A new paper in the New England Journal of Medicine reports increased breakthrough infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. This is despite the widespread rollout of COVID-19 vaccines in the US. The paper examines the reasons for this phenomenon.
Study: Efficacy of Covid-19 vaccines over 9 months in North Carolina. Credit: Alexander Lukatskiy/Shutterstock
background
The unprecedented speed at which vaccines were being developed to counter the explosion in COVID-19 cases and the overwhelming demands placed on healthcare facilities to treat moderate to critical illnesses were a modern marvel. The first two vaccines to receive emergency use authorization were developed on a messenger ribonucleic acid (mRNA) platform, and both reported approximately 95% efficacy in late-stage clinical trials.
Johnson & Johnson’s third vaccine was then approved for emergency use.
Despite the initial drop in cases, there was a spike in breakthrough infections from the summer of 2021 and through the fall. This has been the subject of many studies. However, most were not yet large enough to determine the reasons for the observed increase in infections – whether due to declining immunity or because the emerging variants, particularly the delta variant, are more transmissible and more resistant to antibody-mediated neutralization are after a vaccination or natural infection.
The current study uses immunization surveillance data collected from North Carolina. This is important as it provides a basis for evaluating the effectiveness of vaccines in real-world conditions. The aim was to estimate the vaccine efficacy for all three vaccines in the US against infection, symptomatic illness and death in the three months after vaccination.
North Carolina’s population is diverse, with more Black, Asian, and Pacific Islander people than the national average. The most commonly used vaccine was the Pfizer, followed by the Moderna vaccine.
What did the study show?
The two-dose regimens of each of the mRNA vaccines showed peak efficacy of about 95% two months after the first dose, but then began to decline. For the Pfizer vaccine, the nadir was about 67% at seven months, versus 80% for Moderna at that point. Thus, the effectiveness of the two vaccines showed a difference of seven percentage points from four to seven months and ten percentage points after ten months.
For the J&J vaccine (single-shot regimen), efficacy peaked at 75% at one month, began to decline almost immediately, and reached 59% at five months. At the time of the study, only five months of follow-up was available because this vaccine was first used much later than the other two.
However, the 10 and 15 percentage point drop in efficacy in those who received the first dose of the Moderna and Pfizer mRNA vaccines, respectively, prior to March 2021 compared to the earlier drop suggests an additional contribution from immune escape properties of the delta variant, exacerbating the decline in vaccine-induced protection.
Data on hospitalizations was incomplete, but available data shows that Pfizer’s protection against critical illnesses requiring hospitalization at two months was 96% versus 97% for Moderna. For seven months, it stabilized at 88% and 94%, respectively. For the J&J vaccine, peak efficacy was 86% at two months and dropped to 80% by 6 months.
The least effectiveness against infection or hospitalization was in older adults (65 years or older) compared to younger ones. Nonetheless, the overall trends were similar across most parameters, including gender, race, geographic location, and nationwide immunization rates. The failure to observe different rates of decline consistent with the phase of the pandemic, as would occur in groups vaccinated over different time periods, suggests that waning immunity is the main reason for the rise in infections.
For deaths from COVID-19, Pfizer and Moderna vaccines provided 98% and 99% protection at two months, respectively, and remained at 91% and 96%, respectively, at up to 7 months. For the J&J vaccine, these were 86% and >70, respectively, but with lower confidence.
Thus, all three vaccines were best suited to prevent serious and fatal illnesses due to SARS-CoV-2 infection, although they also did a superior job of preventing infection over time. The mRNA vaccines were consistently more protective than the J&J vaccine.
What are the effects?
The results of this study demonstrate the effectiveness of the vaccine in real-world settings in a population with symptomatic and asymptomatic infections covering all grades. All three COVID-19 vaccines were extremely effective in reducing the risk of hospitalization and death. The mRNA vaccines were more effective, particularly against serious illness and death, and against infection.
The decline in protection against infection over time was due to declining immunity and the emergence of the Delta variant. In Israel, for example, the breakthrough infection rate was 60% higher in those who had been double-vaccinated in January than in those who had received both doses in March 2021, while serious illness was 80% higher in the former group.
Follow-up studies are warranted, combining multi-state data to validate these estimates of vaccine efficacy beyond nine months and the efficacy of additional booster doses. This could also help in deciding the need for such programs.
