Exploring the waning effect of mRNA vaccines against COVID-19 in the elderly

In a recent study posted to the medRxiv* preprint server, researchers determined the vaccine effectiveness (VE) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in older individuals. The results confirmed a waning effect of vaccines against both coronavirus disease 2019 (COVID-19) infection and severe disease among the elderly population.

Study: Waning Effectiveness of SARS-CoV-2 mRNA Vaccines in Older Adults: A Rapid Review. Image Credit: Melinda Nagy/ShutterstockStudy: Waning Effectiveness of SARS-CoV-2 mRNA Vaccines in Older Adults: A Rapid Review. Image Credit: Melinda Nagy/Shutterstock


The emergence of several highly mutated SARS-CoV-2 variants of concern (VOCs) along with the declining VE increased the risk of resurgence of COVID-19 cases. The Food and Drug Administration (FDA) granted Emergency Use Authorization (EUA) for the Pfizer-BioNTech and Moderna mRNA vaccines booster dose on September 22, 2021, and October 20, 2021, respectively, in specific vulnerable groups, including adults aged 65 years or older.

However, there is only limited evidence regarding the longevity of the COVID-19 mRNA vaccine-conferred protection against SARS-CoV-2 infection and severe disease in older adults. Moreover, the existing studies in these populations varied across vaccine types, geographical factors, follow-up periods, and the SARS-CoV-2 VOCs.

The study

In the present study, the researchers conducted a rapid review of PubMed-indexed studies available by November 4, 2021, demonstrating the VE of mRNA-based BNT162b2 and mRNA1283 vaccines currently approved in the United States (US) among older adults. Eight eligible studies from the PubMed database were selected for the study. The researchers assessed VE in adults stratified by study period and age groups with more emphasis on the elderly population to enhance the evidence-based public health policy.

The researchers focused on the number of participants, the observation period, and the definition and estimations of VE of the included studies. Studies with older participants also assessing VE for young adults were included. Further, studies were stratified based on those determining COVID-19 VE against SARS-CoV-2 infection versus severe disease, which was represented by COVID-19-associated hospitalizations or deaths.

Three calendar periods were defined in the study in association with the emergence of the SARS-CoV-2 Delta variant - the early period representing SARS-CoV-2 cases before the emergence of the Delta variant, the middle period when Delta became more widespread, and the late period when Delta was the predominant circulating virus.


The results indicated that all the eight studies included evaluated VE in individuals aged 65 years or older, and among that, six studies also accounted for VE in young adults. The mRNA1273 and BNT162b2 vaccine effectiveness, either individually or combined, were evaluated by six studies, whereas one study determined the BNT162b2 VE. All eight studies except one were classified as either early or middle period studies, and one was a late period study.

An early study conducted from December 14, 2020, to March 14, 2021, reported 93% VE for mRNA vaccines in the elderly against the SARS-CoV-2 infection. However, a middle period study from December 14, 2020, to August 8, 2021, showed that older adults had 61% VE against SARS-CoV-2 infection.

 According to three early studies, the mRNA VE against severe COVID-19 in older adults varied from 87.3% to 96.8%. Further, three middle period studies reported 80% to 90% mRNA VE against severe COVID-19 in older individuals, from December 14, 2020, to August 8, 2021. A late study conducted among US veterans reported 70.1%-75.5% mRNA VE against COVID-19-associated death in older adults from July 1-October 31, 2021.

An early study reported 89% VE against SARS-CoV-2 infection in young adults, whereas a middle period study noted 73% VE against SARS-CoV-2 infection in this group. Moreover, the mRNA VE against severe COVID-19 among young adults was 75–97% in an early study and 91– 95% in four middle period studies. A late study reported 81.5% and 84.3% VE for the mRNA1273 and BNT162b2 vaccines, respectively, against COVID-19-associated death in young adults.


According to the authors, this is the first study demonstrating age-disaggregated durability of COVID-19 mRNA vaccines' effectiveness, emphasizing older adults.

Young adults' VE against severe COVID-19 was around 90%, whereas older adults' VE was at or below 90% based on the middle period studies included in the present review. While these findings indicate the COVID-19 VE wanes off rapidly in older adults compared to young, careful interpretation should be made since these studies exhibited variations in durations of observation periods after vaccination.

Overall, the study indicated that VE declines in the elderly, posing a higher risk for COVID-19-associated morbidity and mortality in this group. Thus, the findings support the recent FDA EUA and Centers for Disease Control and Prevention (CDC) recommendation of COVID-19 booster dose vaccination in 65 years or older individuals.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Shanet Susan Alex

Written by

Shanet Susan Alex

Shanet Susan Alex, a medical writer, based in Kerala, India, is a Doctor of Pharmacy graduate from Kerala University of Health Sciences. Her academic background is in clinical pharmacy and research, and she is passionate about medical writing. Shanet has published papers in the International Journal of Medical Science and Current Research (IJMSCR), the International Journal of Pharmacy (IJP), and the International Journal of Medical Science and Applied Research (IJMSAR). Apart from work, she enjoys listening to music and watching movies.


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