In a recently published study British Medical Journal (BMJ)Researchers evaluated the efficacy of a fourth dose of vaccine against coronavirus disease 2019 (COVID-19) among long-term care residents.
Long-term care (LTC) residents are at increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and infection with serious consequences. LTC homes in Ontario, Canada are publicly funded and provide medical and housing support and personal and nursing care for people with disabilities or neurological disorders. LTC residents in Ontario have been disproportionately affected by COVID-19, accounting for nearly two-thirds of fatalities during the first two pandemic waves.
Vaccination of LTC residents resulted in a significant reduction in infections and deaths relative to non-vaccinated controls. A third vaccine dose (the first booster) was offered to LTC residents from August 2021, and the fourth vaccine (the second booster) administration began on December 30, 2021. Moderna’s SpikeVax (mRNA-1273) was preferred for the second booster.
about study
In the current study, the researchers estimated the marginal effectiveness of the fourth vaccine dose compared to the third dose. The authors implemented a test-negative design and determined marginal effectiveness (fourth versus third) and vaccine effectiveness (fourth dose) among residents of 626 licensed LTC homes in Ontario. Subjects were excluded if they had received a second booster before December 30, 2021, or had tested SARS-CoV-2-positive in the past 30 days.
Only those who have been vaccinated against mRNA (BNT162b2.) [Pfizer] or mRNA-1273) were included in the study for all four doses. Estimates of vaccine effectiveness were limited to SARS-CoV-2 Omicron. Spike(S)-gene target failure (SGTF) testing or whole-genome sequencing was used for variant identification. Delta-infected cases were excluded. Provincial datasets on COVID-19 testing, vaccination, and health administrative information were combined using unique encoded identifiers.
Three outcomes were measured: infection (SARS-CoV-2 positivity), symptomatic infection and serious outcome. Residents were considered to be 1) cases if they tested positive at least once a week or 2) controls if all tests were negative that week. Frequencies and means were calculated for categorical and continuous variables, respectively.
Test negative controls were compared to test positive cases using standardized differences. Those vaccinated with the third dose 84 days before the index test (the first SARS-CoV-2 positive test) were compared with those who received the third, second, first, or no vaccine dose <84 days and the fourth dose < or 7 days before the test.
test result
More than 87% of LTC residents in Ontario were tested for SARS-CoV-2 from December 30, 2021 to April 27, 2022. There were 13,654 omicron-positive cases and 20,862 test-negative controls. The majority of residents (80.1%) were tested multiple times during the study period. More than half of the cases (58.1%) and controls (53.3%) received only three vaccines, and a greater proportion (38.2%) of controls received a second booster than cases (28%).
The marginal effectiveness of the fourth dose at 7 days post-vaccination was 19% against infection, 31% against symptomatic infection, and 40% against severe outcomes at 84 days before the index trial, compared to immunization with the third dose. The corresponding estimates were 16% against infection, 20% against symptomatic infection and 29% against severe outcomes, compared to residents who were vaccinated with a third dose 84 days before the index test.
Seven days after the fourth dose, the vaccine’s effectiveness was 49% against infection, 69% against symptomatic infection, and 86% against severe outcomes. The vaccine effectiveness of the third dose administered 84 days before the trial was 37% against infection, 55% against symptomatic infection and 77% against severe outcomes. Vaccine effectiveness was similar between residents receiving three mRNA-1273 doses and those receiving two BNT162b2 doses and one mRNA-1273 vaccine.
The majority of LTC residents (95%) received the mRNA-1273 vaccine as a second booster, and similar vaccine effectiveness against infection and serious outcomes was noted across all vaccination combinations. Nevertheless, vaccine effectiveness against symptomatic infection was higher in those receiving four mRNA-1273 doses or three BNT162b2 doses and one mRNA-1273 dose than in those receiving two BNT162b2 vaccines and two mRNA-1273 vaccines.
conclusion
The fourth vaccination offered a modest increase in effectiveness against infections, symptomatic infections and serious consequences compared to the third dose (received ≥ 84 days earlier). But the marginal effectiveness was low if the third dose was given less than 84 days before. This roughly suggested an interval of three months between the third and fourth doses.
Vaccine effectiveness against infection, symptomatic infection and serious outcomes was higher for second-booster recipients than for triple-vaccinated residents. In conclusion, a fourth COVID-19 mRNA vaccine increased protection against measured outcomes among LTC residents during the Omicron-dominant phase, although the duration of protection requires investigation.