A recent study conducted by Portuguese scientists has claimed that mRNA-based coronavirus disease 2019 (COVID-19) vaccines are less effective against the delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Moreover, in breakthrough infections by delta variant, vaccines are less effective in reducing viral loads. The study is currently available on the medRxiv* preprint server.
*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
Background
The delta variant of SARS-CoV-2 belonging to the B.1.617 lineage was first identified in India during the second pandemic wave. Soon after identification, the variant has spread rapidly within and outside the country, causing a sharp increase in new COVID-19 cases globally. In Portugal, the delta variant has been first detected in April 2021 and has rapidly become dominant, accounting for 90% of all new cases by June 2021.
Both in clinical trials and real-world pandemic setups, the majority of currently available COVID-19 vaccines have shown high efficacy in preventing SARS-CoV-2 infection and symptomatic COVID-19. However, after the emergence of the delta variant, several vaccine-breakthrough cases have been reported in many countries. This suggests that the delta variant is capable of escaping vaccine-induced immune responses.
In the current study, the scientists have examined the effectiveness of mRNA-based COVID-19 vaccines against the delta (B.1.617.2) and alpha (B.1.1.7; first identified in the UK) variants. Moreover, they have investigated whether these vaccines can reduce viral burdens in breakthrough cases.
Study design
A total of 2,097 laboratory-confirmed COVID-19 cases were included in the study. The identification of causative viral variants was made by whole-genome sequencing or spike gene target failure analysis.
Two mRNA vaccines were considered in the study: BNT162b2 developed by Pfizer/BioNTech and mRNA-1273 developed by Moderna. Based on vaccination status, the enrolled cases were divided into different categories: unvaccinated prior to COVID-19 diagnosis; disease diagnosis within or after 14 days of 1st vaccine dose; and disease diagnosis within or after 14 days of 2nd vaccine dose.
Ct value paired means distribution (Ct N and Ct ORF1ab) by variant and vaccination status
Important observations
Of all enrolled cases, 1,366 were with delta infection and 731 were with alpha infection. The number of individuals aged above 70 years was significantly higher among delta cases compared to that among alpha cases.
About 12% of fully vaccinated individuals exhibited delta breakthrough infection, whereas alpha breakthrough infections were observed in only 5% of fully vaccinated individuals. A similar trend was observed among partially vaccinated individuals. This observation suggests that mRNA vaccines are less effective against the delta variant compared to that against the alpha variant.
Viral load
For both alpha and delta infections, relatively lower viral loads were observed in fully vaccinated individuals compared to that in unvaccinated individuals. However, irrespective of vaccination status, the average viral load was higher in delta infections compared to that in alpha infections. Importantly, although the viral load was comparatively lower in vaccine breakthrough cases, the average difference in viral load between vaccinated and unvaccinated patients was significantly higher for alpha infections compared to that for delta infections (Ct value of 4.49 vs. Ct value of 2.24).
A statistically significant difference in average viral load was observed for the alpha variant between partially vaccinated and unvaccinated individuals. In contrast, no such difference was observed for the delta variant. This indicates that partial vaccination is not effective in reducing viral load in individuals with delta infection.
Study significance
Overall, the study findings reveal that mRNA-based COVID-19 vaccines are less effective against the delta variant than that against the alpha variant. In other words, compared to the alpha variant, the delta variant of SARS-CoV-2 may be less susceptible to vaccine-mediated neutralization. In both vaccinated and unvaccinated individuals, delta infection is associated with a higher viral load than alpha infection.
Importantly, although a comparatively reduced viral load has been observed in vaccinated individuals, this reduction is 50% lower for delta infections compared to that for alpha infections. This indicates that the impact of vaccination on viral load is less pronounced in individuals with delta breakthrough infections.
Individuals with high viral loads are generally believed to be more likely to transmit the virus to others. Thus, based on the study findings, the scientists suggest that proper implementation of non-pharmacological control measures together with vaccination is required to control viral transmission.
*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.
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