In a recent study published in The British Medical Journal (BMJ), researchers evaluated the effectiveness of the fourth dose of the 2019 coronavirus disease vaccine (COVID-19) among long-term care residents.
Study: Efficacy of a fourth dose of covid-19 mRNA vaccine against the omicron variant among long-term care residents in Ontario, Canada: negative test design study. Image credit: Tequiero / Shutterstock
Long-term care (LTC) residents have an increased risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and severe outcomes. LTC homes in Ontario, Canada, are publicly funded and offer medical and housing support and personal and nursing care for people with disabilities or neurocognitive disorders. LTC residents in Ontario have been disproportionately affected by COVID-19, accounting for approximately two-thirds of fatalities during the first two pandemic waves.
Vaccination of LTC residents resulted in a marked decrease in infections and deaths relative to unvaccinated controls. A third dose of vaccine (first booster) was offered to LTC residents beginning in August 2021 and the fourth vaccine administration (second booster) began on December 30, 2021. Spikevax from Moderna was preferred ( mRNA-1273) for the second reinforcement.
About the study
In the present study, the researchers estimated the marginal efficacy of the fourth dose of vaccine compared to a third dose. The authors implemented a negative test design and determined marginal efficacy (fourth versus third) and vaccine efficacy (fourth dose) among residents of 626 licensed LTC homes in Ontario. Subjects were excluded if they received the second booster before December 30, 2021 or if they tested SARS-CoV-2-positive for the past 30 days.
Only those vaccinated with mRNA vaccines (BNT162b2 [Pfizer] or mRNA-1273) for all four doses were included in the study. Estimation of vaccine effectiveness was limited to SARS-CoV-2 Omicron. Spike gene failure (SGTF) targeting or whole genome sequencing was used to identify the variant. Delta-infected cases were excluded. Provincial data sets on COVID-19 testing, vaccinations, and health administrative information were linked using unique coded identifiers.
Three outcomes were measured: infection (SARS-CoV-2 positivity), symptomatic infection, and severe outcomes. Residents were considered 1) cases if they tested positive at least once a week or 2) tests if negative on all tests that week. Frequencies and means were calculated for categorical and continuous variables, respectively.
Negative test controls were compared with positive test cases using standardized differences. Those vaccinated with a third dose ≥ 84 days before the index test (first positive test for SARS-CoV-2) were compared with those who received the third, second, first or no dose of vaccine <84 days and the fourth dose 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 positive Omicron cases and 20,862 negative controls. The majority of residents (80.1%) were tested several times during the study period. More than half of the cases (58.1%) and controls (53.3%) received only three doses of vaccine, and a higher proportion of controls (38.2%) received the second booster than the cases ( 28%). The marginal effectiveness of the fourth dose ≥ 7 days after vaccination was 19% against infection, 31% against symptomatic infection, and 40% against severe outcomes compared with those vaccinated with a third dose ≥ 84 days before the index test. The corresponding estimates compared to vaccinated residents with a third dose <84 days before the index test were 16% against infection, 20% against symptomatic infection, and 29% against severe outcomes. After seven days of the fourth dose, the effectiveness of the vaccine was 49% against infection, 69% against symptomatic infection, and 86% against severe outcomes. The effectiveness of the third-dose vaccine given ≥ 84 days before the trial was 37% against infection, 55% against symptomatic infection, and 77% against severe outcomes. The efficacy of the vaccine was similar between residents who received three doses of mRNA-1273 and those who received two doses of BNT162b2 and one mRNA vaccine-1273. The majority of LTC residents (95%) received the mRNA-1273 vaccine as a second booster, and a similar effectiveness of the vaccine against infection was observed and severe outcomes in all vaccination combinations. However, the efficacy of the symptomatic infection vaccine was higher among recipients of four doses of mRNA-1273 or three doses of BNT162b2 and one dose of mRNA-1273 than those who received two doses of BNT162b2 and two mRNA-1273 vaccines. A fourth vaccination offered a marginal increase in efficacy over the third dose (received ≥ 84 days earlier) against infection, symptomatic infection, and severe outcomes. But marginal efficacy was lower if the third dose was administered less than 84 days earlier. This broadly suggested the three-month interval between the third and fourth doses. The efficacy of the vaccine against infection, symptomatic infection, and severe outcomes was greater for second booster recipients than for residents with triple vaccination. In conclusion, a fourth COVID-19 mRNA vaccine increased protection against measured outcomes among LTC residents during the dominant phase of Omicron, although the duration of protection should be investigated.Discoveries
Conclusions