Effectiveness of inactivated and Ad5-nCoV COVID-19 vaccines against SARS-CoV-2 Omicron BA. 2 variant infection, severe illness, and death

Abstract

Background: Limited data are available on the effectiveness of inactivated and Ad5-nCoV COVID-19 vaccines in real-world use-especially against Omicron variants in SARS-CoV-2 infection-naïve population.

Methods: A matched case-control study was conducted among people aged ≥ 3 years between 2 December 2021 and 13 May 2022. Cases were SARS-CoV-2-infected individuals, individuals with severe/critical COVID-19, or COVID-19-related deaths. Controls were selected from consecutively test-negative individuals at the same time as cases were diagnosed and were exact-matched on year-of-age, gender, birthplace, illness onset date, and residential district in ratios of 1:1 with infected individuals and 4:1 with severe/critical COVID-19 and COVID-19-related death. Additionally, two subsets were constructed to analyze separate vaccine effectiveness (VE) of inactivated vaccines (subset 1) and Ad5-vectored vaccine (subset 2) against each of the three outcomes.

Results: Our study included 612,597 documented SARS-CoV-2 infections, among which 1485 progressed to severe or critical illness and 568 died. Administering COVID-19 vaccines provided limited protection against SARS-CoV-2 infection across all age groups (overall VE: 16.0%, 95% CI: 15.1-17.0%) but high protection against severe/critical illness (88.6%, 85.8-90.8%) and COVID-19-related death (91.6%, 86.8-94.6%). In subset 1, inactivated vaccine showed 16.3% (15.4-17.2%) effective against infection, 88.6% (85.8-90.9%) effective against severe/critical COVIID-19, and 91.7% (86.9-94.7%) against COVID-19 death. Booster vaccination with inactivated vaccines enhanced protection against severe COVID-19 (92.7%, 90.1-94.6%) and COVID-19 death (95.9%, 91.4-98.1%). Inactivated VE against infection began to wane 12 weeks after the last dose, but two and three doses sustained high protection levels (> 80%) against severe/critical illness and death, while subset 2 showed Ad5-vectored vaccine was 13.2% (10.9-15.5%) effective against infection and 77.9% (15.6-94.2%) effective against severe/critical COVIID-19.

Conclusions: Our real-world study found high and durable two- and three-dose inactivated VE against Omicron-associated severe/critical illness and death across all age groups, but lower effectiveness against Omicron infection, which reinforces the critical importance of full-series vaccination and timely booster dose administration for all eligible individuals.

Keywords: COVID-19; Case-control study; Inactivated vaccine; Vaccine effectiveness.

Fig. 1

Participant enrollment flowchart

Fig. 2

Vaccination status in the control group and cumulative documented SARS-CoV-2 infections by age grouping in Shanghai, 1 December 2021 through 13 May 2022. Also shown are public health and social measures implemented during the study period. Data for the cumulative incidence of SARS-CoV-2 infection was provided by Shanghai Health Commission

Fig. 3

Vaccine effectiveness of inactivated vaccines against documented SARS-CoV-2 infection, severe or critical illness, and COVID-19 death in the matched case-control study. VEs were from univariate conditional logistic regression and were unadjusted for baseline characteristics for the exact matching process. The effectiveness of at least one dose of inactivated vaccines was estimated in the whole population and in subgroups defined by strata of age, gender, and resident region. The effectiveness of each vaccination course was estimated in the whole population

Fig. 4

VE (%) of inactivated vaccine against documented SARS-CoV-2 infection, severe or critical illness, and death by doses and time interval. Data are presented with VEs (black points) and 95% confidence intervals (color zones). To visualize the trend of vaccine effectiveness (dark blue lines), we smoothed the VE results by performing three spline interpolations of the calculated data points for the corresponding time period. Small sample sizes of corresponding cells lead to wide confidence intervals. Eight individuals had severe/critical illness and two died within first-dose intervals