Real-world effectiveness of mRNA COVID-19 vaccines in the elderly during the Delta and Omicron variants: Systematic review.

Background: As of 31 December 2022, there were over 6.6 million coronavirus disease 2019 (COVID-19) deaths and over 651 million cases across 200 countries worldwide. Despite the increase in vaccinations and booster shots, COVID-19 cases and deaths continue to remain high. While the effectiveness of these vaccines has already been established by different manufacturers, the fact remains that these vaccines were created quickly for global emergency use, tested under controlled clinical conditions from voluntary subjects and age groups whose general characteristics may differ from the actual general population.

Aim: To conduct a systematic review to determine the real-world effectiveness of mRNA COVID-19 vaccines in the elderly during the predominance of Delta and Omicron variants in preventing COVID-19 related infection, hospital, intensive care unit (ICU) admission and intubation, and death.

Methods: A combination of Medical Subject Headings and non-Medical Subject Headings was carried out to identify all relevant research articles that meets the inclusion and exclusion criteria from PubMed, Cochrane, CINAHL, Scopus, ProQuest, Embase, Web of Science, and Google Scholar databases, as well as qualified research studies from pre-print servers using medRxiv and Research Square, published from January 1, 2021 - December 31, 2022.

Results: As per the inclusion and exclusion criteria, the effectiveness of Pfizer-BioNTech and Moderna vaccines were evaluated from an estimated total study population of 26,535,692 using infection, hospital, ICU admission and intubation, and death as outcome measures from studies published between 2021 and 2022, conducted in New York, Finland, Canada, Costa Rica, Qatar, Greece, and Brazil. The risk of bias was evaluated using risk of bias in nonrandomized studies of interventions (ROBINS-I) tool for cohort, case-control, and cross-sectional studies. While clinical trial data on Pfizer-BioNTech and Moderna vaccines demonstrated 94% vaccine effectiveness in the elderly, the results in this study showed that vaccine effectiveness in real-world settings is marginally lower against infection (40%-89%), hospitalization (92%), ICU admission and intubation (98%-85%), and death (77%-87%) with an indication of diminished effectiveness of vaccine over time. Furthermore, 2 doses of mRNA vaccines are inadequate and only provides interim protection.

Conclusion: Because of the natural diminishing effectiveness of the vaccine, the need for booster dose to restore its efficacy is vital. From a research perspective, the use of highly heterogeneous outcome measures inhibits the comparison, contrast, and integration of the results which makes data pooling across different studies problematic. While pharmaceutical intervention like vaccination is important to fight an epidemic, utilizing common outcome measurements or carrying out studies with minimal heterogeneity in outcome measurements, is equally crucial to better understand and respond to an international health crisis.