Comparative Single-Dose mRNA and ChAdOx1 Vaccine Effectiveness Against Severe Acute Respiratory Syndrome Coronavirus 2, Including Variants of Concern: Test-Negative Design, British Columbia, Canada
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Abstract
Background
In British Columbia, Canada, most adults 50–69 years old became eligible for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in April 2021, with chimpanzee adenoviral vectored vaccine (ChAdOx1) restricted to ≥55-year-olds and second doses deferred ≥6 weeks to optimize single-dose coverage.
Methods
Among adults 50–69 years old, single-dose messenger RNA (mRNA) and ChAdOx1 vaccine effectiveness (VE) against SARS-CoV-2 infection and hospitalization, including variant-specific, was assessed by test-negative design between 4 April and 2 October 2021.
Results
Single-dose VE included 11 861 cases and 99 544 controls. Median of postvaccination follow-up was 32 days (interquartile range, 15–52 days). Alpha, Gamma, and Delta variants comprised 23%, 18%, and 56%, respectively, of genetically characterized viruses. At 21–55 days postvaccination, single-dose mRNA and ChAdOx1 VE (95% confidence interval [CI]) was 74% (71%–76%) and 59% (53%–65%) against any infection and 86% (80%–90%) and 94% (85%–97%) against hospitalization, respectively. VE (95% CI) was similar against Alpha and Gamma infections for mRNA (80% [76%–84%] and 80% [75%–84%], respectively) and ChAdOx1 (69% [60%–76%] and 66% [56%–73%], respectively). mRNA VE was lower at 63% (95% CI, 56%–69%) against Delta but 85% (95% CI, 71%–92%) against Delta-associated hospitalization (nonestimable for ChAdOx1).
Conclusions
A single mRNA or ChAdOx1 vaccine dose gave important protection against SARS-CoV-2, including early variants of concern. ChAdOx1 VE was lower against infection, but 1 dose of either vaccine reduced the hospitalization risk by >85% to at least 8 weeks postvaccination. Findings inform program options, including longer dosing intervals.
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SciScore for 10.1101/2021.09.20.21263875: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Field Sample Permit: Data sources and exclusions: Specimens were sampled from the provincial database that captures all RT-PCR testing for SARS-CoV-2 in BC along with client, collection and testing details although symptoms and onset dates are not consistently captured.
IRB: Ethics statement: Data linkages and analyses were authorized by the Provincial Health Officer under the Public Health Act and exempt from research ethics board review.Sex as a biological variable Source population: There are ∼1.4 million adults 50-69-years-old in BC (27% of the 5.2 million population) of whom 51% are 50-59 years and 51% are women [12]. Randomization Three approaches were explored for test-negative control … SciScore for 10.1101/2021.09.20.21263875: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Field Sample Permit: Data sources and exclusions: Specimens were sampled from the provincial database that captures all RT-PCR testing for SARS-CoV-2 in BC along with client, collection and testing details although symptoms and onset dates are not consistently captured.
IRB: Ethics statement: Data linkages and analyses were authorized by the Provincial Health Officer under the Public Health Act and exempt from research ethics board review.Sex as a biological variable Source population: There are ∼1.4 million adults 50-69-years-old in BC (27% of the 5.2 million population) of whom 51% are 50-59 years and 51% are women [12]. Randomization Three approaches were explored for test-negative control selection: (1) all negative specimens; (2) only the most recent negative specimen; or (3) only one randomly-selected negative specimen. Blinding not detected. Power Analysis The latter was chosen balancing the capacity to genetically characterize all contributing case viruses, and the vaccine coverage and infection rates required for a sufficient number of vaccinated, variant-specific cases driving statistical power. Table 2: Resources
Software and Algorithms Sentences Resources Detailed methods for genetic characterization are provided in Supplementary Material 1, predicated foremost on whole genome sequencing but also RT-PCR single-nucleotide polymorphism screen for Alpha and Gamma variants [10,15,16]. Gammasuggested: (GAMMA, RRID:SCR_009484)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:The main limitation of our study, as elsewhere, is reliance on general laboratory submissions and clinical or surveillance data subject to missing information, misclassification, and selection bias. We attempted to standardize the likelihood of test-positivity by excluding specimens collected for non-clinical screening purposes (e.g. private testing). Testing for vaccine-associated adverse events mimicking but not due to COVID-19 (e.g., flu-like symptoms) may explain positively-biased VE estimates during the first few days following vaccination, which persisted longer for ChAdOx1 perhaps owing to heightened vaccine safety concerns. Aligned with that hypothesis, we highlight lower test-positivity among vaccinated individuals during days 0-3 vs. 4-7 post-vaccination (Supplementary Table 4). The TND partially standardizes for healthcare seeking behaviours, while other variations associated with both vaccination and exposure risk could still play a role. We cannot rule out residual bias and confounding. Unlike mRNA vaccines, ChAdOx1 was available to eligible age groups in BC through pharmacies without awaiting invitation to public clinics; those at higher risk may have preferentially received this vaccine, contributing to lower VE. Conversely, if ChAdOx1 recipients were generally more risk averse in their behaviours our ChAdOx1 VE may also be an over-estimate. Reassuring against bias in either direction, ChAdOx1 estimates reported here align well with clinical trial findings. In ...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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