Abstract and Introduction
CDC recommends that all persons aged ≥18 years receive a single COVID-19 vaccine booster dose ≥2 months after receipt of an Ad.26.COV2.S (Janssen [Johnson & Johnson]) adenovirus vector-based primary series vaccine; a heterologous COVID-19 mRNA vaccine is preferred over a homologous (matching) Janssen vaccine for booster vaccination. This recommendation was made in light of the risks for rare but serious adverse events following receipt of a Janssen vaccine, including thrombosis with thrombocytopenia syndrome and Guillain-Barré syndrome†, and clinical trial data indicating similar or higher neutralizing antibody response following heterologous boosting compared with homologous boosting. Data on real-world vaccine effectiveness (VE) of different booster strategies following a primary Janssen vaccine dose are limited, particularly during the period of Omicron variant predominance. The VISION Network§ determined real-world VE of 1 Janssen vaccine dose and 2 alternative booster dose strategies: 1) a homologous booster (i.e., 2 Janssen doses) and 2) a heterologous mRNA booster (i.e., 1 Janssen dose/1 mRNA dose). In addition, VE of these booster strategies was compared with VE of a homologous booster following mRNA primary series vaccination (i.e., 3 mRNA doses). The study examined 80,287 emergency department/urgent care (ED/UC) visits¶ and 25,244 hospitalizations across 10 states during December 16, 2021–March 7, 2022, when Omicron was the predominant circulating variant.** VE against laboratory-confirmed COVID-19–associated ED/UC encounters was 24% after 1 Janssen dose, 54% after 2 Janssen doses, 79% after 1 Janssen/1 mRNA dose, and 83% after 3 mRNA doses. VE for the same vaccination strategies against laboratory-confirmed COVID-19–associated hospitalizations were 31%, 67%, 78%, and 90%, respectively. All booster strategies provided higher protection than a single Janssen dose against ED/UC visits and hospitalizations during Omicron variant predominance. Vaccination with 1 Janssen/1 mRNA dose provided higher protection than did 2 Janssen doses against COVID-19–associated ED/UC visits and was comparable to protection provided by 3 mRNA doses during the first 120 days after a booster dose. However, 3 mRNA doses provided higher protection against COVID-19–associated hospitalizations than did other booster strategies during the same time interval since booster dose. All adults who have received mRNA vaccines for their COVID-19 primary series vaccination should receive an mRNA booster dose when eligible. Adults who received a primary Janssen vaccine dose should preferentially receive a heterologous mRNA vaccine booster dose ≥2 months later, or a homologous Janssen vaccine booster dose if mRNA vaccine is contraindicated or unavailable. Further investigation of the durability of protection afforded by different booster strategies is warranted.
VISION Network methods have been previously published. Across 306 ED/UC clinics and 164 hospitals from 10 states, all medical encounters among adults aged ≥18 years with a COVID-19–like illness diagnosis†† who had received molecular testing (primarily with reverse transcription–polymerase chain reaction) for SARS-CoV-2 during the 14 days before through 72 hours after the medical encounter were considered eligible. The study period began on the earliest day the Omicron variant accounted for ≥50% of sequenced isolates at each site based on state and national surveillance data (state range = December 16–26, 2021). Vaccination status was categorized based on number and type of vaccine doses received (1 Janssen dose, 2 Janssen doses, 1 Janssen/1 mRNA dose, and 3 mRNA doses§§). Patients with no record of vaccination were considered unvaccinated. Because a booster dose following a primary Janssen dose was recommended on October 15, 2021, to ensure accurate comparisons across booster strategies, patients vaccinated with a booster dose >120 days before the index date¶¶ were excluded. In addition, patients were excluded if they 1) received only 1 or 2 primary mRNA vaccine doses or >3 mRNA vaccine doses, or received >2 mRNA doses following a primary Janssen dose; 2) received the first Janssen dose 1–13 days earlier or a booster dose 1–6 days earlier; or 3) received a booster dose following a primary Janssen dose earlier than the recommended interval (<2 months after dose 1) or an mRNA booster dose earlier than the recommended interval (<5 months after dose 2).***
Using a test-negative design, investigators estimated VE by comparing the odds of a positive SARS-CoV-2 test result between vaccinated and unvaccinated patients using multivariable logistic regression models.[3,4] Models were adjusted using inverse propensity to be vaccinated weights (calculated separately for each VE estimate) and with age, calendar week of index date, geographic area, local virus circulation (percentage of SARS-CoV-2–positive results from testing within the counties surrounding the facility on the date of the encounter), patient comorbidities including immunocompromise†††, and factors not balanced by propensity to be vaccinated included as covariates.§§§ A statistically significant difference was indicated by nonoverlapping 95% CIs or standardized mean or proportion differences ≥0.2, indicating nonnegligible difference in distributions of vaccination or infection status. All statistical analyses were conducted using R software (version 4.1.2; R Foundation). This study was reviewed and approved by the institutional review boards at participating sites or under a reliance agreement with the Westat, Inc. institutional review board.¶¶¶
The study included 80,287 encounters among patients with COVID-19–like illness seeking care at ED/UC facilities (Table 1); 64.8% were unvaccinated, 5.6% had received 1 Janssen dose, 0.6% had received 2 Janssen doses, 1.6% had received 1 Jansen/1 mRNA dose, and 27.4% had received 3 mRNA doses. Among booster strategies, the median interval between receipt of the most recent dose and the ED/UC encounter ranged from 49 to 59 days.
Overall, VE against laboratory-confirmed COVID-19–associated ED/UC encounters was significantly higher among patients who had received any booster dose (range = 54%–83%) compared with those who had received only 1 Janssen dose (24%) (Table 2). Among booster strategies, VE against laboratory-confirmed COVID-19–associated ED/UC encounters was significantly higher among patients who had received 1 Janssen/1 mRNA (79%) or 3 mRNA doses (83%) than among patients who had received 2 Janssen doses (54%).
The study included 25,244 hospitalizations among patients with COVID-19–like illness (Table 3); 61.1% were unvaccinated, 5.7% had received 1 Janssen dose, 0.6% had received 2 Janssen doses, 1.5% had received 1 Janssen/1 mRNA dose, and 31.0% had received 3 mRNA doses. Among booster strategies, the median interval between receipt of the most recent dose and hospitalization ranged from 48 to 59 days.
Overall, VE against laboratory-confirmed COVID-19–associated hospitalization was significantly higher among patients who had received any booster dose (range = 67%–90%) compared with patients who had received 1 Janssen dose (31%) (Table 2). Among booster strategies, VE against hospitalizations was significantly higher among patients who had received 3 mRNA doses (90%). VE against hospitalizations was 78% after 1 Janssen/1 mRNA dose and 67% after 2 Janssen doses; however, CIs overlapped.
Morbidity and Mortality Weekly Report. 2022;71(13):495-502. © 2022 Centers for Disease Control and Prevention (CDC)