infection and severe outcomes. VE against infection declined over time due to waning immunity and emerging immune escape variants. The decline in VE resulted in the need to offer booster doses to the general population, provide additional protection for immunocompromised individuals, and develop variant-specific vaccines. Updated vaccines provided robust protection against severe outcomes, including hospitalization and death, despite variant evolution. Conclusion: The findings emphasized the importance of booster doses and variant-specific vaccines, particularly as immunity wanes over time and new, more transmissible variants like Delta, Omicron, and their subvariants emerge. The findings were crucial in shaping public health policies, guiding booster recommendations, and ensuring the protection of high-risk populations. Real-world evidence played an essential role in regulatory decision-making during the pandemic, offering valuable insights into the Moderna COVID-19 vaccine performance over time and in diverse populations.
Tseng et al. (Sun,) studied this question.