Effectiveness of mRNA-1273 against SARS-CoV-2 omicron and delta variants

Abstract

Background The recently emerged SARS-CoV-2 omicron variant raised concerns around potential escape from vaccine-elicited immunity. Limited data are available on real-world vaccine effectiveness (VE) of mRNA-1273 against omicron. Here, we report VE of 2 or 3 mRNA-1273 doses against infection and hospitalization with omicron and delta, including among immunocompromised individuals. Methods This test negative study was conducted at Kaiser Permanente Southern California. Cases were individuals aged ≥18 years testing positive by RT-PCR with specimens collected between 12/6/2021 and 12/23/2021 with variant determined by spike gene status. Randomly sampled test negative controls were 5:1 matched to cases by age, sex, race/ethnicity, and specimen collection date. Conditional logistic regression models were used to evaluate adjusted odds ratio (aOR) of vaccination with mRNA-1273 doses between cases and controls. VE(%) was calculated as (1-aOR)x100. Results 6657 test positive cases (44% delta, 56% omicron) were included. The 2-dose VE against omicron infection was 30.4% (95% CI, 5.0%-49.0%) at 14-90 days after vaccination and declined quickly thereafter. The 3-dose VE was 95.2% (93.4%-96.4%) against delta infection and 62.5% (56.2%-67.9%) against omicron infection. The 3-dose VE against omicron infection was low among immunocompromised individuals (11.5%; 0.0%-66.5%). None of the cases (delta or omicron) vaccinated with 3 doses were hospitalized compared to 53 delta and 2 omicron unvaccinated cases. Conclusions VE of 3 mRNA-1273 doses against infection with delta was high and durable, but VE against omicron infection was lower. VE against omicron infection was particularly low among immunocompromised individuals. No 3-dose recipients were hospitalized for COVID-19.

Clinical outcomes associated with Omicron (B.1.1.529) variant and BA.1/BA.1.1 or BA.2 subvariant infection in southern California

“…This result is consistent with studies showing reduced neutralization efficiency of two and three doses of BNT162b2 vaccine against the Omicron variant (versus non-Omicron variants) [3,26]. Similarly, in multiple settings, vaccination with two doses showed slightly lower effectiveness against hospitalization with Omicron vs. Delta variant infections [6][7][8]. Our finding of higher relative protection against Delta variant infections is reassuring considering the greater severity observed in infections with the Delta variant as compared to the Omicron variant.…”

“…We have quantified two aspects of comparative severity of Omicron vs. Delta variant infections: the risk of progression to severe endpoints among diagnosed cases, and the risk of progression to acute respiratory symptoms among those first diagnosed before symptoms onset. While attenuation of disease severity in association with the Omicron variant is an encouraging finding, prior evidence of higher transmissibility of Omicron variant infections [27], as well as immune evasion from prior infection [28] and vaccination [6–8], are concerning. Rapid spread of the Omicron variant in a compressed time period has led to unprecedented surges in COVID-19 among our study population and others globally.…”

“…Reduced neutralization of the Omicron variant has been reported in studies using plasma specimens from individuals with complete (two-or three-dose) mRNA vaccine series [3], and from patients with prior SARS-CoV-2 infection [4]. Epidemiologic data from South Africa have suggested higher rates of Omicron variant infections among persons with prior SARS-CoV-2 infection, as compared to observations with previous variants [5], while early observational studies have suggested reduced effectiveness of COVID-19 vaccines against Omicron variant infection [6][7][8]. However, increases in SARS-CoV-2 infections following emergence of the Omicron variant have not been associated with parallel increases in hospitalizations and deaths in the same proportions experienced during previous waves [9][10][11].…”

Increased risk of infection with SARS-CoV-2 Omicron BA.1 compared with Delta in vaccinated and previously infected individuals, the Netherlands, 22 November 2021 to 19 January 2022

“…This is in accordance with in vitro studies that showed a 30–40-fold reduction in neutralisation of the Omicron variant compared with wild type when using convalescent sera or sera of individuals who had completed the primary vaccination series [ 5 - 7 ]. Several studies have reported a substantial reduction in vaccine effectiveness against infection with the Omicron variant compared with Delta after primary vaccination [ 13 - 16 ]. After booster vaccination, the vaccine effectiveness against infection with the Omicron variant increased but was still lower than against Delta [ 14 - 18 ].…”

Effectiveness of COVID-19 vaccines against Omicron or Delta symptomatic infection and severe outcomes

“…3 A reduction in neutralizing antibodies against Omicron following second and third doses of mRNA vaccines has been established, [4][5][6][7][8][9] but real-world data evaluating vaccine performance against Omicron infection are still emerging. [10][11][12][13][14][15][16][17][18] We previously estimated vaccine effectiveness (VE) against infection (irrespective of symptoms or severity) in the initial period following identification of Omicron in Ontario, in order to support urgent public health decisions. 19 At that time, data on symptoms were unavailable, and few cases involved hospital admission to evaluate severe outcomes.…”