Effectiveness of Covid-19 Vaccines over a 9-Month Period in North Carolina

Abstract
BACKGROUND
The duration of protection afforded by coronavirus disease 2019 (Covid-19) vaccines in the United States is unclear. Whether the increase in postvaccination infections during the summer of 2021 was caused by declining immunity over time, the emergence of the B.1.617.2 (delta) variant, or both is unknown.

METHODS
We extracted data regarding Covid-19–related vaccination and outcomes during a 9-month period (December 11, 2020, to September 8, 2021) for approximately 10.6 million North Carolina residents by linking data from the North Carolina Covid-19 Surveillance System and the Covid-19 Vaccine Management System. We used a Cox regression model to estimate the effectiveness of the BNT162b2 (Pfizer–BioNTech), mRNA-1273 (Moderna), and Ad26.COV2.S (Johnson & Johnson–Janssen) vaccines in reducing the current risks of Covid-19, hospitalization, and death, as a function of time elapsed since vaccination.

RESULTS
For the two-dose regimens of messenger RNA (mRNA) vaccines BNT162b2 (30 μg per dose) and mRNA-1273 (100 μg per dose), vaccine effectiveness against Covid-19 was 94.5% (95% confidence interval [CI], 94.1 to 94.9) and 95.9% (95% CI, 95.5 to 96.2), respectively, at 2 months after the first dose and decreased to 66.6% (95% CI, 65.2 to 67.8) and 80.3% (95% CI, 79.3 to 81.2), respectively, at 7 months. Among early recipients of BNT162b2 and mRNA-1273, effectiveness decreased by approximately 15 and 10 percentage points, respectively, from mid-June to mid-July, when the delta variant became dominant. For the one-dose regimen of Ad26.COV2.S (5×1010 viral particles), effectiveness against Covid-19 was 74.8% (95% CI, 72.5 to 76.9) at 1 month and decreased to 59.4% (95% CI, 57.2 to 61.5) at 5 months. All three vaccines maintained better effectiveness in preventing hospitalization and death than in preventing infection over time, although the two mRNA vaccines provided higher levels of protection than Ad26.COV2.S.

CONCLUSIONS
All three Covid-19 vaccines had durable effectiveness in reducing the risks of hospitalization and death. Waning protection against infection over time was due to both declining immunity and the emergence of the delta variant.

Discussion

The estimates of vaccine effectiveness from this study are consistent with and complement the estimates of vaccine efficacy from phase 3 trials.^1-3,18,19 Specifically, the estimated peak levels for the three vaccines in this study are similar to those in phase 3 trials, although phase 3 trials were not powered to determine when the peak occurs. The large sample size of this study allowed us to pinpoint the timing of the peak. The estimates of long-term vaccine effectiveness against Covid-19 shown in this study are lower than results based on limited phase 3 trial data^18,19; however, our study included both symptomatic and asymptomatic infections, and vaccine effectiveness against asymptomatic infection is expected to be lower than that against symptomatic infection, which was the primary end point in the phase 3 trials.

Our results showed that the effectiveness of the two messenger RNA (mRNA) vaccines — BNT162b2 and mRNA-1273 — was very high and durable against hospitalization and death and that mRNA-1273 was somewhat more effective than BNT162b2 against Covid-19. Note that BNT162b2 was given at a lower dose than mRNA-1273 (30 μg per injection vs. 100 μg per injection). In addition, Ad26.COV2.S offered a high level of protection against hospitalization and death, and its effectiveness against Covid-19 reached a peak level similar to that of the two mRNA vaccines 1 month after vaccination and then started to decline.

A recent study from Israel showed that the rate of Covid-19 during the period of July 11 to 31, 2021, among persons who had become fully vaccinated with BNT162b2 in January was 1.6 times as high as the rate among persons who had become fully vaccinated with BNT162b2 in March, and the rate ratio for severe disease was more than 1.8.¹¹ These differences seem more substantial than those observed in the main analysis of our study; however, when a vaccine is highly effective, comparison of the event rates between persons vaccinated in two different time periods conveys a greater sense of waning than comparison of the vaccine effectiveness. Indeed, in our study, the rate of Covid-19 during the period of July 11 to 31, 2021, among persons who had received the second dose of BNT162b2 in January was 1.5 times as high as the rate among persons who had received the second dose of BNT162b2 in March; the rate ratio for hospitalization could not be calculated because of small numbers and incomplete data. A recent study from the state of New York compared vaccine effectiveness in May, June, July, and August of 2021 among persons who were vaccinated in January–February, March, and April of 2021.¹² The life-table method was used to estimate hazard rates over 7-day intervals. The resulting estimates of vaccine effectiveness are unstable, and the confidence intervals are too wide to lead to firm conclusions.

Our study was observational and thus was limited by confounding bias. We adjusted for measured confounders (age, sex, race or ethnic group, geographic region, and county-level vaccination rate). Of greater importance, we measured the time to disease occurrence from the start of the study in order to compare disease incidence between vaccinated and unvaccinated persons on the same date, thus avoiding confounding due to time trends (e.g., level of community transmission and prevalence of new variants). However, persons who choose not to be vaccinated may differ from those who choose to be vaccinated in terms of their use of other prevention measures. In addition, persons who have Covid-19 symptoms may delay vaccination. It would be difficult to quantify the potential bias caused by these confounding factors.

This study included data regarding vaccination history only for persons who were vaccinated in North Carolina by a North Carolina state provider or federal pharmacy provider. Recipient-level vaccination data for North Carolina residents who were vaccinated outside North Carolina and for residents who were vaccinated through a federal entity (Department of Defense, Veterans Health Administration, Indian Health Service, or Federal Bureau of Prisons) are not available through CVMS and therefore were not included in the analysis. Those data represent less than 5% of total vaccine administrations in North Carolina.

Routinely linked communicable-disease and vaccine-registry data from comprehensive statewide surveillance systems are useful for studying vaccine effectiveness. The methods developed for this study can be applied to surveillance-linked laboratory and vaccination data from other states. By combining data from multiple states, we would be able to gain a more comprehensive understanding of vaccine effectiveness in the United States. With additional follow-up data, we would be able to evaluate not only the effectiveness of the original vaccine series beyond 9 months but also the effectiveness of the booster programs and the need for additional boosters.

Source: NEJM