In a recent The Lancet Infectious Diseases study, researchers assess how fast the Alpha and Delta variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmit by estimating the generation time of the variants from transmission data in a household study.
Study: Generation time of the alpha and delta SARS-CoV-2 variants: an epidemiological analysis. Image Credit: MIA Studio / Shutterstock.com
Introduction
SARS-CoV-2, the virus responsible for the coronavirus disease 2019 (COVID-19), has mutated into different variants throughout the current pandemic. Before the currently dominant Omicron (B.1.1.529) variant emerged, the SARS-CoV-2 Delta (B.1.617.2) variant was the dominant circulating strain throughout both the United Kingdom and most countries around the world. Despite the protection conferred through vaccination, the Delta variant presented a high risk of severe disease as compared to previous strains of SARS-CoV-2.
Defining virus transmissibility
The speed and strength of a variant is a measure of its transmissibility. The speed of the variant refers to the rate at which it grows at the population level. Moreover, variant speed is measured by the exponential growth rate, which can be inferred from the infection incidence data in a given population.
Comparatively, the strength of the variant reflects its transmissibility and is measured by its time-dependent reproduction number. The reproduction number, which reflects the infectiousness of a virus, refers to the number of individuals that each infected person is estimated to infect in a given population.
The relationship between the speed and strength of a variant is determined by the generation time, which is the time between infection events in infector-infectee pairs. The generation time is required in most modeling studies on transmission and control of variants. Thus, this parameter is rigorously used by epidemiologists to monitor the spread of viruses and assess the effectiveness of interventions according to daily reported new cases.
Taken together, an increased number of COVID-19 cases is attributable to high virus transmission, a shorter generation time, or a combination of these factors.
The ever-changing nature of SARS-CoV-2 variants
Although scientists have previously estimated the SARS-CoV-2 central mean generation time at 3.44-7.5 days, the data used in that study was collected early on in the COVID-19 pandemic. Following the emergence of novel SARS-CoV-2 variants, the characteristics of viral transmission are expected to change.
To this end, one study conducted when the Alpha variant was the dominant circulating strain indicated a shorter generation time between September 2020 and November 2020. The shorter the generation time, the quicker is the virus transmitted. This estimation of up-to-date generation time is important for estimating the reproduction number, which is essential for epidemiological studies.
To date, the effect of different variants on SARS-CoV-2 generation time has not been compared. In order to acquire this information, analysis of infector-infectee pair datasets is required, which is possible in household studies. In the present household study, researchers aim to investigate whether the generation time of the SARS-CoV-2 Delta variant is shorter than that of the Alpha variant in the U.K.
About the study
The researchers provided an epidemiological analysis using data from an ongoing prospective household study from the U.K. Health Security Agency (UKHSA) between February 2021 to September 2021. The dominant circulating strain transitioned from the Alpha to the Delta variant during the period when this study was conducted.
The researchers recruited only households that had an index positive case, which was confirmed by polymerase chain reaction (PCR) assay. Because the household study also included genomic sequencing of the positive cases, the researchers were able to assess the generation times for individuals infected by the Alpha and Delta variant.
Using mathematical modeling, the researchers estimated the generation time for the Alpha and Delta variants. More specifically, the Markov chain Monte Carlo (MCMC) was used to fit the transmission model to the data with the following assumptions:
- SARS-CoV-2 has a mean incubation period distribution of 5.8 days
- Asymptomatic carriers are 35% infectious as compared to symptomatic individuals with COVID-19
- Vaccinated individuals are less susceptible to COVID-19 as compared to unvaccinated individuals
- Vaccination status does not alter the infectiousness potential of an individual
- There is a single primary source of infection in each household transmission cluster.
Several other parameters were estimated for each variant. These included the mean latent period, which is defined as the time between being infected to becoming infectious, the symptomatic infectious period, and the overall transmissibility (βo).
Notably, βo represents the anticipated number of household transmissions caused by a single and non-symptomatic individual infected with SARS-CoV-2 in an unvaccinated household. The overall transmissibility parameter also assumes that after each transmission event, the newly infected individual is replaced by another susceptible individual.
Together these parameters were used to calculate the intrinsic generation time distribution, household generation time distribution, and posterior estimates of percentage reduction in these quantities for both the SARS-CoV-2 Alpha and Delta variants.
Study findings
During the study period, the researchers recruited a total of 227 households consisting of 559 participants. While the Alpha variant was detected in 131 households, which included 243 infections in 334 participants, between February 2021 and May 2021, the Delta variant was found in 96 households, which amounted to 174 infections in 225 participants, between May 2021 and August 2021.
As compared to the Alpha variant, the mean intrinsic generation time was about 4.7 days for the Delta variant, which was shorter than the 5.5 days for the Alpha variant. Furthermore, the Delta variant also had a mean household generation time of 3.2 days, which was 28% shorter than that of the Alpha variant at 4.5 days.
The household transmission of the Delta variant typically occurred earlier on in the SARS-CoV-2 infection as compared to viral transmissions that occurred with the Alpha variant. Furthermore, the Delta variant had a mean household serial interval of 1.8 days, which was shorter than that of the Alpha variant at 3.5 days.
The type of variant had a greater impact on the household generation time as compared to other factors such as age and vaccination status.
Conclusions
The estimated transmissibility of SARS-CoV-2 variants depends on the speed of the viral transmission; therefore, the effectiveness of anti-SARS-CoV-2 interventions is also determined by this viral characteristic. Thus, generation time and reproduction number estimates are critical for epidemiological analyses, particularly for newly emerging viruses and strains of SARS-CoV-2.
In the current study, researchers applied advanced mathematical modeling techniques to estimate generation time for SARS-CoV-2 Delta and Alpha variants using transmission data from a household study conducted in the U.K. Taken together, the findings from the current study confirm the higher transmissibility of the Delta variant within households as compared to the Alpha variant.
Journal reference:
- Hart, M. S., Miller, E., Andrews, N. J., et al. (2022). Generation time of the alpha and delta SARS-CoV-2 variants: an epidemiological analysis. The Lancet Infectious Diseases. doi:10.1016/S1473-3099(22)00001-9.
