SARS-CoV-2 Delta variant associated with more breakthrough infections

A US-based study conducted in the National Capital Region has recently compared the infectious virus loads in vaccinated and unvaccinated individuals infected with the delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

The study highlights that compared to the previously circulating alpha variant, the delta variant is associated with higher infectious virus load and a lower level of humoral immunity in the upper respiratory tract. The study is currently available on the medRxiv* preprint server prior to peer review.

Background

With the progression of coronavirus disease 2019 (COVID-19) pandemic, the evolution of the SARS-CoV-2 genome has resulted in the emergence of viral variants of concern (VOCs) that have significantly increased transmissibility, infectivity, and virulence. One such VOC is the delta variant which was first detected in India during the second pandemic wave. Soon after emergence, the delta variant has rapidly spread globally and replaced the previously dominating alpha variant.

According to available literature, the delta variant is capable of inducing breakthrough infections in fully vaccinated individuals, and that delta infections are associated with high viral loads.

The study

In the current study, the scientists have estimated the prevalence of SARS-CoV-2 variants in the National Capital Region by analyzing the whole genome sequencing of 2,785 clinical isolates. Moreover, they have analyzed cases with delta and alpha infections to investigate the disease severity, viral load, presence of infectious viruses, and levels of IgG-specific anti-SARS-CoV-2 infections in the upper respiratory tract.

Important observations

During the 6-month study period, sequencing of 2,785 genomes revealed the delta variant gradually replaced the alpha variant in the National Capital Region. Compared to the alpha variant, the delta variant caused a significant induction in vaccine breakthrough infections. However, most of these breakthrough cases were associated with a significantly longer duration between vaccination and infection.

Cycle threshold (Ct) values of Alpha, Delta, and control variants. A) Ct values of B.1.2 (N = 254), Alpha (N = 562), and Delta (N = 98) variants from all samples with available Ct values. B and C) Correlation of Ct values and ranges of days after the onset of symptoms B) 0 to 5 days, C) >5 days. For this analysis, samples from asymptomatic patients were not included (N: B.1.2 = 214, Alpha = 511, Delta = 75). D) Ct values of Alpha and Delta variants broken down by vaccination status. Alpha (unvacccinated, N = 442, fully vaccinated N = 42), Delta (unvaccinated, N = 47, fully vaccinated N = 23). For this analysis, samples from partially vaccinated patients were not included. E and F) Correlation of Ct values and ranges of days after the onset of symptoms of the Alpha and Delta variants divided by the vaccination status. E) 0 to 5 days, F) >5 days. One-way ANOVA * p < 0.05, ** p < 0.001, ***, p < 0.0001.
Cycle threshold (Ct) values of Alpha, Delta, and control variants. A) Ct values of B.1.2 (N = 254), Alpha (N = 562), and Delta (N = 98) variants from all samples with available Ct values. B and C) Correlation of Ct values and ranges of days after the onset of symptoms B) 0 to 5 days, C) >5 days. For this analysis, samples from asymptomatic patients were not included (N: B.1.2 = 214, Alpha = 511, Delta = 75). D) Ct values of Alpha and Delta variants broken down by vaccination status. Alpha (unvaccinated, N = 442, fully vaccinated N = 42), Delta (unvaccinated, N = 47, fully vaccinated N = 23). For this analysis, samples from partially vaccinated patients were not included. E and F) Correlation of Ct values and ranges of days after the onset of symptoms of the Alpha and Delta variants divided by the vaccination status. E) 0 to 5 days, F) >5 days. One-way ANOVA * p < 0.05, ** p < 0.001, ***, p < 0.0001.

Clinical consequences

Both alpha and delta variants were associated with comparable clinical consequences in terms of hospital admission and mortality. Compared to a previously circulating SARS-CoV-2 variant (B.1.2 lineage), the alpha variant exhibited a significantly higher number of symptomatic infections, hospitalizations, and intensive care unit (ICU) admissions. However, the COVID-19 related mortality remained similar for these variants.

Infections in vaccinated and unvaccinated individuals

A significantly higher frequency of symptomatic infections was observed in vaccine breakthrough cases with the delta variant compared to that in the alpha-related breakthrough cases. However, the duration between vaccination and breakthrough infection was considerably higher for the delta variant than for the alpha variant.

No significant difference in hospitalization was observed between alpha and delta infections in both vaccinated and unvaccinated individuals. However, unlike delta breakthrough infections, vaccine breakthrough infections with the alpha variant were associated with multiple comorbidities, including hypertension, kidney disease, heart failure, and coronary artery disease.

Viral load in upper respiratory tract

Among vaccine breakthrough cases, delta infections were associated with significantly higher viral loads compared to alpha infections. However, within each variant, no significant difference in viral load was observed between vaccinated and unvaccinated individuals.     

Similarly, more infectious viruses were detected in individuals with delta infection compared to alpha infection cases. Vaccinated individuals with alpha breakthrough infections showed a significantly lower amount of contagious virus than unvaccinated individuals. In contrast, an equivalent amount of infectious virus was detected in vaccinated and unvaccinated individuals with delta infections.

Humoral immunity in upper respiratory tract

Among cases with alpha infection, significantly higher levels of IgG-specific anti-SARS-CoV-2 antibodies were observed in vaccinated individuals compared to that in unvaccinated individuals.

In the case of delta infection, the number of individuals with detectable antibody levels was higher in the vaccinated group compared to the unvaccinated group. However, no significant difference in antibody level was observed between the two groups.

Importantly, for both alpha and delta breakthrough infections, a lower antibody level in the upper respiratory tract was associated with a higher amount of infectious virus.

Study significance

The study findings indicate that the delta variant of SARS-CoV-2 is capable of inducing symptomatic infection even in vaccinated individuals. In addition, Delta infections are associated with higher infectious virus loads compared to alpha infections. Importantly, no impact of vaccination on infectious virus load has been observed among individuals with delta infections.

Furthermore, the study highlights that the risk of acquiring delta breakthrough infections increases with an increase in the interval since the last vaccination.

*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.

Journal reference:
Dr. Sanchari Sinha Dutta

Written by

Dr. Sanchari Sinha Dutta

Dr. Sanchari Sinha Dutta is a science communicator who believes in spreading the power of science in every corner of the world. She has a Bachelor of Science (B.Sc.) degree and a Master's of Science (M.Sc.) in biology and human physiology. Following her Master's degree, Sanchari went on to study a Ph.D. in human physiology. She has authored more than 10 original research articles, all of which have been published in world renowned international journals.

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