A team of scientists from the United States reveals an increased prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) D614G variant in Washington State is associated with multiple viral introductions and the variation in the timing of implementing control measures. The study findings also indicate that the D614G viral variant is associated with higher viral load, but not with disease severity. The study is currently available on the medRxiv* preprint server.
Since its emergence in December 2019 in China, the rapid spread of SARS-CoV-2 has caused a significant economic and healthcare burden worldwide. A sharp increase in coronavirus disease 2019 (COVID-19) trajectories in different parts of the world are primarily attributed to the repeated introduction of different viral variants together with the timing of implementation of control measures.
In the United States, the first COVID-19 case was reported in Washington State on 19 January 2020. Afterward, repeated viral introduction events from around the world have been reported in Washington State. Studies have shown that the SARS-CoV-2 variant introduced later in the region contains D614G mutation, which is known to increase the viral transmission efficiency. People infected with this variant have a higher viral load; however, no correlation has been observed between D614G containing SARS-CoV-2 variant and disease severity.
In the current study, the scientists performed genetic sequencing of 3940 SARS-CoV-2 variants isolated from patients between February and July 2020 in Washington State to investigate viral introduction events from different parts of the world and local transmission of SARS-CoV-2. They also investigated the impact of viral loads on the rate of transmission and the relationship between D614G mutation and COVID-19 severity.
SARS-CoV-2 phylogeny highlighting D614G split and cases through time in Washington State. (A) Phylogenetic tree of 10,051 sequences from Washington State and around the world. Tips are colored based on sampling location. This is a time-calibrated phylogeny with time shown on the x-axis. The split between 614D sequences (blue) and 614G (orange) sequences is shown as a bar to the right of the phylogeny. (B-E) Confirmed cases and genetic makeup of SARS-CoV-2 across Washington State and individual counties. The green line shows a 7 day moving average of daily confirmed cases. The bar plots show weekly sequenced cases in our dataset. Cases due to the 614D variant are shown in blue and cases due to the 614G variant are shown in orange.
The scientists observed that at the beginning of February, the 614D variant of SARS-CoV-2 was the major variant responsible for the initial COVID-19 outbreak. However, the multiple-entry events of the D614G variant eventually replaced the D614D variant in Washington State. They observed that the spread of SARS-CoV-2 was maximum when the effective reproduction number was 2 – 3. The effective reproduction number defines the number of individuals secondarily infected by a single infectious individual in a population that contains both susceptible and non-susceptible individuals.
Regarding control measures, they observed that a reduction in workplace mobility in King county due to work-from-home strategies was associated with reduced effective reproduction number of SARS-CoV-2 D614D variant. Unlike county-specific clustered cases of D614D variant, a high prevalence of D614G cases was observed throughout the state. A reduction in effective reproduction number of D614G was found to be associated with a reduction in mobility outside King county.
The scientists estimated that in Washington State, the viral introduction events were less than 10% in the initial phase of the pandemic, which eventually increased above 10% later on. Of these introduction cases, the proportion of D614G cases (more than 10%) were significantly higher than in D614D cases (less than 3%). Additionally, they observed that the population-level differences in the proportion of these two viral variants might be due to repeated introductions of the D614G variant and differences in the timing of implementing control measures.
D614G mutation and COVID-19 outcome
The scientists observed that patients infected with the D614G variant had higher viral load than those infected with the D614D variant. Regarding factors influencing the clinical outcome, they observed that age and higher viral load are the main predictors of hospitalization; however, there was no evidence indicating that the D614G variant is associated with severe COVID-19 outcome.
Taken together, the current study findings suggest that higher frequency and transmissibility of D614G variant in different parts of Washington State is associated with repeated viral entry and variation in the timing of implementing control measures. The higher viral load associated with the D614G variant does not seem to affect the rate of infection and severity of COVID-19. Therefore, proper implementation of control measures, such as inter- and intra-state travel restrictions, are of prime importance to effectively contain the pandemic.
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.