Infection with the SARS-CoV-2 Delta Variant is Associated with Higher Infectious Virus Loads Compared to the Alpha Variant in both Unvaccinated and Vaccinated Individuals

Abstract

BackgroundThe emerging SARS-CoV-2 variant of concern (VOC) B.1.6.17.2 (Delta) quickly displaced the B.1.1.7 (Alpha) and is associated with increases in COVID-19 cases nationally. The Delta variant has been associated with greater transmissibility and higher viral RNA loads in both unvaccinated and fully vaccinated individuals. Data is lacking regarding the infectious virus load in Delta infected individuals and how that compares to individuals infected with other SARS-CoV-2 lineages.MethodsWhole genome sequencing of 2,785 clinical isolates was used to characterize the prevalence of SARS-CoV-2 lineages circulating in the National Capital Region between January and July 2021. Clinical chart reviews were performed for the Delta, Alpha, and B.1.2 (a control predominant lineage prior to both VOCs) variants to evaluate disease severity and outcome and Cycle threshold values (Cts) were compared. The presence of infectious virus was determined using Vero-TMPRSS2 cells and anti-SARS-CoV-2 IgG levels were determined from upper respiratory specimen. An analysis of infection in unvaccinated and fully vaccinated populations was performed.ResultsThe Delta variant displaced the Alpha variant to constitute 88.2% of the circulating lineages in the National Capital Region by July, 2021. The Delta variant associated with increased breakthrough infections in fully vaccinated individuals that were mostly symptomatic when compared to the Alpha breakthrough infections, though it is important to note there was a significantly longer period of time between vaccination and infection with Delta infections. The recovery of infectious virus on cell culture was significantly higher with the Delta variant compared to Alpha in both vaccinated and unvaccinated groups. The impact of vaccination on reducing the recovery of infectious virus from clinical samples was only observed with Alpha variant infections but was strongly associated with low localized SARS-CoV-2 IgG for both variants. A comparison of Ct values showed a significant decrease in the Delta compared to Alpha with no significant differences between unvaccinated and vaccinated groups.ConclusionsOur data indicate that the Delta variant is associated with increased infectious virus loads when compared to the Alpha variant and decreased upper respiratory antiviral IgG levels. Measures to reduce transmission in addition to increasing vaccinations rates have to be implemented to reduce Delta variant spread.FundingNIH/NIAID Center of Excellence in Influenza Research and Surveillance contract HHS N2772201400007C, Johns Hopkins University, Maryland department of health, Centers for Disease Control and Prevention contract 75D30121C11061.

Longitudinal analysis of SARS-CoV-2 vaccine breakthrough infections reveal limited infectious virus shedding and restricted tissue distribution

“…A study performed in Israel estimated that vaccination with the BNT162b2 (Pfizer/BioNTech) mRNA vaccine substantially reduced the potential for transmission among household contacts 2 . Other recent data have suggested that vaccinated individuals may shed virus (as measured by RTqPCR) at similar levels to unvaccinated individuals, particularly when infected with the Delta variant 3–5 . Some interpretations of these preliminary studies have suggested that the risk for secondary transmission is similar for vaccinated and unvaccinated individuals.…”

Spike Protein NTD mutation G142D in SARS-CoV-2 Delta VOC lineages is associated with frequent back mutations, increased viral loads, and immune evasion

“…The Delta variant of concern (VOC) quickly overtook other VOCs (Alpha, Beta, Gamma, Epsilon, Lota) and by late August 2021 accounted for over 98% of new COVID-19 cases in the United States (https://covid.cdc.gov/covid-data-tracker/#variant-proportions). SARS-CoV-2 viral loads are significantly higher in both vaccinated and unvaccinated individuals infected by Delta VOC (1). At least in part this appears to be driven by increased infectivity due to the furin cleavage enhancing P681R mutation (2).…”

Mathematical Modeling of Vaccines That Prevent SARS-CoV-2 Transmission

“…The relative infectiousness of the virus in asymptomatic people is another area of uncertainty in our model projections and this value might shift with emergence of new variants of concern. Our intra-host model was fit to early viral load data from the pandemic and has not been updated for new variants which may have higher viral loads [73][74][75]. Other models with different assumptions fit to separate sets of viral kinetic data well [25,76,77], and may provide slightly different results when considering inter-host transmission probabilities.…”