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To date, the European Centre for Disease Prevention and Control (ECDC) and World Health Organization (WHO) have defined four severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) - Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2) variants. The extent of a breakthrough by VOCs into vaccine- or infection-induced immunity is not well understood yet.
Image: Increased risk of infection with SARS-CoV-2 Beta, Gamma, and Delta variant compared to Alpha variant in vaccinated individuals. Image Credit: Imilian/Shutterstock
A study recently posted to the medRxiv* pre-print server investigated whether vaccine- or infection-induced immunity is relatively less effective against infection by specific VOCs.
Study design
The study's researchers used national epidemiological and molecular surveillance data from national community testing in the Netherlands from March to August 2021. The national surveillance database is linked to sequence data through a sample identifier supplied during national community testing. Using this data, they analyzed a total of 28,578 sequenced SARS-CoV-2 samples. The proportion of four VOC were assessed in SARS-CoV-2 positive individuals who were unvaccinated, vaccinated, or had a previous infection. Samples from recently vaccinated individuals, irrespective of their previous infection status, were excluded as they possibly had an incomplete immune response.
From January 2021, the dominance of the Alpha variant increased, and it became the dominant strain in the Netherlands before being replaced by the Delta variant. The Delta variant emerged in June 2021 and was responsible for nearly all the SARS-CoV-2 infections in the country from August 2021 onwards.
In the Netherlands, sequencing of randomly selected RT-PCR positive samples helped monitor mutations in the SARS-CoV-2 virus. The community testing samples of partially or fully vaccinated individuals, plus cases with known prior laboratory-confirmed infection, were sourced on a 3-weekly basis to be included in the study that supplied an additional 1,516 samples for a more detailed investigation of VOCs after vaccination or reinfection.
Key findings
Of the 661,658 positive coronavirus disease 2019 (COVID-19) cases reported in the Netherlands, 5.8% and 3.9% were partially and fully vaccinated, respectively, and the remaining 1.6% were previously infected. In the partially vaccinated category, 65% of individuals received Comirnaty, 19.3% Vaxzevria, 9.8% Janssen, and 5.9% Spikevax vaccines. These are the results for samples collected from March 1st to August, 31st, 2021.
The Alpha variant accounted for the biggest share of infections up to June 2021, causing 94.4% of infections. A small proportion of infections were caused by the Beta and Gamma variants at 1.3% each. An increase in the proportion of Delta variant cases was observed from May to August 2021, from 0.9% to 98.7%, although this pattern was observed across individuals with different immune statuses.
A total of 17,890 Alpha, 209 Beta, 250 Gamma, 11,937 Delta, and 535 other variant sequences were detected. The percentage-wise share of Alpha, Beta, Gamma, Delta, and remaining variant sequences was 58%, 0.7%, 0.8%, and 38.7%, and 1.7%, respectively.
Results of logistic regression analysis
Using VOC as a dependent variable and the immune status of individuals as an independent variable in the logistic regression method, odds ratios (ORs) with 95% confidence interval (CI) for any vaccine type were calculated separately for COVID-19 vaccines - Comirnaty, Spikevax, Vaxzevria, and Janssen. The calculations deriving a 95% CI indicate that vaccine protection is significant.
The analysis showed that full vaccination was significantly associated with the Beta, Gamma, or Delta variant infection with 3.1, 2.3, and 1.9 ORs compared to the Alpha variant. An OR equal to 1.9 for Delta implies a reduction of vaccine effectiveness from 90% to 80%. The association for partial vaccination was less strong and not significant for Beta and Gamma, but still significant for Delta compared to Alpha (OR: 1.6).
The researchers did not find a significant association between previous infection and the Beta (OR 1.4), Gamma (OR 0.3), or Delta (OR 1.0) variant over the Alpha variant. As data indicated significantly higher involvement of the Delta variant in younger age groups, adjustment for the age group became particularly significant during the study. Note that analyses were adjusted for the 10-year age group and sex, using 40-49 years as reference.
Effect of vaccination
The researchers did an additional analysis on time since vaccination, stratifying the fully vaccinated by 14-59 and more than 60 days between complete vaccination and the date used for statistics (DUFS), which is the date relative to which vaccination status is determined. For instance, in symptomatic cases, this is the date of symptom onset. In individuals with a 14-59 days gap between COVID-19 onset and last vaccine dose compared to individuals with 60 days and more (95%CI 1.0-2.1), the association was higher (95% CI 1.6-3.4) for the Delta variant. A similar trend was seen for the Beta and Gamma variants, although with a wider CI.
These findings suggest that the difference in vaccination efficacy (VE) reduces over time since vaccination between the Delta and Alpha variants, most likely due to waning immunity. Further, when stratified by vaccine type, for Comirnaty and Janssen COVID-19 vaccine, the association between the fully vaccinated group and infection with the Delta variant was significant, but not for the Spikevax and Vaxzevria vaccines. The association between partial vaccination and the Delta variant was only significant for the Comirnaty and Vaxzevria vaccines.
Conclusions
The study's results point out several important observations. First, naïve and previously infected individuals are equally susceptible to any of the investigated VOCs.
Second, there is no evidence that vaccination-induced immunity gives better protection against infection compared to the immunity from previous infection. However, vaccination is preferred over primary infection to protect individuals against severe disease, as that has a higher risk of hospitalization or death, especially in older persons or individuals with underlying health conditions considering cumulative risk from two infections.
Lastly, the study results confirmed lower vaccine effectiveness against the Delta variant and the Beta and Gamma variants, compared to the Alpha variant even after being fully vaccinated, regardless of the vaccine used. These findings could help in devising new vaccine strategies against COVID-19 for the future.
*Important notice
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.